Podcasts about Multivariate

In this episode, I'm joined by Hamlet Azarian, a seasoned marketing executive with over 20 years of experience in scaling early-stage startups from ideation to success. Hamlet breaks down his data-driven approach to marketing, emphasizing the importance of multivariate testing, customer personas, and psychographics to deeply understand user needs. We discuss actionable strategies, such as rapid testing of ideas through prototypes and landing pages, and leveraging tools like Hotjar and CallRail to optimize customer engagement. Hamlet also highlights the power of focusing on progress over perfection and shares insights from his journey of building an agency with a mission to educate and empower future marketers. Whether you're a creative professional, an entrepreneur, or simply curious about growth marketing, this episode is packed with insights to help you take your ideas to the next level.Timestamps:(00:00) - Introduction to Hamlet Azarian(01:30) - Early-stage startup dynamics(03:00) - Example: Scaling Camino Financial(08:00) - Multivariate testing and audience targeting(15:00) - Understanding customer personas and psychographics(25:00) - Building marketing strategies through interviews(32:50) - Optimizing landing pages and pre-launch campaigns(38:20) - Growth mindset and startup culture(50:30) - Tools and tech stack for data-driven marketing(54:00) - Closing thoughts and action stepsCheck out today's guest, Hamlet Azarian:Hamlet's LinkedIn: https://www.linkedin.com/in/hamletazarianAzarian Growth Agency's Website: https://azariangrowthagency.com/Hamlet's Website: https://hamletazarian.com/Check out The Futur:Website: https://www.thefutur.com/Courses: https://www.thefutur.com/shopLinkedin: https://www.linkedin.com/company/the-futur/Podcasts: https://thefutur.com/podcastInstagram: https://www.instagram.com/thefuturishere/Facebook: https://www.facebook.com/theFuturisHere/Twitter: https://x.com/thefuturishereTikTok: https://www.tiktok.com/@thefuturishereYoutube:https://www.youtube.com/thefuturishereCheck out Chris Do:Website: https://zaap.bio/thechrisdoLinkedIn:https://www.linkedin.com/in/thechrisdo/Facebook:https://www.facebook.com/BizOfDesignInstagram:https://www.instagram.com/thechrisdo/Twitter:

Today we give you our second conversation with Dr. Andrew Kiselica regarding aspects of neuropsychological test interpretation, with the current discussion focusing on multivariate base rates. Show notes are available at www.NavNeuro.com/161 _________________ If you'd like to support the show, here are a few easy ways: 1) Get CE credits for listening to select episodes: www.NavNeuro.com/INS  2) Tell your friends and colleagues about it 3) Subscribe (free) and leave an Apple Podcasts rating/review: www.NavNeuro.com/itunes 4) Check out our book Becoming a Neuropsychologist, and leave it an Amazon rating   Thanks for listening, and join us next time as we continue to navigate the brain and behavior! [Note: This podcast and all linked content is intended for general educational purposes only and does not constitute the practice of psychology or any other professional healthcare advice and services. No professional relationship is formed between hosts and listeners. All content is to be used at listeners' own risk. Users should always seek appropriate medical and psychological care from their licensed healthcare provider.]

เคยได้ยินเกี่ยวกับ MVT (Multivariate Testing) หรือยัง?

In this week's episode Patrick and Greg discuss Cattell's data box and try to better understand what it is, what it is not, and how we might make use of this in practice. Along the way they also discuss illegal knives, baseball cards, the Cubs and the Mariners, bicentennial quarters, how to load a dishwasher, horrible people, anal retentive friends, Flat Stanley, Dungeons & Dragons, pricing yourself out of business, needing 20 friends, being super pedantic, The Full Monty, stereograms, and magical statistical accessories.Stay in contact with Quantitude! Web page: quantitudepod.org TwitterX: @quantitudepod YouTube: @quantitudepod Merch: redbubble.com

Deepthy Varghese, MSN, ACNP, FNP, Northside Hospital is joined by Hung-Fat Tse, Sr., MD, University of Hong Kong and Glenn Young, MBBS, Royal Adelaide Hospital to discuss the effectiveness of the PRECISE-DAPT score with the CHA2DS2VASC score in predicting thromboembolic risk in nonvalvular atrial fibrillation (AF) patients undergoing transesophageal echocardiography (TEE) before AF ablation. 428 patients were analyzed, with 60 in the thrombogenic positive group and 368 in the thrombogenic milieu negative group. Multivariate logistic regression revealed that the PRECISE-DAPT score independently predicted thrombogenic milieu presence (OR: 1.145, CI: 1.083–1.211, p < 0.001). The study concluded that the PRECISE-DAPT score is a valuable predictor of thromboembolic risk in AF patients undergoing TEE before ablation procedures.   https://www.hrsonline.org/education/TheLead https://jafib-ep.com/journal/february-2024-volume-17-issue-1/original-research-the-predictive-value-of-precise-dapt-scores-for-thrombogenic-milieu-of-the-left-atrium-in-patients-awaiting-af-ablation/   Host Disclosure(s): D. Varghese: Nothing to disclose   Contributor Disclosure(s): H. Tse: Research: Abbott Medical, Medtronic Inc., Boston Scientific, AstraZeneca, Daiichi Sankyo, Pfizer/BMS, Amgen, Bayer Healthcare Pharmaceuticals, Sanofi, Conoraria/Speaking/Teaching: Abbott Medical, Medtronic Inc., Boston Scientific, AstraZeneca, Daiichi Sankyo, Pfizer/BMS, Amgen, Bayer Healthcare Pharmaceuticals, Sanofi, Boehringer Ingelheim, Biotronik G. Young: Nothing to disclose This episode has .25 ACE credits associated with it. If you want credit for listening to this episode, please visit the episode page on HRS365     https://www.heartrhythm365.org/URL/TheLeadEpisode72

Send us a Text Message.Could your website be underperforming without you even knowing it? Today, on "SEO is Not That Hard," I'm Ed Dawson and we're going to unlock the secrets behind effective SEO strategies that can transform your online presence. This episode kicks off with the power of main content (MC) and why it's the lifeblood of your webpage, driving user engagement through text, images, videos, and interactive tools. We'll demystify the dreaded manual penalties from Google and walk you through actionable steps to safeguard your site's ranking. Plus, we'll break down what marketplaces like eBay and Amazon mean for your SEO strategy and clarify the role of merchants in affiliate marketing to help you maximize your traffic.But that's not all! We'll expose the clandestine tactics black hat SEOs use to shield their "money sites" from penalties, revealing how they cleverly spam tier one links to boost their rankings without directly touching their main site. Next, get ready to elevate your optimization game with an in-depth look at multivariate testing. Discover how this advanced technique outperforms traditional A/B split testing by analyzing multiple page versions simultaneously, giving you quicker, more comprehensive results. Whether you're a seasoned SEO expert or just starting out, this episode is packed with insights that can take your website to new heights.SEO Is Not That Hard is hosted by Edd Dawson and brought to you by KeywordsPeopleUse.comYou can get your free copy of my 101 Quick SEO Tips at: https://seotips.edddawson.com/101-quick-seo-tipsTo get a personal no-obligation demo of how KeywordsPeopleUse could help you boost your SEO then book an appointment with me nowSee Edd's personal site at edddawson.comAsk me a question and get on the show Click here to record a questionFind Edd on Twitter @channel5Find KeywordsPeopleUse on Twitter @kwds_ppl_use"Werq" Kevin MacLeod (incompetech.com)Licensed under Creative Commons: By Attribution 4.0 Licensehttp://creativecommons.org/licenses/by/4.0/

In this JCO Precision Oncology Article Insights episode, Mitchell Elliot provides a summary on "Serial Postoperative Circulating Tumor DNA Assessment Has Strong Prognostic Value During Long-Term Follow-Up in Patients With Breast Cancer" by Shaw, et al published on May 1st, 2024. TRANSCRIPT The guest on this podcast episode has no disclosures to declare.  Mitchell Elliott: Hello and welcome to the JCO Precision Oncology Article Insights. I'm your host, Mitchell Elliott, an ASCO Journal editorial fellow. Today I will be providing a summary of the article titled, “Serial Postoperative Circulating Tumor DNA Assessment Has Strong Prognostic Value During Long Term Follow up in Patients with Breast Cancer,” by Dr. Jacqueline Shaw and colleagues.  Circulating tumor DNA is shed readily into the peripheral blood by tumors. ctDNA makes up a small fraction of the total cell free DNA in the peripheral blood and can be detected using highly sensitive assays. ctDNA assays can be tumor-informed where blood samples are tested for the presence of tumor specific mutations, which are selected by sequencing the primary tumor, so the panels are patient specific. Tumor agnostic assays also exist which are typically looking for the presence of cancer driver mutations or cancer derived methylation signals, which are not patient specific but rather cancer specific. Several retrospective analyses of clinical trials and cohorts have demonstrated that the identification of ctDNA in patients in follow-up can predict relapse in breast cancer, lung cancer, and colon cancer. Personalized tumor informed assays have demonstrated high technical specificity, but to date there is no gold standard assay identified and no direct comparison between all of the available assays. While the literature to date has demonstrated that identification of ctDNA prior to clinical relapse is possible, no study has demonstrated that it improves patient outcomes.  In this specific study, the authors evaluated the Signatera assay, a tumor informed assay based on whole exome sequencing, enabling the design of personalized panels for up to 16 tumor specific variants detected via multiplex PCR next generation sequencing. This was evaluated in the exploratory breast lead interval study or EBLIS, which is a study based out of the United Kingdom. EBLIS is a multicenter prospective cohort study funded by Cancer Research UK and the National Institute of Health Research that opened for recruitment in 2012. This was a retrospective analysis so no results were directly shared with patients or physicians. Patients were eligible if they were 18 years or older, had histologically confirmed breast cancer and must have completed all surgery and chemotherapy within three years of entry into the study. They had to have an adjuvant online risk relapse at greater than 65% or mortality of greater than 50% at 10 years, which defines a very high risk subgroup for study enrollment.  The results of this study and the baseline patient characteristics reflected the predefined clinical risk. The majority received neoadjuvant or adjuvant chemotherapy. Most patients were diagnosed with invasive ductal carcinoma and were staged 2b to 3c. There were 156 patients identified from this cohort after 28 had insufficient DNA and 3 had unsuccessful whole exome sequencing, which are required for the assay generation. Of the 156 patients, there were 1136 plasma time points evaluated. Of the 1136 plasma time points, ctDNA was identified in 46, which represents approximately 4% of the total time points in this high risk cohort. 34 patients have experienced disease relapse, including 22 with hormone receptor positive HER2 negative disease, three with hormone receptor positive HER2 positive disease, seven with triple negative breast cancer, and two with hormone receptor negative HER2 positive disease. ctDNA was detected in 30 of the 34 patients who had a subsequent relapse with a patient specific sensitivity of 88.2%. Relapse was predicted with a lead time interval of up to 38 months with a median of around 10.5 months ranging from 0 to 38 months. 100% of relapses were detected through ctDNA in patients with hormone receptor positive HER2 positive disease, triple negative breast cancer and hormone receptor negative HER2 positive disease.  Patients with a positive ctDNA test had a poor recurrence free survival with a hazard ratio of 52.98 with a 95% confidence interval of 18.32 to 153.2 with a statistically significant p value. Patients also had a significantly reduced overall survival if ctDNA was detected in the adjuvant setting. Multivariate models incorporating clinical pathologic variables and ctDNA status were analyzed. In this, ctDNA status remained the most significant factor associated with recurrence free survival and overall survival. Interestingly, concurrent ctDNA analyses and CA 15-3 measurements were available for 100 patients. CA 15-3 status was defined as positive and negative at the cutoff value of 30 units per milliliter. A Fisher's exact test showed a borderline statistically significant correlation between ctDNA status and CA 15-3, with a p value of 0.053. Again, multivariate analyses indicated that ctDNA was independent of CA 15-3 in predicting recurrence free survival and overall survival. Interestingly, ctDNA was not detected in 4 patients who experienced subsequent disease relapse, even with consistent and frequent sampling. Furthermore, ctDNA was detected in 5 out of 122 patients who did not have a subsequent recurrence, all being hormone receptor positive HER2 negative. These patients also had mature follow up. It is unknown if there was a change in the adjuvant treatment associated with subsequent negative tests, and follow up continues.   In summary, the study reaffirms that personalized ctDNA assays have high technical sensitivity and specificity for the identification of patients at risk for disease relapse. The test is highly predictive of recurrence in patients with breast cancer, especially with triple negative subtype where all patients had ctDNA detected prior to clinical relapse. However, for patients with hormone receptor positive breast cancer, these results suggest that this test needs to be used with caution, as a small proportion of patients experience disease relapse with negative tests and others whose tests are positive have not yet relapsed. It is unknown if these patients with ctDNA detected have radiographically overt metastatic disease in the absence of clinical symptoms, as concurrent radiographic surveillance was not performed in the standard of care follow up. Prospective clinical trials are required to define a role for ctDNA surveillance in clinical care.  Again, I'm Mitchell Elliot, a JCO Precision Oncology editorial fellow. Thank you for listening to the JCO Precision Oncology Article Insight, and please tune in for the next topic. Don't forget to give us a rating or review and be sure to subscribe so you never miss an episode. You can find all ASCO shows at www.asco.org/podcasts.  The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.  Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.      

In this episode, I speak with Nicolas Mirjolet, CEO and Co-Head of Research at Quantica Capital.We begin with Nicolas's experience operating a statistical arbitrage fund, where he provides his thoughts as to what makes a strategy easier or harder to scale a business on. Nicolas also provides some context for his somewhat counter-intuitive view that the larger players had a bigger edge in this capital constrained space.We then transition to Quantica's flagship managed futures program. Nicolas explains that while Quantica is a price-based trend follower, they apply a multivariate approach to their signal analysis. We discuss how the approach works and how it contrasts against a standard univariate approach. Specifically, Nicolas shares his thoughts on how the multivariate approach impacts the portfolio return profile and why you may want more or fewer variables in your signal universe than your tradable market universe.We end the conversation with Quantica's most recent quarterly research paper, which provides quantitative insight into the convexity versus robustness tradeoff trend managers make when they add more markets to their portfolio.Please enjoy my conversation with Nicolas Mirjolet.

​This episode of Chew on CRO delves into the intricacies of brand development, emphasizing the importance of understanding product-market fit at different stages. It highlights the significance of repeat purchase behavior as a crucial metric and the role of conversion rate in driving sales. The problem-agitate-solve approach is recommended for effective messaging. Consistency in messaging from ads to landing pages is crucial for conversions. Avoiding assumptions about brand pricing based on customer perceptions is advised. This episode also explains type one and type two error rates in data analysis and stresses the importance of considering the entire customer journey in testing metrics. 0:00 - Intro​ 1:27 - Understanding post-acquisition strategies based on brand stage. ​3:00 - The stages of consumer behavior. ​6:03 - Utilizing different platforms for marketing to super users. ​7:04 - Analyzing the value proposition and sales pitch for effective scaling. ​9:01 - Evaluating repeat purchase rates for long-term scalability. ​11:06 - Problem-Agitate-Solve. ​14:05 - Ensuring message congruency from ads to landing pages. ​16:01 - Distinguishing between type I and type II errors. ​21:31 - Understanding different mentalities of audiences. ​22:03 - Repeat purchase rates and unit economics for long-term growth. ​23:30 - The impact of perceived value of offers. ​24:08 - Analyzing results based on different types of traffic. ​25:10 - Knowing when to stop a test and reevaluate hypotheses. ​26:03 - Deep segmentation and cohort analysis. ​27:00 - Correlation vs. causation. ​28:00 - Multivariate testing. ​32:18 - Evaluating performance through average revenue per user. ​35:55 - How LTV may be misleading. Follow us, subscribe to our newsletter, and to see our exclusive merch check out https://chewonthis.io/ Ron Shah - https://twitter.com/obviceo Ash Melwani - https://twitter.com/ashvinmelwani Chew On This - https://twitter.com/chewonthisdtc

Anthea Sargeaunt is the CEO and Co-founder of 2S Water. Multivariate, real-time non-contact sensing is one of the holy grails of water management. Getting it right will allow all stakeholders to understand what is in their water in real time. And if we can get it really right, this knowledge will allow a host of improvements in water management, including reduced chemical and energy use, reduced pollution, reduced fines, improved health outcomes, improving the pace and cadence of experimentation with new technology. The list is very long indeed. Anthea and her team have taken a fascinating pathway from problem selection to massively leveraging their equity through grants. She is an exceptional founder and person and one of the best founder communicators I have met. I loved her insights into the importance of public speaking as you're building a company. Please do enjoy my conversation with the excellent Anthea Sargeaunt.  Subscribe to The Fundamental Molecule here: https://www.burntislandventures.com/the-fundamental-molecule For the full show notes, transcript, and links to mentioned content, check out the episode page here: https://podcasts.apple.com/us/podcast/the-fundamental-molecule/id1714287205 ----------- Anthea's entrepreneurial journey, spanning from early ventures to the oil and gas sector, showcases her problem-solving prowess and industry acumen. Today, she and Tom explore partnership complexities and grant acquisition, stressing understanding partner expectations and grant funding's role in startup growth. Anthea's insights emphasize genuine connections, adaptable communication, and infrastructure investment for streamlined product development. This dialogue not only underscores innovation's transformative power but also offers guidance for aspiring water entrepreneurs, marking a pivotal moment in industry evolution. Episode Highlights: 0:00 Start 0:49 Introduction 1:50 Anthea's career to date 6:10 2S Water's genesis 8:30 Its product and the problem it solves 10:43 Understanding the problem 14:39 Establishing early customer relationships with large companies 16:50 Pros and cons of this early engagement 18:19 Crossing the Chasm and Anthea's implementation of it 21:11 Navigating partnerships 27:00 Funding with grants 29:19 Key skills in writing grants 32:48 What surprised Anthea most about the water sector 34:32 What she has learned since joining it 35:19 Anthea's advice based on these learnings 37:05 Her experience in the Lithium market 39:52 Working with family 42:24 Anthea's speaking and presenting skills and their value 46:01 Her most important piece of advice for aspiring water entrepreneurs Links: Burnt Island Ventures: https://www.burntislandventures.com/ 2S Water: https://www.2swater.com/ Quotes: "I've always been surprised at water treatment operators. They're such a special breed of people. They do it because they love it.” "In the mining sector, when we look at it, there is no other real path to the market than through the large multinationals." "If you don't have that kind of insight coming from the other side of the table, it's hard to get it anywhere else." "Partnerships are completely fundamental... cultivating them is vitally important." "Writing a grant is much like any other sales process... understand what the grant organization is trying to accomplish." "The lab isn't the field... get out into the field as fast as you can."

Jake and Anthony are joined by Casey Dreier, Chief of Space Policy at The Planetary Society, to talk about the latest on Mars Sample Return, JPL layoffs, and everything space policy.TopicsOff-Nominal - YouTubeEpisode 142 (with Casey Dreier) - YouTubeHow layoffs at JPL can be traced to a stalemate in Congress | The Planetary SocietyThe path forward for Mars Sample Return | The Planetary SocietyThe U.S. Senate threatens to cancel Mars Sample Return | The Planetary SocietyThe Planetary Exploration Budget Dataset | The Planetary SocietyThe 2024 Day of Action | The Planetary SocietyFollow CaseyCasey Dreier | The Planetary SocietyThe Planetary SocietyFollow Off-NominalSubscribe to the show! - Off-NominalSupport the show, join the DiscordOff-Nominal (@offnom) / TwitterOff-Nominal (@offnom@spacey.space) - Spacey SpaceFollow JakeWeMartians Podcast - Follow Humanity's Journey to MarsWeMartians Podcast (@We_Martians) | TwitterJake Robins (@JakeOnOrbit) | TwitterJake Robins (@JakeOnOrbit@spacey.space) - Spacey SpaceFollow AnthonyMain Engine Cut OffMain Engine Cut Off (@WeHaveMECO) | TwitterMain Engine Cut Off (@meco@spacey.space) - Spacey SpaceAnthony Colangelo (@acolangelo) | TwitterAnthony Colangelo (@acolangelo@jawns.club) - jawns.club

In this week's episode, host Anna Rose (https://twitter.com/annarrose) and cohost Nico Mohnblatt (https://twitter.com/nico_mnbl) catch up with Ulrich Haböck (https://twitter.com/UHaboeck), an applied cryptographer at Polygon Labs (https://polygon.technology/). This episode revolves around Ulrich's journey into applied zero-knowledge cryptography, transitioning from an academic environment to being a full-time practitioner. They discuss his contributions to the field, including his many write-ups and manuscripts as well as his breakthrough research on Multivariate lookups with his work logUp. They also cover his work on logarithmic derivative lookups using GKR with Shahar Papini, as well as his innovative approaches to STARKs over finite fields that are not ‘NTT-friendly'. This episode offers a deep dive into the complexities and breakthroughs in applied cryptography. Here's some additional links for this episode: A summary on the FRI low degree test by Ulrich Haböck (https://eprint.iacr.org/2022/1216.pdf) Brakedown's expander code by Ulrich Haböck (https://eprint.iacr.org/2023/769.pdf) Improving LogUp with GKR - By Ulrich from Polygon (https://www.youtube.com/watch?v=DCEg61ExwK4) Improving logarithmic derivative lookups using GKR by Papini and Haböck (https://eprint.iacr.org/2023/1284) flookup: Fractional decomposition-based lookups in quasi-linear time independent of table size by Gabizon and Khovratovich (https://eprint.iacr.org/2022/1447.pdf) Bulletproofs++: Next Generation Confidential Transactions via Reciprocal Set Membership Arguments by Eagen Kanjalkar, Ruffing and Nick (https://eprint.iacr.org/2022/510.pdf) ZK8: Hyperplonk: PLONK without FFTs and with high degree gates - Benedikt Bünz (https://www.youtube.com/watch?v=2JDBD5oMS0w) ZK9: logUp - Lookup arguments based on the logarithmic derivative - Ulrich Haböck (https://www.youtube.com/watch?v=qv_5dF2_C4g) ZK10: Degree tricks in DEEP STARKs - Shahar Papini (https://www.youtube.com/watch?v=lHmiSuaLxhE) Orion: Zero Knowledge Proof with Linear Prover Time by Xie, Zhang and Song (https://eprint.iacr.org/2022/1010.pdf) Reed-Solomon Codes over the Circle Group by Haböck, Lubarov and Nabaglo (https://eprint.iacr.org/2023/824) Marlin: Preprocessing zkSNARKs with Universal and Updatable SRS by Chiesa, Hu, Maller, Mishra, Vesely and Ward (https://eprint.iacr.org/2019/1047.pdf) ZK Hack IV online is coming soon, visit zhhack.dev/zkhackIV (https://zkhack.dev/zkhackIV/) for the latest news! Launching soon, Namada (https://namada.net/) is a proof-of-stake L1 blockchain focused on multichain, asset-agnostic privacy, via a unified shielded set. Namada is natively interoperable with fast-finality chains via IBC, and with Ethereum using a trust-minimised bridge. Follow Namada on Twitter @namada (https://twitter.com/namada) for more information and join the community on Discord discord.gg/namada (http://discord.gg/namada). If you like what we do: * Find all our links here! @ZeroKnowledge | Linktree (https://linktr.ee/zeroknowledge) * Subscribe to our podcast newsletter (https://zeroknowledge.substack.com) * Follow us on Twitter @zeroknowledgefm (https://twitter.com/zeroknowledgefm) * Join us on Telegram (https://zeroknowledge.fm/telegram) * Catch us on YouTube (https://zeroknowledge.fm/)

In this week's episode, Anna (https://twitter.com/annarrose) and cohost Brendan Farmer (https://twitter.com/_bfarmer) catch up with Jim Posen (https://twitter.com/jimpo_potamus) and Radi Cojbasic (https://twitter.com/radi_cojbasic) from Ulvetanna (https://www.ulvetanna.io/). They cover the origin story of Ulvetanna and their work on the ZK hardware/software intersection before moving on to discuss Binius, a new proving system they developed which is optimised for hardware. Binius is built on towers of binary fields and draws on recent breakthroughs on SNARKs. This work continues the trend towards the use of smaller fields and was inspired by the development of new lookup arguments, work done on multilinear provers and sum-check as well as the use of recursive composition in SNARKs. Here's some additional links for this episode: Succinct Arguments over Towers of Binary Fields by Diamond and Posen (https://eprint.iacr.org/2023/1784.pdf) Binius: a Hardware-Optimized SNARK (https://www.ulvetanna.io/news/binius-hardware-optimized-snark) Episode 170: Hardware for ZKPs & VDFs with Supranational (https://zeroknowledge.fm/170-2/) Episode 266: ZK Hardware Sessions with Zprize Pt. 1 (https://zeroknowledge.fm/266-2/) Episode 267: ZK Hardware Sessions with Zprize Pt. 2 (https://zeroknowledge.fm/267-2/) Scalable, transparent, and post-quantum secure computational integrity by Ben-Sasson, Bentov, Horesh, Riabzev (https://eprint.iacr.org/2018/046.pdf) Multivariate lookups based on logarithmic derivatives by Ulrich Haböck (https://eprint.iacr.org/2022/1530.pdf) Episode 250: What's the Deal with Hash Functions? (https://zeroknowledge.fm/250-2/) Plonky2: Fast Recursive Arguments with PLONK and FRI by Polygon Zero Team (https://docs.rs/crate/plonky2/latest/source/plonky2.pdf) ZK Hack IV online is coming soon, get notified by signing up to the mailing list here (https://www.subscribepage.com/zkhackiv)! Launching soon, Namada (https://namada.net/) is a proof-of-stake L1 blockchain focused on multichain, asset-agnostic privacy, via a unified shielded set. Namada is natively interoperable with fast-finality chains via IBC, and with Ethereum using a trust-minimised bridge. Follow Namada on Twitter @namada (https://twitter.com/namada) for more information and join the community on Discord discord.gg/namada (http://discord.gg/namada). If you like what we do: * Find all our links here! @ZeroKnowledge | Linktree (https://linktr.ee/zeroknowledge) * Subscribe to our podcast newsletter (https://zeroknowledge.substack.com) * Follow us on Twitter @zeroknowledgefm (https://twitter.com/zeroknowledgefm) * Join us on Telegram (https://zeroknowledge.fm/telegram) * Catch us on YouTube (https://zeroknowledge.fm/)

Becky Winslow, BS, PharmD Host and Pharmacogenomics Medical Science Liaison; Behnaz Sarrami, MS, PharmD, Host and Pharmacogenomics Medical Science Liaison; Thierry Dervieux, PharmD, PhD, Chief Scientific Officer at Prometheus Laboratories Disclaimer: Behnaz Disclaimer: These are my personal views and opinions, and I am not speaking on behalf of Castle Biosciences, Inc. Becky Disclaimer: These are my personal views and opinions, and I am not speaking on behalf of any other entity.   Transcription:  1 00:00:06,190 --> 00:00:19,620 You're listening to the Pharmacy podcast Network in a world where one size fits all medications dominate the pharmaceutical industry. 2 00:00:20,079 --> 00:00:24,750 Precision medicine brings a ray of hope for those seeking customized health care. 3 00:00:25,350 --> 00:00:32,830 Pharmacists have a unique opportunity to help people in need of specialized testing to ensure medications work as intended. 4 00:00:33,540 --> 00:00:44,680 Welcome to PGX for pharmacists where we unravel the wonders of precision medicine and its potential to revolutionize the way we approach pharmacy care. 5 00:00:45,169 --> 00:00:52,790 Get ready to uncover the secrets behind pharmacogenomics and how it's transforming lives one genome at a time. 6 00:00:52,799 --> 00:00:53,189 Hello, 7 00:00:53,200 --> 00:00:53,950 everyone. 8 00:00:54,159 --> 00:00:55,080 I'm your host, 9 00:00:55,090 --> 00:00:56,389 Doctor Becky Winslow. 10 00:00:56,409 --> 00:01:09,860 And you're listening to the PGX for Pharmacist podcast that we magazine recognized in 2021 as the ninth most listened to genetics podcasts in the world on the PGX for Pharmacist podcast. 11 00:01:09,870 --> 00:01:16,690 We explore all things pharmacogenomics related and our mission is to educate and advocate for PGX. 12 00:01:16,769 --> 00:01:23,849 We accomplish this mission through exclusive interviews with highly qualified and well experienced pharmacogenomics. 13 00:01:23,860 --> 00:01:29,720 Industry leaders such as today's special guest and my name is Baas Sami, 14 00:01:29,730 --> 00:01:32,739 the co-host of PGX for Pharms podcast, 15 00:01:32,750 --> 00:01:33,860 Pharmacogenomics, 16 00:01:33,870 --> 00:01:36,819 medical science liaison and a mentor to pharmacist. 17 00:01:36,889 --> 00:01:40,239 Connect with us on linkedin and let's get a conversation going. 18 00:01:40,269 --> 00:01:46,720 We want to hear from you and how you're impacting pharmacogenomic stakeholders and what you have learned throughout your journey. 19 00:01:48,510 --> 00:01:49,010 Ok. 20 00:01:49,019 --> 00:01:50,819 So without any further ado, 21 00:01:50,839 --> 00:01:54,769 I'm extremely pleased to introduce to our audience. 22 00:01:54,919 --> 00:01:56,059 Doctor Theory Devo, 23 00:01:57,239 --> 00:02:01,129 the Chief Scientific Officer at Prometheus Laboratories, 24 00:02:01,139 --> 00:02:08,139 and Perme Prometheus Laboratories is a reference clinical laboratory that's focused on the diagnosis, 25 00:02:08,149 --> 00:02:13,330 prognosis and monitoring of immune mediated inflammatory diseases. 26 00:02:13,970 --> 00:02:14,229 So, 27 00:02:14,240 --> 00:02:14,649 thank you, 28 00:02:14,660 --> 00:02:17,759 Doctor De for joining us on the podcast. 29 00:02:17,770 --> 00:02:18,589 Today. 30 00:02:18,600 --> 00:02:23,190 I'm excited to share your and Prometheus's story with our audience. 31 00:02:23,649 --> 00:02:25,630 Um in particular, 32 00:02:25,639 --> 00:02:45,369 I'm excited about you sharing your career journey as a farm D phd and Chief scientific officer and designer of the Predictor PK AD A which is a precision guided dosing test for the optimization of Humira Remicade and their bio cylinders. 33 00:02:46,119 --> 00:02:46,449 So, 34 00:02:46,460 --> 00:03:04,220 one of Bana's and my main goals for this episode of the PGX for Pharmacist podcast is to expand our audience's notion of what a PGX test looks like and to inspire them to think bigger than the traditional box PGX test. 35 00:03:04,229 --> 00:03:08,020 Most of them or most of you are uh familiar with. 36 00:03:09,020 --> 00:03:09,429 So, 37 00:03:09,440 --> 00:03:22,179 Doctor D uh I'd like to start the podcast by having our guests um introduce themselves and elaborate on how you are a pharmacogenomics expert. 38 00:03:23,619 --> 00:03:23,800 Yeah, 39 00:03:23,809 --> 00:03:24,250 thank you, 40 00:03:24,259 --> 00:03:25,759 Becky for having me. 41 00:03:25,770 --> 00:03:26,850 Uh uh Yes. 42 00:03:26,860 --> 00:03:27,289 So I am a, 43 00:03:27,300 --> 00:03:30,820 I am a pharmacist uh with uh a family who is a, 44 00:03:30,830 --> 00:03:33,039 a doctorate in pharmacokinetics. 45 00:03:33,539 --> 00:03:44,520 Uh I completed my studies in France and I came as a postdoc uh fellow uh to work in the United States about 20 years ago to work on the pharmacogenomic of anti cancer agents, 46 00:03:44,929 --> 00:03:49,160 uh primarily uh six Maturin as well as methotrexate. 47 00:03:49,169 --> 00:03:50,550 After my post doc, 48 00:03:50,770 --> 00:03:52,960 uh I moved uh in industry for promet. 49 00:03:53,490 --> 00:04:01,429 So I have a large experience in uh uh the implementation of pharmacogenetics testing in immune mediated inflammatory disease. 50 00:04:01,509 --> 00:04:12,550 Our lab Rome was the first uh clinical laboratory in the United States to offer the fin uh metyl transfer genotyping as well as the thin metabolites. 51 00:04:12,559 --> 00:04:13,029 So, 52 00:04:13,050 --> 00:04:21,989 uh uh of uh of 70 publications in the field and uh I'm very uh very excited to have uh to be on the postcard with you uh uh today. 53 00:04:23,660 --> 00:04:24,220 All right. 54 00:04:24,230 --> 00:04:27,359 So thank you for qualifying yourself as an expert. 55 00:04:27,369 --> 00:04:27,619 So, 56 00:04:27,630 --> 00:04:32,839 let's jump right in and delve into your current PGX work. 57 00:04:32,850 --> 00:04:33,279 So, 58 00:04:33,489 --> 00:04:36,540 if you'll tell us um a little about Prometheus, 59 00:04:36,549 --> 00:04:38,000 specifically, 60 00:04:38,010 --> 00:04:40,350 what is Prometheus's mission? 61 00:04:40,359 --> 00:04:43,799 And how are you guys going about accomplishing your mission? 62 00:04:44,760 --> 00:04:44,980 Yeah, 63 00:04:44,989 --> 00:04:45,700 sure. 64 00:04:45,709 --> 00:04:47,459 Uh So Promet is a, 65 00:04:47,470 --> 00:04:52,790 is a reference uh clinical laboratory based in Southern California in San Diego. 66 00:04:53,230 --> 00:04:56,809 Uh The company has been there for uh over 25 years. 67 00:04:56,820 --> 00:05:03,950 We are uh specialize in the differential diagnosis of autoimmune G I disease uh disorders, 68 00:05:04,059 --> 00:05:06,019 uh gastrointestinal disorder, 69 00:05:06,230 --> 00:05:08,619 uh and inflammatory bowel disease. 70 00:05:08,980 --> 00:05:10,299 And over the years, 71 00:05:10,309 --> 00:05:16,600 we have developed a portfolio of a differentiated solution to facilitate the diagnosis, 72 00:05:16,609 --> 00:05:17,470 the prognosis, 73 00:05:17,480 --> 00:05:18,429 the monitoring, 74 00:05:18,660 --> 00:05:21,910 as well as therapy selection with pharmacogenetics testing, 75 00:05:21,920 --> 00:05:24,730 which we are offering to our clinical laboratory. 76 00:05:24,829 --> 00:05:26,350 And most importantly, 77 00:05:26,410 --> 00:05:27,299 uh recently, 78 00:05:27,309 --> 00:05:35,660 we are uh uh developing some uh uh testing solution with the credit topic care test to optimize treatment to uh biologics. 79 00:05:36,470 --> 00:05:37,130 Ok. 80 00:05:37,140 --> 00:05:37,329 Well, 81 00:05:37,339 --> 00:05:37,450 that, 82 00:05:37,459 --> 00:05:38,049 that's great. 83 00:05:38,059 --> 00:05:46,100 Can you also tell us uh about the Prois Library of Precision Medicine Tests for inflammatory bowel disease for patients? 84 00:05:46,109 --> 00:05:49,230 how they benefit medication therapy management. 85 00:05:49,239 --> 00:05:56,429 Stakeholders across the IB DS patients journey from diagnosis to treatment to disease, 86 00:05:56,440 --> 00:06:02,049 monitoring through remission and how they differ from other lab tests for IBD and his treatments. 87 00:06:02,709 --> 00:06:03,209 Yes. 88 00:06:03,220 --> 00:06:03,369 So, 89 00:06:03,380 --> 00:06:04,399 so we uh our, 90 00:06:04,410 --> 00:06:10,100 our clinical laboratory offers some uh highly specialized test to facilitate the, 91 00:06:10,109 --> 00:06:16,779 the diagnostic of uh to facilitate the differential diagnosis of uh uh inflammatory bowel disease. 92 00:06:16,790 --> 00:06:22,359 So we are following uh testing solution with uh serological testing, 93 00:06:22,529 --> 00:06:23,799 for example, 94 00:06:23,809 --> 00:06:38,410 uh uh piana as as as well as uh macro microbial uh uh antibodies that are present uh uh in Crohn's disease as well as uh over uh auto uh auto antibodies that are present in er colitis. 95 00:06:39,339 --> 00:06:43,684 These are conditions that are uh uh somewhat difficult to treat. 96 00:06:43,704 --> 00:06:49,994 Uh And uh we are uh uh offering those tests to uh help uh gastroenterologist. 97 00:06:50,015 --> 00:06:51,114 Uh uh first of all, 98 00:06:51,125 --> 00:07:03,434 to establish a differential diagnosis of IBD as compared to other uh condition typically uh uh irritable bowel syndrome as well as over gastrointestinal disorder. 99 00:07:03,445 --> 00:07:05,635 When the diagnostic is established, 100 00:07:05,910 --> 00:07:31,839 uh we offer uh testing to uh establish a prognosis where we're gonna in inform the clinician that the patient has a more aggressive uh disease that will require more aggressive treatment where uh we can uh provide the testing solution to initiate uh uh the most appropriate therapy for uh for the patient uh with uh a testing where we are uh basically uh you know, 101 00:07:31,850 --> 00:07:36,559 establish de determining some genotyping with the fit transferal genotyping. 102 00:07:36,570 --> 00:07:37,279 For example, 103 00:07:37,290 --> 00:07:40,250 where we can uh indicate that the patient is, 104 00:07:40,260 --> 00:07:45,079 is likely uh to present with a side effect to those medication. 105 00:07:45,399 --> 00:07:46,170 And once you know, 106 00:07:46,179 --> 00:07:47,799 the the treatment is initiative, 107 00:07:47,809 --> 00:08:16,089 we have a portfolio of solution uh to facilitate the monitoring of the disease of the inflammatory bowel disease as well as the dosing optimization with uh uh the answer test which uh measure blood level uh for uh uh monoclonal antibodies that are indicated in the treatment of IB start with starting with Infliximab Adalimumab as well as uh Tein and vidal. 108 00:08:16,980 --> 00:08:24,040 So we have a comprehensive portfolio to uh to surround the clinician with uh a variety of testing solution. 109 00:08:24,049 --> 00:08:30,250 With our goal being to improve the uh the outcome uh of patients with uh with diabetes. 110 00:08:30,260 --> 00:08:34,520 And I think that the pharmacist has a very important role to play from that perspective. 111 00:08:35,179 --> 00:08:36,039 So theory, 112 00:08:36,049 --> 00:08:40,239 could you elaborate for us more on the predictor test? 113 00:08:40,249 --> 00:08:42,758 Um especially since you designed that test, 114 00:08:42,768 --> 00:08:44,218 we'd really like to know, 115 00:08:44,489 --> 00:08:45,039 um you know, 116 00:08:45,049 --> 00:08:49,638 what did that take and what role does it play in your suite of testing? 117 00:08:51,049 --> 00:08:51,270 Yeah. 118 00:08:51,280 --> 00:08:51,890 Sure. 119 00:08:51,900 --> 00:08:52,510 So the, 120 00:08:52,520 --> 00:08:52,570 the, 121 00:08:52,580 --> 00:08:52,989 the, 122 00:08:53,000 --> 00:08:53,229 the, 123 00:08:53,239 --> 00:08:59,960 the predictor test is uh uh is uh is utilized when the patient is receiving treatment. 124 00:09:00,280 --> 00:09:18,190 It's been speci specifically designed to optimize uh biological uh uh disease modifiers such as Infliximab adalimumab that are co therapies in the treatment of inflammatory bowel disease as well as other immune uh mediated inflammatory. 125 00:09:18,200 --> 00:09:21,549 This is what the test does is to you connect the blood specimen, 126 00:09:22,229 --> 00:09:23,049 uh you know, 127 00:09:23,059 --> 00:09:24,750 with dosing information. 128 00:09:25,039 --> 00:09:41,989 And what we do is to uh uh provide guidance uh to clinician with uh respect of the best dose to give in order to achieve the best the level which is the most consistent with uh uh the disease control that needs to be achieved for the patient. 129 00:09:42,169 --> 00:09:43,729 Typically a vast majority, 130 00:09:43,739 --> 00:09:46,159 about two third of a third to two third, 131 00:09:46,169 --> 00:09:54,669 a third of patient uh tend to be uh uh unresponsive uh to this uh very expensive medication. 132 00:09:54,989 --> 00:09:57,960 Uh Not because they don't have the uh you know, 133 00:09:57,969 --> 00:09:59,289 typically because they have a, 134 00:09:59,299 --> 00:09:59,590 you know, 135 00:09:59,599 --> 00:10:05,599 pharmacokinetic uh suboptimal pharmacokinetic uh that makes them uh you know, 136 00:10:05,609 --> 00:10:09,440 unresponsive because uh not enough drug has been given. 137 00:10:09,450 --> 00:10:18,469 So what we do with a predictor test is to basically estimate the pa the pharmacokinetic uh parameter for the patient. 138 00:10:18,750 --> 00:10:24,729 And from then uh re report the best dose uh to give in order to achieve the, 139 00:10:24,760 --> 00:10:31,570 the level which is consistent with the uh the most uh uh effective disease control to be achieved for the patient. 140 00:10:32,169 --> 00:10:33,059 So we are offering, 141 00:10:33,070 --> 00:10:38,049 we have developed a test for the Infliximab as well as Adalimumab which is Humira, 142 00:10:38,909 --> 00:10:41,309 but these are antimony causes factor. 143 00:10:41,460 --> 00:10:49,549 And we are also developing the test for vidur as well as uh is that are widely used also in the treatment of, 144 00:10:49,559 --> 00:10:51,969 of uh inflammatory bubble disease. 145 00:10:51,979 --> 00:10:52,669 Wow, 146 00:10:52,679 --> 00:10:55,450 uh for MET is a suite of tests. 147 00:10:55,460 --> 00:11:00,940 Goes well beyond um the PGX testing that our audience is most familiar with, 148 00:11:01,299 --> 00:11:08,679 uh which typically only includes snips for cyp genes and some pharmacodynamic genes. 149 00:11:08,690 --> 00:11:31,424 This is really exciting um genes and biomarkers related to immunology are not commonly found in what I call the box PGX tests such as those uh made by large uh laboratory manufacturing companies um where the panel has a set number of genes and uh you know, 150 00:11:31,434 --> 00:11:36,054 it was developed by a larger laboratory for maybe smaller laboratories use. 151 00:11:36,729 --> 00:11:39,010 So my understanding, 152 00:11:39,020 --> 00:11:53,729 having talked with you extensively theory is that immunology has fewer PGX test available because it's actually more difficult say than oncology to research and develop tests. 153 00:11:53,739 --> 00:11:54,119 So, 154 00:11:54,130 --> 00:12:00,729 could you elaborate for our audience on the difficulties that are associated with immunology, 155 00:12:00,739 --> 00:12:05,830 research and developing tests uh for immunology versus say oncology? 156 00:12:06,330 --> 00:12:06,530 Yeah, 157 00:12:06,539 --> 00:12:07,049 sure. 158 00:12:07,059 --> 00:12:09,969 So in uh in immunology, 159 00:12:09,979 --> 00:12:11,590 as compared to oncology, 160 00:12:11,599 --> 00:12:17,169 there is no such a thing such as a somatic mutation where for example, 161 00:12:17,179 --> 00:12:18,429 you're gonna have a behalf, 162 00:12:18,440 --> 00:12:18,659 you know, 163 00:12:18,669 --> 00:12:20,349 that indicates that the patient, 164 00:12:20,679 --> 00:12:20,919 you know, 165 00:12:20,929 --> 00:12:25,239 is likely to benefit or not from some treatment in immunology. 166 00:12:25,250 --> 00:12:26,750 This is far more complicated, 167 00:12:26,760 --> 00:12:28,830 complicated for the reason, 168 00:12:29,239 --> 00:12:31,020 starting with uh the fact that, 169 00:12:31,030 --> 00:12:31,179 you know, 170 00:12:31,190 --> 00:12:36,219 the response to this uh medication uh are multifactorial. 171 00:12:36,260 --> 00:12:37,820 And the fact that uh you know, 172 00:12:37,830 --> 00:12:39,380 the mutation that uh the, 173 00:12:39,390 --> 00:12:39,619 the, 174 00:12:39,630 --> 00:12:45,190 the single nucleotide polymorphism in the GM line which uh uh you know, 175 00:12:45,200 --> 00:12:52,429 can potentially associate with uh with outcome uh uh uh uh a lo in advance, 176 00:12:52,440 --> 00:12:58,359 meaning that uh they're gonna have a weak association uh with a response to those medications. 177 00:12:58,369 --> 00:13:09,609 So there is a necessity in immunology to combine multiple genetic polymorphism together in order to achieve uh some uh performances characteristics that will make uh you know, 178 00:13:09,619 --> 00:13:09,859 the, 179 00:13:09,869 --> 00:13:10,380 the, 180 00:13:10,390 --> 00:13:10,520 the, 181 00:13:10,530 --> 00:13:13,219 the clinician uh you know, 182 00:13:13,419 --> 00:13:15,619 uh order the test and most importantly, 183 00:13:15,630 --> 00:13:15,840 the, 184 00:13:15,849 --> 00:13:16,179 the, 185 00:13:16,190 --> 00:13:17,739 the payer to pay for the test. 186 00:13:17,750 --> 00:13:20,469 So this field has been uh you know, 187 00:13:20,479 --> 00:13:20,679 is, 188 00:13:20,690 --> 00:13:21,705 is moving for, 189 00:13:21,715 --> 00:13:21,994 you know, 190 00:13:22,005 --> 00:13:24,575 there are some tests that are being developed right now. 191 00:13:24,924 --> 00:13:39,034 But the biggest challenge is to be able to achieve again the the threshold of uh of performance that makes the test is variable enough uh to be uh again ordered by the clinician and the utilize uh to the benefit of the patient. 192 00:13:39,659 --> 00:13:41,200 I couldn't agree with you more. 193 00:13:41,210 --> 00:13:53,489 Um I've worked on the payer side or market access side of pharmacogenomics and even uh with a box test for which there's um a lot of research data available, 194 00:13:53,500 --> 00:13:55,119 even with those, 195 00:13:55,130 --> 00:13:59,760 it's sometimes difficult uh to get payers um to see the value. 196 00:13:59,770 --> 00:14:01,640 So I absolutely agree with you. 197 00:14:01,940 --> 00:14:03,679 Um The fact that you guys are, 198 00:14:03,690 --> 00:14:11,789 are uh investing in producing the data necessary says a lot about your laboratory. 199 00:14:11,979 --> 00:14:12,559 Um you know, 200 00:14:12,570 --> 00:14:15,380 and how committed you are to this testing and, 201 00:14:15,390 --> 00:14:17,320 and how you believe in the testing. 202 00:14:18,039 --> 00:14:23,640 So I just want to make sure that our audience recognizes that, 203 00:14:24,359 --> 00:14:24,619 you know, 204 00:14:24,630 --> 00:14:31,820 Prometheus doesn't simply provide tests to determine if drugs for IBD will be effective and safe. 205 00:14:32,190 --> 00:14:36,900 Um And maybe what the dose of the drug should be for the patient, 206 00:14:36,909 --> 00:14:40,219 but you have that whole suite of tests. 207 00:14:40,229 --> 00:14:47,380 Um the diagnostic test for the differential diagnosis all the way through remission. 208 00:14:48,030 --> 00:14:53,390 So can you elaborate you elaborated on it some in the previous question? 209 00:14:53,400 --> 00:15:01,229 But um can you tell us the difference between how you had to actually develop the test? 210 00:15:01,520 --> 00:15:02,530 Um You didn't, 211 00:15:02,539 --> 00:15:03,059 in other words, 212 00:15:03,070 --> 00:15:10,659 purchase a test from another manufacturer with the biomarkers that you include in your testing. 213 00:15:10,669 --> 00:15:16,830 Can you elaborate on how much more difficult it is to to develop a test from scratch? 214 00:15:18,169 --> 00:15:18,320 Yeah, 215 00:15:18,330 --> 00:15:18,659 sure. 216 00:15:18,669 --> 00:15:18,809 I mean, 217 00:15:18,820 --> 00:15:22,070 this is this is challenging for multiple and first of all, 218 00:15:22,080 --> 00:15:23,130 you need to have the, 219 00:15:23,419 --> 00:15:27,450 you need to have a clinical data set available with specimen available. 220 00:15:27,460 --> 00:15:28,159 Uh you know, 221 00:15:28,169 --> 00:15:28,780 in front, 222 00:15:28,859 --> 00:15:29,770 obviously, 223 00:15:29,859 --> 00:15:30,890 available. 224 00:15:31,200 --> 00:15:35,890 Uh So we are leveraging a pro meters a large bi bank of specimen. 225 00:15:36,299 --> 00:15:37,190 Uh as I said, 226 00:15:37,200 --> 00:15:39,719 Prometheus has been founded 25 years ago. 227 00:15:39,729 --> 00:15:40,599 So over the, 228 00:15:40,760 --> 00:15:41,919 the past two decades, 229 00:15:41,929 --> 00:15:54,849 we have been able to assemble a large uh substrate of data and specimen which we are uh uh using to uh uh establish our proof of concept if you will. 230 00:15:54,859 --> 00:16:07,559 And then when we have uh identify some genetic polymorphism that are uh adequately uh associated with uh uh disease outcome and disease progression as well as uh toxicity. 231 00:16:07,969 --> 00:16:11,469 Then we are entering validation phase where we are uh you know, 232 00:16:11,570 --> 00:16:14,789 using validation cohorts where we are again, 233 00:16:14,969 --> 00:16:22,630 combining multiple modalities together uh patient demographic as well as genetic marker together with theological marker. 234 00:16:22,640 --> 00:16:23,190 Actually, 235 00:16:23,500 --> 00:16:27,419 to come up with some Multivariate models that are uh again, 236 00:16:27,429 --> 00:16:39,250 bringing the performances characteristics of the pharmacogenomic test or its combination with our marker to the level where it's supposed to be in the first place to meet uh uh payer. 237 00:16:39,650 --> 00:16:41,190 And uh obviously, 238 00:16:41,200 --> 00:16:41,760 again, 239 00:16:41,770 --> 00:16:45,320 the patient uh to the benefit of the patient and to, 240 00:16:45,330 --> 00:16:46,619 to improve its outcome, 241 00:16:46,739 --> 00:16:47,429 the outcome. 242 00:16:48,340 --> 00:16:53,380 I think what you're describing really is the future of pharmacogenomics. 243 00:16:53,390 --> 00:16:54,599 Um In other words, 244 00:16:54,609 --> 00:17:03,419 not singing out pharmacogenomics as you know the end all and be all in the treatment paradigm. 245 00:17:03,559 --> 00:17:08,040 But using a PGX test in combination with, 246 00:17:08,050 --> 00:17:09,069 like you mentioned, 247 00:17:09,250 --> 00:17:11,160 other serological tests, 248 00:17:11,170 --> 00:17:12,959 maybe other genetic tests. 249 00:17:13,290 --> 00:17:14,890 Um But you know, 250 00:17:14,900 --> 00:17:25,869 I think what we want our audience to really wrap their heads around is that PGX is just a piece of that larger puzzle um from diagnosis to treatment to, 251 00:17:25,880 --> 00:17:26,910 to remission. 252 00:17:27,239 --> 00:17:29,880 So I think you guys are absolutely, 253 00:17:29,890 --> 00:17:31,579 you're already in the future. 254 00:17:31,589 --> 00:17:32,849 In other words, 255 00:17:32,859 --> 00:17:33,130 you know, 256 00:17:33,140 --> 00:17:39,689 you're already providing all these different uh tests um like you mentioned to, 257 00:17:39,699 --> 00:17:44,310 to facilitate from diagnosis to remission to remission. 258 00:17:44,660 --> 00:17:45,520 That's correct. 259 00:17:45,530 --> 00:17:45,829 Yeah. 260 00:17:46,349 --> 00:17:55,089 So um you've given us so much great information about uh the tests that that you guys offer. 261 00:17:55,329 --> 00:18:02,060 Can you explain to our audience um your newest test? 262 00:18:02,069 --> 00:18:03,859 Uh the responder test. 263 00:18:04,150 --> 00:18:12,979 And um what role it will play in the paradigm from the diagnosis of IBD to remission? 264 00:18:14,050 --> 00:18:14,260 Yeah, 265 00:18:14,270 --> 00:18:14,760 sure. 266 00:18:14,770 --> 00:18:15,569 So we, 267 00:18:15,579 --> 00:18:18,069 we are doing things a little bit different than other. 268 00:18:18,079 --> 00:18:19,489 We do believe that uh you know, 269 00:18:19,500 --> 00:18:21,449 the it has to be simple. 270 00:18:21,459 --> 00:18:24,189 Uh uh We can obviously construct some very, 271 00:18:24,199 --> 00:18:33,530 very complex algorithm and there are some tests that do that with a very sophisticated machine learning based tools that are available using neural networks, 272 00:18:33,540 --> 00:18:33,729 you know, 273 00:18:33,739 --> 00:18:34,790 those sorts of things. 274 00:18:34,800 --> 00:18:39,729 But we have taken on a different approach where with the responder test, 275 00:18:39,739 --> 00:18:40,329 we are basically, 276 00:18:40,339 --> 00:18:45,160 we are taking an approach which is very simple to address the first and foremost. 277 00:18:45,170 --> 00:18:53,020 Most important aspect of responding uh predicting response to uh to medication is the pharmacokinetics. 278 00:18:53,280 --> 00:19:03,250 Uh You cannot be responding to a drug if the drug is not given and you obviously cannot respond to a drug if the drug is not metabolized adequately. 279 00:19:03,359 --> 00:19:06,349 And this is what we are doing with the responder test. 280 00:19:06,579 --> 00:19:09,010 We are addressing some uh uh you know, 281 00:19:09,020 --> 00:19:11,630 fundamental issues with those uh biologist, 282 00:19:11,640 --> 00:19:12,410 for example, 283 00:19:12,660 --> 00:19:15,170 uh the anti tumor necrosis factors. 284 00:19:15,180 --> 00:19:15,650 So, 285 00:19:15,750 --> 00:19:19,199 such as uh Infliximab and Adalimumab, 286 00:19:19,209 --> 00:19:23,050 it is well known uh that uh uh those drugs, 287 00:19:23,060 --> 00:19:25,689 first of all are prone to immunization. 288 00:19:25,989 --> 00:19:36,949 Uh Meaning that uh uh the drug itself uh is recognized by the immune system uh and digested by the antigen presenting cells. 289 00:19:36,959 --> 00:19:42,209 If you will uh where you gonna have uh uh an immune uh uh response, 290 00:19:42,380 --> 00:19:56,979 uh mounted a cancer drug to produce uh immunogen that will severely impact its pharmacokinetics where the labels will be inadequate to produce uh the desired uh anti-inflammatory effects. 291 00:19:56,989 --> 00:19:57,150 So, 292 00:19:57,160 --> 00:19:58,890 we are with the risk conductors, 293 00:19:58,900 --> 00:20:01,040 we are combining two things together. 294 00:20:01,189 --> 00:20:07,959 First of all is the genetic test itself which uh predicts the risk of immun immunization. 295 00:20:07,969 --> 00:20:18,010 The name of the test is on HL A uh DQ A 105 ali uh that uh uh promotes the presentation of the, 296 00:20:18,020 --> 00:20:19,130 of the, 297 00:20:19,140 --> 00:20:19,910 of Infliximab, 298 00:20:20,010 --> 00:20:20,750 for example, 299 00:20:20,760 --> 00:20:32,130 to the T cell repertoire in order to uh promote the Ronon expansion and the formation of the anti antibodies together with uh another dimension which is the clearance, 300 00:20:32,140 --> 00:20:33,670 which is as important. 301 00:20:33,949 --> 00:20:36,209 Uh One of the key issue is the, 302 00:20:36,219 --> 00:20:36,770 the, 303 00:20:36,780 --> 00:20:41,239 the monoclonal antibodies and uh such as Infliximab or Adalimumab. 304 00:20:41,329 --> 00:20:42,280 But in fact, 305 00:20:42,290 --> 00:20:45,890 a neon antibodies that those drugs are uh you know, 306 00:20:45,900 --> 00:20:49,010 cleared and consumed uh from the, 307 00:20:49,020 --> 00:20:50,949 from the central compartment if you will, 308 00:20:50,959 --> 00:20:54,520 since we are doing a little bit of uh uh pharmacokinetics here. 309 00:20:54,530 --> 00:20:56,020 And uh uh you know, 310 00:20:56,030 --> 00:21:06,670 if the patient present who is uh a high degree of inflammatory burden is gonna have uh the patient will have a high clearance and that's gonna worsen uh in the, 311 00:21:06,680 --> 00:21:13,939 in the presence again of the HL AD Q A 105 genetic marker that uh associate with uh immunization. 312 00:21:13,949 --> 00:21:16,859 So I but this is a combination of both, 313 00:21:17,199 --> 00:21:19,359 these are the predictive factors of pharmacokinetic, 314 00:21:20,359 --> 00:21:38,209 which we combine together where the patient presenting with a risk of immunization as well as accelerated clearance due to the fact that the patient has high inflammation or due to the fact that they are so intrinsic pharmacokinetic properties that makes that the patient, 315 00:21:38,219 --> 00:21:38,300 you know, 316 00:21:38,310 --> 00:21:39,479 will clear the drug very, 317 00:21:39,489 --> 00:21:40,260 very fast. 318 00:21:40,560 --> 00:21:41,670 For example, 319 00:21:41,680 --> 00:21:46,819 due to the inefficient uh recirculation of the drug itself with the new, 320 00:21:46,869 --> 00:21:46,930 the, 321 00:21:46,939 --> 00:21:50,599 the the in the reticular on the system. 322 00:21:50,920 --> 00:21:51,619 Together, 323 00:21:51,630 --> 00:22:02,109 those patients presenting with uh uh together these uh poor prognostic factor of pharmacokinetic origin will tend to be severely underdose, 324 00:22:02,380 --> 00:22:06,719 will not be responding to the drug uh adequately as and they, 325 00:22:06,729 --> 00:22:10,719 and they probably should in the first place if you are able to address uh you know, 326 00:22:10,729 --> 00:22:12,270 the the the exposure. 327 00:22:12,439 --> 00:22:14,079 So what we do with this test, 328 00:22:14,089 --> 00:22:21,640 we will be able to inform uh the clinic that the patient is at risk of achieving, 329 00:22:21,650 --> 00:22:30,829 of achieving suboptimal pharmacokinetics and therefore being able to adjust the dose uh uh to start with more adequately. 330 00:22:30,839 --> 00:22:38,650 So that the the the proper uh exposure is achieved uh during induction to again to, 331 00:22:38,660 --> 00:22:39,040 to, 332 00:22:39,050 --> 00:22:39,380 to, 333 00:22:39,390 --> 00:22:40,890 to achieve a better outcome. 334 00:22:41,040 --> 00:22:47,270 And I think the pharmacist will have a very important role to play here in terms of absolutely, 335 00:22:47,280 --> 00:22:51,239 that information is priceless in the management of these medications. 336 00:22:51,250 --> 00:22:54,930 So thanks for elaborating on that. 337 00:22:56,010 --> 00:22:59,040 And if I may add in our previous conversation, 338 00:22:59,050 --> 00:23:00,810 uh before the recording of podcast, 339 00:23:00,819 --> 00:23:08,869 we had discussed um you guys' robust platform for collaborating with payers to obtain market access and reimbursements for the test. 340 00:23:09,109 --> 00:23:14,109 But without stealing the Thunder from uh Prometheus market access and reimbursement team, 341 00:23:14,199 --> 00:23:22,619 can you please uh briefly detail how Prometheus has proactively worked with payers to solve the problem. 342 00:23:22,920 --> 00:23:27,349 Um the population health problem by building the evidence payers want, 343 00:23:27,359 --> 00:23:41,170 want to see um about your test before you go to the market and then build the test and then hope the payers will see the value and the result and then that will improve the market access and reimbursement for your um precision medicine test. 344 00:23:42,160 --> 00:23:42,339 Yeah. 345 00:23:42,349 --> 00:23:43,180 So briefly I can, 346 00:23:43,189 --> 00:23:43,579 I'm, 347 00:23:43,589 --> 00:23:46,619 I'm probably not the right person to answer that question. 348 00:23:46,630 --> 00:23:47,369 We have a very, 349 00:23:47,380 --> 00:23:52,400 very efficient market access group uh uh pro meters that does a splendid job. 350 00:23:52,410 --> 00:23:59,780 But uh uh uh what I can tell you that we have an evidence uh uh development plan in place where we, 351 00:23:59,790 --> 00:24:14,000 we are establishing the clinical utility of our testing solution by demonstrating uh the payer value uh with respect of uh patient management and uh uh and the, 352 00:24:14,010 --> 00:24:16,630 and the impact of our technology on the, 353 00:24:16,640 --> 00:24:18,119 on physician behavior. 354 00:24:18,430 --> 00:24:21,319 Uh We have uh uh already uh you know, 355 00:24:21,329 --> 00:24:25,160 commercialized uh two of those tests for which we have initiated, 356 00:24:25,170 --> 00:24:29,040 initiated the Power studies uh that uh uh you know, 357 00:24:29,050 --> 00:24:32,000 already provide uh you know, 358 00:24:32,104 --> 00:24:34,484 differentiated and the value to, 359 00:24:34,494 --> 00:24:35,915 to the payer where we are, 360 00:24:35,925 --> 00:24:36,025 the, 361 00:24:36,035 --> 00:24:46,005 the clinicians are basically using our technology to make treatment decision uh as well as uh some prospective clinicality study which we are initiating, 362 00:24:46,145 --> 00:24:47,555 initiating to. 363 00:24:47,564 --> 00:24:48,574 Um uh again, 364 00:24:48,584 --> 00:24:49,425 demonstrate the, 365 00:24:49,435 --> 00:24:49,915 the, 366 00:24:49,925 --> 00:24:50,244 the, 367 00:24:50,255 --> 00:24:53,594 the payer value you uh uh we can certainly follow up with, 368 00:24:53,604 --> 00:24:58,755 uh you can certainly follow up with our market access group uh uh as appropriate there. 369 00:24:58,765 --> 00:25:00,765 Uh They can fill you with more information. 370 00:25:01,349 --> 00:25:01,589 No, 371 00:25:01,599 --> 00:25:02,520 that totally makes sense. 372 00:25:02,530 --> 00:25:03,310 That totally makes sense. 373 00:25:03,319 --> 00:25:10,890 But um we're excited that you're also farm d So how did you get to this role of outside the box path? 374 00:25:10,900 --> 00:25:11,550 There? 375 00:25:11,640 --> 00:25:17,530 There may be a pharmacist student or pharmacist wanting to switch or transition into a role such as yours, 376 00:25:17,540 --> 00:25:19,609 which is a Chief Scientific Officer. 377 00:25:19,619 --> 00:25:20,609 I want to learn more. 378 00:25:20,619 --> 00:25:23,920 So how would you um can you talk a little bit about that? 379 00:25:24,560 --> 00:25:24,780 Well, 380 00:25:24,790 --> 00:25:26,270 we are clinical laboratories. 381 00:25:26,280 --> 00:25:29,400 So in order to uh uh to be in my role, 382 00:25:29,410 --> 00:25:34,020 you need to have uh uh you need to have expertise in clinical laboratory science. 383 00:25:34,030 --> 00:25:36,140 So for the students is basically, 384 00:25:36,150 --> 00:25:36,300 you know, 385 00:25:36,310 --> 00:25:40,770 to do the family degree and then complete the family degree with uh a doctorate, 386 00:25:40,780 --> 00:25:40,930 you know, 387 00:25:40,939 --> 00:25:44,260 which is uh focus on clinical laboratory science. 388 00:25:44,270 --> 00:25:46,079 So you can achieve uh uh you know, 389 00:25:46,089 --> 00:25:47,640 the all the elements you need to be, 390 00:25:47,650 --> 00:25:48,219 for example, 391 00:25:48,229 --> 00:25:53,189 board certified uh as uh as as medical laboratory director. 392 00:25:53,199 --> 00:25:55,160 So you can uh uh so, 393 00:25:55,170 --> 00:25:55,589 uh yeah, 394 00:25:55,599 --> 00:25:56,030 this is, 395 00:25:56,040 --> 00:25:56,400 this is, 396 00:25:56,410 --> 00:25:57,209 this is uh you know, 397 00:25:57,219 --> 00:25:59,160 a great opportunity I think for pharmacies, 398 00:25:59,170 --> 00:26:10,800 there is an absolute need to uh have the clinical pharmacist provide uh uh drug information to healthcare professional as well as uh assist patient with the monitoring of their disease, 399 00:26:10,810 --> 00:26:15,229 the effectiveness of the therapy and um and uh you know, 400 00:26:15,239 --> 00:26:16,060 monitoring the, 401 00:26:16,069 --> 00:26:20,969 the side effect and the toxicity from uh from those uh those medication. 402 00:26:24,650 --> 00:26:24,959 Well, 403 00:26:24,969 --> 00:26:32,119 the I know our audience is going to have uh additional questions for you. 404 00:26:32,130 --> 00:26:32,540 I mean, 405 00:26:32,989 --> 00:26:35,609 you've provided them with so much great information, 406 00:26:35,619 --> 00:26:44,959 but it's only the beginning of what they could possibly learn um about um the testing that you do for IBD and, 407 00:26:44,969 --> 00:26:46,729 and even your career path. 408 00:26:47,050 --> 00:26:47,530 So, 409 00:26:47,540 --> 00:26:49,300 if you wouldn't mind telling us, 410 00:26:49,310 --> 00:26:51,359 um because we have to wrap up, 411 00:26:51,369 --> 00:26:52,670 unfortunately, 412 00:26:53,150 --> 00:26:55,810 this episode of the podcast, 413 00:26:55,819 --> 00:27:00,250 uh could you tell us how our audience members might be able to contact you directly. 414 00:27:01,260 --> 00:27:01,449 Yeah, 415 00:27:01,459 --> 00:27:07,079 I can be contacted on my uh on my email at TT W at como slab dot com. 416 00:27:07,949 --> 00:27:08,810 All right. 417 00:27:09,069 --> 00:27:09,300 Well, 418 00:27:09,310 --> 00:27:14,290 thank you again so much uh for joining us on this episode. 419 00:27:14,300 --> 00:27:15,290 We really, 420 00:27:15,300 --> 00:27:29,530 really hope that our listeners um ideas of not only what PGX can be but how PGX can be utilized in a comprehensive testing suite. 421 00:27:29,709 --> 00:27:35,670 We really hope that our a our audience will um listen in and learn this information. 422 00:27:36,280 --> 00:27:37,869 Um And to our audience, 423 00:27:37,880 --> 00:27:39,439 thank you for tuning in. 424 00:27:39,449 --> 00:27:42,619 We really hope that you've learned from this episode. 425 00:27:43,130 --> 00:27:46,339 Uh We do a whole lot of PG Xing here on this podcast. 426 00:27:46,349 --> 00:27:48,380 We talk about PGX Science, 427 00:27:48,390 --> 00:27:52,030 clinical application and the business of PGX. 428 00:27:52,260 --> 00:27:54,880 So we'd love to hear about from you. 429 00:27:55,099 --> 00:27:56,479 I love to hear from you. 430 00:27:56,489 --> 00:27:58,439 Um What can we teach you? 431 00:27:58,449 --> 00:28:00,920 What more can we teach you through our podcast? 432 00:28:00,930 --> 00:28:12,349 So please drop us a message on linkedin and let us know and please share this link to this podcast link episode with everyone so they can tune in and listen to the PGX for promises podcast. 433 00:28:12,520 --> 00:28:15,369 Leave us a review on Apple podcast or Spotify. 434 00:28:15,459 --> 00:28:18,130 And you can also visit us on PGX four, 435 00:28:18,140 --> 00:28:22,989 the number four Rx dot com to listen to all our other episodes. 436 00:28:23,000 --> 00:28:23,079 Well, 437 00:28:23,089 --> 00:28:23,790 thank you. 438 00:28:24,199 --> 00:28:28,750 Thanks for your interest in PGX and for spending some time with us. 439 00:28:28,760 --> 00:28:35,670 Please share this podcast and leave us a review on Apple podcasts or Spotify for all of our episodes. 440 00:28:35,680 --> 00:28:39,390 Please visit PGX for Rx dot com. 441 00:28:39,569 --> 00:28:43,380 That's PGX for Rx dot com.  

Becky Winslow, BS, PharmD Host and Pharmacogenomics Medical Science Liaison; Behnaz Sarrami, MS, PharmD, Host and Pharmacogenomics Medical Science Liaison; Thierry Dervieux, PharmD, PhD, Chief Scientific Officer at Prometheus Laboratories In this episode of the PGX for Pharmacists Podcast, Dr. Thierry Dervieux, Dr. Behnaz Sarrami, and I discuss Dr. Dervieux's career as a PharmD, PhD, and chief scientific officer who has designed a pharmacogenomics test prescribers may use to optimize biosimilars for autoimmune gastrointestinal diseases. Dr. Dervieux will illustrate to our audience pharmacogenomics' potential beyond Tier 1 and 2 genetic testing by describing the clinical validity and utility of his laboratory's suite of tests in the autoimmune gastrointestinal disease diagnosis and treatment market. Behnaz and I hope this episode will inspire pharmacists interested in pharmacogenomics to think beyond the boxed PGx test most laboratories offer when they think about PGx and consider all the biological systems in which genetics impacts drugs' efficacy and safety. Disclaimer: Behnaz Disclaimer: These are my personal views and opinions, and I am not speaking on behalf of Castle Biosciences, Inc. Becky Disclaimer: These are my personal views and opinions, and I am not speaking on behalf of any other entity.   Transcription: 1 00:00:06,190 --> 00:00:19,620 You're listening to the Pharmacy podcast Network in a world where one size fits all medications dominate the pharmaceutical industry. 2 00:00:20,079 --> 00:00:24,750 Precision medicine brings a ray of hope for those seeking customized health care. 3 00:00:25,350 --> 00:00:32,830 Pharmacists have a unique opportunity to help people in need of specialized testing to ensure medications work as intended. 4 00:00:33,540 --> 00:00:44,680 Welcome to PGX for pharmacists where we unravel the wonders of precision medicine and its potential to revolutionize the way we approach pharmacy care. 5 00:00:45,169 --> 00:00:52,790 Get ready to uncover the secrets behind pharmacogenomics and how it's transforming lives one genome at a time. 6 00:00:52,799 --> 00:00:53,189 Hello, 7 00:00:53,200 --> 00:00:53,950 everyone. 8 00:00:54,159 --> 00:00:55,080 I'm your host, 9 00:00:55,090 --> 00:00:56,389 Doctor Becky Winslow. 10 00:00:56,409 --> 00:01:09,860 And you're listening to the PGX for Pharmacist podcast that we magazine recognized in 2021 as the ninth most listened to genetics podcasts in the world on the PGX for Pharmacist podcast. 11 00:01:09,870 --> 00:01:16,690 We explore all things pharmacogenomics related and our mission is to educate and advocate for PGX. 12 00:01:16,769 --> 00:01:23,849 We accomplish this mission through exclusive interviews with highly qualified and well experienced pharmacogenomics. 13 00:01:23,860 --> 00:01:29,720 Industry leaders such as today's special guest and my name is Baas Sami, 14 00:01:29,730 --> 00:01:32,739 the co-host of PGX for Pharms podcast, 15 00:01:32,750 --> 00:01:33,860 Pharmacogenomics, 16 00:01:33,870 --> 00:01:36,819 medical science liaison and a mentor to pharmacist. 17 00:01:36,889 --> 00:01:40,239 Connect with us on linkedin and let's get a conversation going. 18 00:01:40,269 --> 00:01:46,720 We want to hear from you and how you're impacting pharmacogenomic stakeholders and what you have learned throughout your journey. 19 00:01:48,510 --> 00:01:49,010 Ok. 20 00:01:49,019 --> 00:01:50,819 So without any further ado, 21 00:01:50,839 --> 00:01:54,769 I'm extremely pleased to introduce to our audience. 22 00:01:54,919 --> 00:01:56,059 Doctor Theory Devo, 23 00:01:57,239 --> 00:02:01,129 the Chief Scientific Officer at Prometheus Laboratories, 24 00:02:01,139 --> 00:02:08,139 and Perme Prometheus Laboratories is a reference clinical laboratory that's focused on the diagnosis, 25 00:02:08,149 --> 00:02:13,330 prognosis and monitoring of immune mediated inflammatory diseases. 26 00:02:13,970 --> 00:02:14,229 So, 27 00:02:14,240 --> 00:02:14,649 thank you, 28 00:02:14,660 --> 00:02:17,759 Doctor De for joining us on the podcast. 29 00:02:17,770 --> 00:02:18,589 Today. 30 00:02:18,600 --> 00:02:23,190 I'm excited to share your and Prometheus's story with our audience. 31 00:02:23,649 --> 00:02:25,630 Um in particular, 32 00:02:25,639 --> 00:02:45,369 I'm excited about you sharing your career journey as a farm D phd and Chief scientific officer and designer of the Predictor PK AD A which is a precision guided dosing test for the optimization of Humira Remicade and their bio cylinders. 33 00:02:46,119 --> 00:02:46,449 So, 34 00:02:46,460 --> 00:03:04,220 one of Bana's and my main goals for this episode of the PGX for Pharmacist podcast is to expand our audience's notion of what a PGX test looks like and to inspire them to think bigger than the traditional box PGX test. 35 00:03:04,229 --> 00:03:08,020 Most of them or most of you are uh familiar with. 36 00:03:09,020 --> 00:03:09,429 So, 37 00:03:09,440 --> 00:03:22,179 Doctor D uh I'd like to start the podcast by having our guests um introduce themselves and elaborate on how you are a pharmacogenomics expert. 38 00:03:23,619 --> 00:03:23,800 Yeah, 39 00:03:23,809 --> 00:03:24,250 thank you, 40 00:03:24,259 --> 00:03:25,759 Becky for having me. 41 00:03:25,770 --> 00:03:26,850 Uh uh Yes. 42 00:03:26,860 --> 00:03:27,289 So I am a, 43 00:03:27,300 --> 00:03:30,820 I am a pharmacist uh with uh a family who is a, 44 00:03:30,830 --> 00:03:33,039 a doctorate in pharmacokinetics. 45 00:03:33,539 --> 00:03:44,520 Uh I completed my studies in France and I came as a postdoc uh fellow uh to work in the United States about 20 years ago to work on the pharmacogenomic of anti cancer agents, 46 00:03:44,929 --> 00:03:49,160 uh primarily uh six Maturin as well as methotrexate. 47 00:03:49,169 --> 00:03:50,550 After my post doc, 48 00:03:50,770 --> 00:03:52,960 uh I moved uh in industry for promet. 49 00:03:53,490 --> 00:04:01,429 So I have a large experience in uh uh the implementation of pharmacogenetics testing in immune mediated inflammatory disease. 50 00:04:01,509 --> 00:04:12,550 Our lab Rome was the first uh clinical laboratory in the United States to offer the fin uh metyl transfer genotyping as well as the thin metabolites. 51 00:04:12,559 --> 00:04:13,029 So, 52 00:04:13,050 --> 00:04:21,989 uh uh of uh of 70 publications in the field and uh I'm very uh very excited to have uh to be on the postcard with you uh uh today. 53 00:04:23,660 --> 00:04:24,220 All right. 54 00:04:24,230 --> 00:04:27,359 So thank you for qualifying yourself as an expert. 55 00:04:27,369 --> 00:04:27,619 So, 56 00:04:27,630 --> 00:04:32,839 let's jump right in and delve into your current PGX work. 57 00:04:32,850 --> 00:04:33,279 So, 58 00:04:33,489 --> 00:04:36,540 if you'll tell us um a little about Prometheus, 59 00:04:36,549 --> 00:04:38,000 specifically, 60 00:04:38,010 --> 00:04:40,350 what is Prometheus's mission? 61 00:04:40,359 --> 00:04:43,799 And how are you guys going about accomplishing your mission? 62 00:04:44,760 --> 00:04:44,980 Yeah, 63 00:04:44,989 --> 00:04:45,700 sure. 64 00:04:45,709 --> 00:04:47,459 Uh So Promet is a, 65 00:04:47,470 --> 00:04:52,790 is a reference uh clinical laboratory based in Southern California in San Diego. 66 00:04:53,230 --> 00:04:56,809 Uh The company has been there for uh over 25 years. 67 00:04:56,820 --> 00:05:03,950 We are uh specialize in the differential diagnosis of autoimmune G I disease uh disorders, 68 00:05:04,059 --> 00:05:06,019 uh gastrointestinal disorder, 69 00:05:06,230 --> 00:05:08,619 uh and inflammatory bowel disease. 70 00:05:08,980 --> 00:05:10,299 And over the years, 71 00:05:10,309 --> 00:05:16,600 we have developed a portfolio of a differentiated solution to facilitate the diagnosis, 72 00:05:16,609 --> 00:05:17,470 the prognosis, 73 00:05:17,480 --> 00:05:18,429 the monitoring, 74 00:05:18,660 --> 00:05:21,910 as well as therapy selection with pharmacogenetics testing, 75 00:05:21,920 --> 00:05:24,730 which we are offering to our clinical laboratory. 76 00:05:24,829 --> 00:05:26,350 And most importantly, 77 00:05:26,410 --> 00:05:27,299 uh recently, 78 00:05:27,309 --> 00:05:35,660 we are uh uh developing some uh uh testing solution with the credit topic care test to optimize treatment to uh biologics. 79 00:05:36,470 --> 00:05:37,130 Ok. 80 00:05:37,140 --> 00:05:37,329 Well, 81 00:05:37,339 --> 00:05:37,450 that, 82 00:05:37,459 --> 00:05:38,049 that's great. 83 00:05:38,059 --> 00:05:46,100 Can you also tell us uh about the Prois Library of Precision Medicine Tests for inflammatory bowel disease for patients? 84 00:05:46,109 --> 00:05:49,230 how they benefit medication therapy management. 85 00:05:49,239 --> 00:05:56,429 Stakeholders across the IB DS patients journey from diagnosis to treatment to disease, 86 00:05:56,440 --> 00:06:02,049 monitoring through remission and how they differ from other lab tests for IBD and his treatments. 87 00:06:02,709 --> 00:06:03,209 Yes. 88 00:06:03,220 --> 00:06:03,369 So, 89 00:06:03,380 --> 00:06:04,399 so we uh our, 90 00:06:04,410 --> 00:06:10,100 our clinical laboratory offers some uh highly specialized test to facilitate the, 91 00:06:10,109 --> 00:06:16,779 the diagnostic of uh to facilitate the differential diagnosis of uh uh inflammatory bowel disease. 92 00:06:16,790 --> 00:06:22,359 So we are following uh testing solution with uh serological testing, 93 00:06:22,529 --> 00:06:23,799 for example, 94 00:06:23,809 --> 00:06:38,410 uh uh piana as as as well as uh macro microbial uh uh antibodies that are present uh uh in Crohn's disease as well as uh over uh auto uh auto antibodies that are present in er colitis. 95 00:06:39,339 --> 00:06:43,684 These are conditions that are uh uh somewhat difficult to treat. 96 00:06:43,704 --> 00:06:49,994 Uh And uh we are uh uh offering those tests to uh help uh gastroenterologist. 97 00:06:50,015 --> 00:06:51,114 Uh uh first of all, 98 00:06:51,125 --> 00:07:03,434 to establish a differential diagnosis of IBD as compared to other uh condition typically uh uh irritable bowel syndrome as well as over gastrointestinal disorder. 99 00:07:03,445 --> 00:07:05,635 When the diagnostic is established, 100 00:07:05,910 --> 00:07:31,839 uh we offer uh testing to uh establish a prognosis where we're gonna in inform the clinician that the patient has a more aggressive uh disease that will require more aggressive treatment where uh we can uh provide the testing solution to initiate uh uh the most appropriate therapy for uh for the patient uh with uh a testing where we are uh basically uh you know, 101 00:07:31,850 --> 00:07:36,559 establish de determining some genotyping with the fit transferal genotyping. 102 00:07:36,570 --> 00:07:37,279 For example, 103 00:07:37,290 --> 00:07:40,250 where we can uh indicate that the patient is, 104 00:07:40,260 --> 00:07:45,079 is likely uh to present with a side effect to those medication. 105 00:07:45,399 --> 00:07:46,170 And once you know, 106 00:07:46,179 --> 00:07:47,799 the the treatment is initiative, 107 00:07:47,809 --> 00:08:16,089 we have a portfolio of solution uh to facilitate the monitoring of the disease of the inflammatory bowel disease as well as the dosing optimization with uh uh the answer test which uh measure blood level uh for uh uh monoclonal antibodies that are indicated in the treatment of IB start with starting with Infliximab Adalimumab as well as uh Tein and vidal. 108 00:08:16,980 --> 00:08:24,040 So we have a comprehensive portfolio to uh to surround the clinician with uh a variety of testing solution. 109 00:08:24,049 --> 00:08:30,250 With our goal being to improve the uh the outcome uh of patients with uh with diabetes. 110 00:08:30,260 --> 00:08:34,520 And I think that the pharmacist has a very important role to play from that perspective. 111 00:08:35,179 --> 00:08:36,039 So theory, 112 00:08:36,049 --> 00:08:40,239 could you elaborate for us more on the predictor test? 113 00:08:40,249 --> 00:08:42,758 Um especially since you designed that test, 114 00:08:42,768 --> 00:08:44,218 we'd really like to know, 115 00:08:44,489 --> 00:08:45,039 um you know, 116 00:08:45,049 --> 00:08:49,638 what did that take and what role does it play in your suite of testing? 117 00:08:51,049 --> 00:08:51,270 Yeah. 118 00:08:51,280 --> 00:08:51,890 Sure. 119 00:08:51,900 --> 00:08:52,510 So the, 120 00:08:52,520 --> 00:08:52,570 the, 121 00:08:52,580 --> 00:08:52,989 the, 122 00:08:53,000 --> 00:08:53,229 the, 123 00:08:53,239 --> 00:08:59,960 the predictor test is uh uh is uh is utilized when the patient is receiving treatment. 124 00:09:00,280 --> 00:09:18,190 It's been speci specifically designed to optimize uh biological uh uh disease modifiers such as Infliximab adalimumab that are co therapies in the treatment of inflammatory bowel disease as well as other immune uh mediated inflammatory. 125 00:09:18,200 --> 00:09:21,549 This is what the test does is to you connect the blood specimen, 126 00:09:22,229 --> 00:09:23,049 uh you know, 127 00:09:23,059 --> 00:09:24,750 with dosing information. 128 00:09:25,039 --> 00:09:41,989 And what we do is to uh uh provide guidance uh to clinician with uh respect of the best dose to give in order to achieve the best the level which is the most consistent with uh uh the disease control that needs to be achieved for the patient. 129 00:09:42,169 --> 00:09:43,729 Typically a vast majority, 130 00:09:43,739 --> 00:09:46,159 about two third of a third to two third, 131 00:09:46,169 --> 00:09:54,669 a third of patient uh tend to be uh uh unresponsive uh to this uh very expensive medication. 132 00:09:54,989 --> 00:09:57,960 Uh Not because they don't have the uh you know, 133 00:09:57,969 --> 00:09:59,289 typically because they have a, 134 00:09:59,299 --> 00:09:59,590 you know, 135 00:09:59,599 --> 00:10:05,599 pharmacokinetic uh suboptimal pharmacokinetic uh that makes them uh you know, 136 00:10:05,609 --> 00:10:09,440 unresponsive because uh not enough drug has been given. 137 00:10:09,450 --> 00:10:18,469 So what we do with a predictor test is to basically estimate the pa the pharmacokinetic uh parameter for the patient. 138 00:10:18,750 --> 00:10:24,729 And from then uh re report the best dose uh to give in order to achieve the, 139 00:10:24,760 --> 00:10:31,570 the level which is consistent with the uh the most uh uh effective disease control to be achieved for the patient. 140 00:10:32,169 --> 00:10:33,059 So we are offering, 141 00:10:33,070 --> 00:10:38,049 we have developed a test for the Infliximab as well as Adalimumab which is Humira, 142 00:10:38,909 --> 00:10:41,309 but these are antimony causes factor. 143 00:10:41,460 --> 00:10:49,549 And we are also developing the test for vidur as well as uh is that are widely used also in the treatment of, 144 00:10:49,559 --> 00:10:51,969 of uh inflammatory bubble disease. 145 00:10:51,979 --> 00:10:52,669 Wow, 146 00:10:52,679 --> 00:10:55,450 uh for MET is a suite of tests. 147 00:10:55,460 --> 00:11:00,940 Goes well beyond um the PGX testing that our audience is most familiar with, 148 00:11:01,299 --> 00:11:08,679 uh which typically only includes snips for cyp genes and some pharmacodynamic genes. 149 00:11:08,690 --> 00:11:31,424 This is really exciting um genes and biomarkers related to immunology are not commonly found in what I call the box PGX tests such as those uh made by large uh laboratory manufacturing companies um where the panel has a set number of genes and uh you know, 150 00:11:31,434 --> 00:11:36,054 it was developed by a larger laboratory for maybe smaller laboratories use. 151 00:11:36,729 --> 00:11:39,010 So my understanding, 152 00:11:39,020 --> 00:11:53,729 having talked with you extensively theory is that immunology has fewer PGX test available because it's actually more difficult say than oncology to research and develop tests. 153 00:11:53,739 --> 00:11:54,119 So, 154 00:11:54,130 --> 00:12:00,729 could you elaborate for our audience on the difficulties that are associated with immunology, 155 00:12:00,739 --> 00:12:05,830 research and developing tests uh for immunology versus say oncology? 156 00:12:06,330 --> 00:12:06,530 Yeah, 157 00:12:06,539 --> 00:12:07,049 sure. 158 00:12:07,059 --> 00:12:09,969 So in uh in immunology, 159 00:12:09,979 --> 00:12:11,590 as compared to oncology, 160 00:12:11,599 --> 00:12:17,169 there is no such a thing such as a somatic mutation where for example, 161 00:12:17,179 --> 00:12:18,429 you're gonna have a behalf, 162 00:12:18,440 --> 00:12:18,659 you know, 163 00:12:18,669 --> 00:12:20,349 that indicates that the patient, 164 00:12:20,679 --> 00:12:20,919 you know, 165 00:12:20,929 --> 00:12:25,239 is likely to benefit or not from some treatment in immunology. 166 00:12:25,250 --> 00:12:26,750 This is far more complicated, 167 00:12:26,760 --> 00:12:28,830 complicated for the reason, 168 00:12:29,239 --> 00:12:31,020 starting with uh the fact that, 169 00:12:31,030 --> 00:12:31,179 you know, 170 00:12:31,190 --> 00:12:36,219 the response to this uh medication uh are multifactorial. 171 00:12:36,260 --> 00:12:37,820 And the fact that uh you know, 172 00:12:37,830 --> 00:12:39,380 the mutation that uh the, 173 00:12:39,390 --> 00:12:39,619 the, 174 00:12:39,630 --> 00:12:45,190 the single nucleotide polymorphism in the GM line which uh uh you know, 175 00:12:45,200 --> 00:12:52,429 can potentially associate with uh with outcome uh uh uh uh a lo in advance, 176 00:12:52,440 --> 00:12:58,359 meaning that uh they're gonna have a weak association uh with a response to those medications. 177 00:12:58,369 --> 00:13:09,609 So there is a necessity in immunology to combine multiple genetic polymorphism together in order to achieve uh some uh performances characteristics that will make uh you know, 178 00:13:09,619 --> 00:13:09,859 the, 179 00:13:09,869 --> 00:13:10,380 the, 180 00:13:10,390 --> 00:13:10,520 the, 181 00:13:10,530 --> 00:13:13,219 the clinician uh you know, 182 00:13:13,419 --> 00:13:15,619 uh order the test and most importantly, 183 00:13:15,630 --> 00:13:15,840 the, 184 00:13:15,849 --> 00:13:16,179 the, 185 00:13:16,190 --> 00:13:17,739 the payer to pay for the test. 186 00:13:17,750 --> 00:13:20,469 So this field has been uh you know, 187 00:13:20,479 --> 00:13:20,679 is, 188 00:13:20,690 --> 00:13:21,705 is moving for, 189 00:13:21,715 --> 00:13:21,994 you know, 190 00:13:22,005 --> 00:13:24,575 there are some tests that are being developed right now. 191 00:13:24,924 --> 00:13:39,034 But the biggest challenge is to be able to achieve again the the threshold of uh of performance that makes the test is variable enough uh to be uh again ordered by the clinician and the utilize uh to the benefit of the patient. 192 00:13:39,659 --> 00:13:41,200 I couldn't agree with you more. 193 00:13:41,210 --> 00:13:53,489 Um I've worked on the payer side or market access side of pharmacogenomics and even uh with a box test for which there's um a lot of research data available, 194 00:13:53,500 --> 00:13:55,119 even with those, 195 00:13:55,130 --> 00:13:59,760 it's sometimes difficult uh to get payers um to see the value. 196 00:13:59,770 --> 00:14:01,640 So I absolutely agree with you. 197 00:14:01,940 --> 00:14:03,679 Um The fact that you guys are, 198 00:14:03,690 --> 00:14:11,789 are uh investing in producing the data necessary says a lot about your laboratory. 199 00:14:11,979 --> 00:14:12,559 Um you know, 200 00:14:12,570 --> 00:14:15,380 and how committed you are to this testing and, 201 00:14:15,390 --> 00:14:17,320 and how you believe in the testing. 202 00:14:18,039 --> 00:14:23,640 So I just want to make sure that our audience recognizes that, 203 00:14:24,359 --> 00:14:24,619 you know, 204 00:14:24,630 --> 00:14:31,820 Prometheus doesn't simply provide tests to determine if drugs for IBD will be effective and safe. 205 00:14:32,190 --> 00:14:36,900 Um And maybe what the dose of the drug should be for the patient, 206 00:14:36,909 --> 00:14:40,219 but you have that whole suite of tests. 207 00:14:40,229 --> 00:14:47,380 Um the diagnostic test for the differential diagnosis all the way through remission. 208 00:14:48,030 --> 00:14:53,390 So can you elaborate you elaborated on it some in the previous question? 209 00:14:53,400 --> 00:15:01,229 But um can you tell us the difference between how you had to actually develop the test? 210 00:15:01,520 --> 00:15:02,530 Um You didn't, 211 00:15:02,539 --> 00:15:03,059 in other words, 212 00:15:03,070 --> 00:15:10,659 purchase a test from another manufacturer with the biomarkers that you include in your testing. 213 00:15:10,669 --> 00:15:16,830 Can you elaborate on how much more difficult it is to to develop a test from scratch? 214 00:15:18,169 --> 00:15:18,320 Yeah, 215 00:15:18,330 --> 00:15:18,659 sure. 216 00:15:18,669 --> 00:15:18,809 I mean, 217 00:15:18,820 --> 00:15:22,070 this is this is challenging for multiple and first of all, 218 00:15:22,080 --> 00:15:23,130 you need to have the, 219 00:15:23,419 --> 00:15:27,450 you need to have a clinical data set available with specimen available. 220 00:15:27,460 --> 00:15:28,159 Uh you know, 221 00:15:28,169 --> 00:15:28,780 in front, 222 00:15:28,859 --> 00:15:29,770 obviously, 223 00:15:29,859 --> 00:15:30,890 available. 224 00:15:31,200 --> 00:15:35,890 Uh So we are leveraging a pro meters a large bi bank of specimen. 225 00:15:36,299 --> 00:15:37,190 Uh as I said, 226 00:15:37,200 --> 00:15:39,719 Prometheus has been founded 25 years ago. 227 00:15:39,729 --> 00:15:40,599 So over the, 228 00:15:40,760 --> 00:15:41,919 the past two decades, 229 00:15:41,929 --> 00:15:54,849 we have been able to assemble a large uh substrate of data and specimen which we are uh uh using to uh uh establish our proof of concept if you will. 230 00:15:54,859 --> 00:16:07,559 And then when we have uh identify some genetic polymorphism that are uh adequately uh associated with uh uh disease outcome and disease progression as well as uh toxicity. 231 00:16:07,969 --> 00:16:11,469 Then we are entering validation phase where we are uh you know, 232 00:16:11,570 --> 00:16:14,789 using validation cohorts where we are again, 233 00:16:14,969 --> 00:16:22,630 combining multiple modalities together uh patient demographic as well as genetic marker together with theological marker. 234 00:16:22,640 --> 00:16:23,190 Actually, 235 00:16:23,500 --> 00:16:27,419 to come up with some Multivariate models that are uh again, 236 00:16:27,429 --> 00:16:39,250 bringing the performances characteristics of the pharmacogenomic test or its combination with our marker to the level where it's supposed to be in the first place to meet uh uh payer. 237 00:16:39,650 --> 00:16:41,190 And uh obviously, 238 00:16:41,200 --> 00:16:41,760 again, 239 00:16:41,770 --> 00:16:45,320 the patient uh to the benefit of the patient and to, 240 00:16:45,330 --> 00:16:46,619 to improve its outcome, 241 00:16:46,739 --> 00:16:47,429 the outcome. 242 00:16:48,340 --> 00:16:53,380 I think what you're describing really is the future of pharmacogenomics. 243 00:16:53,390 --> 00:16:54,599 Um In other words, 244 00:16:54,609 --> 00:17:03,419 not singing out pharmacogenomics as you know the end all and be all in the treatment paradigm. 245 00:17:03,559 --> 00:17:08,040 But using a PGX test in combination with, 246 00:17:08,050 --> 00:17:09,069 like you mentioned, 247 00:17:09,250 --> 00:17:11,160 other serological tests, 248 00:17:11,170 --> 00:17:12,959 maybe other genetic tests. 249 00:17:13,290 --> 00:17:14,890 Um But you know, 250 00:17:14,900 --> 00:17:25,869 I think what we want our audience to really wrap their heads around is that PGX is just a piece of that larger puzzle um from diagnosis to treatment to, 251 00:17:25,880 --> 00:17:26,910 to remission. 252 00:17:27,239 --> 00:17:29,880 So I think you guys are absolutely, 253 00:17:29,890 --> 00:17:31,579 you're already in the future. 254 00:17:31,589 --> 00:17:32,849 In other words, 255 00:17:32,859 --> 00:17:33,130 you know, 256 00:17:33,140 --> 00:17:39,689 you're already providing all these different uh tests um like you mentioned to, 257 00:17:39,699 --> 00:17:44,310 to facilitate from diagnosis to remission to remission. 258 00:17:44,660 --> 00:17:45,520 That's correct. 259 00:17:45,530 --> 00:17:45,829 Yeah. 260 00:17:46,349 --> 00:17:55,089 So um you've given us so much great information about uh the tests that that you guys offer. 261 00:17:55,329 --> 00:18:02,060 Can you explain to our audience um your newest test? 262 00:18:02,069 --> 00:18:03,859 Uh the responder test. 263 00:18:04,150 --> 00:18:12,979 And um what role it will play in the paradigm from the diagnosis of IBD to remission? 264 00:18:14,050 --> 00:18:14,260 Yeah, 265 00:18:14,270 --> 00:18:14,760 sure. 266 00:18:14,770 --> 00:18:15,569 So we, 267 00:18:15,579 --> 00:18:18,069 we are doing things a little bit different than other. 268 00:18:18,079 --> 00:18:19,489 We do believe that uh you know, 269 00:18:19,500 --> 00:18:21,449 the it has to be simple. 270 00:18:21,459 --> 00:18:24,189 Uh uh We can obviously construct some very, 271 00:18:24,199 --> 00:18:33,530 very complex algorithm and there are some tests that do that with a very sophisticated machine learning based tools that are available using neural networks, 272 00:18:33,540 --> 00:18:33,729 you know, 273 00:18:33,739 --> 00:18:34,790 those sorts of things. 274 00:18:34,800 --> 00:18:39,729 But we have taken on a different approach where with the responder test, 275 00:18:39,739 --> 00:18:40,329 we are basically, 276 00:18:40,339 --> 00:18:45,160 we are taking an approach which is very simple to address the first and foremost. 277 00:18:45,170 --> 00:18:53,020 Most important aspect of responding uh predicting response to uh to medication is the pharmacokinetics. 278 00:18:53,280 --> 00:19:03,250 Uh You cannot be responding to a drug if the drug is not given and you obviously cannot respond to a drug if the drug is not metabolized adequately. 279 00:19:03,359 --> 00:19:06,349 And this is what we are doing with the responder test. 280 00:19:06,579 --> 00:19:09,010 We are addressing some uh uh you know, 281 00:19:09,020 --> 00:19:11,630 fundamental issues with those uh biologist, 282 00:19:11,640 --> 00:19:12,410 for example, 283 00:19:12,660 --> 00:19:15,170 uh the anti tumor necrosis factors. 284 00:19:15,180 --> 00:19:15,650 So, 285 00:19:15,750 --> 00:19:19,199 such as uh Infliximab and Adalimumab, 286 00:19:19,209 --> 00:19:23,050 it is well known uh that uh uh those drugs, 287 00:19:23,060 --> 00:19:25,689 first of all are prone to immunization. 288 00:19:25,989 --> 00:19:36,949 Uh Meaning that uh uh the drug itself uh is recognized by the immune system uh and digested by the antigen presenting cells. 289 00:19:36,959 --> 00:19:42,209 If you will uh where you gonna have uh uh an immune uh uh response, 290 00:19:42,380 --> 00:19:56,979 uh mounted a cancer drug to produce uh immunogen that will severely impact its pharmacokinetics where the labels will be inadequate to produce uh the desired uh anti-inflammatory effects. 291 00:19:56,989 --> 00:19:57,150 So, 292 00:19:57,160 --> 00:19:58,890 we are with the risk conductors, 293 00:19:58,900 --> 00:20:01,040 we are combining two things together. 294 00:20:01,189 --> 00:20:07,959 First of all is the genetic test itself which uh predicts the risk of immun immunization. 295 00:20:07,969 --> 00:20:18,010 The name of the test is on HL A uh DQ A 105 ali uh that uh uh promotes the presentation of the, 296 00:20:18,020 --> 00:20:19,130 of the, 297 00:20:19,140 --> 00:20:19,910 of Infliximab, 298 00:20:20,010 --> 00:20:20,750 for example, 299 00:20:20,760 --> 00:20:32,130 to the T cell repertoire in order to uh promote the Ronon expansion and the formation of the anti antibodies together with uh another dimension which is the clearance, 300 00:20:32,140 --> 00:20:33,670 which is as important. 301 00:20:33,949 --> 00:20:36,209 Uh One of the key issue is the, 302 00:20:36,219 --> 00:20:36,770 the, 303 00:20:36,780 --> 00:20:41,239 the monoclonal antibodies and uh such as Infliximab or Adalimumab. 304 00:20:41,329 --> 00:20:42,280 But in fact, 305 00:20:42,290 --> 00:20:45,890 a neon antibodies that those drugs are uh you know, 306 00:20:45,900 --> 00:20:49,010 cleared and consumed uh from the, 307 00:20:49,020 --> 00:20:50,949 from the central compartment if you will, 308 00:20:50,959 --> 00:20:54,520 since we are doing a little bit of uh uh pharmacokinetics here. 309 00:20:54,530 --> 00:20:56,020 And uh uh you know, 310 00:20:56,030 --> 00:21:06,670 if the patient present who is uh a high degree of inflammatory burden is gonna have uh the patient will have a high clearance and that's gonna worsen uh in the, 311 00:21:06,680 --> 00:21:13,939 in the presence again of the HL AD Q A 105 genetic marker that uh associate with uh immunization. 312 00:21:13,949 --> 00:21:16,859 So I but this is a combination of both, 313 00:21:17,199 --> 00:21:19,359 these are the predictive factors of pharmacokinetic, 314 00:21:20,359 --> 00:21:38,209 which we combine together where the patient presenting with a risk of immunization as well as accelerated clearance due to the fact that the patient has high inflammation or due to the fact that they are so intrinsic pharmacokinetic properties that makes that the patient, 315 00:21:38,219 --> 00:21:38,300 you know, 316 00:21:38,310 --> 00:21:39,479 will clear the drug very, 317 00:21:39,489 --> 00:21:40,260 very fast. 318 00:21:40,560 --> 00:21:41,670 For example, 319 00:21:41,680 --> 00:21:46,819 due to the inefficient uh recirculation of the drug itself with the new, 320 00:21:46,869 --> 00:21:46,930 the, 321 00:21:46,939 --> 00:21:50,599 the the in the reticular on the system. 322 00:21:50,920 --> 00:21:51,619 Together, 323 00:21:51,630 --> 00:22:02,109 those patients presenting with uh uh together these uh poor prognostic factor of pharmacokinetic origin will tend to be severely underdose, 324 00:22:02,380 --> 00:22:06,719 will not be responding to the drug uh adequately as and they, 325 00:22:06,729 --> 00:22:10,719 and they probably should in the first place if you are able to address uh you know, 326 00:22:10,729 --> 00:22:12,270 the the the exposure. 327 00:22:12,439 --> 00:22:14,079 So what we do with this test, 328 00:22:14,089 --> 00:22:21,640 we will be able to inform uh the clinic that the patient is at risk of achieving, 329 00:22:21,650 --> 00:22:30,829 of achieving suboptimal pharmacokinetics and therefore being able to adjust the dose uh uh to start with more adequately. 330 00:22:30,839 --> 00:22:38,650 So that the the the proper uh exposure is achieved uh during induction to again to, 331 00:22:38,660 --> 00:22:39,040 to, 332 00:22:39,050 --> 00:22:39,380 to, 333 00:22:39,390 --> 00:22:40,890 to achieve a better outcome. 334 00:22:41,040 --> 00:22:47,270 And I think the pharmacist will have a very important role to play here in terms of absolutely, 335 00:22:47,280 --> 00:22:51,239 that information is priceless in the management of these medications. 336 00:22:51,250 --> 00:22:54,930 So thanks for elaborating on that. 337 00:22:56,010 --> 00:22:59,040 And if I may add in our previous conversation, 338 00:22:59,050 --> 00:23:00,810 uh before the recording of podcast, 339 00:23:00,819 --> 00:23:08,869 we had discussed um you guys' robust platform for collaborating with payers to obtain market access and reimbursements for the test. 340 00:23:09,109 --> 00:23:14,109 But without stealing the Thunder from uh Prometheus market access and reimbursement team, 341 00:23:14,199 --> 00:23:22,619 can you please uh briefly detail how Prometheus has proactively worked with payers to solve the problem. 342 00:23:22,920 --> 00:23:27,349 Um the population health problem by building the evidence payers want, 343 00:23:27,359 --> 00:23:41,170 want to see um about your test before you go to the market and then build the test and then hope the payers will see the value and the result and then that will improve the market access and reimbursement for your um precision medicine test. 344 00:23:42,160 --> 00:23:42,339 Yeah. 345 00:23:42,349 --> 00:23:43,180 So briefly I can, 346 00:23:43,189 --> 00:23:43,579 I'm, 347 00:23:43,589 --> 00:23:46,619 I'm probably not the right person to answer that question. 348 00:23:46,630 --> 00:23:47,369 We have a very, 349 00:23:47,380 --> 00:23:52,400 very efficient market access group uh uh pro meters that does a splendid job. 350 00:23:52,410 --> 00:23:59,780 But uh uh uh what I can tell you that we have an evidence uh uh development plan in place where we, 351 00:23:59,790 --> 00:24:14,000 we are establishing the clinical utility of our testing solution by demonstrating uh the payer value uh with respect of uh patient management and uh uh and the, 352 00:24:14,010 --> 00:24:16,630 and the impact of our technology on the, 353 00:24:16,640 --> 00:24:18,119 on physician behavior. 354 00:24:18,430 --> 00:24:21,319 Uh We have uh uh already uh you know, 355 00:24:21,329 --> 00:24:25,160 commercialized uh two of those tests for which we have initiated, 356 00:24:25,170 --> 00:24:29,040 initiated the Power studies uh that uh uh you know, 357 00:24:29,050 --> 00:24:32,000 already provide uh you know, 358 00:24:32,104 --> 00:24:34,484 differentiated and the value to, 359 00:24:34,494 --> 00:24:35,915 to the payer where we are, 360 00:24:35,925 --> 00:24:36,025 the, 361 00:24:36,035 --> 00:24:46,005 the clinicians are basically using our technology to make treatment decision uh as well as uh some prospective clinicality study which we are initiating, 362 00:24:46,145 --> 00:24:47,555 initiating to. 363 00:24:47,564 --> 00:24:48,574 Um uh again, 364 00:24:48,584 --> 00:24:49,425 demonstrate the, 365 00:24:49,435 --> 00:24:49,915 the, 366 00:24:49,925 --> 00:24:50,244 the, 367 00:24:50,255 --> 00:24:53,594 the payer value you uh uh we can certainly follow up with, 368 00:24:53,604 --> 00:24:58,755 uh you can certainly follow up with our market access group uh uh as appropriate there. 369 00:24:58,765 --> 00:25:00,765 Uh They can fill you with more information. 370 00:25:01,349 --> 00:25:01,589 No, 371 00:25:01,599 --> 00:25:02,520 that totally makes sense. 372 00:25:02,530 --> 00:25:03,310 That totally makes sense. 373 00:25:03,319 --> 00:25:10,890 But um we're excited that you're also farm d So how did you get to this role of outside the box path? 374 00:25:10,900 --> 00:25:11,550 There? 375 00:25:11,640 --> 00:25:17,530 There may be a pharmacist student or pharmacist wanting to switch or transition into a role such as yours, 376 00:25:17,540 --> 00:25:19,609 which is a Chief Scientific Officer. 377 00:25:19,619 --> 00:25:20,609 I want to learn more. 378 00:25:20,619 --> 00:25:23,920 So how would you um can you talk a little bit about that? 379 00:25:24,560 --> 00:25:24,780 Well, 380 00:25:24,790 --> 00:25:26,270 we are clinical laboratories. 381 00:25:26,280 --> 00:25:29,400 So in order to uh uh to be in my role, 382 00:25:29,410 --> 00:25:34,020 you need to have uh uh you need to have expertise in clinical laboratory science. 383 00:25:34,030 --> 00:25:36,140 So for the students is basically, 384 00:25:36,150 --> 00:25:36,300 you know, 385 00:25:36,310 --> 00:25:40,770 to do the family degree and then complete the family degree with uh a doctorate, 386 00:25:40,780 --> 00:25:40,930 you know, 387 00:25:40,939 --> 00:25:44,260 which is uh focus on clinical laboratory science. 388 00:25:44,270 --> 00:25:46,079 So you can achieve uh uh you know, 389 00:25:46,089 --> 00:25:47,640 the all the elements you need to be, 390 00:25:47,650 --> 00:25:48,219 for example, 391 00:25:48,229 --> 00:25:53,189 board certified uh as uh as as medical laboratory director. 392 00:25:53,199 --> 00:25:55,160 So you can uh uh so, 393 00:25:55,170 --> 00:25:55,589 uh yeah, 394 00:25:55,599 --> 00:25:56,030 this is, 395 00:25:56,040 --> 00:25:56,400 this is, 396 00:25:56,410 --> 00:25:57,209 this is uh you know, 397 00:25:57,219 --> 00:25:59,160 a great opportunity I think for pharmacies, 398 00:25:59,170 --> 00:26:10,800 there is an absolute need to uh have the clinical pharmacist provide uh uh drug information to healthcare professional as well as uh assist patient with the monitoring of their disease, 399 00:26:10,810 --> 00:26:15,229 the effectiveness of the therapy and um and uh you know, 400 00:26:15,239 --> 00:26:16,060 monitoring the, 401 00:26:16,069 --> 00:26:20,969 the side effect and the toxicity from uh from those uh those medication. 402 00:26:24,650 --> 00:26:24,959 Well, 403 00:26:24,969 --> 00:26:32,119 the I know our audience is going to have uh additional questions for you. 404 00:26:32,130 --> 00:26:32,540 I mean, 405 00:26:32,989 --> 00:26:35,609 you've provided them with so much great information, 406 00:26:35,619 --> 00:26:44,959 but it's only the beginning of what they could possibly learn um about um the testing that you do for IBD and, 407 00:26:44,969 --> 00:26:46,729 and even your career path. 408 00:26:47,050 --> 00:26:47,530 So, 409 00:26:47,540 --> 00:26:49,300 if you wouldn't mind telling us, 410 00:26:49,310 --> 00:26:51,359 um because we have to wrap up, 411 00:26:51,369 --> 00:26:52,670 unfortunately, 412 00:26:53,150 --> 00:26:55,810 this episode of the podcast, 413 00:26:55,819 --> 00:27:00,250 uh could you tell us how our audience members might be able to contact you directly. 414 00:27:01,260 --> 00:27:01,449 Yeah, 415 00:27:01,459 --> 00:27:07,079 I can be contacted on my uh on my email at TT W at como slab dot com. 416 00:27:07,949 --> 00:27:08,810 All right. 417 00:27:09,069 --> 00:27:09,300 Well, 418 00:27:09,310 --> 00:27:14,290 thank you again so much uh for joining us on this episode. 419 00:27:14,300 --> 00:27:15,290 We really, 420 00:27:15,300 --> 00:27:29,530 really hope that our listeners um ideas of not only what PGX can be but how PGX can be utilized in a comprehensive testing suite. 421 00:27:29,709 --> 00:27:35,670 We really hope that our a our audience will um listen in and learn this information. 422 00:27:36,280 --> 00:27:37,869 Um And to our audience, 423 00:27:37,880 --> 00:27:39,439 thank you for tuning in. 424 00:27:39,449 --> 00:27:42,619 We really hope that you've learned from this episode. 425 00:27:43,130 --> 00:27:46,339 Uh We do a whole lot of PG Xing here on this podcast. 426 00:27:46,349 --> 00:27:48,380 We talk about PGX Science, 427 00:27:48,390 --> 00:27:52,030 clinical application and the business of PGX. 428 00:27:52,260 --> 00:27:54,880 So we'd love to hear about from you. 429 00:27:55,099 --> 00:27:56,479 I love to hear from you. 430 00:27:56,489 --> 00:27:58,439 Um What can we teach you? 431 00:27:58,449 --> 00:28:00,920 What more can we teach you through our podcast? 432 00:28:00,930 --> 00:28:12,349 So please drop us a message on linkedin and let us know and please share this link to this podcast link episode with everyone so they can tune in and listen to the PGX for promises podcast. 433 00:28:12,520 --> 00:28:15,369 Leave us a review on Apple podcast or Spotify. 434 00:28:15,459 --> 00:28:18,130 And you can also visit us on PGX four, 435 00:28:18,140 --> 00:28:22,989 the number four Rx dot com to listen to all our other episodes. 436 00:28:23,000 --> 00:28:23,079 Well, 437 00:28:23,089 --> 00:28:23,790 thank you. 438 00:28:24,199 --> 00:28:28,750 Thanks for your interest in PGX and for spending some time with us. 439 00:28:28,760 --> 00:28:35,670 Please share this podcast and leave us a review on Apple podcasts or Spotify for all of our episodes. 440 00:28:35,680 --> 00:28:39,390 Please visit PGX four Rx dot com. 441 00:28:39,569 --> 00:28:43,380 That's PGX four Rx dot com.  

Digital signatures are the foundation of our digital trust. With this, Bob has a key pair: a private key and a public key. In order to provide his identity, he signs a hash of a message with his private key, and then Alice proves this with his public key. Currently, we mainly use RSA, ECDSA and EdDSA for our signature methods, and where DSA signatures (which use discrete logs) have been dropped for their creation. For example, ECDSA is used with Bitcoin and Ethereum, and RSA is often used to identify Web sites. EdDSA is now on the rise, and is part of the FIPS-186–5 standard. Unforunately, we will need to replace these methods — as quantum computers can crack them. The other area that needs to be replaced is key exchange and public key encryption. These days we typically use ECDH (Elliptic Curve Diffie Hellman) for key exchange, and RSA for public key encryption. These will have to be replaced with quantum-robust methods — Post Quantum Cryptography (PQC). Goodbye RSA and ECC, and Hello to PQC And, so, using Shor's algorithm, quantum computers will be able to crack RSA, discrete logs and ECC (Elliptic Curve Cryptography), and so we need to remove RSA, ECDSA and EdDSA and replace them with methods that are quantum robust. For this, NIST has been running a competition for the last few years, and where CRYSTALS-Dilithium and SPHINCS+ were selected as the winners for PQC digital signatures. There are no other candidates that are being assessed from the previous round. Overall, Dilithium is a lattice-based method, while SPHINCS+ uses a hash-based signature method. But what if these methods are cracked? Well, it happened to two of the finalists for the NIST competition: Rainbow and SIKE, and where the methods were cracked in the final round of the competition. For KEM (Key Exchange Mechanisms) to replace ECDH (Elliptic Curve Diffie Hellman) and Public Key Encryption (PKE) to replace RSA, NIST has standardized CRYSTALS-Kyber, and is still assessing BIKE, Classic McEliece, HQC, and SIKE. Additional Signatures: Round 1 And, so, NIST is on the look-out for alternatives for Dilithium and has set up a new competition [here]: In the first round, we have: Code-based Signatures: CROSS (Codes and Restricted Objects Signature Scheme); Enhanced pqsigRM; FuLeeca; LESS (Linear Equivalence Signature Scheme) and MEDS (Matrix Equivalence Digital Signature Wave). Isogenies: SQIsign. Lattice based: EagleSign; EHTv3 and EHTv4; HAETAE; HAWK; HuFu (Hash-and-Sign Signatures From Powerful Gadgets); Raccoon; and SQUIRRELS (Square Unstructured Integer Euclidean Lattice Signature). MPC in the head: MIRA; MiRitH (MinRank in the Head); MQOM (MQ on my Mind); PERK; RYDE; and SDitH (Syndrome Decoding in the Head). Multivariate Signatures (Oil and Vinegar): 3WISE; Biscuit; DME-Sign; HPPC (Hidden Product of Polynomial Composition); MAYO; PROV (PRovable unbalanced Oil and Vinegar); QR-UOV; SNOVA; TUOV (Triangular Unbalanced Oil and Vinegar); UOV (Unbalanced Oil and Vinegar); and VOX. Symmetric-based Signatures: AIMer; Ascon-Sign; FAEST; and SPHINCS-alpha. Doing a quick count, we have: Multivariate: 11; Lattice: 7; Code-based: 5; MPC-in-the-head: 5; Symmetric-based: 4; and Isogenies: 1. So, multivariate seems to be leading the way, with lattice methods being popular too. But poor old isogenies only has one contender. This may be due to the crack on an isogeny-based method (Supersingular Isogeny Key Encapsulation SIKE), or that isogenies are better suited to key exchange techniques. And so, let's look at the basic methods and some previous examples. Multivariate — Unbalanced Oil and Vinegar (UOV) With multivariate cryptography, we have n variables within polynomial equations. For example, if we have four variables (w,x,y,z) and an order of two, we could have [here]: w²+4wx+3x²+2wy−4wz+2wx+6xz=387 Generally, this is a hard problem to solve, so we want to make it easy if we know a secret. In this case, I know that the solution is w=7,x=4,y=5, and z=6. Oil and Vinegar Makes A Hard Problem Easy Fixing The Hole In The Internet in a Post Quantum World medium.com   Lattice To understand lattice cryptography, you need to understand polynomials, as our bit values are converted into polynomials. Our operations are then conducted with polynomial multiplies and addition, and taken with a (mod p) operation (and where p will be the maximum value we generate for the polynomial values). The Magic of Lattice and The Eye of a Falcon To understand lattice cryptography, you need to understand polynomials, as our bit values are converted into… medium.com   Code-based This method was created in 1978 with the McEliece cryptosystem but has barely been used in real applications. The McEliece method uses linear codes that are used in error-correcting codes and involves matrix-vector multiplication. An example of a linear code is Hamming code [here]. McEliece and Rust: Edging Slowly To A NIST Standard for PQC We live in a world that is dominated by large (and faceless) corporations, but it is individuals who have often built… medium.com   MPC-in-the-head These methods use non-interactive zero-knowledge proofs of knowledge and MPC (Multiparty Computation). With MPC we can split a problem into a number of computing elements, and these can be worked on in order to produce the result, and where none of the elements can see the working out at intermediate stages. The great advantage of this method is that we only use symmetric key methods (block ciphers and hashing functions). Let's Go For A Post-Quantum Picnic And then there were three: CRYSTALS Dilithium, Falcon and Rainbow. These are the finalists for the NIST standard for… medium.com   Symmetric These methods uses standard cryptographic methods such as symmetric key encryption and hashes. Typically they use AES and SHA3 — and which are quantum robust. Isogenies If we have two elliptic curves (E1 and E2), we can create a function that maps a point (P) on E1 to a point Q on E2. This function is known as an isogeny. If we can map this function, every point on E1 can be mapped to E2. Our secret key is then the isogeny and the public key is the elliptic curve. For key exchange, Bob and Alice mix their isogeny and the other side's curve to generate a secret curve. Isogenies? The End Game for Public Key Encryption? Well, we are now at the final stage of NIST's post-quantum cryptography standardization, and which started in 2016: medium.com   Conclusions Exciting times are ahead as the methods go up and against each. In the last competition, some of the methods fell because of a problem with their parameters (Rainbow — UOV) or because of a core weakness (isogenies). But, this time, they are all likely to come back strong and (hopefully) compete well against the lattice methods.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.29.551128v1?rss=1 Authors: Hsiao, P.-Y. A., Kim, M. J., Chou, F.-C. B., Chen, P.-H. A. Abstract: We used functional magnetic resonance imaging and showed that state anxiety modulated extrastriate cortex activity in response to emotionally charged visual images. State anxiety and neuroimaging data from 53 individuals were subjected to an intersubject representational similarity analysis (ISRSA), wherein the geometries between neural and behavioral data are compared. This analysis identified the extrastriate cortex (fusiform gyrus and area MT) to be the sole region whose activity patterns covaried with state anxiety. Importantly, we show that this brain-behavior association is revealed when treating state anxiety data as a multidimensional response pattern, rather than a single composite score. This suggests that ISRSA using multivariate distances may be more sensitive in identifying the shared geometries between self-report questionnaires and brain imaging data. Overall, our findings demonstrate that a transient state of anxiety may influence how visual information, especially those relevant to the valence dimension, is processed in the extrastriate cortex. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.27.550851v1?rss=1 Authors: Ezzyat, Y., Kragel, J. E., Solomon, E. A., Lega, B. C., Aronson, J. P., Jobst, B. C., Gross, R. E., Sperling, M. R., Worrell, G. A., Sheth, S. A., Wanda, P. A., Rizzuto, D. S., Kahana, M. J. Abstract: Direct electrical stimulation of the brain, when applied or optimized in a closed-loop manner, can lead to improvements in memory (Ezzyat et al., 2018) and mood (Scangos et al., 2021a). In these approaches, brain states control the timing of stimulation or the choice of parameters, which build off the notion that stimulations neural and behavioral effects depend on brain state at the time of delivery (Ezzyat et al., 2017; Scangos et al., 2021b). Although closed-loop algorithms provide greater control over stimulations physiological and behavioral effects, variability in outcomes remains a primary challenge for using stimulation for clinical and experimental neuromodulation. Here, we evaluate the hypothesis that stimulations behavioral and physiological effects depend on the anatomical and functional network properties of the stimulation target. Closed-loop stimulation was delivered via intracranially-implanted electrodes as neurosurgical patients studied and recalled word lists. Multivariate classifiers, trained to predict momentary lapses in memory function, triggered stimulation of the lateral temporal cortex (LTC) during the study phase of the task. We found that stimulating LTC locations with high functional network connectivity led to greater physiological and behavioral effects of stimulation. Further, stimulation specifically improved memory performance when delivered to targets near white matter pathways. These data reveal how functional and anatomical networks mediate stimulations physiological and behavioral effects, provide further evidence that closed-loop LTC stimulation modulates episodic memory, and suggest future strategies for stimulation targeting for effective neuromodulation. Significance StatementDirect electrical stimulation, when applied in closed-loop, can improve cognitive function (Ezzyat et al., 2018; Scangos et al., 2021a), however variability in outcomes remains a key challenge. We examined how the anatomical and functional network characteristics of the stimulation target predict variability in stimulations physiological and behavioral effects, focusing on stimulation of the lateral temporal cortex (LTC) during an episodic memory task. Stimulating LTC locations with high functional network connectivity produces greater physiological and behavioral effects of stimulation, while stimulating targets near white matter pathways produced the most robust behavioral improvement. The data reveal how functional and anatomical networks mediate stimulations physiological and behavioral effects and suggest future strategies for optimal targeting of stimulation for neuromodulation. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.27.550851v1?rss=1 Authors: Ezzyat, Y., Kragel, J. E., Solomon, E. A., Lega, B. C., Aronson, J. P., Jobst, B. C., Gross, R. E., Sperling, M. R., Worrell, G. A., Sheth, S. A., Wanda, P. A., Rizzuto, D. S., Kahana, M. J. Abstract: Direct electrical stimulation of the brain, when applied or optimized in a closed-loop manner, can lead to improvements in memory (Ezzyat et al., 2018) and mood (Scangos et al., 2021a). In these approaches, brain states control the timing of stimulation or the choice of parameters, which build off the notion that stimulations neural and behavioral effects depend on brain state at the time of delivery (Ezzyat et al., 2017; Scangos et al., 2021b). Although closed-loop algorithms provide greater control over stimulations physiological and behavioral effects, variability in outcomes remains a primary challenge for using stimulation for clinical and experimental neuromodulation. Here, we evaluate the hypothesis that stimulations behavioral and physiological effects depend on the anatomical and functional network properties of the stimulation target. Closed-loop stimulation was delivered via intracranially-implanted electrodes as neurosurgical patients studied and recalled word lists. Multivariate classifiers, trained to predict momentary lapses in memory function, triggered stimulation of the lateral temporal cortex (LTC) during the study phase of the task. We found that stimulating LTC locations with high functional network connectivity led to greater physiological and behavioral effects of stimulation. Further, stimulation specifically improved memory performance when delivered to targets near white matter pathways. These data reveal how functional and anatomical networks mediate stimulations physiological and behavioral effects, provide further evidence that closed-loop LTC stimulation modulates episodic memory, and suggest future strategies for stimulation targeting for effective neuromodulation. Significance StatementDirect electrical stimulation, when applied in closed-loop, can improve cognitive function (Ezzyat et al., 2018; Scangos et al., 2021a), however variability in outcomes remains a key challenge. We examined how the anatomical and functional network characteristics of the stimulation target predict variability in stimulations physiological and behavioral effects, focusing on stimulation of the lateral temporal cortex (LTC) during an episodic memory task. Stimulating LTC locations with high functional network connectivity produces greater physiological and behavioral effects of stimulation, while stimulating targets near white matter pathways produced the most robust behavioral improvement. The data reveal how functional and anatomical networks mediate stimulations physiological and behavioral effects and suggest future strategies for optimal targeting of stimulation for neuromodulation. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.17.548986v1?rss=1 Authors: Bailey, K. M., Sami, S., Smith, F. Abstract: Whilst previous research has linked attenuation of the mu rhythm to the observation of specific visual categories, and even to a potential role in action observation via a putative mirror neuron system, much of this work has not considered what specific type of information might be coded in this oscillatory response when triggered via vision. Here, we sought to determine whether the mu rhythm contains content-specific information about the identity of familiar (and also unfamiliar) graspable objects. In the present study, right-handed participants (N=27) viewed images of both familiar (apple, wine glass) and unfamiliar (cubie, smoothie) graspable objects, whilst performing an orthogonal task at fixation. Multivariate pattern analysis (MVPA) revealed significant decoding of familiar, but not unfamiliar, visual object categories in the mu rhythm response. Thus, simply viewing familiar graspable objects may automatically trigger activation of associated tactile and/or motor properties in sensorimotor areas, reflected in the mu rhythm. In addition, we report significant attenuation in the central beta band for both familiar and unfamiliar visual objects, but not in the mu rhythm. Our findings highlight how analysing two different aspects of the oscillatory response, either attenuation or the representation of information content, provide complementary views on the role of the mu rhythm in response to viewing graspable object categories. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.11.548408v1?rss=1 Authors: Thomas, E. R., Haarsma, J., Nicholson, J., Yon, D., Kok, P., Press, C. Abstract: Predictive processing frameworks of cortical functioning propose that neural populations in different cortical layers serve distinct roles in representing the world. There are distinct testable theories within this framework that we examined with a 7T fMRI study, where we contrasted responses in primary visual cortex (V1) to expected (75% likely) and unexpected (25%) Gabor orientations. Multivariate decoding analyses revealed an interaction between expectation and layer, such that expected events could be decoded with comparable accuracy across layers, while unexpected events could only be decoded in superficial laminae. These results are in line with predictive processing accounts where expected virtual input is injected into deep layers, while superficial layers process the error with respect to expected signals. While this account of cortical processing has been popular for decades, such distinctions have not previously been demonstrated in the human sensory brain. We discuss how both prediction and error processes may operate together to shape our unitary perceptual experiences. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.10.548319v1?rss=1 Authors: Alho, J., Gotsopoulos, A., Silvanto, J. Abstract: Conscious experiences normally result from the flow of external input into our sensory systems. However, we can also create conscious percepts independently of sensory stimulation. These internally generated percepts are referred to as mental images, and they have many similarities with real visual percepts. Consequently, mental imagery is often referred to as "seeing in the mind's eye". While the neural basis of imagery has been widely studied, the interaction between internal and external sources of visual information has received little interest. Here we examined this question by using fMRI to record brain activity of healthy human volunteers while they were performing visual imagery that was distracted with a concurrent presentation of a visual stimulus. Multivariate pattern analysis (MVPA) was used to identify the brain basis of this interaction. Visual imagery was reflected in several brain areas in ventral temporal, lateral occipitotemporal, and posterior frontal cortices, with a left-hemisphere dominance. The key finding was that imagery content representations in the left lateral occipitotemporal cortex were disrupted when a visual distractor was presented during imagery. Our results thus demonstrate that the representations of internal and external visual information interact in brain areas associated with the encoding of visual objects and shapes. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.05.547821v1?rss=1 Authors: Cabral, L., Calabro, F., Foran, W., Parr, A., Ojha, A., Rasmussen, J., Ceschin, R., Panigrahy, A., Luna, B. Abstract: In the perinatal period, reward and cognitive systems begin trajectories, influencing later psychiatric risk. The basal ganglia is critical for reward and cognitive processing but early development is understudied. To assess age-related development, we used a measure of basal ganglia physiology, specifically brain tissue iron, obtained from nT2* signal in rsfMRI, linked to dopaminergic processing. We used data from the Developing Human Connectome Project (N=464) to assess how moving from the prenatal to the postnatal environment affects rsfMRI nT2*, modeling gestational and postnatal age separately for basal ganglia subregions in linear models. We didn't find associations with tissue iron and gestational age [Range:24.29-42.29] but found positive associations with postnatal age [Range:0-17.14] in the pallidum and putamen, but not the caudate. We tested if there was an interaction between preterm birth and postnatal age, finding early preterm infants (GA less than 35 weeks) had higher iron levels and changed less over time. To assess multivariate change, we used support vector regression to predict age from voxel-wise nT2* maps. We could predict postnatal but not gestational age when maps were residualized for the other age term. This provides evidence subregions differentially change with postnatal experience and early preterm birth may disrupt trajectories. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.06.29.547012v1?rss=1 Authors: Klink, H., Kaiser, D., Stecher, R., Ambrus, G. G., Kovacs, G. Abstract: Recognizing a stimulus as familiar is an important capacity in our everyday life. Recent investigation of visual processes has led to important insights into the nature of the neural representations of familiarity for human faces. Still, little is known about how familiarity affects the neural dynamics of non-face stimulus processing. Here we report the results of an EEG study, examining the representational dynamics of personally familiar scenes. Participants viewed highly variable images of their own apartments and unfamiliar ones, as well as personally familiar and unfamiliar faces. Multivariate pattern analyses were used to examine the time course of differential processing of familiar and unfamiliar stimuli. Time resolved classification revealed that familiarity is decodable from the EEG data similarly for scenes and faces. The temporal dynamics showed delayed onsets and peaks for scenes as compared to faces. Familiarity information, starting at 200 ms, generalized across stimulus categories and led to a robust familiarity effect. In addition, familiarity enhanced category representations in early (250 to 300 ms) and later ( greater than 400 ms) processing stages. Our results extend previous face familiarity results to another stimulus category and suggest that familiarity as a construct can be understood as a general, stimulus-independent processing step during recognition. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.06.26.546549v1?rss=1 Authors: Carta, S., Alickovic, E., Zaar, J., Lopez Valdes, A., Di Liberto, G. Abstract: Hearing impairment alters the sound input received by the human auditory system, reducing speech comprehension in noisy multi-talker auditory scenes. Despite such challenges, attentional modulation on the envelope tracking in multi-talker scenarios is comparable between normal hearing (NH) and hearing impaired (HI) participants, with previous research suggesting an over-representation of the speech envelopes in HI individuals (see, e.g., Fuglsang et al. 2020 and Presacco et al. 2019), even though HI participants reported difficulties in performing the task. This result raises an important question: What speech-processing stage could reflect the difficulty in attentional selection, if not envelope tracking? Here, we use scalp electroencephalography (EEG) to test the hypothesis that such difficulties are underpinned by an over-representation of phonological-level information of the ignored speech sounds. To do so, we carried out a re-analysis of an EEG dataset where EEG signals were recorded as HI participants fitted with hearing aids attended to one speaker (target) while ignoring a competing speaker (masker) and spatialised multi-talker background noise. Multivariate temporal response function analyses revealed that EEG signals reflect stronger phonetic-feature encoding for target than masker speech streams. Interestingly, robust EEG encoding of phoneme onsets emerged for both target and masker streams, in contrast with previous work on NH participants and in line with our hypothesis of an over-representation of the masker. Stronger phoneme-onset encoding emerged for the masker, pointing to a possible neural basis for the higher distractibility experienced by HI individuals. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

In this week's episode, Anna Rose (https://twitter.com/annarrose) dives back into accumulation schemes with Benedikt Bünz (https://twitter.com/benediktbuenz) and Binyi Chen (https://twitter.com/Charles_Chen533) from Espresso Systems (https://espressosys.com/). They discuss ProtoStar and how it compares to works such as Nova and HyperNova, as well as explore some definitions for commonly used terms in the accumulation literature. Here's some additional links for this episode: Espresso Systems CAPE (https://docs.espressosys.com/cape) Espresso Sequencer (https://hackmd.io/@EspressoSystems/EspressoSequencer) Bulletproofs: Short Proofs for Confidential Transactions and More by Bünz, Bootle, Boneh, Poelstra, Wuille and Maxwell (https://eprint.iacr.org/2017/1066.pdf) Verifiable Delay Functions by Boneh, Bonneau, Bünz and Fisch (https://eprint.iacr.org/2018/601.pdf) HyperPlonk: Plonk with Linear-Time Prover and High-Degree Custom Gates by Chen, Bünz, Boneh and Zhang (https://eprint.iacr.org/2022/1355) Protostar: Generic Efficient Accumulation/Folding for Special-sound Protocols by Bünz and Chen (https://eprint.iacr.org/2023/620.pdf) Proof-Carrying Data without Succinct Arguments by Bünz, Chiesa, Lin, Mishra and Spooner (https://eprint.iacr.org/2020/1618.pdf) Proof-Carrying Data from Accumulation Schemes by Bünz, Chiesa, Mishra, and Spooner (https://eprint.iacr.org/2020/499) Multivariate lookups based on logarithmic derivatives by Haböck (https://eprint.iacr.org/2022/1530.pdf) Halo Infinite: Proof-Carrying Data from Additive Polynomial Commitments by Boneh, Drake, Fisch, Gabizon (https://eprint.iacr.org/2020/1536.pdf) Incrementally Verifiable Computation or Proofs of Knowledge Imply Time/Space Efficiency by Valiant (https://www.cs.purdue.edu/homes/pvaliant/uniqueCS.pdf) Recursive Proof Composition without a Trusted Setup by Bowe, Grigg, and Hopwood (https://eprint.iacr.org/2019/1021.pdf) Episode 40: Benedikt Bünz on Bulletproofs and Verifiable Delay Functions (https://zeroknowledge.fm/40-2/) Episode 277: Nova and Beyond with Srinath Setty (https://zeroknowledge.fm/277-2/) Check out the ZK Jobs Board here: ZK Jobs (https://jobsboard.zeroknowledge.fm/). Find your next job working in ZK! Aztec Network (https://aztec.network/) is building a next-generation encrypted blockchain powered by Ethereum. The team is proud to announce Noir (https://aztec.network/noir) - the world's first universal zk-language. Noir makes it safe and intuitive to write zk circuits and encrypted smart contracts, enabling novel use-cases like encrypted DeFi, private governance, and zk gaming. As a universal language, Noir is domain-specific, but blockchain agnostic. Build powerful zk applications compatible with multiple proving systems and verify your program on any EVM chain. Get started with Noir today at docs.aztec.network/noir (https://docs.aztec.network/noir) If you like what we do: * Find all our links here! @ZeroKnowledge | Linktree (https://linktr.ee/zeroknowledge) * Subscribe to our podcast newsletter (https://zeroknowledge.substack.com) * Follow us on Twitter @zeroknowledgefm (https://twitter.com/zeroknowledgefm) * Join us on Telegram (https://zeroknowledge.fm/telegram) * Catch us on YouTube (https://zeroknowledge.fm/)

Nico Schuck is Professor and head of the research group 'Mechanisms of learning and change' at the University of Hamburg, where his research focuses on the neuroscience of learning, memory, and cognitive maps. In this conversation, we discuss his work on cognitive maps and replay in Orbitofrontal Cortex and Hippocampus, decoding even brief events with fMRI, and much more.BJKS Podcast is a podcast about neuroscience, psychology, and anything vaguely related, hosted by Benjamin James Kuper-Smith.Support the show: https://geni.us/bjks-patreonTimestamps00:00: Nico's work elicits 'limited enthusiasm'04:36: Multivariate decoding with fMRI13:23: Start discussing Nico's paper 'Human OFC represents a cognitive map of state space'19:39: Weird tasks in computational neuroscience27:30: Start discussing Nico's paper ' Sequential replay of nonspatial task states in the human hippocampus'36:45: How can the slow fMRI signal pick up on very fast neural dynamics?43:02: What is Orbitofrontal Cortex and what does it do?49:24: Some books and papers more people should read55:17: Something Nico wishes he'd learnt sooner56:40: Advice for young scientistsPodcast linksWebsite: https://geni.us/bjks-podTwitter: https://geni.us/bjks-pod-twtNico's linksWebsite: https://geni.us/schuck-webGoogle Scholar: https://geni.us/schuck-scholarTwitter: https://geni.us/schuck-twtBen's linksWebsite: https://geni.us/bjks-webGoogle Scholar: https://geni.us/bjks-scholarTwitter: https://geni.us/bjks-twtReferencesAly & Turk-Browne (2016). Attention stabilizes representations in the human hippocampus. Cerebral Cortex.Bishop (2006). Pattern recognition and machine learning. New York: Springer.Kaplan, Schuck & Doeller (2017). The role of mental maps in decision-making. Trends in Neurosciences.Knudsen & Wallis (2022). Taking stock of value in the orbitofrontal cortex. Nature Reviews Neuroscience.Moneta, Garvert, Heekeren & Schuck (2023). Task state representations in vmPFC mediate relevant and irrelevant value signals and their behavioral influence. Nature Communications.Schuck, Cai, Wilson & Niv (2016). Human orbitofrontal cortex represents a cognitive map of state space. Neuron.Schuck & Niv (2019). Sequential replay of nonspatial task states in the human hippocampus. Science.Shepard (1987). Toward a universal law of generalization for psychological science. Science.Skaggs & McNaughton (1996). Replay of neuronal firing sequences in rat hippocampus during sleep following spatial experience. Science.Sutton & Barto (2018). Reinforcement learning: An introduction. MIT press.Tang, LeBel, Jain & Huth (2023). Semantic reconstruction of continuous language from non-invasive brain recordings. Nature Neuroscience.Todd, Nystrom & Cohen(2013). Confounds in multivariate pattern analysis: theory and rule representation case study. Neuroimage.Wilson, Takahashi, Schoenbaum & Niv (2014). Orbitofrontal cortex as a cognitive map of task space. Neuron.

Karly Rager is back on the podcast and is joined by Casey Elliott to talk about the factors that affect climbing performance. We've got three engineers in one podcast, and we geek out on the data! Do things like weight, height, and ape index affect how hard you can climb? Is max finger strength more important than days spent climbing outside? Listen to find out!Check out The Nugget on YouTube:youtube.com/@thenuggetclimbingThe Nugget is brought to you by BetterHelp!betterhelp.com/NUGGETUse this link for 10% off your first month!Check out Crimpd!crimpd.comOr download the Crimpd app!Check out Green Chef!greenchef.com/nugget60Use code "NUGGE60" at checkout for 60% off plus free shipping!Check out Rumpl!rumpl.com/nuggetUse code "NUGGET" at checkout for 10% off your first order!Check out Rhino Skin Solutions!rhinoskinsolutions.comUse code “NUGGET” at checkout for 20% off your next order!And check out EP 22 with Justin Brown to learn more about how to use Rhino products! We are supported by these amazing BIG GIVERS:Leo Franchi, Michael Roy, David Lahaie, Robert Freehill, Jeremiah Johnson, Scott Donahue, Eli Conlee, Skyler Maxwell, Craig Lee, Mark and Julie Calhoun, Yinan Liu, Renzollama, Zach Emery, and Brandt MickolasBecome a Patron:patreon.com/thenuggetclimbingShow Notes:  thenuggetclimbing.com/episodes/karly-and-caseyNuggets:0:06:18 – Karly's time in El Salto, Mexico0:09:39 – Casey joins us from a legit recording studio, his engineering studies, and coaching vs. engineering0:16:06 – An update from Karly on Project Direct, and how she got connected to Casey0:19:19 – Decision fatigue, and wearing lots of hats0:20:42 – Casey's climbing and coaching background0:25:51 – Mikey Schaefer calls out Casey, and the connection between dating and projecting routes0:30:03 – What was the goal of this multi-variate statistical analysis?0:32:59 – What is a multivariate statistical analysis, and how does it work?0:40:09 – The 600 people whose data was used in this analysis, and getting away from statements like “I have 5.13 finger strength”0:49:12 – What % of climbers have climbed 5.13?0:50:56 – List of the variables used in this analysis0:53:45 – Casey's simple model using three variables0:55:15 – How important is climbing outside vs. max finger strength?0:56:35 – Why climbing outside ended up being the most heavily weighted variable in the multivariate model0:59:10 – Higher-end statistics require interpretation1:00:47 – Check out their blog post and the climbing calculator!1:02:08 – Do height, weight, wing span, or BMI affect how hard you can climb?1:07:57 – Thoughts on how age affects how hard you can climb, and playing to your strengths as a short climber1:09:37 – What the data doesn't tell us1:11:06 – The range of climbing abilities in the 600 participants1:12:36 – How the coefficient for max hangs turned out to be negative, and what that likely means1:18:08 – What should people spend their time on to get better at climbing?1:20:59 – How training can lead to expectations, and getting good before you get strong1:24:38 – Getting creative with skill drills1:25:34 – Watching climbing videos, and filming your Kilter Board sessions1:27:49 – Diving deeper into what you should do to climb harder boulders and sport routes1:32:06 – Looking for low-hanging fruit1:35:03 – How Karly used the online calculator before her trip to El Salto1:36:08 – How to use the online climbing calculator, and how to take the assessment1:39:34 – How many outdoor days does it take to be a master?1:42:35 – Injury prevention isn't captured in the model1:43:41 – What variables would Karly and Casey like to see in their dream multi-variate statistical analysis?1:46:39 – What is Mikey Schafer up to?1:48:16 – Skiing this winter, and finishing his masters1:48:52 – The momentum that comes with doing hard things, and looking at high performers1:51:56 – Final thoughts and wrap up

Founder Dash is here, and it's free to use! Better understand your data and get started for free today.In this episode of Adspend, we have Dan Pantelo, the founder of Marpipe, joining us to discuss strategies for maximizing advertising success. From dynamic product ads to proper feed setup, Dan shares valuable insights on leveraging Marpipe's user-friendly tools, optimizing catalog feeds, and implementing effective DPA and multivariate AB testing. Tune in to discover how to revolutionize your advertising campaigns and stay ahead in the ever-evolving world of digital marketing.Connect with Dan: https://www.linkedin.com/in/danpantelo/Check out Marpipe: https://www.marpipe.com/Oh. And before we forget...Join 20,000+ of the best ecommerce marketers + operators and get marketing breakdowns, expert advice, and insider marketing resources straight to your inbox, right here.Connect with us on social!

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.05.04.539347v1?rss=1 Authors: Green, D. C., Reynard, L., Henstock, J., Reppe, S., Gutvik, K., Peffers, M., Shanley, D., Clegg, P. D., Canty-Laird, E. G. Abstract: Background: Age is a significant risk factor for functional decline and disease of the musculoskeletal system, yet few biomarkers exist to facilitate ageing research in musculoskeletal tissues. Multivariate models based on DNA methylation, termed epigenetic clocks, have shown promise as markers of biological age. However, the accuracy of existing epigenetic clocks in musculoskeletal tissues are no more, and often less accurate than a randomly sampled baseline model. Results: We developed a highly accurate epigenetic clock, MskAge, that is specific to tissues and cells of the musculoskeletal system. MskAge was built using a penalised genetic algorithm islands model that addresses multi-tissue clock bias. The final model was trained on the transformed principal components of CpGs selected by the genetic algorithm, which are significantly enriched for pathways terms related to the skeletal system and mesenchyme development. We show that MskAge tracks epigenetic ageing ex vivo and in vitro. Epigenetic age estimates are rejuvenated to zero with cellular reprogramming and are accelerated at a rate of 0.45 years per population doubling. Remarkably, MskAge explains more variance associated with in vitro ageing of fibroblasts than the purpose-developed skin and blood clock. Conclusion: The precision of MskAge and its ability to capture perturbations in biological ageing make it a promising research tool for musculoskeletal and ageing biologists. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

India Policy Watch #1: Don't Concentrate Insights on issues relevant to India— RSJIn one of the recent editions on the Hindenburg short-selling saga, I had written about how easily the Adani group had spread itself into a diverse range of sectors. The group was highly leveraged because it was so keen on getting into newer sectors and then winning bids in them with metronomic efficiency. Generally speaking, it is difficult to run a conglomerate of different businesses. You might argue that each business can be handled by a competent management team who will use the brand name and deep pockets of the parent group to build a solid business. But it is easier said than done. Capital allocation decisions, which lie at the heart of executing a business strategy, are difficult within a single line of business. They become hugely complicated within a conglomerate of businesses. Misallocation of capital, lack of focus and inability to stay competitive against smaller, nimbler players eventually follow. Soon, the businesses need to be hived off, and you find companies convincing would-be investors on how they are doing fewer things and doing them well instead of spreading themselves too thin. This is the usual cycle. Yet, you see conglomerates appearing on the business landscape across countries. In some cases, these are businesses integrating vertically or finding interesting adjacencies in their business. This kind of makes sense in the Coase-ian “Nature of Firm” way. I mean, if the transaction costs of finding someone to do a particular work are higher than you doing it yourself, sure, go ahead and do it yourself. But beyond that, there should be no economic reason for having conglomerates. Unless you have one of these conditions in the economy: a) Cost of capital is high, and access to it is difficult. Newer players find it difficult to access capital to start new businesses while older, established players with free cash flow can muscle their way into unrelated but lucrative new sectors only because they have access to capital at a lower rate. b) The playing field isn't level for newer players to make a dent. Through a mix of friendly regulations, ‘working' the networks and M&A activities, the bigger players continue to have an advantage going into a new sector over smaller players who might have expertise in cracking those sectors open.c) There's relatively little ease of doing business in those sectors or in the evening overall. The established conglomerates with an army of people, lawyers and consultants can get started relatively faster and capture the market than new entrants. You don't have to be a genius to see where the Indian policy-making framework is on the above conditions. There's common and easy access to capital through a large number of PEs and VC funds but only for a particular kind of ‘flavour of the season' variety. This also is getting difficult to access. The market for other forms of capital isn't deep enough. In the same vein, long-term capital for greenfield projects where the credit risk has to be borne by the issuer isn't available. There is always a whiff of regulatory capture especially in sectors where the government is closely involved bin decision making. Lastly, we might have moved up in the ‘ease of doing business' rankings, but it isn't clear yet how this has changed things on the ground. New businesses still find going tough for them. All of the above means that in the past five years, we are reversing a trend seen since the ‘91 reforms. That of increasing salience of conglomerates in India. You don't have to research too hard. Just take a look at any sector - already big or one that is emerging - you will have the same spectacle of a few large corporate groups getting themselves into all sorts of businesses, from defence to semiconductors or from airlines to carbonated soft drinks only because they believe they can take advantage of market distortions.As if to illustrate this point further, here's news that's only a day old. Here's Moneycontrol  reporting:“The shares of Mukesh Ambani-led Reliance Industries Ltd (RIL) rallied 3.5 percent in the morning trade on March 31 after the company said secured creditors, unsecured creditors and shareholders would meet on May 2 to approve the proposed demerger of Reliance Strategic Ventures.After the approval, the unit, which is the financial services subsidiary of the oil-to-telecom conglomerate, would be renamed Jio Financial Services.Benefits that shall accrue on the demerger of the financial services business will be the creation of an independent company focusing exclusively on financial services and exploring opportunities in the sector, the independent company can attract different sets of investors, strategic partners, lenders and other stakeholders having a specific interest in the financial services business, a financial services company can have a higher leverage (as compared to the Demerged Company) for its growth and, unlocking the value of the demerged undertaking for the shareholders of the demerged company, the conglomerate said in an exchange filing.”This isn't out of the ordinary. If you search for similar news items from the last five years, you will notice the same pattern of large conglomerates (usually the big 5) muscling into other or newer sectors because they think they have the capital and they will be able to manage the sector well. While one cannot blame these conglomerates for their ambitions, this trend suggests we might have tipped over from being pro-markets to pro-business. Coincidentally, as I was writing this, we had a paper authored by Viral Acharya (former Deputy Governor, RBI) on the opportunities and challenges for the Indian economy published by the Brookings Institution and being discussed in the media. Acharya has highlighted the concentration of power in Indian industry as a particularly worrying trend. He writes (I have paraphrased a bit):“A striking feature of this rise in industrial concentration by private companies is that it is in part due to the growing footprint of “Big-5” industrial conglomerates, based on the overall share of assets in non-financial sectors in 2021. Data shows the following patterns.First, until 2010, the Big-5 increased their footprint in more and more industrial sectors, broadening their reach to 40 NIC-2-digit non-financial sectors. After this breadth first strategy came the depth-next strategy. Starting in 2015, the Big-5 started acquiring larger and larger share within the sectors where they were present. In particular, their share in total assets of the non-financial sectors rose from 10% in 1991 to nearly 18% in 2021, whereas the share of the next big five (Big 6-10) business groups fell from 18% in 1992 to less than 9%. In other words, Big-5 grew not just at the expense of the smallest firms, but also of the next largest firms.Next, this growth of Big-5 appears to be driven in part by their growing share of overall Mergers & Acquisitions (M&A) activity. Even though the aggregate number of M&A deals has dropped since 2011, the share of M&A deals by the Big-5 has doubled from under 3% in 2015 to 6% in 2021, without such an increase being seen in the next five biggest groups. Arguably, this growth has also been supported by a conscious industrial policy of creating “national champions” via preferential allocation of projects and in some cases regulatory agencies turning a blind eye to predatory pricing. Equally importantly, given the high tariffs, Big-5 groups do not have to compete with international peers in many sectors where they are present and derive most of their revenues domestically.”Acharya then goes on to list the usual downstream problems of such an increase in market power concentration - inefficient allocation of capital, favouritism in project allocation, regulatory interference, related party transactions, over-leveraging while becoming too big to fail and crowding out new players. But he also makes an important claim that this concentration of market power is one of the reasons for persistent core inflation. He concludes:“In summary, creating national champions, which is considered by many as the industrial policy of “new India”, appears to be feeding directly into keeping prices at a high level, with the possibility that it is feeding “core” inflation's persistent high level.”I won't go as far as Acharya yet on this thesis. As he admits, there's more work that needs to be done here, but his conclusion on pricing remaining high because of industry concentration does pass the smell test. And it should concern policy makers. I know there are many who will ask what's wrong in creating ‘national champions' like the tiger economies did between the 70s-90s. But there are a few differences in our case. Firstly, the focus on creating national champions elsewhere was to choose specific sectors where they might have a comparative advantage, invest in them, especially on technology and then win in global markets through an export-oriented strategy. It is a somewhat flawed approach, but it still makes sense for a low-income economy to do this. But we aren't really doing this in India. Our so-called national champions are focused on domestic markets where there's no particular need to have them. In fact, there is only a monopoly risk here with the attendant problems of price cartelisation and poor customer service. Also, the limited focus on exports that these big five domestic players have as of now is largely linked to natural resources and not large-scale, job-creating manufacturing setups. It is unclear how the broader economy is benefitting from this apparent design. Secondly, the successful national champion model in other economies didn't need high import tariffs to support their ambitions like it is now the case in India. We have written about this many times in the past. Higher tariffs will reduce the competitiveness of the domestic players in those sectors to compete globally. It is counterintuitive to have a high tariff regime if you want to build national champions. After all, global markets are much larger than the domestic market, and that's where these conglomerates must be competing. Thirdly, what's the government getting out of the apparent tilting, if it is intentional, of the playing field in favour of these players? If the idea is to have national champions despite the obvious flaws in this intent, it makes sense to have stakes in these ventures to participate in the value being created. Lastly, the overall economy will benefit if the process of creating such champions leads to factor market reforms and real ease of doing business for other participants in the process. Else, the larger players will continue to get ahead not because of better products or innovation but simply because they know how to manage the system. In other words, it is the 1970s all over again with a tadka of markets.It is difficult to see how we can trace our way back from this path, given the apparent lack of opposition and the already dominant position of these conglomerates in industry and media. Also, any walking back will require some bold antitrust kind of measures (it is what Acharya suggests) which is quite impossible in India. Possibly, the only medium-term scenario is these conglomerates start stepping on each other's toes as they continue to diversify their businesses and that competition alleviates the problems of concentration. But that might be too late in coming, or they might have a tacit understanding of the rules of the game in competing with one another. It will distort markets further. Maybe this is a tad alarmist, but it is important to acknowledge there's way too much diversification among the top conglomerates in India and that's always a sign of market distortion. India Policy Watch #2: We Need an Agnipath for India's DiplomacyInsights on issues relevant to India— Pranay KotasthaneIn edition #198, I highlighted that at least three areas of the Indian executive need a quick state capacity boost. These were: the Ministry of External Affairs, Ministry of Electronics & Information Technology (MeitY), and economic regulatory bodies such as the Competition Commission of India (CCI). Then I came across this tweet from the External Affairs Minister, which acted as a positive reinforcement for this line of thinking. Managing these engagements in an unsettled world order needs an immediate boost in India's foreign policy capacity. Solutions like incremental increases in the Indian Foreign Service (IFS), while required, will be too slow.What we need today is a ‘surge hiring' strategy. The external affairs ministry, in fact, was the first union ministry to experiment with a broader lateral entry for government officers in 2015. It also opened up positions in its policy planning and research division for people in academia and the private sector. However, these tentative trials seem to have lost steam. The underlying reason is the internal resistance from the foreign service officers, who see such attempts as a threat to their career progression.The surge hiring strategy should try a different approach. It should attempt to hire a much larger number of people below ambassadorial positions. This way, the cadre protection impulse can be side-stepped. Instead of targeting joint secretary levels, two fellowships could be attempted: one for fresh graduates and another for young professionals working within and outside the government (thanks to Nitin Pai for this idea). Given the growing prominence of technology and economic issues as foreign policy domains, this approach would help build institutional knowledge within the ministry. More importantly, the surge should target staffing for the headquarter functions in Delhi for managing various engagements and new initiatives. Indian missions abroad can continue to be led by IFS officers. Past attempts at lateral hiring were advertised as single posts in the unreserved category. By opening up a larger number of positions concurrently, the government could retain existing norms on reservations and quotas. Finally, the surge hiring strategy should have a sunset clause and a well-defined recruitment target. If it is conceptualised as a non-recurring measure keeping the current geopolitical situation in mind, it will resonate with the opposition and the parliament.With the Agnipath experiment of the defence ministry, the idea of short-term employment within the government has gained some acceptability. It is no longer anathema to the government but an idea whose time has come. Without a surge in foreign policy capacity, we will only have great ideas but tardy implementation, resulting in a perennially underperforming foreign policy. Matsyanyaaya: Reflections on the QuadBig fish eating small fish = Foreign Policy in action— Pranay KotasthaneLast week, I attended a US State Department sponsored programme that aims to invigorate think tank research on Quad collaboration in the four countries. As part of the first segment of this programme, five representatives from each country's think tanks were hosted in the US. What follows are my reflections on the Quad as a geopolitical formation, based on what I saw in this programme.* Quad ranks higher on the US foreign policy agenda than I had expected. My prior assumption was that given the multiple alliances that the US leads, a new, amorphous grouping such as the Quad wouldn't rank high on its priority list. However, the interactions with the officials suggested a conscious effort to infuse energy into the Quad. * The Quad is being positioned visibly and intentionally as a positive force that would bring benefits to the Indo-Pacific at large, rather than as an anti-China “alliance”. This is the reason why the interactions as part of the grouping have spawned into six leader-level working groups—on COVID-19 Response and Global Health Security, Climate, Critical and Emerging Technologies, Cyber, Space, and Infrastructure, and at least three initiatives—Indo-Pacific Partnership for Maritime Domain Awareness, Semiconductor Supply Chain Initiative, and the Quad Fellowship. The strategy, if there is one, seems to be to throw several balls up in the air, knowing fully well that some of them will get dropped, while others might be caught on their way back by all four countries, or only a subset amongst them.* As the Quad is not a traditional security alliance, its success metric will also be different. Not all cooperation will be Quad-labelled, and some of it might come in bilateral or trilateral formats. So, the increased cooperation between Japan and Australia on defence ties, and between India and Australia on economic ties, are also indicators that the Quad is moving in the right direction. * While the rationale for Quad collaboration in many areas is often “common interests” or “shared values”, an underrated frame is “mutual complementarities”. In many spheres, especially in technology, the Quad is an attractive forum for cooperation precisely because each country has complementary strengths. * Positioning Quad as a force for good in the Indo-Pacific—rather than a geopolitical grouping against China— in many areas runs the obvious risk of underperformance and loss of credibility. In international affairs, efforts at providing benefits to another country are usually known by their failures more than their successes. For instance, in May 2021, the Quad Vaccine Partnership targeted the provision of 1 billion COVID-19 vaccines. Even though the four countries individually delivered 670 million doses, including 265 million doses in the Indo-Pacific, the demand for vaccines waned by the end of 2022. The dominant narrative was that the Vaccine Partnership had failed, even though it had made a significant contribution. HomeWorkReading and listening recommendations on public policy matters* [Podcast] We were on Shruti Rajagopalan's excellent podcast Ideas of India to discuss our book and the Indian State's many puzzles. * [Podcast] A Puliyabaazi on citizencraft featuring Nitin Pai.* [Paper] This paper by Isha Bhatnagar offers evidence that gender equitable preferences are rising in India. From the abstract:Over more than a quarter-century period (1992–1993 to 2019–2021), I find a significant decline in son preference from 40 to 18 percent and an increase in gender-equitable preferences among most subpopulations. Multivariate analysis shows that for all survey years, education and frequent exposure to television significantly increased the odds of gender-equitable preferences. In the last decade, community norms supporting women's employment are also associated with gender-equitable preferences. In addition, decomposition analysis shows that compared to compositional change, social norm change accounts for two-thirds of the rise in gender-equitable preferences. These findings suggest that rising norms of gender equality have the potential to dismantle gender-biased preferences in India. This is a public episode. If you would like to discuss this with other subscribers or get access to bonus episodes, visit publicpolicy.substack.com

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.28.534534v1?rss=1 Authors: Zavaglia, M., Malherbe, C., Schlaadt, S., Nachev, P., Hilgetag, C. C. Abstract: Lesion analysis reveals causal contributions of brain regions to brain functions. Various strategies have been used for inferring brain functions from brain lesions. These approaches can be broadly categorized as univariate or multivariate methods. Here we analysed data from 581 patients with acute ischemic injury, parcellated into 41 Brodmann areas, and systematically investigated the inferences made by univariate and multivariate lesion analysis methods via ground-truth simulations, in which we defined a priori contributions of brain areas to assumed brain function. Particularly, we analysed single-region models, with only single areas presumed to contribute functionally, and multiple-region models, with two contributing regions. The analyses consistently showed a considerably better performance of multivariate than univariate methods in terms of accuracy and mis-inference error. Specifically, the univariate approaches of Lesion Symptom Mapping as well as Lesion Symptom Correlation mis-inferred substantial contributions from several areas even in the single-region models, and also when accounting for lesion size. Of the multivariate approaches, the game-theoretical Multi-perturbation Shapley value Analysis typically showed the best performance. Our findings suggest that multivariate approaches produce highly reliable lesion inferences, without requiring lesion size consideration, while the application of univariate methods may yield substantial mis-localizations that limit the reliability of functional attributions. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

New techniques allow unprecedented insight into the underwater behaviour of Australia's flatback sea turtles. Then we chat about some newly described spiny lizards from Peru. Become a Patreon: https://www.patreon.com/herphighlights Merch: https://www.redbubble.com/people/herphighlights/shop Full reference list available here: http://www.herphighlights.podbean.com Main Paper References: Hounslow JL, Fossette S, Byrnes EE, Whiting SD, Lambourne RN, Armstrong NJ, Tucker AD, Richardson AR, Gleiss AC. 2022. Multivariate analysis of biologging data reveals the environmental determinants of diving behaviour in a marine reptile. Royal Society Open Science 9:211860. DOI: 10.1098/rsos.211860. Species of the Bi-Week: Venegas PJ, García-Ayachi LA, Chávez-Arribasplata JC, García-Bravo A. 2022. Four new species of polychromatic spiny-tailed iguanian lizards, genus Stenocercus (Iguania: Tropiduridae), from Peru. Zootaxa 5115:1–28. DOI: 10.11646/zootaxa.5115.1.1. Editing and Music: Podcast edited by Emmy – https://www.fiverr.com/emmyk10  Intro/outro – Treehouse by Ed Nelson Species Bi-week theme – Michael Timothy Other Music – The Passion HiFi, https://www.thepassionhifi.com

Scientists can now comprehensively scan the genome, testing variation across millions of genetic markers. Large consortia of scientists are analyzing data from millions of individuals. Multivariate methods enable scientists to identify genes involved in “normal” processes rather than specific disorders or traits. These advances can have a widespread effect on medicine and society. However, such rapid progress brings ethical, social, and legal challenges, including the need for increased diversity to ensure that all people benefit from advances in the field. To discuss this research, Dr. Teresa Treat, Professor of Psychology at University of Iowa, interviews Danielle M. Dick, Professor at the Department of Psychiatry and researcher at the Rutgers Addiction Research Center, at Rutgers University.

A/B testing alone doesn't cut it anymore when it comes to ad creative. Even though it's automated and typically executed in-market, A/B testing delivers the shallowest level of data available. It can tell you which of two or three ads was the higher performer — but never why. There's got to be a better way! *blows hair out of face, infomercial-style.* In episode 3 of Resting Ad Face, our VP of Performance Marketing, Susan Wenograd, and I talked about: - the major downfalls of A/B testing - why brands today need a deeper level of creative insights - how a different kind of creative testing (spoiler alert: multivariate testing) can get you there.

This edition we dive into: • What HubSpot CTAs are • The 4 Main Benefits of HubSpot CTAs • Where to use them • The types of CTAs (Simple, Multivariate, Smart) • Examples of CTAs • Reporting on CTAs • Using CTAs in Lists, Reports, Workflows • Associating CTAs with HubSpot campaigns • Permissions for limiting access to CTAs • Plus, when not to use HubSpot CTAs Full show notes available at: https://www.hubshots.com/episodes/episode-281 Recorded: Thursday 15 June 2022 | Published: Friday 24 June 2022

Episode 150! So much fanfare, so exciting. But alas. Let's talk about my ultramarathon, how a strong baseline of fitness and health is multivariate. Also, my new career in “Nutritional Comedy.” Become a Patreoner Join my Small Steppers 12-week program (learn Awareness Based Habit Change!) Want to talk to me about my SMALL STEP INTENSIVE? […]

A bite-sized episode where we each share 1 brain-related thing we learnt that you can use so level up your life...in less than 5 (maybe 6) minutes. Think biases, mental models, thinking tools and the latest science on how to live a better life.  If you're loving the show, please do us a teeny tiny favour and subscribe/follow on your favourite podcast platform. It helps us massively and we help you get the latest BrainTools episode as soon as it drops.  Where can you connect with us? Instagram: @braintoolspodcast TikTok: @braintools Website: www.braintools.com.au    

Back in 2019, Christine gave an awesome talk at our in-person San Francisco summit about how she had built an engineering org of ~30 with a 50:50 gender balance (Male : not male). In this episode, Christine shares what has changed as the organization has scaled to ~300 and her experiences as a first-time ScaleUp founder navigating hypergrowth.PARTNERThanks to our partner CloudZero — Cloud Cost Intelligence Platform. Control cost and drive better decisions with CloudZero cloud cost intelligence. The CloudZero platform provides visibility into cloud spend without the typical pitfalls of legacy cloud cost management tools, like endless tagging or clunky Kubernetes support. Optimize unit economics, decentralize cost data to engineering, and create a shared language between finance and technical teams. CloudZero helps you organize cloud spending better than anyone else.Join companies like Drift, Rapid7, and SeatGeek by visiting cloudzero.com/ctoconnection to get started.

Today on Sojourner Truth: President Biden and other world leaders descend on the United Nations for the annual general assembly meeting. Focused areas include COVID-19, the environmental crisis, and growing income inequality worldwide. What has emerged from presentations by heads of state so far? Our guest is Dr. Gerald Horne, Moores Professor of History & African-American Studies at the University of Houston. The Democrats' economic agenda is hanging by a thread in Congress, as there is push-back against the cost of President Biden's care economy proposals. The Republicans threaten to not lift the debt ceiling, therefore threatening the entire Biden proposal. What's going on? We get an update from economist Max Wolff, a Founding Partner at Multivariate, which provides capital markets access and data science solutions to growth companies and institutional investors. Who is not getting the $600 California stimulus check? Our guest is Sherriel Weithers, a previous intern for the Sojourner Truth team, as well as a volunteer who works with at-risk teens and fights for the rights of others.

Today on Sojourner Truth: President Biden and other world leaders descend on the United Nations for the annual general assembly meeting. Focused areas include COVID-19, the environmental crisis, and growing income inequality worldwide. What has emerged from presentations by heads of state so far? Our guest is Dr. Gerald Horne, Moores Professor of History & African-American Studies at the University of Houston. The Democrats' economic agenda is hanging by a thread in Congress, as there is push-back against the cost of President Biden's care economy proposals. The Republicans threaten to not lift the debt ceiling, therefore threatening the entire Biden proposal. What's going on? We get an update from economist Max Wolff, a Founding Partner at Multivariate, which provides capital markets access and data science solutions to growth companies and institutional investors. Who is not getting the $600 California stimulus check? Our guest is Sherriel Weithers, a previous intern for the Sojourner Truth team, as well as a volunteer who works with at-risk teens and fights for the rights of others.

Today on Sojourner Truth: President Biden and other world leaders descend on the United Nations for the annual general assembly meeting. Focused areas include COVID-19, the environmental crisis, and growing income inequality worldwide. What has emerged from presentations by heads of state so far? Our guest is Dr. Gerald Horne, Moores Professor of History & African-American Studies at the University of Houston. The Democrats' economic agenda is hanging by a thread in Congress, as there is push-back against the cost of President Biden's care economy proposals. The Republicans threaten to not lift the debt ceiling, therefore threatening the entire Biden proposal. What's going on? We get an update from economist Max Wolff, a Founding Partner at Multivariate, which provides capital markets access and data science solutions to growth companies and institutional investors. Who is not getting the $600 California stimulus check? Our guest is Sherriel Weithers, a previous intern for the Sojourner Truth team, as well as a volunteer who works with at-risk teens and fights for the rights of others.

Today on Sojourner Truth: President Biden and other world leaders descend on the United Nations for the annual general assembly meeting. Focused areas include COVID-19, the environmental crisis, and growing income inequality worldwide. What has emerged from presentations by heads of state so far? Our guest is Dr. Gerald Horne, Moores Professor of History & African-American Studies at the University of Houston. The Democrats' economic agenda is hanging by a thread in Congress, as there is push-back against the cost of President Biden's care economy proposals. The Republicans threaten to not lift the debt ceiling, therefore threatening the entire Biden proposal. What's going on? We get an update from economist Max Wolff, a Founding Partner at Multivariate, which provides capital markets access and data science solutions to growth companies and institutional investors. Who is not getting the $600 California stimulus check? Our guest is Sherriel Weithers, a previous intern for the Sojourner Truth team, as well as a volunteer who works with at-risk teens and fights for the rights of others.

Today on Sojourner Truth: President Biden and other world leaders descend on the United Nations for the annual general assembly meeting. Focused areas include COVID-19, the environmental crisis, and growing income inequality worldwide. What has emerged from presentations by heads of state so far? Our guest is Dr. Gerald Horne, Moores Professor of History & African-American Studies at the University of Houston. The Democrats' economic agenda is hanging by a thread in Congress, as there is push-back against the cost of President Biden's care economy proposals. The Republicans threaten to not lift the debt ceiling, therefore threatening the entire Biden proposal. What's going on? We get an update from economist Max Wolff, a Founding Partner at Multivariate, which provides capital markets access and data science solutions to growth companies and institutional investors. Who is not getting the $600 California stimulus check? Our guest is Sherriel Weithers, a previous intern for the Sojourner Truth team, as well as a volunteer who works with at-risk teens and fights for the rights of others.

Today on Sojourner Truth: President Biden and other world leaders descend on the United Nations for the annual general assembly meeting. Focused areas include COVID-19, the environmental crisis, and growing income inequality worldwide. What has emerged from presentations by heads of state so far? Our guest is Dr. Gerald Horne, Moores Professor of History & African-American Studies at the University of Houston. The Democrats' economic agenda is hanging by a thread in Congress, as there is push-back against the cost of President Biden's care economy proposals. The Republicans threaten to not lift the debt ceiling, therefore threatening the entire Biden proposal. What's going on? We get an update from economist Max Wolff, a Founding Partner at Multivariate, which provides capital markets access and data science solutions to growth companies and institutional investors. Who is not getting the $600 California stimulus check? Our guest is Sherriel Weithers, a previous intern for the Sojourner Truth team, as well as a volunteer who works with at-risk teens and fights for the rights of others.

Today on Sojourner Truth: Donald Trump's taxes with economist Max Wolff. On Sunday, September 27, The New York Times released a groundbreaking report that exposed something Donald Trump has long fought to keep secret: his taxes. Since taking power in 2017, Trump has broken with tradition set by previous presidents by not only refusing to release his tax returns, but by carrying out a legal battle to keep them a secret. However, The New York Times has retrieved tax-return data for Trump and the hundreds of companies that make up his business organization going back more than 20 years. The newspaper published key findings from the data on Sunday, revealing information about his failing properties, numerous tax write-offs, an audit battle and his hundreds of millions of dollars of debt. Trump reportedly paid $750 in federal income taxes in 2016. In his first year in the White House, in 2017, he paid another $750. He had paid no income taxes at all in 10 of the previous 15 years, mainly because he reported losing much more money than he made. Meanwhile, in 2016, most households in the middle 20 percent of the U.S. income distribution paid an average of $2,200 in federal income taxes, according to the Congressional Budget Office, a nonpartisan government agency. Max Wolff is a Founding Partner at Multivariate, which provides capital markets access and data science solutions to growth companies and institutional investors, as well as a professor at The New School University Milano Graduate Program. Max appears regularly on Reuters, CNBC, CNN, CGTN China, BBC, NPR, Bloomberg, The Wall Street Journal, The financial Times and other outlets. We also return to our occasional series on Thailand, where villagers fighting a mining company have scored a victory for the environment. Also, one of their grassroots leaders is under threat of assassination. Our guests are Pranom Somwong and Liz Hilton. Pranom Somwong is a Thailand-based representative of Protection International, an international organization dedicated to the protection of human rights defenders. It works to enhance the security and the protection of threatened civil society actors with non-violent means. Liz Hilton is a member of the Empower Foundation, a large network of sex workers based in South East Asia. Originally from Australia, Liz joined Empower as an advocacy volunteer and has now been working with the organization for over 28 years. Hotel workers are being squeezed by The Langham hotel in Pasadena, California. What's going on? Our guest is Yesenia Ortiz. Yesenia, a single mother of three kids, has worked at The Langham Hotel in Pasadena, California, for three years, until she was fired due to COVID-19. She and her coworkers are calling on Major League Baseball officials, who are staying at the hotel for the postseason, to support them in getting their jobs back as well as urging Gov. Gavin Newsom to sign AB 3216, a statewide right of recall and worker retention law. Gov. Newsom has until September 30 to sign the law.

Today on Sojourner Truth: Donald Trump's taxes with economist Max Wolff. On Sunday, September 27, The New York Times released a groundbreaking report that exposed something Donald Trump has long fought to keep secret: his taxes. Since taking power in 2017, Trump has broken with tradition set by previous presidents by not only refusing to release his tax returns, but by carrying out a legal battle to keep them a secret. However, The New York Times has retrieved tax-return data for Trump and the hundreds of companies that make up his business organization going back more than 20 years. The newspaper published key findings from the data on Sunday, revealing information about his failing properties, numerous tax write-offs, an audit battle and his hundreds of millions of dollars of debt. Trump reportedly paid $750 in federal income taxes in 2016. In his first year in the White House, in 2017, he paid another $750. He had paid no income taxes at all in 10 of the previous 15 years, mainly because he reported losing much more money than he made. Meanwhile, in 2016, most households in the middle 20 percent of the U.S. income distribution paid an average of $2,200 in federal income taxes, according to the Congressional Budget Office, a nonpartisan government agency. Max Wolff is a Founding Partner at Multivariate, which provides capital markets access and data science solutions to growth companies and institutional investors, as well as a professor at The New School University Milano Graduate Program. Max appears regularly on Reuters, CNBC, CNN, CGTN China, BBC, NPR, Bloomberg, The Wall Street Journal, The financial Times and other outlets. We also return to our occasional series on Thailand, where villagers fighting a mining company have scored a victory for the environment. Also, one of their grassroots leaders is under threat of assassination. Our guests are Pranom Somwong and Liz Hilton. Pranom Somwong is a Thailand-based representative of Protection International, an international organization dedicated to the protection of human rights defenders. It works to enhance the security and the protection of threatened civil society actors with non-violent means. Liz Hilton is a member of the Empower Foundation, a large network of sex workers based in South East Asia. Originally from Australia, Liz joined Empower as an advocacy volunteer and has now been working with the organization for over 28 years. Hotel workers are being squeezed by The Langham hotel in Pasadena, California. What's going on? Our guest is Yesenia Ortiz. Yesenia, a single mother of three kids, has worked at The Langham Hotel in Pasadena, California, for three years, until she was fired due to COVID-19. She and her coworkers are calling on Major League Baseball officials, who are staying at the hotel for the postseason, to support them in getting their jobs back as well as urging Gov. Gavin Newsom to sign AB 3216, a statewide right of recall and worker retention law. Gov. Newsom has until September 30 to sign the law.

Today on Sojourner Truth: Donald Trump's taxes with economist Max Wolff. On Sunday, September 27, The New York Times released a groundbreaking report that exposed something Donald Trump has long fought to keep secret: his taxes. Since taking power in 2017, Trump has broken with tradition set by previous presidents by not only refusing to release his tax returns, but by carrying out a legal battle to keep them a secret. However, The New York Times has retrieved tax-return data for Trump and the hundreds of companies that make up his business organization going back more than 20 years. The newspaper published key findings from the data on Sunday, revealing information about his failing properties, numerous tax write-offs, an audit battle and his hundreds of millions of dollars of debt. Trump reportedly paid $750 in federal income taxes in 2016. In his first year in the White House, in 2017, he paid another $750. He had paid no income taxes at all in 10 of the previous 15 years, mainly because he reported losing much more money than he made. Meanwhile, in 2016, most households in the middle 20 percent of the U.S. income distribution paid an average of $2,200 in federal income taxes, according to the Congressional Budget Office, a nonpartisan government agency. Max Wolff is a Founding Partner at Multivariate, which provides capital markets access and data science solutions to growth companies and institutional investors, as well as a professor at The New School University Milano Graduate Program. Max appears regularly on Reuters, CNBC, CNN, CGTN China, BBC, NPR, Bloomberg, The Wall Street Journal, The financial Times and other outlets. We also return to our occasional series on Thailand, where villagers fighting a mining company have scored a victory for the environment. Also, one of their grassroots leaders is under threat of assassination. Our guests are Pranom Somwong and Liz Hilton. Pranom Somwong is a Thailand-based representative of Protection International, an international organization dedicated to the protection of human rights defenders. It works to enhance the security and the protection of threatened civil society actors with non-violent means. Liz Hilton is a member of the Empower Foundation, a large network of sex workers based in South East Asia. Originally from Australia, Liz joined Empower as an advocacy volunteer and has now been working with the organization for over 28 years. Hotel workers are being squeezed by The Langham hotel in Pasadena, California. What's going on? Our guest is Yesenia Ortiz. Yesenia, a single mother of three kids, has worked at The Langham Hotel in Pasadena, California, for three years, until she was fired due to COVID-19. She and her coworkers are calling on Major League Baseball officials, who are staying at the hotel for the postseason, to support them in getting their jobs back as well as urging Gov. Gavin Newsom to sign AB 3216, a statewide right of recall and worker retention law. Gov. Newsom has until September 30 to sign the law.

Today on Sojourner Truth: Donald Trump's taxes with economist Max Wolff. On Sunday, September 27, The New York Times released a groundbreaking report that exposed something Donald Trump has long fought to keep secret: his taxes. Since taking power in 2017, Trump has broken with tradition set by previous presidents by not only refusing to release his tax returns, but by carrying out a legal battle to keep them a secret. However, The New York Times has retrieved tax-return data for Trump and the hundreds of companies that make up his business organization going back more than 20 years. The newspaper published key findings from the data on Sunday, revealing information about his failing properties, numerous tax write-offs, an audit battle and his hundreds of millions of dollars of debt. Trump reportedly paid $750 in federal income taxes in 2016. In his first year in the White House, in 2017, he paid another $750. He had paid no income taxes at all in 10 of the previous 15 years, mainly because he reported losing much more money than he made. Meanwhile, in 2016, most households in the middle 20 percent of the U.S. income distribution paid an average of $2,200 in federal income taxes, according to the Congressional Budget Office, a nonpartisan government agency. Max Wolff is a Founding Partner at Multivariate, which provides capital markets access and data science solutions to growth companies and institutional investors, as well as a professor at The New School University Milano Graduate Program. Max appears regularly on Reuters, CNBC, CNN, CGTN China, BBC, NPR, Bloomberg, The Wall Street Journal, The financial Times and other outlets. We also return to our occasional series on Thailand, where villagers fighting a mining company have scored a victory for the environment. Also, one of their grassroots leaders is under threat of assassination. Our guests are Pranom Somwong and Liz Hilton. Pranom Somwong is a Thailand-based representative of Protection International, an international organization dedicated to the protection of human rights defenders. It works to enhance the security and the protection of threatened civil society actors with non-violent means. Liz Hilton is a member of the Empower Foundation, a large network of sex workers based in South East Asia. Originally from Australia, Liz joined Empower as an advocacy volunteer and has now been working with the organization for over 28 years. Hotel workers are being squeezed by The Langham hotel in Pasadena, California. What's going on? Our guest is Yesenia Ortiz. Yesenia, a single mother of three kids, has worked at The Langham Hotel in Pasadena, California, for three years, until she was fired due to COVID-19. She and her coworkers are calling on Major League Baseball officials, who are staying at the hotel for the postseason, to support them in getting their jobs back as well as urging Gov. Gavin Newsom to sign AB 3216, a statewide right of recall and worker retention law. Gov. Newsom has until September 30 to sign the law.

Today on Sojourner Truth: Donald Trump's taxes with economist Max Wolff. On Sunday, September 27, The New York Times released a groundbreaking report that exposed something Donald Trump has long fought to keep secret: his taxes. Since taking power in 2017, Trump has broken with tradition set by previous presidents by not only refusing to release his tax returns, but by carrying out a legal battle to keep them a secret. However, The New York Times has retrieved tax-return data for Trump and the hundreds of companies that make up his business organization going back more than 20 years. The newspaper published key findings from the data on Sunday, revealing information about his failing properties, numerous tax write-offs, an audit battle and his hundreds of millions of dollars of debt. Trump reportedly paid $750 in federal income taxes in 2016. In his first year in the White House, in 2017, he paid another $750. He had paid no income taxes at all in 10 of the previous 15 years, mainly because he reported losing much more money than he made. Meanwhile, in 2016, most households in the middle 20 percent of the U.S. income distribution paid an average of $2,200 in federal income taxes, according to the Congressional Budget Office, a nonpartisan government agency. Max Wolff is a Founding Partner at Multivariate, which provides capital markets access and data science solutions to growth companies and institutional investors, as well as a professor at The New School University Milano Graduate Program. Max appears regularly on Reuters, CNBC, CNN, CGTN China, BBC, NPR, Bloomberg, The Wall Street Journal, The financial Times and other outlets. We also return to our occasional series on Thailand, where villagers fighting a mining company have scored a victory for the environment. Also, one of their grassroots leaders is under threat of assassination. Our guests are Pranom Somwong and Liz Hilton. Pranom Somwong is a Thailand-based representative of Protection International, an international organization dedicated to the protection of human rights defenders. It works to enhance the security and the protection of threatened civil society actors with non-violent means. Liz Hilton is a member of the Empower Foundation, a large network of sex workers based in South East Asia. Originally from Australia, Liz joined Empower as an advocacy volunteer and has now been working with the organization for over 28 years. Hotel workers are being squeezed by The Langham hotel in Pasadena, California. What's going on? Our guest is Yesenia Ortiz. Yesenia, a single mother of three kids, has worked at The Langham Hotel in Pasadena, California, for three years, until she was fired due to COVID-19. She and her coworkers are calling on Major League Baseball officials, who are staying at the hotel for the postseason, to support them in getting their jobs back as well as urging Gov. Gavin Newsom to sign AB 3216, a statewide right of recall and worker retention law. Gov. Newsom has until September 30 to sign the law.