Podcasts about Janssen

Dr. Christina Rahm has worked as a medical, clinical, and research scientist in the pharmaceutical, nutraceutical, and biotechnology industries for Janssen, Johnson & Johnson, Biogen Idec/Biogen, UCB, Bristol Meyers Squibb, and Alexion. Additionally, she worked on the corporate side for Pfizer, Biogen, and Janssen and is currently the Chairman of International Science Nutrition Society and Chief Science Officer for ROOT Wellness. Dr. Rahm has also served as a formulator for several companies and manufacturing labs, including her own. She has created multiple provisional patents, proprietary formulas, and trade secrets in addition to authoring her first book, Cure the Causes: Live the Life you Want, Not the One Prescribed. Through years of laboratory research and ethical observations, she has developed a personalized and predictive consulting company working on everything from the environment to DNA and detox wellness plans in which Dr. Rahm helps clients reset their bodies and minds to be spiritually, mentally, emotionally, and physically balanced.

The Advent Adventure zit erop. Genieten van de feestdagen en daarna vallen we in een diep zwart gat. We vonden het nog tijd om het gehele avontuur the evalueren in The Advent Evaluation.We hebben dit keer geen bier meegenomen. We zaten nog vol met alle verhalen. In deze 2-wekelijkse podcast praten Juan en Marc kort bij. De één zorgt voor het bier en de ander voor het onderwerp. 

Welcome back to the studio.  This is My Day of Play, where you're taken into the real events and actions of how it happens long before the process of editing or cleaning up.  The original purpose of these episodes was to give my broadcasting students something to edit, to practice with and to call their own.  Then I realized that you are just as important.  Share the reality of how it really went.  We begin things with Victora Castillo creator of Fugitive Hunters Mexico on A&E. Then we'll leap into a revealing conversation with film and screenwriter Joshua Zetumer the creator of Hulu's/FX's Say Nothing. And we'll wrap things up with Sarah Janssen, the editor of one of the biggest selling books of all time… The Almanac!   This is My Day of Play.  Completely unedited in the way of meeting the wizard behind the curtain.  Become a supporter of this podcast: https://www.spreaker.com/podcast/arroe-collins-unplugged-totally-uncut--994165/support.

In jener Zeit wurde der Engel Gabriel von Gott in eine Stadt in Galiläa namens Nazaret zu einer Jungfrau gesandt. Sie war mit einem Mann namens Josef verlobt, der aus dem Haus David stammte. Der Name der Jungfrau war Maria.Der Engel trat bei ihr ein und sagte: Sei gegrüßt, du Begnadete, der Herr ist mit dir. Sie erschrak über die Anrede und überlegte, was dieser Gruß zu bedeuten habe.Da sagte der Engel zu ihr: Fürchte dich nicht, Maria; denn du hast bei Gott Gnade gefunden. Siehe, du wirst schwanger werden und einen Sohn wirst du gebären; dem sollst du den Namen Jesus geben. Er wird groß sein und Sohn des Höchsten genannt werden. Gott, der Herr, wird ihm den Thron seines Vaters David geben. Er wird über das Haus Jakob in Ewigkeit herrschen und seine Herrschaft wird kein Ende haben.Maria sagte zu dem Engel: Wie soll das geschehen, da ich keinen Mann erkenne?Der Engel antwortete ihr: Heiliger Geist wird über dich kommen und Kraft des Höchsten wird dich überschatten. Deshalb wird auch das Kind heilig und Sohn Gottes genannt werden. Siehe, auch Elisabet, deine Verwandte, hat noch in ihrem Alter einen Sohn empfangen; obwohl sie als unfruchtbar gilt, ist sie schon im sechsten Monat. Denn für Gott ist nichts unmöglich.Da sagte Maria: Siehe, ich bin die Magd des Herrn; mir geschehe, wie du es gesagt hast.Danach verließ sie der Engel.(© Ständige Kommission für die Herausgabe der gemeinsamen liturgischen Bücher im deutschen Sprachgebiet)Das Lukasevangelium ist der erste Teil eines Doppelwerks; der zweite Teil ist die Apostelgeschichte. Lukas will den engen Zusammenhang zwischen der Verkündigung Jesu und dem österlichen Aufbruch der Kirche zeigen. Er richtet sein Werk an Theophilos (deutsch: Freund Gottes), den er tiefer in den Glauben einführen will. Als Verfasser gilt traditionell Lukas, der Begleiter des Paulus. Er schreibt einen eleganten Stil, der den kulturellen Anspruch des Christentums widerspiegelt.

In jener Zeit wurde der Engel Gabriel von Gott in eine Stadt in Galiläa namens Nazaret zu einer Jungfrau gesandt. Sie war mit einem Mann namens Josef verlobt, der aus dem Haus David stammte. Der Name der Jungfrau war Maria. Der Engel trat bei ihr ein und sagte: Sei gegrüßt, du Begnadete, der Herr ist mit dir. Sie erschrak über die Anrede und überlegte, was dieser Gruß zu bedeuten habe. Da sagte der Engel zu ihr: Fürchte dich nicht, Maria; denn du hast bei Gott Gnade gefunden. Siehe, du wirst schwanger werden und einen Sohn wirst du gebären; dem sollst du den Namen Jesus geben. Er wird groß sein und Sohn des Höchsten genannt werden. Gott, der Herr, wird ihm den Thron seines Vaters David geben. Er wird über das Haus Jakob in Ewigkeit herrschen und seine Herrschaft wird kein Ende haben. Maria sagte zu dem Engel: Wie soll das geschehen, da ich keinen Mann erkenne? Der Engel antwortete ihr: Heiliger Geist wird über dich kommen und Kraft des Höchsten wird dich überschatten. Deshalb wird auch das Kind heilig und Sohn Gottes genannt werden.  Siehe, auch Elisabet, deine Verwandte, hat noch in ihrem Alter einen Sohn empfangen; obwohl sie als unfruchtbar gilt, ist sie schon im sechsten Monat. Denn für Gott ist nichts unmöglich. Da sagte Maria: Siehe, ich bin die Magd des Herrn; mir geschehe, wie du es gesagt hast. Danach verließ sie der Engel. (© Ständige Kommission für die Herausgabe der gemeinsamen liturgischen Bücher im deutschen Sprachgebiet) Das Lukasevangelium ist der erste Teil eines Doppelwerks; der zweite Teil ist die Apostelgeschichte. Lukas will den engen Zusammenhang zwischen der Verkündigung Jesu und dem österlichen Aufbruch der Kirche zeigen. Er richtet sein Werk an Theophilos (deutsch: Freund Gottes), den er tiefer in den Glauben einführen will. Als Verfasser gilt traditionell Lukas, der Begleiter des Paulus. Er schreibt einen eleganten Stil, der den kulturellen Anspruch des Christentums widerspiegelt.

Zur Zeit des Herodes, des Königs von Judäa, gab es einen Priester namens Zacharías, der zur Abteilung des Abíja gehörte. Seine Frau stammte aus dem Geschlecht Aarons; ihr Name war Elisabet. Beide lebten gerecht vor Gott und wandelten untadelig nach allen Geboten und Vorschriften des Herrn. Sie hatten keine Kinder, denn Elisabet war unfruchtbar und beide waren schon in vorgerücktem Alter. Es geschah aber: Als seine Abteilung wieder an der Reihe war und er den priesterlichen Dienst vor Gott verrichtete, da traf ihn, wie nach der Priesterordnung üblich, das Los, in den Tempel des Herrn hineinzugehen und das Rauchopfer darzubringen. Während er nun zur festgelegten Zeit das Rauchopfer darbrachte, stand das ganze Volk draußen und betete. Da erschien dem Zacharías ein Engel des Herrn; er stand auf der rechten Seite des Rauchopferaltars. Als Zacharías ihn sah, erschrak er und es befiel ihn Furcht. Der Engel aber sagte zu ihm: Fürchte dich nicht, Zacharías! Dein Gebet ist erhört worden. Deine Frau Elisabet wird dir einen Sohn gebären; dem sollst du den Namen Johannes geben. Du wirst dich freuen und jubeln und viele werden sich über seine Geburt freuen. Denn er wird groß sein vor dem Herrn. Wein und berauschende Getränke wird er nicht trinken und schon vom Mutterleib an wird er vom Heiligen Geist erfüllt sein. Viele Kinder Israels wird er zum Herrn, ihrem Gott, hinwenden. Er wird ihm mit dem Geist und mit der Kraft des Elíja vorangehen, um die Herzen der Väter den Kindern zuzuwenden und die Ungehorsamen zu gerechter Gesinnung zu führen und so das Volk für den Herrn bereit zu machen. Zacharías sagte zu dem Engel: Woran soll ich das erkennen? Denn ich bin ein alter Mann und auch meine Frau ist in vorgerücktem Alter. Der Engel erwiderte ihm: Ich bin Gábriel, der vor Gott steht, und ich bin gesandt worden, um mit dir zu reden und dir diese frohe Botschaft zu bringen. Und siehe, du sollst stumm sein und nicht mehr reden können bis zu dem Tag, an dem dies geschieht, weil du meinen Worten nicht geglaubt hast, die in Erfüllung gehen, wenn die Zeit dafür da ist. Inzwischen wartete das Volk auf Zacharías und wunderte sich, dass er so lange im Tempel blieb. Als er dann herauskam, konnte er nicht mit ihnen sprechen. Da merkten sie, dass er im Tempel eine Erscheinung gehabt hatte. Er gab ihnen nur Zeichen und blieb stumm. Als die Tage seines Dienstes zu Ende waren, kehrte er nach Hause zurück. Bald darauf wurde seine Frau Elisabet schwanger und lebte fünf Monate lang zurückgezogen. Sie sagte: Der Herr hat mir geholfen; er hat in diesen Tagen gnädig auf mich geschaut und mich von der Schmach befreit, mit der ich unter den Menschen beladen war.(© Ständige Kommission für die Herausgabe der gemeinsamen liturgischen Bücher im deutschen Sprachgebiet)

Mit der Geburt Jesu Christi war es so: Maria, seine Mutter, war mit Josef verlobt; noch bevor sie zusammengekommen waren, zeigte sich, dass sie ein Kind erwartete – durch das Wirken des Heiligen Geistes. Josef, ihr Mann, der gerecht war und sie nicht bloßstellen wollte, beschloss, sich in aller Stille von ihr zu trennen. Während er noch darüber nachdachte, siehe, da erschien ihm ein Engel des Herrn im Traum und sagte: Josef, Sohn Davids, fürchte dich nicht, Maria als deine Frau zu dir zu nehmen; denn das Kind, das sie erwartet, ist vom Heiligen Geist. Sie wird einen Sohn gebären; ihm sollst du den Namen Jesus geben; denn er wird sein Volk von seinen Sünden erlösen. Dies alles ist geschehen, damit sich erfüllte, was der Herr durch den Propheten gesagt hat: Siehe: die Jungfrau wird ein empfangen und einen Sohn gebären, und sie werden ihm den Namen Immanuel geben, das heißt übersetzt: Gott mit uns. Als Josef erwachte, tat er, was der Engel des Herrn ihm befohlen hatte, und nahm seine Frau zu sich. (Mt 1,18-24)(© Ständige Kommission für die Herausgabe der gemeinsamen liturgischen Bücher im deutschen Sprachgebiet)

Zur Zeit des Herodes, des Königs von Judäa, gab es einen Priester namens Zacharías, der zur Abteilung des Abíja gehörte. Seine Frau stammte aus dem Geschlecht Aarons; ihr Name war Elisabet. Beide lebten gerecht vor Gott und wandelten untadelig nach allen Geboten und Vorschriften des Herrn. Sie hatten keine Kinder, denn Elisabet war unfruchtbar und beide waren schon in vorgerücktem Alter. Es geschah aber: Als seine Abteilung wieder an der Reihe war und er den priesterlichen Dienst vor Gott verrichtete, da traf ihn, wie nach der Priesterordnung üblich, das Los, in den Tempel des Herrn hineinzugehen und das Rauchopfer darzubringen. Während er nun zur festgelegten Zeit das Rauchopfer darbrachte, stand das ganze Volk draußen und betete. Da erschien dem Zacharías ein Engel des Herrn; er stand auf der rechten Seite des Rauchopferaltars. Als Zacharías ihn sah, erschrak er und es befiel ihn Furcht. Der Engel aber sagte zu ihm: Fürchte dich nicht, Zacharías! Dein Gebet ist erhört worden. Deine Frau Elisabet wird dir einen Sohn gebären; dem sollst du den Namen Johannes geben. Du wirst dich freuen und jubeln und viele werden sich über seine Geburt freuen. Denn er wird groß sein vor dem Herrn. Wein und berauschende Getränke wird er nicht trinken und schon vom Mutterleib an wird er vom Heiligen Geist erfüllt sein. Viele Kinder Israels wird er zum Herrn, ihrem Gott, hinwenden. Er wird ihm mit dem Geist und mit der Kraft des Elíja vorangehen, um die Herzen der Väter den Kindern zuzuwenden und die Ungehorsamen zu gerechter Gesinnung zu führen und so das Volk für den Herrn bereit zu machen. Zacharías sagte zu dem Engel: Woran soll ich das erkennen? Denn ich bin ein alter Mann und auch meine Frau ist in vorgerücktem Alter. Der Engel erwiderte ihm: Ich bin Gábriel, der vor Gott steht, und ich bin gesandt worden, um mit dir zu reden und dir diese frohe Botschaft zu bringen. Und siehe, du sollst stumm sein und nicht mehr reden können bis zu dem Tag, an dem dies geschieht, weil du meinen Worten nicht geglaubt hast, die in Erfüllung gehen, wenn die Zeit dafür da ist. Inzwischen wartete das Volk auf Zacharías und wunderte sich, dass er so lange im Tempel blieb. Als er dann herauskam, konnte er nicht mit ihnen sprechen. Da merkten sie, dass er im Tempel eine Erscheinung gehabt hatte. Er gab ihnen nur Zeichen und blieb stumm. Als die Tage seines Dienstes zu Ende waren, kehrte er nach Hause zurück. Bald darauf wurde seine Frau Elisabet schwanger und lebte fünf Monate lang zurückgezogen. Sie sagte: Der Herr hat mir geholfen; er hat in diesen Tagen gnädig auf mich geschaut und mich von der Schmach befreit, mit der ich unter den Menschen beladen war. (© Ständige Kommission für die Herausgabe der gemeinsamen liturgischen Bücher im deutschen Sprachgebiet)

Mit der Geburt Jesu Christi war es so: Maria, seine Mutter, war mit Josef verlobt; noch bevor sie zusammengekommen waren, zeigte sich, dass sie ein Kind erwartete – durch das Wirken des Heiligen Geistes. Josef, ihr Mann, der gerecht war und sie nicht bloßstellen wollte, beschloss, sich in aller Stille von ihr zu trennen. Während er noch darüber nachdachte, siehe, da erschien ihm ein Engel des Herrn im Traum und sagte: Josef, Sohn Davids, fürchte dich nicht, Maria als deine Frau zu dir zu nehmen; denn das Kind, das sie erwartet, ist vom Heiligen Geist. Sie wird einen Sohn gebären; ihm sollst du den Namen Jesus geben; denn er wird sein Volk von seinen Sünden erlösen. Dies alles ist geschehen, damit sich erfüllte, was der Herr durch den Propheten gesagt hat: Siehe: die Jungfrau wird ein empfangen und einen Sohn gebären, und sie werden ihm den Namen Immanuel geben, das heißt übersetzt: Gott mit uns. Als Josef erwachte, tat er, was der Engel des Herrn ihm befohlen hatte, und nahm seine Frau zu sich. (Mt 1,18-24) (© Ständige Kommission für die Herausgabe der gemeinsamen liturgischen Bücher im deutschen Sprachgebiet)

Buch des Ursprungs Jesu Christi, des Sohnes Davids, des Sohnes Abrahams: Abraham zeugte den Ísaak, Ísaak zeugte den Jakob, Jakob zeugte den Juda und seine Brüder. Juda zeugte den Perez und den Serach mit der Tamar.Perez zeugte den Hezron, Hezron zeugte den Aram, Aram zeugte den Amminádab, Amminádab zeugte den Nachschon, Nachschon zeugte den Salmon. Salmon zeugte den Boas mit der Rahab. Boas zeugte den Obed mit der Rut. Obed zeugte den Ísai, Ísai zeugte David, den König. David zeugte den Salomo mit der Frau des Urija. Salomo zeugte den Rehabeam, Rehabeam zeugte den Abija, Abija zeugte den Asa, Asa zeugte den Joschafat, Joschafat zeugte den Joram, Joram zeugte den Usija. Usija zeugte den Jotam, Jotam zeugte den Ahas, Ahas zeugte den Hiskija, Hiskija zeugte den Manasse, Manasse zeugte den Amos, Amos zeugte den Joschija. Joschija zeugte den Jojachin und seine Brüder; das war zur Zeit der Babylonischen Gefangenschaft.Nach der Babylonischen Gefangenschaft zeugte Jojachin den Schealtiël, Schealtiël zeugte den Serubbabel, Serubbabel zeugte den Abihud, Abihud zeugte den Eljakim, Eljakim zeugte den Azor. Azor zeugte den Zadok, Zadok zeugte den Achim, Achim zeugte den Eliud, Eliud zeugte den Eleasar, Eleasar zeugte den Mattan, Mattan zeugte den Jakob.Jakob zeugte den Josef, den Mann Marias; von ihr wurde Jesus geboren, der der Christus genannt wird.Im Ganzen sind es also von Abraham bis David vierzehn Generationen, von David bis zur Babylonischen Gefangenschaft vierzehn Generationen und von der Babylonischen Gefangenschaft bis zu Christus vierzehn Generationen.(© Ständige Kommission für die Herausgabe der gemeinsamen liturgischen Bücher im deutschen Sprachgebiet)

In jener Zeit, als Jesus in den Tempel ging und dort lehrte, kamen die Hohepriester und die Ältesten des Volkes zu ihm und fragten: In welcher Vollmacht tust du das und wer hat dir diese Vollmacht gegeben? Jesus antwortete und sprach zu ihnen: Auch ich will euch eine Frage stellen. Wenn ihr mir darauf antwortet, dann werde ich euch sagen, in welcher Vollmacht ich das tue. Woher stammte die Taufe des Johannes? Vom Himmel oder von den Menschen? Da überlegten sie und sagten zueinander: Wenn wir antworten: Vom Himmel!, so wird er zu uns sagen: Warum habt ihr ihm dann nicht geglaubt? Wenn wir aber antworten: Von den Menschen!, dann müssen wir uns vor den Leuten fürchten; denn alle halten Johannes für einen Propheten. Darum antworteten sie Jesus: Wir wissen es nicht. Da erwiderte er: Dann sage auch ich euch nicht, in welcher Vollmacht ich das tue. (© Ständige Kommission für die Herausgabe der gemeinsamen liturgischen Bücher im deutschen Sprachgebiet)

Buch des Ursprungs Jesu Christi, des Sohnes Davids, des Sohnes Abrahams: Abraham zeugte den Ísaak, Ísaak zeugte den Jakob, Jakob zeugte den Juda und seine Brüder. Juda zeugte den Perez und den Serach mit der Tamar. Perez zeugte den Hezron, Hezron zeugte den Aram, Aram zeugte den Amminádab, Amminádab zeugte den Nachschon, Nachschon zeugte den Salmon. Salmon zeugte den Boas mit der Rahab. Boas zeugte den Obed mit der Rut. Obed zeugte den Ísai, Ísai zeugte David, den König.  David zeugte den Salomo mit der Frau des Urija. Salomo zeugte den Rehabeam, Rehabeam zeugte den Abija, Abija zeugte den Asa, Asa zeugte den Joschafat, Joschafat zeugte den Joram, Joram zeugte den Usija. Usija zeugte den Jotam, Jotam zeugte den Ahas, Ahas zeugte den Hiskija, Hiskija zeugte den Manasse, Manasse zeugte den Amos, Amos zeugte den Joschija. Joschija zeugte den Jojachin und seine Brüder; das war zur Zeit der Babylonischen Gefangenschaft. Nach der Babylonischen Gefangenschaft zeugte Jojachin den Schealtiël, Schealtiël zeugte den Serubbabel, Serubbabel zeugte den Abihud, Abihud zeugte den Eljakim, Eljakim zeugte den Azor. Azor zeugte den Zadok, Zadok zeugte den Achim, Achim zeugte den Eliud, Eliud zeugte den Eleasar, Eleasar zeugte den Mattan, Mattan zeugte den Jakob. Jakob zeugte den Josef, den Mann Marias; von ihr wurde Jesus geboren, der der Christus genannt wird. Im Ganzen sind es also von Abraham bis David vierzehn Generationen, von David bis zur Babylonischen Gefangenschaft vierzehn Generationen und von der Babylonischen Gefangenschaft bis zu Christus vierzehn Generationen. (© Ständige Kommission für die Herausgabe der gemeinsamen liturgischen Bücher im deutschen Sprachgebiet)

In jener Zeit sprach Jesus zu den Hohepriestern und den Ältesten des Volkes: Was meint ihr? Ein Mann hatte zwei Söhne. Er ging zum ersten und sagte: mein Kind, geh und arbeite heute im Weinberg! Er antwortete: Ich will nicht. Später aber reute es ihn und er ging hinaus. Da wandte er sich an den zweiten und sagte zu ihm dasselbe. Dieser antwortete: Ja, Herr – und ging nicht hin. Wer von den beiden hat den Willen seines Vaters erfüllt? Sie antworteten: Der erste. Da sagte Jesus zu ihnen: Amen, ich sage euch: Die Zöllner und die Dirnen gelangen eher in das Reich Gottes als ihr. Denn Johannes ist zu euch gekommen auf dem Weg der Gerechtigkeit und ihr habt ihm nicht geglaubt; aber die Zöllner und die Dirnen haben ihm geglaubt. Ihr habt es gesehen und doch habt ihr nicht bereut und ihm nicht geglaubt. (© Ständige Kommission für die Herausgabe der gemeinsamen liturgischen Bücher im deutschen Sprachgebiet)

In jener Zeit sprach Jesus zu den Hohepriestern und den Ältesten des Volkes: Was meint ihr? Ein Mann hatte zwei Söhne. Er ging zum ersten und sagte: mein Kind, geh und arbeite heute im Weinberg! Er antwortete: Ich will nicht. Später aber reute es ihn und er ging hinaus. Da wandte er sich an den zweiten und sagte zu ihm dasselbe.  Dieser antwortete: Ja, Herr – und ging nicht hin. Wer von den beiden hat den Willen seines Vaters erfüllt? Sie antworteten: Der erste. Da sagte Jesus zu ihnen: Amen, ich sage euch: Die Zöllner und die Dirnen gelangen eher in das Reich Gottes als ihr. Denn Johannes ist zu euch gekommen auf dem Weg der Gerechtigkeit und ihr habt ihm nicht geglaubt; aber die Zöllner und die Dirnen haben ihm geglaubt. Ihr habt es gesehen und doch habt ihr nicht bereut und ihm nicht geglaubt.  (© Ständige Kommission für die Herausgabe der gemeinsamen liturgischen Bücher im deutschen Sprachgebiet)

In jener Zeit, als Jesus in den Tempel ging und dort lehrte, kamen die Hohepriester und die Ältesten des Volkes zu ihm und fragten: In welcher Vollmacht tust du das und wer hat dir diese Vollmacht gegeben? Jesus antwortete und sprach zu ihnen: Auch ich will euch eine Frage stellen. Wenn ihr mir darauf antwortet, dann werde ich euch sagen, in welcher Vollmacht ich das tue. Woher stammte die Taufe des Johannes? Vom Himmel oder von den Menschen? Da überlegten sie und sagten zueinander: Wenn wir antworten: Vom Himmel!, so wird er zu uns sagen: Warum habt ihr ihm dann nicht geglaubt? Wenn wir aber antworten: Von den Menschen!, dann müssen wir uns vor den Leuten fürchten; denn alle halten Johannes für einen Propheten. Darum antworteten sie Jesus: Wir wissen es nicht. Da erwiderte er: Dann sage auch ich euch nicht, in welcher Vollmacht ich das tue. (© Ständige Kommission für die Herausgabe der gemeinsamen liturgischen Bücher im deutschen Sprachgebiet)

In jener Zeit, als Jesus in den Tempel ging und dort lehrte, kamen die Hohepriester und die Ältesten des Volkes zu ihm und fragten: In welcher Vollmacht tust du das und wer hat dir diese Vollmacht gegeben? Jesus antwortete und sprach zu ihnen: Auch ich will euch eine Frage stellen. Wenn ihr mir darauf antwortet, dann werde ich euch sagen, in welcher Vollmacht ich das tue. Woher stammte die Taufe des Johannes? Vom Himmel oder von den Menschen? Da überlegten sie und sagten zueinander: Wenn wir antworten: Vom Himmel!, so wird er zu uns sagen: Warum habt ihr ihm dann nicht geglaubt? Wenn wir aber antworten: Von den Menschen!, dann müssen wir uns vor den Leuten fürchten; denn alle halten Johannes für einen Propheten. Darum antworteten sie Jesus: Wir wissen es nicht. Da erwiderte er: Dann sage auch ich euch nicht, in welcher Vollmacht ich das tue.  (© Ständige Kommission für die Herausgabe der gemeinsamen liturgischen Bücher im deutschen Sprachgebiet)

JCO Editor-in-Chief Dr. Jonathan Friedberg is joined by colleagues Dr. Jennifer Woyach, Dr. Wojciech Jurczak, and Dr. Matthew Davids to discuss simultaneous publications presented at ASH 2025 on pertibrutinib, a new upfront treatment option for patients with chronic lymphocytic leukemia. TRANSCRIPT The disclosures for guests on this podcast can be found in the show notes. Dr. Jonathan Friedberg: I'm Jonathan Friedberg, editor of Journal of Clinical Oncology, and welcome to JCO After Hours, where we are covering two manuscripts that were presented at the American Society of Hematology meeting 2025 in Orlando, Florida. I am delighted to be joined by colleagues on this call to discuss these pivotal manuscripts which cover the topic of pirtobrutinib, a new upfront treatment option for patients with chronic lymphocytic leukemia. I will first just introduce our guests, Dr. Woyach. Dr. Jennifer Woyach: Hi, my name is Jennifer Woyach. I am from the Ohio State University. Dr. Wojciech Jurczak: Hello, I am Wojciech Jurczak, working at the National Research Institute of Oncology in Krakow, Poland. Dr. Matthew Davids: Hi, I am Matthew Davids from Dana-Farber Cancer Institute in Boston. Dr. Jonathan Friedberg: We are going to start by just learning a little bit about these two trials that were both large, randomized phase 3 studies that I think answered some definitive questions. We will start with your study, Jennifer. If you could just describe the design of your study and the patient population. Dr. Jennifer Woyach: Absolutely. So this is the BRUIN CLL-314 study, and this is a phase 3 randomized trial of pirtobrutinib versus ibrutinib in patients with CLL or SLL who had not previously been treated with a covalent BTK inhibitor. The patients were both treatment-naive and relapsed/refractory, about one-third of the patients treatment-naive, the rest relapsed/refractory, and they were stratified based upon 17p deletion and the number of prior lines of therapy. The primary objective was looking at non-inferiority of overall response rate over the entire treated population as well as the relapsed/refractory patient population. Key secondary objectives included progression-free survival in the intention-to-treat and the smaller relapsed/refractory and treatment-naive populations. Dr. Jonathan Friedberg: And just comment a little bit on the risk of the patients. Dr. Jennifer Woyach: This study was fairly typical of this cohort of patients. Within the relapsed/refractory patient population, there was a median of one prior line of therapy in each of the groups, up to nine prior lines of therapy in the patients included on the study. For the overall cohort, about two-thirds of the patients were IGHV unmutated, about 15% had 17p deletion, 30% had TP53 mutations, and about 35% to 40% had a complex karyotype, which is three or more abnormalities. Dr. Jonathan Friedberg: And what were your findings? Dr. Jennifer Woyach: Regarding the primary outcome, which is the focus of the publication, we did find that pirtobrutinib was indeed non-inferior and actually superior to ibrutinib for overall response rate throughout the entire patient population and in both the relapsed/refractory and treatment-naive cohorts. PFS is a little bit immature at this time but is trending towards also being significantly better in pirtobrutinib-treated patients compared with ibrutinib-treated patients. Probably most significantly, we found this to be the case in the treatment-naive cohort where there was a striking trend to an advantage of pirtobrutinib versus ibrutinib. Dr. Jonathan Friedberg: And the follow-up that you have on that progression-free survival? Dr. Jennifer Woyach: So we have about 18 months follow-up on progression-free survival. Dr. Jonathan Friedberg: The second study, Wojciech, can you just go through the design and patient population that you treated? Dr. Wojciech Jurczak: Thank you, Dr. Friedberg, for this question. So the BRUIN CLL-313 study was, in fact, the first phase 3 study with pirtobrutinib in exclusively untreated CLL patients. It was a randomized study where we challenged pirtobrutinib versus bendamustine-rituximab. At the time we designed the protocol, bendamustine-rituximab was an option as a standard of care, and Bruton tyrosine kinase monotherapy was used far more commonly than nowadays. The primary target of the study was progression-free survival. We took all untreated patients except for those with 17p deletions. Therefore, it is a good representation for intermediate risk. We had about 60% of the population, 56 to be precise, which was unmutated, evenly distributed into two treatment arms. 17p deleted cases were excluded, but we had about 7% and 8% of TP53 mutated patients as well as about 11% and 7%, respectively, in the pirtobrutinib and bendamustine-rituximab arm of patients with complex karyotype. The progression-free survival was in favor of pirtobrutinib and was assessed by an independent review committee. What is important is that the progression-free survival of the bendamustine-rituximab arm was actually similar to the other studies addressing the same questions, like the comparison with ibrutinib in the ALLIANCE study or zanubrutinib in the SEQUOIA study. What was different was the hazard ratio. In our study, it was 0.20. It was one of the longest effect sizes noted in the frontline BTK study. It represented an 80% reduction in progression-free survival or death. If we compare it to ibrutinib or zanubrutinib, it was 0.39 and 0.42 respectively. Presumably, this great effect contributed towards a trend of overall survival difference. Although survival data are not mature enough, there is a clear trend represented by three patients we lost in the pirtobrutinib arm versus 10 patients lost in the bendamustine-rituximab arm. This trend in overall survival is becoming statistically significant despite the fact that there was a possibility of crossover, and effectively 52.9 patients, which means 18 out of 34 patients relapsing in the bendamustine-rituximab arm, were treated by pirtobrutinib. Dr. Jonathan Friedberg: I am going to turn it over to Matt. The question is: why study pirtobrutinib in this patient population? And then with these two studies, how do you find the patients that were treated, are they representative of people who you see? And do you see this maybe being approved and more widely available? Dr. Matthew Davids: I think in terms of the first question, why study this in a frontline population, we have seen very impressive data with pirtobrutinib in a very difficult-to-treat population of CLL patients. This was from the original BRUIN phase 1/2 study where most of the patients had at least two or three lines of therapy, often both a covalent BTK inhibitor and the BCL2 inhibitor venetoclax, and yet they were still responding to pirtobrutinib. The drug was also very well tolerated in that early phase experience. And actually, we have seen phase 3 data from the BRUIN 321 study comparing pirtobrutinib to bendamustine and rituximab in a relapse population as well. So I think that really motivated these studies to look at pirtobrutinib as a first therapy. You know, often in other cancers of course, we want to use our best therapy first, and I think these studies are an initial step at looking at that. In terms of the second question around the patient population, these are pretty representative patient populations, I would say, for most frontline CLL studies. We see patients who are a bit younger and fitter than sort of the general population of CLL patients who are treated in clinical practice, and I think that is true here as well. Median age in the sort of mid-60s here is a bit younger than the typical patients we are treating in practice. But that is not different from other CLL frontline studies that we have seen recently, so I think it makes it a little bit easier as we kind of think across studies to feel comfortable that these are relatively similar populations. Dr. Jonathan Friedberg: How do you see this either getting regulatory approval or potentially being used compared to current standard of care options? Dr. Matthew Davids: So my understanding is that both of these trials were designed with registrational intent in the frontline setting, and they are both positive studies. That is certainly very encouraging in terms of the potential for an approval here. We have seen in terms of the FDA recently some concerns around the proportion of patients who are coming from North America, and my understanding is that is relatively low on these two studies. But nonetheless, the datasets are very impressive, and so I think it is certainly supportive of regulatory approval for frontline pirtobrutinib. Dr. Jonathan Friedberg: I will ask Jennifer a question. The control arm in your study was ibrutinib, and I think many in the audience may recognize that newer, second-generation BTK inhibitors like acalabrutinib and zanubrutinib are more frequently used now if monotherapy is decided. How do you respond to that, and how would you put your results in your pirtobrutinib arm in context with what has been observed with those agents? Dr. Jennifer Woyach: Yeah, that is a great question. Even though in the United States we are predominantly using acalabrutinib or zanubrutinib when choosing a monotherapy BTK inhibitor, this is actually not the case throughout the entire world where ibrutinib is still used very frequently. The head-to-head studies of both acalabrutinib and zanubrutinib compared to ibrutinib have shown us pretty well what the safety profile and efficacy profile of the second-generation BTK inhibitors is. So even though we do not have a head-to-head study of acalabrutinib or zanubrutinib versus pirtobrutinib, I think, given the entirety of data that we have with all of the covalent BTK inhibitors, I think we can safely look at the pirtobrutinib arm here, how the ibrutinib arm compares or performs in context with those other clinical trials. And though we really can not say anything about pirtobrutinib versus acalabrutinib or zanubrutinib, I think we can still get a good idea of what might be the clinical scenarios in which you might want to choose pirtobrutinib. Dr. Jonathan Friedberg: And Wojciech, do you agree with that? Obviously, I think you have acknowledged that chemoimmunotherapy is rarely used anymore as part of upfront treatment for CLL. So, I guess a similar question. If you were to put the pirtobrutinib result in your study in context with, I guess, more contemporary type controls, would you agree that it is competitive? Dr. Wojciech Jurczak: Well, I think that that was the last study ever where bendamustine-rituximab was used as a comparator arm. So we should notice that smashing difference. Because if we look at the progression-free survival at two years, we have 93.4% in pirtobrutinib arm versus 70.7% in bendamustine-rituximab arm. Bendamustine-rituximab arm did the same as in the other trials, like ALLIANCE or SEQUOIA. Pirtobrutinib did exceptionally well, as pirto is not just the very best BTK inhibitor overcoming the resistance, but perhaps even more important for the first line, it is very well tolerated and is a very selective drug. Now, if we look at treatment-related adverse events, the discontinuation rate, they were hardly ever seen. If we compared the adverse events in exposure-adjusted incidence, literally all adverse events were two or three times higher in bendamustine-rituximab arm except for the bleeding tendency, which however was predominantly in CTCAE grade 1 and 2 with just 0.7% of grade 3 hemorrhage. Therefore, I think that we should actually put the best and the safest drugs upfront if we may, and pirtobrutinib is, or should be, the first choice if we choose monotherapy. Now, I understand that we are not presenting you the data of pirtobrutinib in combination with anti-CD20 or with BCL2 inhibitors, but that is to come. Dr. Jonathan Friedberg: Matt, how would you envision, were regulatory approval granted and this were an option, using this in the upfront patient population? Is there anybody who you would preferentially use this or start on this treatment? Or would this be something that you would tend to reserve for second line? Dr. Matthew Davids: So I would say that in general for most of my patients who would want to start with a continuous BTK inhibitor, I would still use a covalent BTK inhibitor, and I say that for a couple of reasons despite the very promising data from these studies. The first is that the follow-up for both of these phase 3 trials is still quite short, in the range of a median 18 to 24 months. And we know that CLL is a marathon, not a sprint, and these patients are going to probably be living for a very long time. And we do have much longer follow-up from the covalent BTK inhibitors, median of 10-year follow-up with ibrutinib and five to six years with zanubrutinib and acalabrutinib respectively. And you know, I do not think that the pirtobrutinib is going to fall off a cliff after two years, but on the other hand, I think there is a lot of value to long-term data in this disease, and that is why I think for most of my patients I would stick with covalent BTK inhibitors. But the other important factor that we need to consider is patients who are younger and may have many different CLL treatments over the years. We have to be very careful, I think, about how we sequence these drugs. We know right now that we can start with covalent BTK inhibitors and then subsequently patients will respond well to the non-covalent inhibitor pirtobrutinib in later lines of therapy. But right now we do not have prospective data the other way around. So how will the patients on these studies who progress on pirtobrutinib respond to covalent BTK inhibitors? We do not know yet. There have not been a lot of progression events, which is great, but we would like to see some data in that respect to feel more comfortable with that sequence. Now, I do think that particularly for older patients and those who have significant cardiovascular comorbidities, if they wanted to go on a continuous BTK inhibitor, I do think these data really strongly support using pirtobrutinib as the BTK inhibitor of choice in that population. In particular, the cardiovascular risks with pirtobrutinib seem to be quite low. I was very struck in the comparison with BR that the rate of AFib was equivalent between the two arms of the study. And that is really the first time we have seen that with any of these BTK inhibitors, no elevated risk of AFib in a randomized study. I think that is the population where it will get the most traction first, is the upfront, sort of older patient with significant cardiovascular comorbidities. And as the data from these studies mature, I think that we will start to see more widespread use of pirtobrutinib in the frontline setting. Dr. Jonathan Friedberg: Jennifer, I am just curious if you have any personal experience or heard anecdotally about after progression on pirtobrutinib the use of other BTK inhibitors and whether there is a growing experience there. Dr. Jennifer Woyach: I do not think that there is much clinical experience, you know, as Matt alluded to, it certainly has not been tested yet. There has been some data in relapsed CLL suggesting that in people who have resistance mutations to covalent BTK inhibitors after treatment with pirtobrutinib, sometimes those mutations go away. I think most of us are concerned that they are probably not actually gone but maybe in compartments that we just have not sampled, suggesting that sort of approach where you might sequence a covalent inhibitor after a non-covalent in somebody who had already been resistant probably would not work that well. But, you know, in this setting where people had never been exposed to a covalent BTK inhibitor before, we really have no idea what the resistance patterns are going to be like. We assume they will be the same as what we have seen in relapsed CLL, but I think we just need some longer follow-up to know for sure. Dr. Wojciech Jurczak: If I may confront Dr. Davids about the use of covalent BTK inhibitors upfront, well, I think that we should abandon the idea of using the first and the second and the third generation, at least if we don't have medical lines. If we endlessly block the same pathway, it is not going to be effective. So if pirtobrutinib gets approval in first, second line, we do not necessarily have to use it in the first line. I am not here in a position to defend that we should treat patients with pirtobrutinib upfront and not BCL2 time-limited regimen. However, the way I look at CLL patients when choosing therapy is not just how should I treat them now, but what would be the best regimen in 5, 10 years if I have to re-treat them. And in some instances, the idea may be that in this setting we would like to have a BTK inhibitor upfront to have a BCL2 inhibitor later to make it time-limited. Although I understand and I agree with Matthew that if we have an elderly, fragile population, then the charm of having a drug taken once a day in a tablet with literally few cardiovascular adverse events might be an option. Dr. Jonathan Friedberg: And I will give Matt the last word whether he wants to respond to that, and also just as a forward-looking issue, I know both investigators have implied that there will be future studies looking at combinations with pirtobrutinib, and if you have any sense as to what you would be looking for there. Dr. Matthew Davids: The field really is heading toward time-limited therapy for most patients, I would say. There is a bit of a discrepancy right now in the field between sort of what we are doing in academic practice and what is done sort of more widely in community practice. And so right now we are going to see evolving datasets comparing these approaches. We are already seeing data now from the CLL17 study with ibrutinib comparing continuous to time-limited venetoclax-based therapy, and we are seeing similar efficacy benefits from these time-limited therapies without the need for continuous treatment. And so that is where I think some of the future studies with pirtobrutinib combining it with venetoclax and other partners are so important. Fortunately, several of these studies are already ongoing, including a phase 3 trial called CLL18, which is looking at pirtobrutinib with venetoclax, comparing that to venetoclax and obinutuzumab. So I am optimistic that we are going to be developing these very robust datasets where we can actually use pirtobrutinib in the frontline setting as a time-limited therapy as a component of a multi-drug regimen. So far, those early data are very promising. Dr. Wojciech Jurczak: Perhaps last but not least, in a single center we have treated over 300 patients with pirtobrutinib. So eventually some of them relapsed. And I must say that our experience on BCL2 inhibitors, not just venetoclax but including sonrotoclax, are appealingly good. Therefore, by using pirtobrutinib even earlier, we do not block the efficacy of other compounds. Dr. Jonathan Friedberg: All right. Well, I want to thank all of our speakers. I also want to congratulate our two guests who presented these very influential papers at the ASH Annual Meeting, and chose to publish them in JCO, so we thank you for that, and Dr. Davids for your commentary - really appreciated. That is this episode of JCO After Hours. Thank you for your attention. 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.   Disclosures Dr. Wojciech Jurczak Consulting or Advisory Role: BeiGene, Lilly, Abbvie/Genentech, Takeda, Roche, AstraZeneca Research Funding: Roche, Takeda, Janssen-Cilag, BeiGene, AstraZeneca, Lilly, Abbvie/Genentech Dr. Jennifer Woyach Consulting or Advisory Role: Pharmacyclics, Janssen, AstraZeneca, Beigene, Loxo, Newave Pharmaceutical, Genentech, Abbvie, Merck Research Funding: Company name: Janssen, Schrodinger, beone, Abbvie, Merck, Loxo/Lilly Dr. Matthew Davids Honoraria: Curio Science, Aptitude Health, Bio Ascend, PlatformQ Health, Plexus Consulting or Advisory Role: Genentech, Janssen, Abbvie, AstraZeneca, Adaptive Biotechnologies, Ascentage Pharma, BeiGene, Lilly, Bristol-Myers Squibb, Genmab, Merck, MEI Pharma, Nuvalent, Inc., Galapagos NV, Schroedinger Research Funding: Ascentage Pharma, Novartis, MEI Pharma, AstraZeneca  

Redemption is not just a future hope—it's a present reality in Christ.

Antwerp-STVV werd een ouderwetse Bosuilrollercoaster: drie keer een voorsprong kwijt, Janssen en Kerk volledig herboren, verkrampte verlengingen en een Nozawa die ondanks een blunder toch nog Man van de Match wordt, met de hulp van Jeron. De Hel van Deurne-Noord brandde weer als in de grote dagen.We fileren de cupmatch, bespreken Oostings eerste echte Bosuilavond, het track record van Antwerp in penaltyreeksen en blikken vooruit naar KRC Genk én de opening van T2 komende zondag!Host: Pieter VerhoevenGasten: Bart De Vré en Jeron DewulfMontage: Thomas Slembrouck:#ad - Onze maandsponsor Studio of Stories heeft de droom om ooit een ceremonie op de Bosuil te mogen leiden... Heb jij plannen in die richting? Contacteer hem via deze link en gebruik code 'DVP26' voor 10% korting!https://bit.ly/4akD49u Hosted on Acast. See acast.com/privacy for more information.

The story today about Daniel and the Lion's Den is a familiar story.There is one reason given to us why he was saved, and that is he trusted in God. What makes Daniel trusting God seem so easy while many of us struggle to even know what it really means to trust God?Let us learn together the key to trust; the answer might actually surprise you, for it is not as complicated as it seems.Join our community:Facebook: https://facebook.com/UECPhilippinesFacebook Group: https://facebook.com/groups/UnitedEvangelicalChurchofthePhilippinesInstagram: https://instagram.com/uecphilippines/Spotify: https://podcasters.spotify.com/pod/show/uecphilippinesViber: https://bitly.com/UECPViberComm

Cam Janssen, born in St. Louis and raised in Eureka, Missouri is the first ever born-and-raised St. Louisan to suit up in the NHL. He was famous for the rough stuff in hockey, and takes great pride in it. He spent several seasons exciting the crowds at the Enterprise Center. Cam has a great way of telling a story…Enjoy!

At the age of 14, Michaela Janssen Pohl became a caregiver for her mother, who lives with MS. I think most of us can agree that just being a teenager carries with it more than enough challenges. Those adolescent years are the years when just about everything in life starts changing. Imagine adding the responsibilities of being a caregiver to all the other things going on in a 14-year-old girl's life. Michaela joins me this week to explain how she found ways to survive and thrive in what can only be described as a challenging situation for any teenager. We'll also explain why you might want to think a little differently about Giving Tuesday this year. We're sharing all the details about the Phase 2 clinical trial focusing on Moderna's investigational Epstein-Barr vaccine and MS (and we'll explain why that might turn out to be important!) We're talking about how MS impacts women's health issues with this year's winner of the Rachel Horne Prize for Women's Research in Multiple Sclerosis, Dr. Kristen Krysko. And we're sharing the results of the Phase 2 clinical trial for PIPE-307, an investigational remyelination therapy. We have a lot to talk about! Are you ready for RealTalk MS??! It's Giving Tuesday (and why that matters more this year than ever before)  :22 This Week: Becoming a caregiver for a parent with MS when you're 14 years old  3:27 A clinical trial focused on an EBV vaccine and MS is recruiting participants  4:25 Dr. Kristen Krysko discusses MS and women's health issues  7:52 Results from the Phase 2 clinical trial for PIPE-307 remyelination therapy  13:48 Michaela Janssen Pohl shares her story of becoming a caregiver at the age of 14  16:55 Share this episode  33:20 Next week's episode  33:40 SHARE THIS EPISODE OF REALTALK MS Just copy this link & paste it into your text or email: https://realtalkms.com/431 ADD YOUR VOICE TO THE CONVERSATION I've always thought about the RealTalk MS podcast as a conversation. And this is your opportunity to join the conversation by sharing your feedback, questions, and suggestions for topics that we can discuss in future podcast episodes. Please shoot me an email or call the RealTalk MS Listener Hotline and share your thoughts! Email: jon@realtalkms.com Phone: (310) 526-2283 And don't forget to join us in the RealTalk MS Facebook group! LINKS If your podcast app doesn't allow you to click on these links, you'll find them in the show notes in the RealTalk MS app or at www.RealTalkMS.com DONATE: The National MS Society https://nationalmssociety.org/donate SIGN UP: Become an MS Activist https://nationalmssociety.org/advocacy PARTICIPATE: Phase 2 Clinical Trial for Moderna's EBV Vaccine and MS https://clinicaltrials.gov/study/NCT06735248 Email: WeCareClinicalTrials@modernatx.com JOIN: The RealTalk MS Facebook Group https://facebook.com/groups/realtalkms REVIEW: Give RealTalk MS a rating and review http://www.realtalkms.com/review Follow RealTalk MS on Twitter, @RealTalkMS_jon, and subscribe to our newsletter at our website, RealTalkMS.com. RealTalk MS Episode 431 Guests: Dr. Kristen Krysko, Michaela Janssen Pohl Privacy Policy

God's Word helps us truly believe in Him that we may find true life in Him.

Rechte Straftaten von jungen Menschen haben in den letzten Jahren deutlich zugenommen. Ein Grund sind die vielen Krisen, mit denen Jugendliche konfrontiert sind, sagt Ausstiegsberaterin Lena Janssen. Die Entwicklung im Westen wird dabei unterschätzt. Janssen, Lena www.deutschlandfunkkultur.de, Interview

Ben Ennis and Brent Gunning wrap up the morning by speaking with Sportsnet.ca's Luke Fox about the Toronto Maple Leafs. They discuss expectations for Brad Treliving's media availability, the impact of David Kämpf, and the toll of injuries on the team. They also speculate on the return of Auston Matthews and whether the Leafs might have missed their championship window. After the break, former NHL player Cam Janssen (25:50) shares his insights on the Leafs and St. Louis Blues, including concerns about Mitch Marner's absence and Craig Berube's coaching status. Ben and Brent conclude with the Crown Royal Canadian moment.The views and opinions expressed in this podcast are those of the hosts and guests and do not necessarily reflect the position of Rogers Sports & Media or any affiliate.

Elias Janssen is one of the stars of the new Netflix film IN YOUR DREAMS which is out today! The animated film is fun for the whole family and Gavin got to sit down with him to talk about the process and what it was like, as well as his personal life and career.

Guest Dr. Sundar Jagannath and host Dr. Davide Soldato discuss JCO article "Long-Term (≥5-Year) Remission and Survival After Treatment With Ciltacabtagene Autoleucel in CARTITUDE-1 Patients With Relapsed/Refractory Multiple Myeloma," and the efficacy of CAR-T cell therapy in patients with heavily pretreated RRMM (relapsed/refractory multiple myeloma). TRANSCRIPT Dr. Davide Soldato: Hello and welcome to JCO After Hours, the podcast where we sit down with authors from some of the latest articles published in the Journal of Clinical Oncology. I am your host, Dr. Davide Soldato, medical oncologist at Ospedale San Martino in Genoa, Italy. Today, we are joined by JCO author, Professor Sundar Jagannath, Professor of Medicine at the Icahn School of Medicine at Mount Sinai and the Tisch Cancer Institute. He also serves as Network Director for the Center of Excellence for Multiple Myeloma, and he is an internationally recognized expert in the field of multiple myeloma. Today, we will be discussing the article titled, "Long-Term Remission and Survival After Treatment With Ciltacabtagene Autoleucel in CARTITUDE-1 Patients With Relapsed/Refractory Multiple Myeloma." Thank you for speaking with us, Professor Jagannath. Dr. Sundar Jagannath: Thank you for having me, Dr. Davide Soldato. It is a pleasure to be here. JCO is a highly recognized journal among the oncologists, so I am very happy and privileged to be here today. Dr. Davide Soldato: Thank you so much for being with us. So, I wanted to start a little bit with the rationale of the study and the population that was included in the study. So, the trial that we are discussing, CARTITUDE-1, was already published before, and we observed very good results with a single infusion of cilta-cel. So we had previously reported a median progression-free survival of 30 months, and median overall survival was not reached. So, I just wanted to ask you if you could guide us a little bit into the population that was included in the study and also explain a little bit to our listeners what is the drug that we are discussing, cilta-cel. Dr. Sundar Jagannath: It is a CAR T-cell. This is a patient's own lymphocytes, which goes through apheresis and is sent to the company, where they modify it and introduce the B cell receptor. In this case, you know, there is a heavy chain gene receptor for the BCMA, and in cilta-cel, there are actually two receptor sites on each molecule, or there are two binding domains on each receptor molecule. So, it is considered to be quite efficacious. As you reported, the earlier results that the patients who participated, 97% of the patient responded. Now, you asked about the patients who participated in the clinical trial. This clinical trial was conducted between July of 2018 and October of 2019. At that time, this was a phase 1b/phase 2 trial, and the whole idea was to take patients who had relapsed all the available treatment regimen so that these patients were considered to have, in the unmet medical need situation. So, what does that entail? That means the patient should have been exposed to a proteasome inhibitor, to an immunomodulatory molecule, and to an anti-CD38 monoclonal antibody and should have received at least three or more prior lines of therapy and should be actually progressing on their last line of therapy. So with that requirement, if you look at it, the median number of prior therapy on the patients who participated was actually six. So patients were heavily pretreated. They had exhausted all available treatment options. So, they can participate in this clinical trial. And if not, there have been real-world evidence, such as LocoMMotion, which had reported what is the outcome for such a patient if they were treated outside of this clinical trial, if they were treated with the then available regimen. Their median progression free survival would have been only 3 months, and most patients would have lost their life within a year. So, this was truly an unmet medical need with patients in a very difficult clinical situation. Let's put it that way. So, those were the patients who participated in this particular trial. Dr. Davide Soldato: Thank you very much. And as we mentioned before, the results that were obtained in this clinical trial were really very interesting. And now, in this issue of the Journal of Clinical Oncology, you are reporting data with a longer follow up. So we are actually at more than 5 years of follow up for the patients included in this trial. So, I just wanted a little bit of insight into why you decided to report these long-term outcomes and what type of information do you think you could provide with this study to the medical community? Dr. Sundar Jagannath: This is very important because this was a clinical trial that was done in patients who were, as I said, in unmet medical need. Most of the patients had prior stem cell transplantation, had gone through a proteasome inhibitor. Many of them have had both Velcade and carfilzomib treatment. Most of them had been exposed to lenalidomide and pomalidomide. And as required, all of the patients had to have had prior exposure to anti-CD38 monoclonal antibody or daratumumab. So, the patients were heavily pretreated. Typically, TIL CAR T-cells came into the field at this particular moment, until then, we were developing small molecules, and they usually would have a PFS of 3 months and median life expectancy of a year, the overall response rate of 30%, and that is how, if you look back, that is how carfilzomib was approved, that is how pomalidomide was approved. So, the drugs which were approved, including daratumumab, you know, the response rate was in the same ballpark. So you would see that most agents, single agents, would have had a response rate in the neighborhood of 30%, the progression-free survival would have been between 3 to 5 months or 6 months at the most, and the life expectancy was short. And here comes a drug, and when I was following the patients at Mount Sinai, I found that there were a subset of patients, they got one-time treatment and they were in complete remission, no trace of cancer with annual evaluation with PET CT and bone marrow evaluation for MRD. So, I said this is remarkable, and this needs to be reported. And I went to the Janssen and company, and they agreed to review the entire experience. This is remarkable that 32 of the 97 patients, or one third of the patients, were alive and progression-free. This is unheard of for any clinical trial until now, that the patient will be progression-free, one third of the patients on a clinical trial will be progression-free, in the late stage of their disease. So that is the most important impact. And that is why this 5-year follow-up results were presented. Dr. Davide Soldato: Thank you very much. That was very clear. And as you said, we are speaking about a population that was heavily pretreated, that had exhausted all type of treatment options outside of a clinical trial. And as you said, one third of the patients was alive and progression-free after 5 years from being included and infused inside of the study. So, considering this population that, as we said, had received all treatment options, I was wondering if you observed any kind of differences in terms of disease characteristics when looking at these patients that had exceptional response, so, alive and progression-free at 5 years, and the patients that sadly had developed a progression after the infusion in the study. Dr. Sundar Jagannath: This is very important because we wanted to see who are the patients who are having this exceptional outcome. And we looked at all the 97 patients. If we look at all the patients, we saw that there were initially, out of the 97, 17 patients died earlier in the disease course due to treatment related complications, etc. But there were about 46 patients who had progression of disease and 32 patients, or one third, were alive without progression of disease. Then we looked at the 46 patients who had progression of disease. Of them, we found that 30 had disease progression and its complication, and there were actually 13 patients who were still alive even after progression of disease. So we decided to compare these 46 patients who had progression of disease versus 32 patients who had no progression of disease to see what is the difference. To our surprise, the age was similar, male, female distribution was similar. High-risk cytogenetics, which we would have thought, you know, that is why we say high-risk disease, the term, high-risk cytogenetics was equally distributed. That was really a surprise. Number of lines of prior therapy, number of exposure to drugs, all of that was the same. So that was also interesting. But a theme did emerge. Patients, in general, tend to have lower burden of disease who had the exceptional outcome. But there is one which we considered as bad, the extramedullary disease. Multiple myeloma being a blood cancer, it is usually in the bone marrow. When it starts growing outside of the bone marrow, the extramedullary disease, usually it portends poor prognosis. But we were surprised that actually there were an equal number of extramedullary disease patients even in the long-term survivor as those who had progressed of disease. So the most important takeaway was patients who had lower burden of disease, they had less number of myeloma cells in their bone marrow, percentage wise, and the soluble BCMA level was lower. Soluble BCMA is an indirect measure of the amount of plasma cells in the patient's body. It is like a tumor burden. So they were low. So, this was an important finding because it has future ramification, as you can understand. If this treatment is made available earlier in the disease course of the patients, where we are able to control the disease better, then more patients are likely to have such wonderful outcomes as one third of the patient experience in the late stage of the disease. Dr. Davide Soldato: So, you already mentioned soluble BCMA as a marker of potentially better prognosis as being correlated to a lower volume of disease. I was wondering if you could give us some more information about the biomarkers that you evaluated in the study. For example, you evaluated a little bit the CAR T expansion kinetics and also some others that I think could be interesting and could point to some population that experienced such important benefit. Dr. Sundar Jagannath: That is a very important point because CAR T-cell, it is a live cell and its efficacy depends upon how well the CAR T-cell is going to function. And then, you know, the patient undergoes apheresis. This is a patient's own lymphocyte. So first and foremost is who would generate good CAR T-cell. Those who have plenty of lymphocytes at the time they are coming for apheresis. This is likely to happen earlier in the course of the disease than in patients who have gone through numerous lines of therapy and exhausted. So, in this particular trial, of course this was in late stage of the disease, and so we were able to show patients who had lower number of T cell in circulation, and the way to measure is if they had more neutrophils and less lymphocytes. So that is what is called as a higher T cell over neutrophil, they did better. If they have more neutrophil than T cells, then they did not do well. So, procurement. The second one is also whether the T cells are more naive, you know, not exhausted T cells. So more naive T cells, if you are able to procure from the patient, they did very well. Now, after the CAR T-cell manufacture, then the expansion, when you put it back into the patient, if the T cells expand very well, so that the effector, that is the CAR T-cells to the tumor ratio is good, so there are more effector cells, the CAR T was able to expand and the amount of tumor was less, then the efficacy was very, very good. As I said, the patients in this group, those who had a lower burden of disease, they did better, and that is because of the CAR T-cell expansion, so the effector to the target ratio was favorable. So that is another important. And then there are also the type of CAR T-cells, having CD4 T cells with central memory phenotype at the peak expansion also makes a difference. So all of that matters. But this is important because the efficacy of the CAR T-cell, it is persistent, long persistent and keeping the cancer down. Its ability to get rid of the cancer completely at the first go around because usually we are not able to detect the CAR T-cells beyond 6 months in the majority of patients and very rarely after a year or two. So it is very uncommon to find the CAR T-cells in circulation or even in the regular bone marrow evaluation. So, efficacy, the expansion, having naive T cells, having good effector to target ratio and more central memory kind of T cell, because if it is all effector T cell, they will get quickly utilized and get exhausted, whereas the central memory cells can expand more and give more effective CAR T-cells. Dr. Davide Soldato: Thank you very much. I was wondering if you could guide us a little bit into what is your opinion regarding the positioning of CAR T-cells given all of these logistics that is necessary compared, for example, with bispecific antibodies against BCMA, which have the same target, but they do not have all of these logistics before being administered to the patient. Dr. Sundar Jagannath: That is a very important question, how to sequence these treatments now that we have two BCMA-directed CAR T-cells available. We have three BCMA-directed bispecific and one GPRC5D-directed bispecific antibodies are available. And so the question comes in for at least the currently approved CAR T-cell therapy, there is an obligatory time. You have to go through apheresis and you have to ship to the company, and there is a manufacturing time, roughly about 2 months before they can receive it. During that time, you want to make sure the patient's disease is under control. So that is a given. There are several ways to look at it when we evaluate the patient and talk to the patient. One good thing is now the two CAR T-cells which are approved, one is cilta-cel we talked about, and the other one is ide-cel. Ide-cel is approved in earlier line of therapy, two or more prior lines of therapy, and cilta-cel is approved in patients who have failed one line of therapy and who are lenalidomide refractory. So, the treatment of CAR T-cell is available earlier. And as I said, when you administer CAR T-cell earlier, you are able to keep the disease burden down, and it is a one and done deal. There is a better quality of life for the patient, and you are able to produce long, durable remission and potentially a cure. Now coming to the bispecific, they are currently available in later lines of therapy. So if you look at it from a patient's perspective, you can use the CAR T-cell earlier and then go through the bispecific therapy. But if the patient comes with relapsed refractory myeloma and has not used the CAR T-cell therapy and has not used the bispecific therapy, then the physicians have to decide which one they want to use. If somebody's disease is rapidly progressing and they need immediate tumor reduction and they have already exhausted all available therapy, then going through BCMA bispecific therapy is quite appropriate. And secondly, CAR T-cell therapy is generally given to somewhat physically more fit patients, whereas bispecific therapy, because you are giving antibody at step-wise dosing in this patient, and you have the ability to stop at any particular dose and then come back and redose, whereas CAR T is, you just give it to them one time, you have a lot more control. So intermediate frail or even frail patients can go through bispecific therapy, whereas it would not be in the best interest of the patient to go through a CAR T-cell therapy when they are frail. So that is another important point. But from the information available, when the patient goes on a BCMA bispecific therapy and they start progressing on treatment, usually it is their T cells are exhausted or the BCMA is no longer expressed on the tumor cells. So coming with CAR T-cell later on is usually not effective, whereas giving CAR T-cell earlier, if the patient relapses later, they have good T-cell function and most of the time the BCMA is still expressed. So you are able to give the BCMA to the maximum benefit by using the CAR T first and BCMA later. So if somebody asked me how to sequence this, just off the bat, you will say CAR T first, BCMA bispecific second. But as I said, there are unique situations. Then there is another potential that is happening. You can change the target. You can use a BCMA against GPRC5D to reduce the tumor, and then go ahead and consolidate it with a CAR T-cell therapy. That is also possible. You are changing the target from GPRC5D to BCMA, the tumor is already down, so the patient is likely to benefit. So these are all newer treatment options which have become available to the physician. So they will have to look at individual patients and decide what is the best course of action for that patient. Dr. Davide Soldato: So, I just wanted to close a little bit with your opinion about how these results translate into clinical practice. So considering this outstanding 5-year data that we have seen, one third of the patients who are alive and progression-free after a single infusion of cilta-cel, do you think that we could start to think about functional cure even in patients who have a diagnosis of relapsed refractory multiple myeloma? Dr. Sundar Jagannath: My feeling is this is important because in this particular study which is published, 12 patients who were followed at Mount Sinai out of the 32 patients who are alive and progression-free, 12 were followed at Mount Sinai. And they were evaluated every year with bone marrow MRD testing by clonoSEQ in 11 of the 12 patients, and one was by multiparametric flow cytometry. So most of them were 10 to the minus 6, not even one in a million cancer cells, and all of them had functional imaging, which is called PET CT every year. So these were patients who had no evidence of disease that we could detect with the technology available today, serologically, in the bone marrow, or anywhere else in the body with a PET CT. They were found to be disease free after a single infusion of cilta-cel. So, that would be almost to the definition of a cure because if you look at cure as a definition for any cancer, cure is defined as a state of complete remission with no trace of cancer that persists over a period of 5 years or longer without maintenance. And that will be applicable for breast cancer, lymphoma, leukemia. So it is a general statement. And if we use that in myeloma too, then I could say that these 12 patients from my center, we proved that they are cured of their myeloma. They are not functionally cured. You've got to remember, there is only cure. That was the definition across all diseases. So there is nothing like a functional cure. They are cured of myeloma. So is myeloma curable? This is the first time we are looking at that. We do know, every physician treating myeloma that there are patients out there, 10 year and beyond, without evidence of disease. This has been published by University of Arkansas, Bart Barlogie's group, who has been saying that myeloma is a curable disease for a long time. And many others have shown long-term follow up. But this one in a late stage disease, we were able to show that they were one treatment with no maintenance. All other studies have been in newly diagnosed myeloma patients. Nobody has shown in late relapse patients on a clinical trial a third of the patient will be progression-free. And 12 of them who were studied were actually disease free. So they were cured of the disease. So if we accept that, then the next question is, first step towards cure is achieving complete remission. They should have no monoclonal protein by any technology you want to use, no measurable residual disease using next gen sequencing or clonoSEQ, and functional imaging whole body PET CT or whole body MRI. So that is important, definition of the complete remission. And then it has to be sustained. That is something the IMWG and IMS, International Myeloma Society, they will have to come together for a consensus. How many years should they be followed and should be in this kind of status with no trace of cancer? Is it, 3 years are enough? 4 years enough? 5 years is enough? For me, I said in this paper, 5 years is a good definition for achieving a potential cure. Then you use the term 'functionally cured'. I have a problem with functionally cured and operationally cured or whatever. Functionally cured was originally put out by Paiva from Spain. There were 8% of newly diagnosed myeloma patients who have, after they go get treated, they will have an MGUS like phenomenon, a small amount of paraprotein detectable, and they are only 8%. And he said that these patients could be off treatment and the disease does not progress. But the problem is when you are giving treatment like maintenance therapy continuously until progression, you do not know exactly who is in the MGUS situation. So you have to have done sophisticated flow cytometry like Paiva did, and it is not quite clinically applicable. So functionally cured applies only for 8% of the people, so it should go out of the vocabulary. Then you can say 'operationally cured'. These are the patients traditionally Bart Barlogie and others showed that they have a large number of patients who have been followed for 10 years with no recurrence of disease, not on treatment. But in those days, they did not have MRD PET CT and all of them done systematically. So that is why they had to come up with a situation where they said they were operationally cured. So yes, myeloma patients have been cured since auto transplant was introduced. I completely agree. It is not new to the CAR T-cell therapy. But the beauty of the CAR T-cell therapy was it was in relapsed refractory myeloma, unmet medical need, number one. Number two, they were studied systematically. It was a clinical trial adjudicated by FDA and EMA for drug approval, cilta-cel was approved. So these patients were carefully followed, and it was a multi-center study. And in that group of patients, we were able to show patients- So, I think this would indicate cure is a reality in myeloma, and as these kind of treatments, immunologic treatment, either it is a CAR T-cell therapy or BCMA bispecific or whatever, there is a chance more patients are likely to be cured, and these treatments have to move forward and so that we are looking towards a cure. That is the beauty of it, and I just thank you for asking and also throwing in this so-called functionally cured, which people like to use casually, and I say it is time to talk more cure and not stuck with functionally cured because that does not allow the field to progress. Dr. Davide Soldato: Thank you very much. That was very interesting. Dr. Sundar Jagannath: And provocative. Dr. Davide Soldato: A little bit, but I think that we needed to close the podcast with this kind of reflection coming from someone who is an expert in the field, as you are. So, I really wanted to thank you for joining us today and for sharing more on your article, which is titled, "Long-Term Remission and Survival After Treatment With Ciltacabtagene Autoleucel in CARTITUDE-1 Patients With Relapsed/Refractory Multiple Myeloma." If you enjoy our show, please leave us a rating and a review and be sure to come back for another episode. You can find all ASCO shows at asco.org/podcasts. Dr. Sundar Jagannath: Thank you. 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.      

No other book has had such a vast and formative effect on the history of the world as the Holy Bible.

Discover the joy of generosity and worship as we explore Philippians 4:14–20 together. When we give for God's purposes, it brings Him joy and draws us closer to His heart. We don't have to fear letting go—God promises to supply all our needs according to the riches of His glory. Be inspired to live open-handed, trusting fully in the One who provides.

Do you know that you are also God's provision to others?

Janssen, Ingo www.deutschlandfunkkultur.de, Studio 9

Today we celebrate and remember the saints that have gone before us.Sunday service times are 9 a.m., 11 a.m., and 4 p.m. at the Mission Campus in Prairie Village, Kansas, and 10 a.m. at the Antioch Campus in Overland Park, Kansas. If you are unable to attend in person, you can worship online at villagepres.org/online. Support the showContact Village Presbyterian Churchvillagepres.orgcommunications@villagepres.org913-262-4200Have a prayer request? pastoral-care@villagepres.orgFacebook @villagepresInstagram @villagepreschurchYouTube @villagepresbyterianchurchTo join in the mission and ministry of Village Church, go to villagepres.org/giving

This episode covers: Cardiology This Week: A concise summary of recent studies Arrhythmias in cardiac amyloidosis Taking the 'O' out of HOCM: managing LVOT obstruction Snapshots Host: Susanna Price Guests: Carlos Aguiar, Stephanie Schwarting, Ahmad Masri Want to watch that episode? Go to: https://esc365.escardio.org/event/2176 Want to watch that extended interview on Arrhythmias in Cardiac Amyloidosis? Go to: https://esc365.escardio.org/event/2176?resource=interview Disclaimer: ESC TV Today is supported by Bristol Myers Squibb and Novartis through an independent funding. The programme has not been influenced in any way by its funding partners. This programme is intended for health care professionals only and is to be used for educational purposes. The European Society of Cardiology (ESC) does not aim to promote medicinal products nor devices. Any views or opinions expressed are the presenters' own and do not reflect the views of the ESC. The ESC is not liable for any translated content of this video. The English language always prevails. Declarations of interests: Stephan Achenbach, Yasmina Bououdina, Nicolle Kraenkel and Susanna Price have declared to have no potential conflicts of interest to report. Carlos Aguiar has declared to have potential conflicts of interest to report: personal fees for consultancy and/or speaker fees from Abbott, AbbVie, Alnylam, Amgen, AstraZeneca, Bayer, BiAL, Boehringer-Ingelheim, Daiichi-Sankyo, Ferrer, Gilead, GSK, Lilly, Novartis, Pfizer, Sanofi, Servier, Takeda, Tecnimede. John-Paul Carpenter has declared to have potential conflicts of interest to report: stockholder Mycardium AI. Davide Capodanno has declared to have potential conflicts of interest to report: Bristol Myers Squibb, Daiichi Sankyo, Sanofi Aventis, Novo Nordisk, Terumo. Konstantinos Koskinas has declared to have potential conflicts of interest to report: honoraria from MSD, Daiichi Sankyo, Sanofi. Ahmad Masri has declared to have potential conflicts of interest to report: research grants from Pfizer, Ionis, Attralus, Cytokinetics and Janssen. Consulting fees from Cytokinetics, BMS, BridgeBio, Pfizer, Ionis, Lexicon, Attralus, Alnylam, Haya, Alexion, Akros, Edgewise, Rocket, Lexeo, Prothena, BioMarin, AstraZeneca, Avidity, Neurimmune, and Tenaya. Steffen Petersen has declared to have potential conflicts of interest to report: consultancy for Circle Cardiovascular Imaging Inc. Calgary, Alberta, Canada. Stephanie Schwarting has declared to have potential conflicts of interest to report: advisory board for Alnylam, Bayer, Pfizer; principal investigator in trials sponsored by Alexion, Novo Nordisk and Intellia. Emma Svennberg has declared to have potential conflicts of interest to report: Abbott, Astra Zeneca, Bayer, Bristol-Myers, Squibb-Pfizer, Johnson & Johnson.

(Insight Meditation Society - Retreat Center) The Third Noble Truth is about the cessation of dukkha (unsatisfactoriness) and the realization of Nibbāna (awakening). Through inspiring stories of modern-day figures like Mae Chee Kaew and Dipa Ma, we see that awakening is possible in this very life.

(Insight Meditation Society - Retreat Center) The Third Noble Truth is about the cessation of dukkha (unsatisfactoriness) and the realization of Nibbāna (awakening). Through inspiring stories of modern-day figures like Mae Chee Kaew and Dipa Ma, we see that awakening is possible in this very life.

(Insight Meditation Society - Retreat Center) The Third Noble Truth is about the cessation of dukkha (unsatisfactoriness) and the realization of Nibbāna (awakening). Through inspiring stories of modern-day figures like Mae Chee Kaew and Dipa Ma, we see that awakening is possible in this very life.

(Insight Meditation Society - Retreat Center) After a brief overview of the four Bbrahmavihāras and their interconnections, the session continues with a brief reflection on upekkhā (equanimity), followed by a guided equanimity meditation.

(Insight Meditation Society - Retreat Center) After a brief overview of the four Bbrahmavihāras and their interconnections, the session continues with a brief reflection on upekkhā (equanimity), followed by a guided equanimity meditation.

ASHP's senior education director Cindy Von Heeringen is joined by Lisa Janssen Carlson, IDS manager, and Craig Michael, data science pharmacist, both from the University of California, San Francisco as they discuss their upcoming Midyear session that focuses on incorporating AI in current pharmacy practice settings to enhance or streamline workflows.   The information presented during the podcast reflects solely the opinions of the presenter. The information and materials are not, and are not intended as, a comprehensive source of drug information on this topic. The contents of the podcast have not been reviewed by ASHP, and should neither be interpreted as the official policies of ASHP, nor an endorsement of any product(s), nor should they be considered as a substitute for the professional judgment of the pharmacist or physician.

Jacqueline (https://jacquelinejanssen.com/) has turned all she has learned about mental illness from her son's mental health journey into incredible advocacy. Her latest book, Every Homeless Person Has a Mother, chronicles Jacqueline's experience as a parent of an adult child with schizoaffective disorder. Jacqueline's son's battle with mental illness started when he was 19 years old. Jacqueline talks about the myriad of therapies and treatments her son received and how he ultimately ended up homeless as a result of anosognosia (https://www.nami.org/about-mental-illness/common-with-mental-illness/anosognosia/) or the lack of ability to recognize and treat his mental illness. Jacqueline has been a tireless advocate for families through her own work and with NAMI (https://www.nami.org/) and encourages families to get involved in their local NAMI chapters. Jacqueline emphasizes that when a loved one is incapable of making decisions for his or her own good, HIPAA (https://www.cdc.gov/phlp/php/resources/health-insurance-portability-and-accountability-act-of-1996-hipaa.html) allows mental health providers to talk to families. Jacqueline also discusses strategies for reunification of families if there is estrangement due to mental illness. Jacqueline graciously shares many resources with listeners:Family Rights and HIPAA Facts: https://drive.google.com/file/d/1W6DO-beIMgMww0xH1QTUBECiSXd85W8H/view?usp=drive_link; HIPAA Decision Tree: https://drive.google.com/file/d/1DsI-DpSCFrZLfgCknTqjaMqXTavh0AGu/view?usp=drive_link; Family Involvement Accelerates Recovery: https://drive.google.com/file/d/1IoCvWj7H56K-F4qtSL5hiGHriEn6Nk8U/view?usp=drive_link; Every Homeless Person Has A Mother: https://everyhomelesspersonhasamother.substack.com; https://www.nationalshatteringsilencecoalition.org/; What I Wish I'd Known: https://drive.google.com/file/d/1KnkPLJKF7TCNyvTwxgnZIhtAcDOCgoYQ/view?usp=drive_link

(Insight Meditation Society - Retreat Center) Right Effort, the 6th step on the Noble Eightfold Path, is not about striving or straining, it is about learning to guide the mind with wisdom and care. In this talk, we reflect on the Four Great Efforts: 1) Preventing the arising of unwholesome states, 2) Abandoning those that have already arisen, 3) Cultivating wholesome qualities, 4) Extending and nourishing wholesome states that are present. These four ways of applying effort, remembered with the acronym PACE, offer a clear and practical way to work with unwholesomeness and support wholesomeness.

Become a Client: https://nomadcapitalist.com/apply/ Get our free Weekly Rundown newsletter and be the first to hear about breaking news and offers: https://nomadcapitalist.com/email Join us for the next Nomad Capitalist Live event: https://nomadcapitalist.com/live/ We are joined from the Nomad Capitalist stage by geopolitics expert Cyrus Janssen. Together with our very own Javier Carrea, he sits down for a chat on one of the most important countries in today's global landscape. The red giant, China. From how Chinese citizens define freedom differently from their Western counterparts, to the ongoing Nvidia chip saga and the Trump trade wars, they dive into everything you need to know about what might soon become the biggest economy in the world. Nomad Capitalist helps clients "go where you're treated best." We are the world's most sought-after firm for offshore tax planning, dual citizenship, international diversification, and asset protection. We use legal and ethical strategies and work exclusively with seven- and eight-figure entrepreneurs and investors. We create and execute holistic, multi-jurisdictional Plans that help clients keep more of their wealth, increase their personal freedom, and protect their families and wealth against threats in their home country. No other firm offers clients access to more potential options to relocate to, bank in, or become a citizen of. Because we do not focus only on one or a handful of countries, we can offer unbiased advice where others can't. Become Our Client: https://nomadcapitalist.com/apply/ Our Website: http://www.nomadcapitalist.com/ About Our Company: https://nomadcapitalist.com/about/ Buy Mr. Henderson's Book: https://nomadcapitalist.com/book/ Disclaimer: Neither Nomad Capitalist LTD nor its affiliates are licensed legal, financial, or tax advisors. All content published on YouTube and other platforms is intended solely for general informational and educational purposes and should not be construed as legal, tax, or financial advice. Nomad Capitalist does not offer or sell legal, financial, or tax advisory services.

(Insight Meditation Society - Retreat Center)

(Insight Meditation Society - Retreat Center) While walking meditation often receives less attention than sitting meditation, it offers numerous benefits worth exploring. In this talk, we will go into the 'Walking Meditation' sutta, where the Buddha outlines five benefits of this practice. We'll conclude with a bonus benefit.

(Insight Meditation Society - Retreat Center) After an introduction to metta meditation, a guided meditation which includes the categories of benefactor, self, dear friend and a neutral being.

(Insight Meditation Society - Retreat Center)