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Last time we spoke about Yamato's Last Stand. In the spring of 1945, as WW2 intensified, the US Marines commenced a fierce assault on Okinawa. Amidst heavy bombardment, the Japanese 32nd Army fortified their positions, preparing for a desperate counteroffensive. Codenamed Operation Ten-Ichi-Go, Japan's final bid involved the legendary battleship Yamato, tasked with a suicidal mission to confront the American fleet. On April 7, 1945, as the Yamato sailed towards its fate, American forces were ready. Hundreds of aircraft descended upon the ship in a coordinated attack, unleashing bombs and torpedoes. Despite its infamous firepower, Yamato struggled against the relentless onslaught. With its systems failing, Captain Aruga and Admiral Ito made the agonizing decision to go down with their ship. As the proud battleship sank, it symbolized both Japan's indomitable spirit and the crushing weight of defeat, forever etching its story into the annals of military history. This episode is the First Okinawa Counteroffensive Welcome to the Pacific War Podcast Week by Week, I am your dutiful host Craig Watson. But, before we start I want to also remind you this podcast is only made possible through the efforts of Kings and Generals over at Youtube. Perhaps you want to learn more about world war two? Kings and Generals have an assortment of episodes on world war two and much more  so go give them a look over on Youtube. So please subscribe to Kings and Generals over at Youtube and to continue helping us produce this content please check out www.patreon.com/kingsandgenerals. If you are still hungry for some more history related content, over on my channel, the Pacific War Channel you can find a few videos all the way from the Opium Wars of the 1800's until the end of the Pacific War in 1945.  Picking up from last time. The Japanese naval-air counteroffensive against Admiral Spruance's forces at Okinawa had been decisively defeated with minimal losses, allowing General Buckner's 10th Army to proceed with the land offensive largely without interference. While General Geiger's Marines advanced toward the sparse Japanese defenses in northern Okinawa, General Hodge's 24th Corps in the south encountered the main enemy line of resistance centered around the Shuri fortified zone. Initially, the 32nd Army had declined to launch a land counteroffensive in conjunction with Operation Ten-Go and the Yamato's suicide attack, fearing that the Americans might execute another amphibious landing at Machinato while the Japanese wasted their strength in a futile effort to reclaim the airfields. However, pressure from Tokyo and Formosa compelled General Ushijima to resume planning for this operation. Ultimately, it was decided that instead of initiating a broad counterattack, the Japanese would deploy a brigade-strength force overnight on April 12 to breach the American lines and advance approximately six miles. If successful, this would be followed by a general attack. Accordingly, Colonel Yoshida Masaru's 22nd Regiment was assigned to the 62nd Division and assembled northeast of Shuri, tasked with attacking through enemy lines east of the Ginowan Road and advancing toward Shimabuku. To bolster this offensive, General Fujioka was also instructed to deploy three reserve battalions for a three-pronged attack from the west aimed at Chatan. However, Colonel Yahara, 32nd Army operations chief, strongly opposed the counterattack plan, feeling that it was not in keeping with the army's defensive mission and that it would waste men. He succeeded in getting the 1st Battalion of the 22d Regiment and elements of the 23d IIB cut from the counterattack force. He made a dire prediction that the infiltrating units, unfamiliar with the terrain in their attack sectors, would get lost, confused, and cut to pieces during a night assault. Taking a sidenote here, I read Yahara's rather famous novel about his experience of the battle for Okinawa and I highly recommend it to all of you. It's a great insight into the perspective of the Japanese and how the leadership were beginning to change their mind on how to go about the war. Yahara, acting without Ushijima's knowledge, advised Fujioka to commit only four battalions to the attack, predicting it would inevitably fail. Meanwhile, the American offensive was still in progress. On April 9, as Major-General George Griner's 27th Division landed at the Orange Beaches near Kadena, the ships of Colonel Waltern Winn's 105th Regiment met with Admiral Blandy's Eastern Islands Attack and Fire Support Group at the Kerama Islands, preparing to move to Tsugen Island overnight. Following a preliminary air and naval bombardment, which saw some Japanese mortar fire in response, Winn's 3rd Battalion successfully landed on the morning of April 10. The Americans then advanced inland with light resistance, quickly securing the northern part of the island but failing to overrun the entrenched enemy positions in Tsugen village. The assault continued the next day against persistent opposition, but organized resistance gradually diminished, allowing the Americans to secure the rest of the island by nightfall, marking the conclusion of the Eastern Islands operation. On April 11, General Shepherd's Marines continued to probe for the main enemy positions in northern Okinawa; the 1st Battalion, 22nd Marines patrolled eastward from their new base at Shana Wan, while the 29th Marines advanced toward Manna. Due to this progress, Buckner decided to fully merge Phases I and II, ordering the 77th Division to capture Iejima on April 16. To the south, Colonel Albert Stebbins's 106th Regiment was attached to the 96th Division, moving toward that division's reserve area, while Colonel Gerard Kelley's 165th Regiment relieved the 17th Regiment in the corps service area. Most significantly, General Bradley continued his attacks on Kakazu Ridge, with the 1st Battalion, 381st Regiment attempting to assault the western slopes but halted short of the ridge crest by determined defenders. At the same time, the 3rd Battalion, 383rd Regiment pushed up the northwest slopes of Kakazu Ridge but was also pinned down by intense Japanese fire. Simultaneously, following an intense artillery bombardment, the 1st Battalion of the 32nd Regiment finally succeeded in breaking into Ouki. However, additional reinforcements were thwarted by heavy Japanese fire, forcing the troops to retreat. With no further advancements, the 7th Division and the 382nd Regiment were relegated to patrolling and mopping up their designated areas over the next few days. At sea, Admiral Ugaki resumed his kamikaze assaults that day, damaging the carriers Essex and Enterprise, the battleship Missouri, and eight destroyers. However, his primary operation commenced on April 12, when he launched approximately 380 aircraft for a second mass Kikisui attack, primarily targeting Admiral Turner's Task Force 51 west of Okinawa. Thanks to cryptanalysis warnings, Turner scrambled his own fighter planes, which successfully shot down 298 Japanese aircraft. Despite attempting numerous missions, Kanoya's specially trained 721st Kokutai Jinrai-Butai “Divine Thunder” unit had so far failed to launch a single Ohka suicide rocket against the Americans. On April 12, however, eight Betty bombers would finally launch six Ohkas against the 5th Fleet, although five Betties never returned. At RPS-14, about 70nm northwest of Okinawa, a Zero plowed into Mannert L. Abele's engine room at 14:40, its 500lb bomb exploding and leaving the destroyer dead in the water. One minute later an Ohka came screaming in at 575mph, slammed into Mannert L. Abele and exploded. She sank in five minutes, losing 97 dead. Mannert L. Abele was the first destroyer hit by an Ohka and the last sunk by one. Destroyer-minesweeper Jeffers, en route to assist Mannert L. Abele, observed a twin-engined bomber eight miles away drop a smoking “belly tank” that suddenly rocketed towards Jeffers “at terrific speed.” Numerous 40mm hits and hard maneuvering saw the Ohka miss Jeffers astern and disintegrate. Additionally 3 battleships, 14 destroyers, 2 destroyer minesweepers, and another landing craft were damaged. Meanwhile, Admiral Rawlings' Task Force 57 was ordered to strike the Shinchiku and Matsuyama airfields in northern Formosa, and over the next two days, 48 Avengers and 40 fighters successfully attacked Shinchiku and Kiirun Harbor. On Okinawa, the 6th Reconnaissance Company captured Bise Saki with minimal resistance, while the 29th Marines faced significant opposition southeast of Manna near Mount Yae-Take, indicating where the main enemy forces were located. This prompted Shepherd to reposition the 3rd Battalion, 22nd Marines to Awa as his new divisional reserve. At the same time, Japanese guerrillas managed to retake Ishikawa, which they would hold for the following two days. Facing south, the 96th Division made another attempt to capture Kakazu but was once again thwarted by the determined defenders. By this time, approximately 5,750 Japanese soldiers were estimated to have been killed in the southern region, while the 24th Corps suffered losses of 451 men killed, 2,198 wounded, and 241 missing. In the afternoon of April 12, 1945, in Warm Springs, Georgia, while sitting for a portrait by Elizabeth Shoumatoff, President Franklin D. Roosevelt said: "I have a terrific headache." He then slumped forward in his chair, unconscious, and was carried into his bedroom. The president's attending cardiologist, Howard Bruenn, diagnosed a massive intracerebral hemorrhage. At 3:35 pm, Roosevelt died at the age of 63. His declining health had been kept secret from the public, leading to shock and sorrow worldwide upon the news of his death. Harry Truman, who was serving as vice president in 1945, succeeded FDR as president. Meanwhile, back in Okinawa, Fujioka initiated his counteroffensive after a heavy artillery bombardment, advancing his four battalions to secretly infiltrate the American lines. On the eastern front, the 22nd Regiment struggled to advance due to becoming disoriented in unfamiliar terrain.  The night attacks suffered from several unexpected problems. Heavy shelling had changed the landscape, blasting away villages and thickets, so that even though night infiltrators knew their maps and thought they knew the terrain, they lacked the landmarks needed to tell them where they actually were. Moreover, frequent illumination shells forced the eyes of night infiltrators to adjust so many times that their capacity to adjust was lost. They became temporarily blinded and so were unable to move. Because of the unfamiliar terrain and flash blindness, the Japanese night fighters had difficulty reaching their assigned objectives. In fact, it was hard for them to reach their jumping-off points. Continuous naval bombardment of crossroads and bridges forced units to rush across in small groups between shells so that the units became strung out on the roads and difficult to control. It was hard to move heavy ammunition and supplies forward because of these interdiction points and the generally churned up roads. Even when units reached their northward assembly points safely by night, they were immediately exposed to aerial observation and artillery fire at dawn, since they lacked enough time to dig in. Units that attacked across American lines safely in darkness had the same problem: they lacked time to dig in and so were utterly exposed to artillery fire at morning light. Night attacks, like flanking maneuvers, were a kind of cure-all in prewar Japanese doctrine. But they failed to provide the expeditious results on Okinawa that IJA doctrine had led the 32d Army Staff to expect. Consequently, Yoshida's four infiltration attempts, each involving about a squad, were effectively repelled by troops from the 32nd, 184th, and 382nd Regiments before midnight. The only significant attack came from around 45 Japanese soldiers against the positions held by Company G of the 184th, which quickly returned fire, forcing the enemy to retreat to their caves and trenches. In contrast, the assault on the 96th Division on the western front was intense, sustained, and well-coordinated. The forward units of Major-General Nakajima Tokutaro's 63rd Brigade launched their own local offensive to maintain pressure on the thin line held by the 382nd and 383rd Regiments, while elements from the 23rd, 272nd, and 273rd Independent Battalions infiltrated the American lines and moved into the Ginowan area. The majority of the 272nd Division launched an assault on American positions at Kakazu Ridge, enduring intense naval and artillery fire but ultimately being repelled by the determined defenders after several hours of combat. By morning, the bodies of 317 enemy soldiers were counted on the ridge, whereas the Americans suffered 50 casualties. Meanwhile, the 273rd Division attacked along the west coast against the recently arrived 2nd Battalion of the 106th Regiment, which decisively repelled the Japanese assault and nearly annihilated the independent battalion. Despite this, some units from the 23rd and 272nd Independent Battalions managed to penetrate approximately 1,000 yards behind American lines between Nishibaru and Kaniku but became isolated after dawn on April 13. Throughout the day, Bradley's troops worked to eliminate these infiltrators, many of whom detonated explosives when trapped. When these units retreated into Japanese lines later that night, only half of their original numbers had survived. Just before midnight, the reserve 9th Company of the 22nd Regiment launched an attack against the 184th Regiment following preparatory artillery fire, but this offensive was quickly disrupted by artillery, mortars, and machine-gun fire. On April 14, Nakajima's forces attempted two more assaults on Kakazu in the early hours, but these attempts were similarly thwarted by artillery and machine-gun fire. Given the failures of the offensives, Ushijima had no choice but to order a suspension of the attack, resulting in a shift to a defensive posture for the Japanese. Over the two days of combat, the 24th Corps reported killing 1,594 Japanese soldiers and capturing four, with losses of fewer than 100 American troops. In the northern region, an extensive air and naval bombardment of Iejima commenced while the Fleet Marine Force Amphibious Reconnaissance Battalion landed on Minna Island, securing it without encountering resistance to position artillery units for General Bruce's upcoming attack, which would involve the 305th and 306th Regiments. Meanwhile, in northern Okinawa, the 29th Marines continued to advance against enemy positions at Yae-Take through vigorous patrolling, preparing for a morning assault the next day. Concerned about the pace of progress, Shepherd relieved Colonel Bleasdale of command, replacing him with veteran Colonel William Whaling. However, Shepherd recognized that taking the 1,200-foot summit would require more than one regiment, so he ordered the 4th Marines to move from the east coast to Yofuke and then to the southwest corner of the Motobu Peninsula. Additionally, Colonel Shapley's 3rd Battalion was tasked with moving to Kawada, while the reinforced 2nd Battalion of the 22nd Marines rapidly advanced up the west coast to secure Hedo Misaki. On April 14, Shepherd initiated a coordinated assault on Yae-Take, with Whaling's 3rd Battalion and Shapley's 2nd Battalion advancing from the area around Toguchi against unexpectedly light resistance, while the rest of the 29th Marines moved out from Itomi to clear the Itomi-Toguchi Road. Although the eastern front faced strong opposition and required a change in strategy to advance southwesterly for better elevation advantage, rapid progress was made on the west, prompting Shapley to commit his reserve 1st Battalion to secure the exposed right flank. At the same time, Whaling's 3rd Battalion and Shapley's 2nd Battalion continued their advance against significantly strengthened enemy resistance, ultimately capturing another ridge located 1,000 yards ahead. Initial opposition consisted of small enemy groups. These hostile covering forces employed every available means to delay and disorganize the advance, and to mislead the attackers as to the location of the battle position. The Japanese would lie in concealment, with weapons zeroed in on a portion of a trail, allowing a considerable number of Marines to pass before opening up on a choice target. An entire platoon was permitted to pass a point on a trail without interference, but when the company commander reached that point with his headquarters section, a burst of machine-gun fire killed him and several others. Officer casualties were excessively high. In an area in which there had been no firing for over half an hour, Major Bernard W. Green, commanding the 1st Battalion, 4th Marines, was killed instantly by machine-gun fire. No one else was hurt, although Major Green was standing with his operations and intelligence officers on either side of him. Lieutenant Colonel Fred D. Beans, Regimental Executive Officer, assumed command of the battalion. "It was like fighting a phantom enemy." For while the hills and ravines were apparently swarming with Japanese, it was difficult to close with them. The small enemy groups, usually built around a heavy Hotchkiss machine gun augmented by Nambus, would frequently change positions in the dense vegetation. Hostile volleys elicited furious Marine fusillades into the area from whence the firing had come. But after laboriously working their way to the spot, the Marines came upon only an occasional bloodstain on the ground. Neither live nor dead Japanese were to be found. One Marine registered his impression of these tactics by blurting out, "Jeez, they've all got Nambus, but where are they?" Meanwhile, the 29th Marines advanced 800 yards up steep slopes despite facing fierce opposition; however, the 1st Battalion eventually found itself pinned down by intense Japanese gunfire. Additionally, Shapley's 3rd Battalion crossed the island via motor march to relieve the 3rd Battalion of the 22nd Marines in division reserve, which then returned to its patrol base at Majiya. To the south, Hodge recognized the need for a full-scale effort to penetrate the fortified Shuri area, so he scheduled a corps attack involving three divisions abreast for April 19. In preparation, he dedicated the following four days to organizing the assault, with the 27th Division taking over from the 96th Division in the western region of its zone, while smaller local attacks were conducted to enhance forward positions. Aware of the impending major attack, the Japanese used this preparatory period to bolster their defenses with additional supporting weapons. Back to the north, on April 15, most of the 29th Marines consolidated their defenses on high ground and exerted constant pressure on the rear of the Yae-Take position through vigorous patrols to the west and northwest. On the other hand, Whaling's 3rd Battalion advanced east and south approximately 900 yards amidst heavy machine-gun, mortar, and artillery fire before being halted by a strong enemy position on Hill 210. Additionally, the 4th Marines faced fierce resistance as Shapley's battalions finally secured Hill 200 and a critical hill mass just southwest of Yae-Take. Fully aware that his primary positions would soon be overrun, Colonel Udo decided to transition to guerrilla tactics by nightfall, relocating his command to the mountainous regions of northern Okinawa via Itomi. In light of these developments, the 1st Battalion, 22nd Marines was placed into division reserve at Awa to allow Shapley's 3rd Battalion to prepare for the following day's assault. On April 16, the offensive resumed, with Whaling's 3rd Battalion swiftly capturing Hill 210 in conjunction with Shapley's 2nd Battalion. Meanwhile, the rest of the 4th Marines secured a ridge just below Yae-Take by midday, while the 29th Marines applied continuous pressure on the rear of Udo's fortified stronghold. While the 4th Marines was storming the fortified position on Yae-Take, the 29th Marines maintained relentless pressure against its rear. The opposition which faced the 29th was similar to that on the front of the 4th. From log-revetted bunkers and occasional concrete emplacements the enemy resisted the advance with increasing stubbornness, supported by machine-guns, mortars, and artillery concealed in ravines and in caves on the high ground. Rugged terrain and an acute supply situation also contributed to the difficulties confronting the 29th Marines in accomplishing its task of clearing the high ground flanking the Itomi-Toguchi Road. The enemy displayed his usual ability to exploit the terrain and derived the maximum benefit from his weapons emplaced in caves and pits and concealed by natural cover. Particularly noteworthy was his use of 20mm dual-purpose cannon against personnel. Fire from these weapons on battalion CPs was a daily occurrence. All roads and natural avenues of approach were covered. Any attempt to move over the easier routes was met with bitter and effective resistance. Consequently, "the method of reducing the enemy positions followed a pattern of 'ridgehopping'," covered by the fires of all supporting weapons. This tactic enabled the attacker to envelop the hostile defenses and reduce them in detail. Numerous abandoned positions and weapons encountered by the 29th indicated that the determination of the Japanese to resist diminished considerably when they were taken from the flank. In contrast to a coordinated advance with all units in contact across a broad front, the action in the zone of the 29th Marines was characterized by attacks that, even when delivered simultaneously, constituted a series of local patrol actions to seize critical positions, followed by mopping up activity within the area. In the afternoon, Shapley's 1st and 3rd Battalions assaulted the formidable mountain, gradually making their way up the steep slope under light and scattered small-arms fire. However, as the Marines reached the peak, they encountered intense fire at close range, which quickly forced them to pull back. After a fierce and close engagement, the 1st Battalion ultimately regained control of Yae-Take, managing to hold the summit against strong Japanese counterattacks, aided by artillery support and Shapley's 2nd Battalion. Meanwhile, at dawn on April 16, two battleships, four cruisers, and seven destroyers under Rear-Admiral Bertram Rodgers launched a heavy bombardment on Iejima, while aircraft bombed and rocketed the island, dropping tanks of napalm on and behind the beaches. Approximately 2,000 Japanese troops, led by Major Igawa Masashi, had destroyed Iejima's airfields and strengthened the central eastern region of the island in an effort to entice the invaders to approach the vulnerable southeastern beaches. Their aim was to annihilate them with concentrated fire from numerous hidden positions in the Pinnacle and the town of Ie. However, the Americans saw through this strategy. Bruce's plan involved landing Lieutenant-Colonel Joseph Coolidge's 305th Regiment on the Red Beaches along the southern coast of Iejima and Colonel Aubrey Smith's 306th Regiment on the Green Beach at the island's southwest tip. The 305th was tasked with advancing eastward to capture additional landing areas, while the 306th was to move north and take control of the airfield. Both regiments would then focus on neutralizing enemy strongholds at the island's eastern end. Following intense air and naval bombardments, amphibious tanks and subsequent waves of amphibious tractors surged toward the landing beaches that morning, supported by rocket fire from LCI gunboats. At 07:58, the forward elements of the 1st Battalion, 305th Regiment successfully landed on the southern coast of Iejima, just south of the airfield, while the 3rd Battalion landed on a different beach, 600 yards to the left, three minutes later. At 08:07, the first waves of the 306th Regiment made landfall on Green Beach. The 305th moved swiftly inland over high dunes and then turned east toward Ie, while the 306th advanced 2,000 yards inland to the airfield's western edge, with the reserve 3rd Battalion securing the island's western end. By the afternoon, the troops advanced rapidly, seizing the airfield with only light resistance, achieving a total gain of about 5,500 yards by nightfall. Conversely, the 305th faced stiffer opposition on its way to Ie, managing to advance only about 800 yards eastward while defending against strong nighttime counterattacks. During the night of 16 April the enemy launched a coordinated attack on the 3d Battalion of the 305th. The attack came with suicidal recklessness. The Japanese were supported by mortars and 70-mm. guns, and were armed with small arms, sharpened stakes, bags of hand grenades, and literally hundreds of satchel charges, some of which had been improvised from mortar shells. Japanese worked up to the perimeters in small groups and either threw their satchel charges at close range or blew themselves up in an effort to take Americans with them. Some of the human bombs were successful, but most of the Japanese were killed before they came within effective range. One American had his arm broken by the flying leg of a Japanese soldier who had blown himself up. After hours of wild fighting in the dark the enemy withdrew, leaving 152 of his dead in and around the 3d Battalion's position.  While back at sea, Admiral Mitscher's Task Force 58 had effectively launched attacks on Amami Oshima, Tokunoshima, Kikaijima, and southern Kyushu over the past four days, the Japanese responded with a series of scattered kamikaze assaults that caused damage to the battleship New York and four destroyers. On April 16, Ugaki initiated his third large-scale Kikisui attack, acutely aware that another failure in the air could spell the doom of Operation Ten-Go. Despite Mitscher's preemptive strikes against Kyushu, where Americans claimed to have destroyed 202 aircraft and damaged 79 at the cost of only nine planes, at least 289 Japanese attackers were still able to launch missions against Spruance's 5th Fleet. Although American interceptors and anti-aircraft fire recorded another 217 kills, the surviving kamikaze pilots managed to sink the destroyer Pringle and inflict damage on the carrier Intrepid, the battleship Missouri, three destroyers, two destroyer minesweepers, and two landing craft. Notably, the destroyer Laffey withstood six kamikaze impacts, four bomb hits, and numerous strafing runs, resulting in 32 fatalities and 71 injuries among its crew. The following day, a smaller attack on April 17 resulted in additional damage to the light carrier Bataan and one destroyer, yet Americans claimed another 49 kills. However, Ugaki had exhausted much of his strength since the invasion began and was left with approximately 598 operational planes. Meanwhile, fighting continued in northern Okinawa, where some surviving troops from Udo advanced toward Nakaoshi to escape the Motobu Peninsula. Supported by heavy artillery barrages and battleship gunfire, the 29th Marines slowly progressed over challenging terrain, encountering only light resistance, as they successfully secured the mountainous area ahead and connected with the 4th Marines. Shapley's 1st and 3rd Battalions continued their push northward toward the Itomi-Toguchi Road, swiftly advancing downhill and completely overwhelming all Japanese defenses in the region. By nightfall, the 4th and 29th Marines had positioned themselves along the elevated terrain overlooking the Itomi-Toguchi Road. The 305th resumed its assault, aiming to capture the high ground behind Red Beaches 3 and 4. The 1st Battalion encountered only minimal resistance along the coast, allowing them to make significant progress, while the 3rd Battalion quickly secured the high ground in its area before being halted by intense machine-gun fire from caves in the coral slopes to the north. A maneuvering strategy followed by an infantry-tank assault eventually neutralized this enemy position, enabling the advance to continue steadily until the 3rd Battalion reached the outskirts of Ie. Due to the strong resistance faced, Bruce opted to deploy Colonel Stephen Hamilton's 307th Regiment on the beaches southwest of Ie. The 2nd and 3rd Battalions were subsequently landed there and launched an attack northeast, quickly advancing approximately 400 yards despite increasingly fierce resistance, ultimately being halted by heavy enemy fire from Bloody Ridge and Government House Hill. Meanwhile, the 306th Regiment maintained its defensive position while probing the enemy's fortifications around Iegusugu. The next day, the 306th began to pivot its right flank and launched an attack toward the Pinnacle with two battalions, making notable progress throughout the day. Concurrently, the 307th continued its advance into Ie despite facing heavy resistance, quickly reaching a standstill in front of Government House Hill. As a result, with the 2nd Battalion effectively immobilized, the decision was made to deploy the 3rd Battalion around to the right flank to launch an assault toward the northeast in the eastern part of the town, while the 3rd Battalion of the 305th Regiment advanced eastward toward Iegusugu. After a heavy preparation by the artillery on Minna Shima, the 3d Battalion, 305th, attacked at 1130 on an 800-yard front. A house-to-house fight ensued amid the rubble of Ie. "Every street became a phase line," one observer reported. The necessity of forming a connecting link over the wide area between the 306th and the 307th made the fight harder. Artillery was ineffective against many enemy positions and could not be used freely because other friendly units were so close by. Self-propelled guns were held up by mines and debris in the narrow streets. After working about halfway through the northwestern section of the town, the troops withdrew to a more secure position on the outskirts, their right (south) flank then being 500 yards west of Government House Hill, and their left (north) flank 100 yards west of the base of Iegusugu. They had made a net gain of only about 350 yards for the day. Similarly, Hamilton's 3rd Battalion achieved moderate success, advancing to a position 300 yards north of the village of Agarii-mae. To protect its right flank, the 1st Battalion of the 305th Regiment positioned itself alongside the 3rd Battalion of the 307th Regiment and launched a northern attack, gaining approximately 1000 yards by day's end before withdrawing to a position about 600 yards east of Agarii-mae. Medium tanks and self-propelled guns covered the gap that developed between the two battalions of the 307th. These weapons put direct fire into caves, pillboxes, and enemy gun positions in the town of Ie and the Pinnacle. They could not be moved close to the enemy positions, however; deadly machine-gun and mortar fire held the infantry back and left the armor vulnerable to suicide attacks by Japanese armed with satchel charges, who hid in holes until the tanks and guns came within range. Meanwhile, after four days of intense fighting, activities in the Motobu area on April 18 were limited to reorganization, consolidating the gains from the previous day, patrolling the Itomi-Toguchi Road, and resupplying. Looking south, Griner called for a nighttime preliminary attack to secure the Machinato Inlet and the Urasoe-Mura Escarpment. As the area was shrouded in smoke during the afternoon, Company G of the 106th Regiment swiftly crossed the inlet and successfully secured Machinato by nightfall, while bridges were constructed at the inlet. The 106th then moved across the bridges, stealthily advancing toward the Urasoe-Mura Escarpment without encountering opposition. Near the summit, the troops launched a surprise ambush against the defenders, ultimately forcing the Japanese to retreat in chaos. With the escarpment secured by dawn, the 106th was prepared to participate in the general attack to the south. I would like to take this time to remind you all that this podcast is only made possible through the efforts of Kings and Generals over at Youtube. Please go subscribe to Kings and Generals over at Youtube and to continue helping us produce this content please check out www.patreon.com/kingsandgenerals. If you are still hungry after that, give my personal channel a look over at The Pacific War Channel at Youtube, it would mean a lot to me. The first Okinawa counteroffensive, as part of Operation Ten-Ichi-Go was not achieving results. Despite overwhelming sacrifices of men and supplies, it seemed hopeless for the Japanese on Okinawa. Those like Colonel Yahara could see the paint on the wall, much to their growing depression.

In this episode of The Path to Freedom Podcast, I sit down with Boris Katsnelson, Managing Director at Black Iron Advisors, to uncover the real playbook for franchise success. Boris shares his unique experience from buying, scaling, and selling franchises for millions to advising franchisors and multi-unit franchisees on successful exits.    If you've ever considered franchising or want to understand how top-performing franchisees build wealth, this episode is packed with insider knowledge and strategies you won't want to miss.    **Boris Katsnelson is a registered representative of Independent Investment Bankers Corp.("IIB"), a FINRA member broker-dealer.  Investment banking services and securities are offered exclusively through IIB.  Boris also serves as Managing Director at Black Iron Advisers. Black Iron Advisers is not affiliated with Independent Investment Bankers Corp.**   What You'll Learn in This Episode:   ✅ How Boris went from investment banking to owning multiple franchise businesses ✅ The differences between emerging, mid-stage, and mature franchise brands  ✅ Why following the franchise system is the #1 key to success  ✅ How Boris acquired underperforming franchises and turned them around  ✅ The role of culture and leadership in franchise growth  ✅ What to consider when buying or selling a franchise  ✅ Insights into the franchise resale market and exit strategies    Timestamps:   ⏳ 00:00 - Welcome to the Path to Freedom Podcast  ⏳ 00:14 - Introducing Boris Katsnelson and his franchise background  ⏳ 03:34 - How Boris got into franchising and his first acquisition  ⏳ 10:48 - Buying an underperforming College Hunks franchise & turning it around  ⏳ 18:11 - The power of culture and leadership in franchising  ⏳ 22:53 - Investing in Primrose Schools & the difference in mature franchise models  ⏳ 32:39 - The importance of choosing the right type of franchise  ⏳ 40:05 - Breaking down emerging, mid-stage, and mature franchises  ⏳ 50:22 - How franchising accelerates wealth creation  ⏳ 58:56 - Key takeaways: Follow the system, know your goals, plan for an exit    Resources & Links:

El Dr. Imanol Martínez Salas, oncólogo clínico del Hospital Universitario Fundación Jiménez Díaz en Madrid, España presentó un análisis de los estudios más relevantes del año 2024 en cáncer de vejiga.SunRISe-1: estudio clínico fase IIb que evaluó la eficacia y seguridad de TAR-200 en combinación con cetrelimab, TAR-200 solo o cetrelimab solo en pacientes con cáncer de vejiga no músculo invasivo de alto riesgo que no responde al bacilo de Calmette-Guérin intravesical que no son elegibles o que eligieron no someterse a una cistectomía radical.NIAGARA: estudio fase III, aleatorizado, abierto, multicéntrico y global, en el cual se evaluó la eficacia y seguridad de durvalumab en combinación con gemcitabina + cisplatino para el tratamiento neoadyuvante seguido de durvalumab solo para el tratamiento adyuvante en pacientes con cáncer de vejiga músculo-invasivo.CheckMate-274: estudio fase III, aleatorizado, doble ciego y multicéntrico en donde se evaluó la eficacia y seguridad de nivolumab adyuvante vs. placebo en pacientes con carcinoma urotelial invasivo de alto riesgo.CheckMate-901: estudio fase III, abierto y aleatorizado de nivolumab combinado con ipilimumab o con quimioterapia estándar frente a quimioterapia estándar en pacientes con cáncer urotelial irresecable o metastásico no tratado previamente.EV-302: estudio fase III, abierto, aleatorizado y controlado de enfortumab vedotin en combinación con pembrolizumab frente a quimioterapia sola en cáncer urotelial localmente avanzado o metastásico no tratado previamente.JAVELIN Bladder 100: estudio fase III, multicéntrico, multinacional, aleatorizado, abierto y de grupos paralelos de avelumab más el mejor tratamiento de soporte vs. el mejor tratamiento de soporte solo como tratamiento de mantenimiento en pacientes con cáncer urotelial localmente avanzado o metastásico cuya enfermedad no progresó tras completar la quimioterapia de primera línea con platino. Fecha de grabación: noviembre de 2024.                     Todos los comentarios emitidos por los participantes son a título personal y no reflejan la opinión de ScienceLink u otros. Se deberá revisar las indicaciones aprobadas en el país para cada uno de los tratamientos y medicamentos comentados. Las opiniones vertidas en este programa son responsabilidad de los participantes o entrevistados, ScienceLink las ha incluido con fines educativos. Este material está dirigido a profesionales de la salud exclusivamente.

Der Bundestag hat das Jahressteuergesetz 2024 verabschiedet und dabei viele Änderungen gegenüber dem ursprünglichen Regierungsentwurf vorgenommen. In dieser Folge beleuchten wir die wesentlichen Neuerungen und ihre Auswirkungen. Ein Schwerpunkt liegt auf der neuen Wegzugsteuer für Kapitalanleger, die nun auch Investmentfonds wie ETFs umfasst und hohe Anforderungen an die Besteuerung stellt. Ist diese Regelung wirklich sinnvoll oder eher überschießend? Wir diskutieren außerdem die Abschaffung der Verlustverrechnungsbeschränkung bei Optionen. Der Wegfall dieser Beschränkung steht im Zusammenhang mit verfassungsrechtlichen Bedenken, wie der Bundesfinanzhof (BFH) im Beschluss vom 7. Juni 2024 (VIII B 113/23) feststellte. Personengesellschaften profitieren von der Anpassung des § 6 Abs. 5 EStG, die eine erleichterte Übertragung von Wirtschaftsgütern zwischen Schwestergesellschaften ermöglicht. Damit wird das Urteil des Bundesverfassungsgerichts (BVerfG) vom 28. November 2023 (BvL 8/13) umgesetzt. Dennoch gibt es verschärfte Regelungen, die eine Übergragung von Personengesellschaftsanteile auf Körperschaften betreffen. Weitere wichtige Themen sind die neuen Regelungen zu Kinderbetreuungskosten, Änderungen bei der gewerbesteuerlichen Grundbesitzkürzung und der erhöhte Erbfallkostenpauschbetrag. Auch die Anpassungen zur Nachweismöglichkeit eines niedrigeren gemeinen Werts eines Grundstücks im Zuge der Grundsteuerreform, wie sie der BFH in zwei AdV-Verfahren (II B 78/23, II B 79/23) entschied, und je der Pauschalbesteuerung von Mobilitätsbudgets werden besprochen. Zudem wird der Abzug von Unterhaltsaufwendungen künftig nur bei Banküberweisung anerkannt – andere Zahlungswege, die Mitnahme von Bargeld, sind damit nicht mehr zulässig.

El Dr. Ricardo Brugés, oncólogo clínico del Instituto Nacional de Cancerología y Centro Javeriano de Oncología en Bogotá, Colombia en conjunto con la Dra. Taysser Sowley, oncóloga médica del Instituto Oncológico Nacional de Panamá, nos presentan un resumen de los estudios que consideran más relevantes en el ámbito de cabeza y cuello expuestos durante el Congreso de ESMO 2024. GORTEC 2017-01 (REACH): estudio fase III, aleatorizado, análisis final de avelumab-cetuximab-radioterapia vs. estándares de atención en pacientes con carcinoma de células escamosas localmente avanzado de cabeza y cuello. LBA36: estudio en donde se abordó la comparación entre la terapia de deprivación androgénica y la quimioterapia en el tratamiento de cánceres de glándulas salivales, específicamente aquellos que son andrógeno-receptores positivos. MYTHOS: estudio fase II, multicéntrico, abierto de trastuzumab deruxtecan en pacientes con cáncer de glándulas salivales recurrente/metastásico HER2-positivo. FRAIL-IMMUNE: estudio fase II, de un solo brazo, multicéntrico, que investiga la eficacia y tolerancia de durvalumab combinado con paclitaxel/carboplatino en pacientes adultos con carcinoma de células escamosas de cabeza y cuello. POPPY: estudio fase II que evalúa la eficacia y el perfil de seguridad de pembrolizumab en pacientes con estado funcional 2 con carcinoma de células escamosas de cabeza y cuello recurrente/metastásico. TACTI-003: estudio fase IIb, aleatorizado que comparó eftilagimod alfa más pembrolizumab vs. pembrolizumab solo en carcinoma de células escamosas de cabeza y cuello recurrente o metastásico de primera línea con CPS ≥1. Fecha de grabación: 11 de octubre de 2024.                        Todos los comentarios emitidos por los participantes son a título personal y no reflejan la opinión de ScienceLink u otros. Se deberá revisar las indicaciones aprobadas en el país para cada uno de los tratamientos y medicamentos comentados. Las opiniones vertidas en este programa son responsabilidad de los participantes o entrevistados, ScienceLink las ha incluido con fines educativos. Este material está dirigido a profesionales de la salud exclusivamente.

Entrevista al gran Francisco Villatoro (Francis. Naukas-La Ciencia de la Mula Francis) Dr. en Matemáticas, Licenciado en Física, ingeniero informático y profesor en la Universidad de Málaga. Estas son las preguntas. ¿Qué es la teoría de cuerdas? Un nuevo paradigma para hacer física, como la física de Newton, la física cuántica o la física relativista. La física de Newton (F=m a) no predice la fuerza entre dos electrones (que viene determinada por los experimentos) ni la fuerza de la gravedad entre dos planetas (que Newton dedujo a partir de las leyes de Kepler). La teoría de cuerdas es un nuevo paradigma que predice todos los universos posibles. Entre ellos está nuestro universo, pero no tenemos ninguna razón por la cual haya sido seleccionado. Según la teoría de cuerdas todo está hecho de cuerdas. ¿Qué son las cuerdas de la teoría de cuerdas? En la teoría de cuerdas todas las partículas como vibraciones de pequeñas cuerdas. Los átomos de John Dalton en el siglo XIX no son los átomos de Demócrito, pues no son elementales, están compuestos de partículas. Las cuerdas de la teoría de cuerdas son los átomos de Demócrito. Diminutas cuerdas con un tamaño en la escala de Planck, 10^-35 metros, unas 10 sixtillonéximas de metro. Tan pequeño que si dilatáramos una de esas cuerdas hasta llegar al tamaño de un átomo de hidrógeno, un ser humano sería tan grande como una galaxia espiral del tamaño de la Vía Láctea. Esta teoría pretende unificar toda la física, tanto la teoría cuántica de partículas como la teoría clásica de la gravedad. Las cuatro fuerzas fundamentales de la física: la gravedad, la electromagnética, la nuclear fuerte, que mantiene a los protones y neutrones unidos en los átomos, y la nuclear débil, responsable de la radiactividad natural, serían unificadas por esta teoría. La teoría de cuerdas predice que el espaciotiempo tiene más de cuatro (3+1) dimensiones. ¿Cuántas dimensiones tiene el espaciotiempo? La teoría de cuerdas es el candidato más firme en la actualidad a describir la gravedad como una teoría cuántica, ya que uno de los modos de vibración de las cuerdas describe los gravitones, las partículas cuánticas de la gravedad. Construir una teoría cuántica de la gravedad es uno de los problemas más difíciles en la historia de la física teórica. La teoría de cuerdas resuelve este y algunos otros problemas, aunque el precio a pagar es la aparición de muchísimos otros todavía no resueltos.?? El espaciotiempo no es un concepto fundamental en teoría de cuerdas, emerge de la interacción fuerte entre muchos gravitones. Hay varias versiones de la teoría en las que el espaciotiempo emerge con un número diferente de dimensiones. Hay cinco teorías en 10D y la llamada teoría M en 11D. Todas estas teorías son equivalentes entre sí y describen la misma física pero desde diferentes puntos de vista. Las dimensiones extra del espacio tiempo 4+6 (o 4+7) están muy curvadas (compactificadas) y no las podemos observar. ¿Cómo describe la teoría de cuerdas todas las partículas fundamentales conocidas? Todas partículas elementales y sus interacciones son descritos por el modelo estándar de partículas. La estructura matemática del modelo es muy sofisticada: describe partículas que distinguen izquierda de derecha, partículas con propiedades estadísticas muy diferentes (fermiones y bosones), además contiene muchísimos elementos de teoría de grupos, integrales en espacios de dimensión infinita, y un largo etcétera.? Durante el desarrollo inicial de la teoría de cuerdas (1968-1984) quedó claro que las únicas formulaciones de la teoría que pueden describir la complejidad del modelo estándar, son las que tienen lugar si se da un nuevo tipo de simetría espaciotemporal conocida como supersimetría. La supersimetría relaciona las partículas fermión con las bosón. Cada partícula en la naturaleza es un bosón o un fermión; los quarks, electrones y neutrinos son fermiones, y los fotones y la partícula de Higgs bosones. Una de las implicaciones físicas de la supersimetría es que dobla el número de partículas conocidas, es decir, por cada fermión (respectivamente bosón) habría un bosón (fermión) que todavía no se ha detectado.?? Las cuerdas con supersimetría se suelen llamar supercuerdas y se conocen cinco teorías de supercuerdas en 10D equivalentes entre sí: la tipo I, la IIA, la IIB, la heterótica HO y la heterótica HE. Además son equivalentes a una teoría de la gravedad supersimétrica en 11D. ¿Se puede probar experimentalmente la teoría de cuerdas? No es fácil. La física cuántica de la gravedad se observa a energías que no podemos explorar en los experimentos y la física cuánticas de las partículas que podemos estudiar en los colisionadores corresponde al vacío de la teoría de cuerdas. Con la tecnología actual no podemos saber si las partículas son realmente cuerdas o no lo son. En los experimentos todas las partículas elementales parecen puntuales. Todas las predicciones de la teoría de cuerdas se pueden estudiar sin la teoría de cuerdas. Por ejemplo, si se descubre la supersimetría (que fue inventada gracias a la teoría de cuerdas) no se demuestra la teoría de cuerdas ya que se pueden construir teorías supersimétricas sin teoría de cuerdas. Observamos 4 dimensiones, ¿cómo se enrollan las dimensiones extra del espaciotiempo para que no las veamos? El universo que observamos tiene tres dimensiones de espacio y una de tiempo; la única forma de que hubiera seis dimensiones extra es que éstas estuvieran "enrolladas" a escalas microscópicas. De la misma forma que un cable fino, el cual puede parecer una línea unidimensional, es una superficie bidimensional con la dimensión que describe su grosor "enrollada", la física que observamos dependería de las formas geométricas que contienen las seis dimensiones enrolladas (o compactificadas). Las matemáticas que describen la compactificación son muy elegantes. Matemáticos reconocidos mundialmente por sus contribuciones en matemáticas fundamentales, hoy trabajan en problemas de teoría de cuerdas. Y viceversa, estructuras matemáticas encontradas por teóricos de cuerdas han despertado tanto interés en el mundo de las matemáticas que han aparecido nuevas áreas de investigación entorno a ellas.? ¿Además de las cuerdas hay otros objetos en la teoría de cuerdas? Hay muchos otros objetos. Los más importantes son las branas y sus cargas, las cuerdas-instantón, los instantones, los fibrados estables, etc. son conceptos asociados a la geometría que describe las dimensiones compactificadas. ¿La teoría de cuerdas apoya la idea del multiverso? Nuestro universo está descrito por un vacío de la teoría de cuerdas, pero hay infinidad de vacíos. La teoría de cuerdas describe todos los universos posibles. Algunos teóricos de cuerdas proponen que todas esas configuraciones existen objetivamente en lo que llaman el multiverso. Combinado con el principio antrópico, dicho grupo de teóricos dice explicar porqué la constante cosmológica observada es tan pequeña. Simplificando, su argumento dice: "casi todas las configuraciones del multiverso corresponden a universos en el que la vida no es posible; obviamente nosotros vivimos en un universo de ese multiverso en el que la vida sí es posible; un análisis estadístico en el multiverso implica que lo más probable es que un universo donde la vida sea posible tenga una constante cosmológica pequeña y positiva" La principal crítica que está recibiendo la teoría de cuerdas es que es incapaz de predecir nada. ¿Sirve para algo una teoría que no predice nada? Se ha llegado a decir que no es una teoría falsable. Como predice todos los universos posibles no podemos comprobar la teoría con nuestro único universo. Lo cierto es que la teoría todavía no está entendida correctamente y que es precipitado sacar conclusiones. Faltan muchos problemas por resolver. Por ejemplo, hay evidencia de que las diversas teorías de cuerdas son límites diferentes de una teoría más profunda conocida como teoría M (donde M se refiere a Matriz, Misterio, Madre. . .). Sin embargo, formular en qué consiste exactamente esta teoría M se está convirtiendo en uno de esos proyectos a largo plazo donde no está claro que el "a largo plazo" no sea lo mismo que ilimitado. ¿La teoría de cuerdas es una teoría de todo? La formulación más completa de la teoría de cuerdas, llamada teoría M, aspira a ser una una teoría final o una teoría de todo que pueda ser formulada utilizando un número finito de principios físicos. Entender la teoría de cuerdas y la teoría M es un proyecto monumental para la comunidad de físicos teóricos y en cualquier momento puede haber sorpresas. También puede haber sorpresas desde la física de partículas (en el LHC) o en la cosmología observacional. ¿Cómo nació la teoría de cuerdas? ¿Cuál es su historia? Durante la década de los 1960 era un intento de explicar la fuerza nuclear fuerte entre el zoo de partículas (hadrones) que se descubrieron en los experimentos. El gran motor fue una fórmula matemática del joven físico italiano, Gabriele Veneziano. Pronto se descubrió que describía cuerdas vibrantes. Leonard Susskind veía las cuerdas con quarks en sus extremos para describir los mesones. Pero los bariones fue más difícil. Pero el modelo estándar eclipsó a la teoría de cuerdas en 1973. La primera revolución en 1984 y la segunda revolución en 1995 nos llevan a la situación actual. ¿Cómo explica la teoría de cuerdas el big bang? Hay muchas variantes, pero algunos defensores de la teoría de cuerdas han sugerido que el big bang no fue el inicio de todo. Si vivimos en una brana (D3) dentro de un espacio 11D donde hay más branas podemos imaginar que dos de estas membranas choquen entre si. Según esta idea, en algún momento anterior al Big Bang dos branas que albergaban universos paralelos se precipitaron la una contra la otra hasta que chocaron (Inflación brana-antibrana, D3-D3bar). Toda esa energía tenía que ir a alguna parte. Así desencadenó el Big Bang, creando la expansión que conocemos y calienta todas las partículas del universo formando una enorme masa ardiente. También hay varios posibles modelos de inflación en teoría de cuerdas: La tensión de un par brana-antibrana actúa como una energía de vacío que produce una fase de expansión acelerada. El inflatón es un campo que mide la distancia entre la brana y la antibrana. Inflación termina con la aniquilación del par, la energía se libera a partículas y radiación, en expansión desacelerada. ¿Cómo explica la teoría de cuerdas los agujeros negros? A bajas energías la dinámica del gravitón de teoría de cuerdas reproduce la Relatividad General. Existen soluciones de tipo agujero negro en teoría de cuerdas, pero involucran estos campos adicionales (compañeros supersimétricos del gravitón => gravitinos, dilatón, dilatinos, ...). La entropía de los agujeros negros de Bekenstein-Hawking se ha explicado gracias a las Dp-branas. Son objetos extensos, con p dimensiones espaciales y que se propagan en el tiempo. En acoplamiento débil se describe como hiperplanos en los que se localizan los extremos de las cuerdas abiertas. Se pueden apilar o superponer N Dp-branas y se forma un horizonte de sucesos como un agujero negro, las llamadas D-branas negras. La descripción con D-branas permite entender los microestados del agujero negro para acoplamiento fuerte. Los microestados del agujero negro corresponden a los microestados de la sopa de cuerdas abiertas entre las Dbranas que forman el agujero negro ¿Tiene otras aplicaciones la teoría de cuerdas? Gracias a la conjetura o correspondencia AdS/CFT de Maldacena. La información de los microestados cuánticos del agujero negro está almacenada sólo en el horizonte. Analogía con un holograma, imagen 2d que almacena info 3d. La información de un sistema con gravedad en D dimensiones se codifica en una teoría sin gravedad en su frontera de (D-1) dimensiones. Teoría SIN gravedad en 4D Teoría CON gravedad en 5D. AdS/CFT es una correspondencia holográfica. Teoría gauge SU(N) en 4d Teoría de cuerdas en AdS5 x S5. Deberían ser equivalentes... y son mucho más tratables que los sistemas originales. Tiene aplicaciones en física de la materia condensada, plasma quarks y gluones, turbulencia, ... etc.

In his weekly clinical update, Dr. Griffin discusses global transmission of mpox, the different clades of the virus and associated pathogenesis, vaccination vs antiviral therapy against mpox and the US's aid response for controlling the African outbreak before reviewing the recent statistics on SARS-CoV-2 infection, authorization and approval of updated COVID vaccines, the economic benefit of an annual COVID vaccine and if the first updated vaccines against XBB.1.5 were effective, where to find PEMGARDA, breakthrough infections when administering PEMGARDA, when to use convalescent plasma, what do when healthcare workers succumb to SARS-CoV-2 infection, and how long COVID differs in children and adolescents. Subscribe (free): Apple Podcasts, Google Podcasts, RSS, email Become a patron of TWiV! Links for this episode mpox epidemic caused by monkeypox clade I in affected African countries (European Centre for Disease Prevention and Control) mpox in Pakistan (Reuters) mpox imported into Pakistan (UNMC Global Center for Health Security) mpox domesticated in Taiwan (Focus Taiwan: CAN English News) clade IIb not Ib in Taiwan (bne Intellinews) WHO: mpox public health emergency of global care (NY Times) Vaccines didn't turn back mpox…..people did (NY Times) Deadlier mpox version in Thailand (NY Times) Antiviral tecovirimat….not so much (NIH News) What about vaccines? (Bavarian Nordic) Invest or not to invest Barvaian Nordic pox vaccine manufacturer? (Yahoo! Finance) US to support Africa's mpox response (CIDRAP) $35M to support mpox outbreak response in central and eastern Africa (USAID From the AMERICAN PEOPLE) COVID-19 deaths (CDC) COVID-19 national and regional trends (CDC) COVID-19 variant tracker (CDC) FDA approves and authorizes updated mRNA COVID-19 vaccines (FDA) Novavax still working on updated COVID-19 vaccine (novavax) COVID-19 variant update (CDC & IDSA) Economic benefit of annual COVID-19 vaccination (JID) Early COVID-19 XBB.1.5 vaccine effectiveness (Influenza and other respiratory viruses) Uptake of COVID-19 vaccines and associated hospitalization due to COVID-19 in pregnancy (Vaccine) Novavax heterologous booster demonstrates lower reactogenicity (JID) Where to get pemgarda (Pemgarda) EUA for the pre-exposure prophylaxis of COVID-19 (INVIYD) Breakthrough from pemivibart/permgarda (bioRxiv) CDC Quarantine guidelines (CDC) Early phase of SARs-CoV-2 infection (COVID.gov) NIH COVID-19 treatment guidelines (NIH) Infectious Disease Society guidelines for treatment and management (ID Society) Drug interaction checker (University of Liverpool) Molnupiravir safety and efficacy (JMV) Convalescent plasma recommendation for immunocompromised (ID Society) What to do when sick with a respiratory virus (CDC) When your healthcare provider is infected/exposed with SARS-CoV-2 (CDC) Managing healthcare staffing shortages (CDC) Steroids,dexamethasone at the right time (OFID) Anticoagulation guidelines (hematology.org) Long COVID differs in children and adolescents (JAMA Network) Letters read on TWiV 1142 Dr. Griffin's COVID treatment summary (pdf) Timestamps by Jolene. Thanks! Intro music is by Ronald Jenkees Send your questions for Dr. Griffin to daniel@microbe.tv

In this episode, we are joined by Tobi Sample, a melanoma survivor, to share an extraordinary and inspiring story. Today, prepare to be moved and inspired as we delve into Tobi's miraculous journey of survival against melanoma. Tobi, ten years ago, faced a diagnosis that would have halted many in their tracks. But not Tobi. To celebrate her 10th anniversary of No Evidence of Disease, she did something most of us only dream of - she climbed Mount Kilimanjaro. ABOUT OUR GUEST Tobi Sample, Melanoma Survivor Tobi Sample was first diagnosed with stage IIb melanoma in 2008. When the cancer returned in 2013, spreading to her spine, humerus, clavicle, sacrum, rib, and lung, she faced a daunting battle. That summer, she found herself too weak to even get out of bed. In a stroke of fortune, her husband discovered a promising clinical trial at UC Chapel, and Tobi was accepted. Over the next year, she bravely traveled from southern Indiana to North Carolina every three weeks. Remarkably, she has been in remission for nearly a decade, showing no evidence of the disease. A lifelong athlete, Sample was resolute in her desire to reclaim her active lifestyle. Gradually, she regained her strength, participating in half-marathons and even training for a 2022 hike up Mount Kilimanjaro. In 2019, Tobi reached out to AIM at Melanoma, driven to initiate a walk in the Louisville area to spread awareness and raise funds for research. She believes firmly, “Until there's a cure, there's more that needs to be done.” Tobi feels immensely grateful for the chance to watch her children mature into adults, now 26 and 23, cherishing the life she fought so hard to protect. --- Support this podcast: https://podcasters.spotify.com/pod/show/aimatmelanoma/support

Doug Wortel is the producer Random Acts Of Comics. He produces several other podcasts as well, but honestly who cares? He is a musician and composer whose work has appeared on the radio, stage, Internet, Television and even university lecture halls but the latter is a long story. His interests include -but are not limited to- comic books, novels, music, film, and brutally humiliating anyone who remotely has a hint of comicsgate/4Chan culture in them.    This episode includes an excerpt of the 1963 alternate version of "Haitian Fight Song" entitled, II B.S by Charles Mingus.  

Welcome to Episode 139 Sponsored by CultTVMan, Sean's Custom Model Tools and Return To Kit FormHostsStuartGeoffFrankDedicated to James from JMC, get better soon.Thanks to our latest Patreon and Buy Me a Coffee Supporters:Check out our What We Like page for lists of what we like. ***************************************LATEST NEWSFrank went to AMPS and got concussed. ***************************************MAILBAGWe want to hear from you! Let us know if you have any comments or suggestions scalemodelpodcast@gmail.com.***************************************LATEST HOBBY ANNOUNCEMENTSTrumpeter June announcementsTamiya Upcoming releasesJagdpanzer 38(t) Hetzer Prague May 1945 in 1/35th scale from Snowman ModelMiniArt's 35th scale M3 Stuart "Early Production" with a full interiorSd.Kfz. 234/2 "Puma" full interior kit from MiniArt 1/35th scaleA new 16th scale Sherman from I love KitAustralian Army M113A1 LRV 1/35Special Hobby is working on a Baltimore Bomber in 1/48FlyHawk 1/350 USS Cowpens CG-63 coming in July1/350 PLAN Type054B Frigate from Magic Factory.Hurricane Mk.IIb trop from Arma in 1/48Hasegawa - 1/72 Queadluun-Rau Max use (Movie Version)What's new at Scalemates.com ***************************************SPONSOR AD #1Cult TV Man***************************************WHAT'S ON THE BENCHStuart - Work continues on the CF-15 what if. Hasegawa does the engine nozzles as five separate parts each. I have lost one to the floor monster so I will be looking for either 3d print or after-market replacements.Geoff - continuing on getting the Martin Mars and the NASA shuttle carrier aircraft and shuttle in 1/144 ready for paint. Ordered decals for the 747 from Drawdecal and the shuttle from Lake County Spaceport.Terry - Some progress on my open projects, I'll get the landing gear on the P-47 and do some minor weathering before dullcoating, then I'll probably mostly use pastels for further weathering. I just want the Regult off my bench. I need to get the decals on that.Frank - Mirror Models Komsomolets T-20 Tractor - started this last week and the interior tub was painted tonight - engine, etc. I made some cloth-looking seat pads as per reference images. Also painted a 1/72 ICM BM-24-12 kit, I picked up 4 at AMPS, got a new Grad but got 3 from the mid-90s. It looks okay…the rocket bed is rough and i'd recommend scratch if you want it to sing[foogallery id="3690"]***************************************WHAT WE ARE READINGStuart - Clear Thinking: Turning Ordinary Moments into Extraordinary Results by Shane ParrishSlow Productivity: The Lost Art of Accomplishment Without Burnout by Cal NewportGeoff - “The Better Angels of Our Nature” by Steven Pinker. Good, factual survey of history establishes that despite what some people seem to think, violence in the West is at a historic low point.Also “Spies in the Sky” by Taylor Downing - a history of aerial intelligence in WW2.Terry - Finished Madeleine Murray's Song of Achilles. It's brilliant. She really brings the Greek characters to life, all these legendary names. I started to wonder how she would finish the story, since the narrator Patroclus must die before Achilles. The end will bring you to tears. What next? The 18th volume of That Time I got Reincarnated as a Slime, so that's a background read. I have some nonfiction to choose from.Frank - Reading Book 2 of the Theodore Roosevelt bio by Edmund Morris - Theodore Rex and picked up Israel - A History by Martin Gilbert***************************************SPONSOR AD #2Seans Custom Model Tools***************************************THINGS WE'VE SEENBuild Guide Pt II: URAL-4320.JPL reestablishes contact with Voyager! The RTGs will die in a few years, but the sturdy probe is again sending data.There's a FB group called Historical Space Models, I have a number of friends in there - have a look. (I can't figure out how to grab a link via the iPad)***************************************THE LAST WORDSMP Ep. 139 is also sponsored by Return To Kit Form (R2KF). Check out their web store!For more modelling podcast goodness, check out other modelling podcasts at modelpodcasts.comPlease leave us a positive review if you enjoy what we're doing!Check us out: FaceBook, YouTube, and our very own websiteWe also have merchandise now. Check it out on Redbubble 

In this solo ep, Tim talks through the history – and indeed, the controversy – of Rhapsody in Blue by George Gershwin. It's one of the most iconic pieces of American music ever composed. But its origin story is a little complicated. Leave it to Timmy to sort it all out!SONGS PLAYED:George Gershwin - Rhapsody in BlueEddie Cantor - If You Knew Susie (Like I Know Susie!)Willie "The Lion" Smith - Keep Your TemperW.C. Handy - St. Louis BluesPaul Simon - Crazy Love, Vol. IIBéla Fleck - Rhapsody in Blue(grass)FURTHER READING:Arranging Gershwin: Rhapsody in Blue and the Creation of an American Icon by Ryan Bañagale‘We must face harms done”: Béla Fleck's defense of George Gershwin's ‘Rhapsody in Blue'DISCLAIMER:Under section 107 of the Copyright Act 1976, allowance is made for “fair use” of copyrighted material in a manner that constitutes quotation, criticism, review, parody, caricature, pastiche, and other legal copyright exceptions. Fair use is a use permitted by copyright statute that might otherwise by infringing.

CME credits: 0.25 Valid until: 29-03-2025 Claim your CME credit at https://reachmd.com/programs/cme/applying-sdm-to-personalize-treatment-discussions-on-recurrence-risk-reduction-in-patients-with-early-stage-melanoma/18105/ This Patient Clinician Connection CME activity, led by Dr. Meghan Mooradian, focuses on the use of adjuvant immunotherapy in early-stage melanoma. The activity aims to educate clinicians on the role of immunotherapy in reducing the risk of disease recurrence post-surgery, particularly in patients with resected stage IIB to III melanoma. Through patient clinical vignettes and audience education vignettes, participants will gain insights into patient-centered approaches, shared decision-making, and the management of immune-related adverse events associated with adjuvant immunotherapy, ultimately enhancing their ability to optimize treatment outcomes and patient care in this setting.=

The city of Indianapolis has been selected to once again host the NFL Combine in 2025. Mickey Shuey from our partners at the IBJ first reported the news that the city beat out other locations such as Dallas and Los Angeles to continue its more than three-decade tradition of hosting the NFL's annual scouting event. IIB's Alex Brown spoke with Visit Indy Senior Vice President Chris Gahl to get his reaction to the news.

The Frontier Psychiatrists started as a room in Clubhouse, and one of the people who made that awesome was Jeremy Fox, P.C. He joins me today for this video podcast to chat about the groundbreaking phase IIb data released by Mind Med today:MM-120 100 µg – the dose achieving the highest level of clinical activity – demonstrated a 7.6-point reduction compared to placebo at Week 4 (-21.3 MM-120 vs. -13.7 placebo; p

இரத்தினவானி  சமுதாய பண்பலை 90.8CR | "வெற்றி சிகரம்" மகாகவி பாரதியின் பிறந்தநாளை முன்னிட்டு சிறப்பு கவியரங்கம் "பார் போற்றும் பாரதி" கவியரங்கம் தலைமை : முனைவர் ந . பரமேஸ்வரி தமிழ் துறை தலைவர். இரத்தினம் கலை மற்றும் அறிவியல் கல்லூரி, கவிஞர்கள்: *மருத்துவர் க. தேவி *கவிச்சுடர் மதிவதனி *கவிஞர் புவனா பிரகாஷ் *கவிஞர் இர.உஷா நந்தினி சதீஷ்குமார் *கவிஞர் செல்வி கு. நந்தினி உதவிப் பேராசிரியர் எஸ்.என்.எம்.வி கலை மற்றும் அறிவியல் கல்லூரி, கோயம்புத்தூர் *கவிஞர் அ. அன்சியா II B.A.ஆங்கில இலக்கியம் எஸ்.என்.எம்.வி கலை மற்றும் அறிவியல் கல்லூரி, கோயம்புத்தூர். இரத்தினம் கலை மற்றும் அறிவியல் கல்லூரி தமிழ்த் துறை உதவி பேராசிரியர்கள் *சி.குமுதா *ஆ.சௌமியா *த.உதயா *சை .பல்கீஸ் அன்பியா *த.லட்சுமி நிகழ்ச்சி ஆக்க்கம் முனைவர் ஜெ மகேந்திரன், நிலை இயக்குனர் இரத்தினவாணி சமுதாய வானொலி 90.8 டிசம்பர் 11, 09Am -10Am & 09Pm -10Pm  | நிகழ்ச்சித்தொகுப்பு முனைவர் ஜெ மகேந்திரன், நிலைய இயக்குனர் இரத்தினவானி  சமுதாய வானொலி 90.8 #இரத்தினவானிசமுதாயபண்பலை #இரத்தினவானிFM   #ஜெமகேந்திரன் #Rjமகேந்திரன் #RjMahendran #RathinavaniFm

Welcome to Episode 130 Sponsored by CultTVMan, Sean's Custom Model Tools and Return To Kit FormHostsStuartGeoffTerrySpecial Guest - George SeletasThanks to our latest Patreon and Buy Me a Coffee Supporters:***************************************LATEST NEWSWelcome Show in GuelphModelFiesta 42, hosted by IPMS Alamo Squadron (San Antonio), will be held on February 10, 2024 at the New Braunfels Civic/Convention Center in New Braunfels, Texas. This year's theme is "Under the Union Jack - All Things British." Pre-registration for the contest is open now, and all the show details are available at modelfiesta.comChris Meddings new bookIPMS Vancouver fall showHorizon Models Contest ResultAK Discontinuing some AK Real Color in preparation for a relaunch ***************************************MAILBAGWe want to hear from you! Let us know if you have any comments or suggestions scalemodelpodcast@gmail.com. Chris Meddings A20The weights are two moulded pieces sandwiched between the nose gear bay and the hull sides***************************************LATEST HOBBY ANNOUNCEMENTSArma Hobby's new "Hurribomber" Mk.IIb 1/48Border Models 1/35 German main battle Tank Leopard 2 A7I Love Kits December Infini model one-touch fully movable tracksAirfix Gloster Meteor F.8 New EditionAirfix 1:48 scale Fairey Gannet AS.1/AS.4Lanmo ShermFairey Gannet Released | AeroScalean Deep Wading Kit1/48 - de Havilland Canada DHC-4 (C-7) Caribou multimedia kit by OzMods - What's new at Scalemates.com***************************************SPONSOR AD #1Cult TV Man***************************************InterviewInterview with George SeletasTelford TripWonderfestCurrent IPMS USA woes and judging systems. ***************************************SPONSOR AD #2Seans Custom Model Tools***************************************WHAT'S ON THE BENCH Stuart - Slow and steady on the Moosaroo Cup. The cab and back bed have been attached to the body. Wheels on later this week. I have some HO-scale sheep I want to add to the diorama. Primed with white, working on dry brushing next.[foogallery id="3512"]Geoff - struggling with rigging the 1/72 Airfix Handley Page 0/400 and got back to a shelf queen - a 1/72 Airfix Albatross DV in Richthofen livery. Also started playing with armour weathering on a Russian tank donated by Frank Donati of our London Club. Next though will be a Christmas project to build “something cool” for a grandson. Thinking about the SR75 Penetrator but in bright colours![foogallery id="3508"]Terry - Got a good coat of NATO black on the Lamda carrier decks, and glosscoat over that. I'm debating whether I need to buff that or just paint markings. It depends on how many decals I will use vs. painting. Also working on this year's Christmas Birds. About 90% done with them. ***************************************WHAT WE ARE READINGStuart - Coming of Age in the Milky Way by Timothy Ferris. Just starting the 19th century. It's fascinating how some discoveries of things were done independently but also some would not have happened without the work done by previous generations.Geoff - SAS Bravo Three Zero by Des Powell and Damien Lewis. Just started, but I already feel terribly inadequate when measured against the SAS!Terry - Still reading Ed Yong's An Immense World. Through hearing, elecrosensory and now into magnetic sense. It's amazing how many senses are modifications of other nerve and chemosensory mechanisms.  ***************************************THINGS WE'VE SEENhttps://www.cozmicscalemodels.com/shopJames Burkes Connections***************************************THE LAST WORDSMP Ep. 130 is also sponsored by Return To Kit Form (R2KF). Check out their web store!For more modelling podcast goodness, check out other modelling podcasts at modelpodcasts.comPlease leave us a positive review if you enjoy what we're doing!Check us out: FaceBook, YouTube, and our very own websiteWe also have merchandise now. Check it out on Redbubble 

Check out our free downloads at nascentmc.com: Implementing AMA Style – 8 Things to Get Right in Your Next Project Needs Assessments – 7 Essentials for Getting Funded Working With Your Medical Writer – 8 Ways to Get the Most out of Them See the full write ups for today's episode at nascentmc.com/podcast  Here are the highlights: BIMZELX (bimekizumab) for Moderate-to-Severe Plaque Psoriasis: The FDA approved BIMZELX for treating moderate-to-severe plaque psoriasis, making it the first psoriasis treatment targeting interleukin 17A and interleukin 17F. The approval follows data from Phase 3 trials and comes after a prior delay due to COVID-related travel restrictions. Neoadjuvant Pembrolizumab for NSCLC: The FDA approved pembrolizumab for neoadjuvant and post-surgical adjuvant treatment in patients with resectable non-small cell lung cancer, adding to its indications in multiple tumor types. The approval was based on the phase 3 KEYNOTE-671 trial data. Adjuvant Nivolumab for Stage IIB/C Melanoma: The FDA granted approval to nivolumab for adjuvant treatment of melanoma in patients aged 12 and older with resected stage IIB or IIC disease, addressing the need to reduce the risk of recurrence. This is supported by the CheckMate76K trial data. Zilucoplan for Myasthenia Gravis: UCB Pharma's zilucoplan, a complement C5 inhibitor, received FDA approval for treating myasthenia gravis (MG), demonstrating rapid improvements in MG-specific efficacy outcomes based on the phase 3 RAISE study. IDP-126 (Cabtreo) First Triple-Combination Drug for Acne: Cabtreo, a triple combination topical gel for acne, received FDA approval as the first fixed-dosed, triple-combination treatment for patients aged 12 and older with acne vulgaris. Penbraya Meningococcal Vaccine in Adolescents: The FDA approved Penbraya, a vaccine covering the five most common serogroups causing meningococcal disease in adolescents, based on Phase 2 and Phase 3 trial data. It's administered as a two-dose series. Voxzogo in Dwarfism: Vosoritide (Voxzogo) was expanded for use in children under 5 with achondroplasia, the most common form of short-limbed dwarfism, after demonstrating safety and efficacy in this age group. QLOSI for blurry age-related near vision: The FDA approved QLOSI, a preservative-free eye solution, for the treatment of presbyopia, improving near visual acuity by pupil modulation and increasing depth of field. Maxigesic IV for Post-Op Pain: Maxigesic IV, a combination of paracetamol and ibuprofen, gained FDA approval for post-operative pain management, offering faster pain relief and reduced opioid usage. Xphozah for Chronic Kidney Disease: Tenapanor (Xphozah) was approved as an add-on therapy for patients with chronic kidney disease who can't tolerate or respond adequately to phosphate binders, based on phase 3 trial data, addressing high blood phosphorus levels. Zymfentra infliximab biosimilar for ulcerative colitis and Crohn's disease: Zymfentra, a subcutaneous infliximab biosimilar, received FDA approval for maintenance therapy in adults with moderately to severely active ulcerative colitis and Crohn's disease, based on LIBERTY-UC and LIBERTY-CD study findings.  Intro and outro music Garden Of Love by Pk jazz Collective    

On this episode of Oncology Unscripted, patient advocates Julie Johnson and Katie Coleman and radiation oncologist Dr. Matt Spraker continue The Insider's Guide to Radiation Therapy! Here are the figures/graphics we referenced during the show:The first figure we discussed, demonstrating the Bragg Peak and the difference between proton and photon (x-ray) beams. The second figure we discussed, comparing 3D photon (x-ray) radiation, intensity modulated radiotherapy with photons (x-ray), passive scatter and intensity modulated proton therapy.Here are some other things we discussed during the show:Relative biological effectiveness in radiobiologyA video about "IMRT for proton therapy", or pencil beam scanning proton therapy, from manufacturer IBA.Brada review of proton evidence, questioning whether the US should open so many proton centers so quickly. Goitein and Cox response to Brada, arguing that the benefit of proton therapy is self-evident.Glatstein, Glick, Kaiser, and Hahn, arguing that trials are needed to prove the benefit of proton therapy.Liao et al., randomized phase II trial of proton versus photon (x-ray) radiotherapy for locally advanced non-small cell lung cancer.RTOG 1308, randomized phase III trial of proton versus photon (x-ray) radiotherapy for locally advanced non-small cell lung cancer. Now filled, awaiting results!Lin et al., randomized phase IIB trial of proton versus photon (x-ray) radiotherapy for locally advanced esophageal cancer.NRG GI-006, randomized phase III trial of proton versus photon (x-ray) radiotherapy for locally advanced esophageal cancer, enrolling now!Oncology Unscripted is a Photon Media production. Intro and Outro music by Emmy-award winning artist Lucas Cantor Santiago.Additional content from Katie Coleman can be found at her website, https://www.katiekickscancer.com/. This show and our opinions are meant for general informational purposes and are not medical advice. We encourage you to reach out to your doctors to discuss your individual case. 

We have landed at our 100th episode, and what an episode it is! HIV & Antivaxxers Part 2. This week Sarah's investigations explain where the rumours around HIV and the covid vaccine originated from and look at if there was any fact amongst the fake news.SourcesCOVID-19 vaccination and HIV-1 acquisition – Authors' reply - The LancetCOVID-19 vaccination and HIV-1 acquisition - The LancetFact Check-Highly virulent variant of HIV circulating in the Netherlands predates COVID-19 pandemic | ReutersCovid: Australian vaccine abandoned over false HIV response - BBC NewsFact check: An Australian vaccine trial did not give trial participants HIV | ReutersSouth Africa rejects Sputnik V Covid-19 vaccine due to HIV concerns (pharmaceutical-technology.com)Overview of STEP and Phambili trial results: two phase IIb test of concept studies investigating the efficacy of MRK ad5 gag/pol/nef sub-type B HIV vaccine - PMC (nih.gov) Hosted on Acast. See acast.com/privacy for more information.

After getting trolled by antivaxxers when we were promoting our free HIV testing service, we decided to bust some of the myths surrounding Covid and HIV. This is a two parter as there were lots of myths to bust!SourcesCOVID-19 vaccination and HIV-1 acquisition – Authors' reply - The LancetCOVID-19 vaccination and HIV-1 acquisition - The LancetFact Check-Highly virulent variant of HIV circulating in the Netherlands predates COVID-19 pandemic | ReutersCovid: Australian vaccine abandoned over false HIV response - BBC NewsFact check: An Australian vaccine trial did not give trial participants HIV | ReutersSouth Africa rejects Sputnik V Covid-19 vaccine due to HIV concerns (pharmaceutical-technology.com)Overview of STEP and Phambili trial results: two phase IIb test of concept studies investigating the efficacy of MRK ad5 gag/pol/nef sub-type B HIV vaccine - PMC (nih.gov) Hosted on Acast. See acast.com/privacy for more information.

Composer John Williams is the defining sound of Hollywood and, arguably, the most widely listened to composer in the world. Kirk decided he needed some help tackling Williams' towering musical legacy, so he enlisted Australian author and musician Dan Golding as his tour guide through Williams' musical world, with a special focus on his groundbreaking score for 1980's Star Wars: The Empire Strikes Back.REFERENCED ON THIS EPISODE:Dan's book Star Wars After Lucas, his ABC radio show Screen Sounds and his podcast Art of the Score"Liberdade" by Dili Allstars"Celebration" from Push Me Pull You by Dan Golding, 2016The Adventures of Robin Hood score by Erich Wolfgang Korngold, 1938Excerpts from Untitled Goose Game as assembled by Dan Golding"Right Time" by Mighty Diamonds/Sly & Robbie, 1976"Peter Gunn" by Henry Mancini, 1959"1. Mars, the Bringer of War" by Gustov Holst from The Planets, Op. 32 as performed by the London Symphony OrchestraExcerpts from Star Wars: A New Hope, Star Wars: The Empire Strikes Back and Star Wars: The Rise of Skywalker, all by John WilliamsThe "Star Wars Music Minute" podcast episode 22 feat. Dan Golding"Medley: Star Wars" by Meco, 1977Bill Murray singing the Star Wars theme on Saturday Night Live, 1978Excerpts from Jurassic Park  by John WilliamsExcerpts from Merry Melodies/Looney Tunes by Carl Stalling"Flash Gordon" by Queen from Flash Gordon, 1980"The Mandalorian" by Ludwig Göransson from The Mandalorian, 2019"If I Fight, You Fight" from Creed by Ludwig Göransson, 2015Excerpts from the Solo: A Star Wars Story score by John Powell, 2018"Moanin," "Wednesday Night Prayer Meeting," "Open Letter to Duke," "Eh's Flat Ah's Flat Too" from Mingus Ah Um and Blues & Roots, by Charles Mingus, 1959"II B.S." by Charles Mingus from Mingus, Mingus, Mingus, Mingus, Mingus, 1964"Work Song" by Duke Ellington from Black Brown & Beige as recorded by Jazz at Lincoln Center in 2020"The Fablemans" by John Williams from The Fablemans, 2022"Beef Lo Mein" by Caroline Shaw from the Fleishman is in Trouble soundtrack, 2019"Movement II: The Big Show" by Wynton Marsalis and Jazz at Lincoln Center from Symphony No. 4: "The Jungle," 2023----LINKS-----SUPPORT STRONG SONGS!Paypal | Patreon.com/StrongsongsMERCH STOREstore.strongsongspodcast.comSOCIAL MEDIAIG: @Kirk_Hamilton | Threads: @Kirk_HamiltonNEWSLETTERhttps://kirkhamilton.substack.com/subscribeJOIN THE DISCORDhttps://discord.gg/GCvKqAM8SmOUTRO SOLO PLAY-A-LONG:https://soundcloud.com/kirkhamilton/strong-songs-outro-music-no-soloSTRONG SONGS PLAYLISTSSpotify | Apple Music | YouTube Music--------------------SEPTEMBER 2023 WHOLE-NOTE PATRONSBen BarronCatherine WarnerDamon WhiteKaya WoodallDan AustinJay SwartzMiriam JoySEAN D WINNIERushDaniel Hannon-BarryAshley HoagChristopher MillerJamie WhiteChristopher McConnellDavid MascettiJoe LaskaKen HirshJezMelanie AndrichJenness GardnerJeanneret Manning Family FourDave SharpeSami SamhuriJeremy DawsonAccessViolationRyan TorvikElliot Jay O'NeillAndre BremerDave FloreySEPTEMBER 2023 HALF-NOTE PATRONSAbraham BenrubiChristopher BrunoChris KotarbaCallum WebbLynda MacNeilDick MorganBen SteinSusan GreenSean MurphyJake YumatillaAlan BroughRandal VegterGo Birds!Whit SidenerRobert Granatdave malloyNick GallowayHeather Johnsonjohn halpinPeter HardingDavidMeghan O'LearyJohn BaumanDax and Dane HuddlestonMartín SalíasTim HowesStu BakerSteve MartinoDr Arthur A GrayCarolinaGary PierceMatt BaxterGiantPredatoryMolluskLuigi BocciaE Margaret WartonCharles McGeeCatherine ClauseEthan BaumanKenIsWearingAHatJordan BlockAaron WadeJamieDeebsPortland Eye CareCarrie SchneiderRichard SneddonJulian RoleffDoreen CarlsonDavid McDarbyWendy GilchristElliot RosenLisa TurnerPaul WayperBruno GaetaKenneth JungAdam StofskyZak RemerRishi SahayAilie FraserVonRob TsukNATALIE MISTILISJosh SingerPhino DeLeonAmy Lynn ThornsenAdam WKelli BrockingtonVictoria YuBrad Clarkmino caposselaSteve PaquinEmma SklarBernard KhooRobert HeuerMatthew GoldenDavid NoahGeraldine ButlerMadeleine MaderJason PrattAbbie BergDoug BelewDermot CrowleyAchint SrivastavaRyan RairighMichael BermanOlivia BishopJohn GisselquistLinda DuffyLiz SegerEoin de BurcaKevin PotterM Shane BordersDallas HockleyJason GerryNathan GouwensLauren ReayEric PrestemonCookies250Damian BradyAngela LivingstoneSarah SulanDiane HughesMichael CasnerLowell MeyerStephen TsoneffWenJack SjogrenGeoff GoldenRobyn FraserPascal RuegerRandy SouzaClare HolbertonDiane TurnerTom ColemanMark PerryDhu WikMelEric HelmJonathan DanielsMichael FlahertyJarrod SchindlerCaro Fieldmichael bochnerNaomi WatsonDavid CushmanAlexanderGavin DoigSam FennTanner MortonAJ SchusterJennifer BushDavid StroudAmanda FurlottiAndrew BakerJules BaileyAndrew FairL.B. MorseBill ThorntonBrian AmoebasBrett DouvilleJeffrey OlsonMatt BetzelNate from KalamazooMelanie StiversRichard TollerAlexander PolsonEarl LozadaJustin McElroyArjun SharmaJames JohnsonKevin MorrellColin Hodo

ASCO: You're listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the voice of the world's oncology professionals. 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. Guests' statements on this 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. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses. The theme of the 2023 ASCO Annual Meeting was “Partnering With Patients: The Cornerstone of Cancer Care and Research.” From June 2 to 6 in Chicago, Illinois, and online, cancer researchers and clinicians from around the world gathered to discuss the latest cancer research and how to ensure that all people receive the cancer care they need. In the Research Round Up series, members of the Cancer.Net Editorial Board discuss the most exciting and practice-changing research in their field presented at the meeting and explain what it means for people with cancer. In today's episode, our guests will discuss new research in melanoma and health equity. First, Dr. Katy Tsai discusses new research in melanoma. Dr. Tsai is a medical oncologist and Assistant Professor of Medicine in the Division of Hematology and Oncology at the University of California, San Francisco. She is also the 2023 Cancer.Net Associate Editor for Melanoma & Skin Cancer. You can view Dr. Tsai's disclosures at Cancer.Net. Dr. Tsai: Hello. Welcome to the ASCO Cancer.Net Research Round Up. I'm Katy Tsai, an associate professor of medicine and the clinical medical director of the Melanoma and Skin Cancer Program at the University of California, San Francisco. I'm happy to be here today to discuss research on melanoma and skin cancers presented at the 2023 ASCO Annual Meeting. I do not have any disclosures relevant to the studies to be discussed. So, it's always exciting to see the latest research presented at ASCO. One theme in particular that I'd like to highlight in this podcast is recent advances in the field of adjuvant therapy. For the listeners who may not be familiar with this terminology, adjuvant therapy refers to drugs given after surgery to try to decrease the risk of cancer recurrence. Specifically, late-breaking abstract 9505 presented updates from KEYNOTE-716, an adjuvant study of pembrolizumab, or pembro, in patients with resected high-risk stage II melanoma. Late-breaking abstract 9503, which I'll also discuss, presented data from KEYNOTE-942, a pivotal study of a personalized cancer vaccine plus pembrolizumab in patients with resected high-risk stage III and stage IV melanoma. So, let's start with KEYNOTE-716. We've known for some time in our field now that adjuvant pembrolizumab or nivolumab can help decrease the risk of recurrence for patients with resected stage III or IV melanoma. What may not be as well-known, however, is that patients with stage IIB or IIC melanomas, in other words, thicker, ulcerated primary melanomas, even without lymph node spread, actually have a comparable risk of melanoma recurrence compared to patients with early stage III melanomas. KEYNOTE-716 was a large, international phase 3 study that randomized patients with stages IIB and C melanoma to receive either pembro or placebo. The positive results showing improvement in relapse-free survival led to approval of adjuvant pembro in December 2021, but what was presented at ASCO was an update on distant metastasis-free survival. This is obviously an important endpoint for us because ultimately, if someone is going to develop widely metastatic disease, unfortunately, it is a development of these distant metastases that we are concerned about. So what we saw here is that with landmark 36-month follow-up, there was a 41% reduction in the risk of developing distant metastasis in patients who were treated with pembro compared to those who received the placebo. In addition, there was a consistent maintained benefit in relapse-free survival, and importantly, no changes in the side effect profile. These are important data because I believe it is practice-changing in the sense that this is a population of patients who historically might not ever have been referred to medical oncology, maybe just monitored serially with their dermatologists. And this is an option that should be discussed. Ultimately, the risk versus benefit about whether to pursue a year of therapy versus maybe consider treatment only at the time of recurrence is a very personalized discussion between a patient and their treating oncologist, but it is an option that should definitely be offered. So let's move on to KEYNOTE-942. The novel drug being tested in this trial is very exciting. We're calling it “individualized neoantigen therapy.” So this is basically a platform that allows us to develop individualized treatment for someone based on characteristics of their own cancer. This involves taking the actual tumor specimen, genomic sequencing, specifically whole-exome sequencing is performed to try to identify any changes in the DNA. And then through a bioinformatic pipeline, the mutations in the DNA that are thought to be most likely to generate proteins that can be bound within presenting molecules are then identified in the computer program, then synthesized within mRNA. So very similar to the way that COVID vaccines have been made. So this actually becomes the actual drug product. So in this study, patients were randomized to receive either pembrolizumab by itself for a year, which is, as we alluded to earlier, standard adjuvant therapy, but then with the addition of this individualized neoantigen therapy starting with dose 3 and then throughout the rest of the year. So the recurrence-free survival data were actually presented earlier this year at another major conference, AACR [American Association for Cancer Research], and were highly positive. At ASCO 2023, I think what was most impressive about the presented data is that distant metastasis-free survival, so again, a similar important endpoint that we discussed with the other trial, is that the distant metastasis-free survival here was quite impressively maintained. There was a hazard ratio of .35, meaning really a 65% reduction in the risk of recurrence for patients who received the personalized neoantigen therapy plus pembrolizumab. So this is a huge advantage for distant metastasis-free survival in this particular population of patients. What was even more intriguing is that usually when we combine therapies, we tend to see additive toxicity, more side effects. And what was really exciting about this particular trial is that the additive toxicity really wasn't as much as you would expect for giving 2 immunotherapies at the same time. I'll also highlight that even though these results are really exciting within melanoma, that part of the reason this data is so exciting is that it represents a really promising platform for therapeutic development and application in other tumors besides melanoma. So this is definitely super exciting. While perhaps not practice-changing in this moment, it's potentially practice-changing. And I look forward to seeing additional data coming in from planned trials using this particular combination in the metastatic setting in addition to the adjuvant setting. So on the whole, I do think that updates in adjuvant therapy for melanoma were super exciting to see at ASCO 2023. As I mentioned earlier, it's a very large conference. A lot of exciting data being presented. So I do think that other themes to pay attention to as we continue to sort through existing data and look forward to incoming data from forthcoming trials is looking at neoadjuvant therapy. For example, drug given before surgery to try to improve long-term outcomes. For example, at ASCO this year, there was interesting neoadjuvant immunotherapy data presented not for melanoma, but for a different type of skin cancer called squamous cell carcinoma. So that would definitely be another theme to pay attention to in the coming months and years. Thinking about novel combinations, for example, what's new in immune checkpoint inhibitors, we've been used to for a long time referring only to anti-PD1 antibodies, anti-CTLA4 antibodies. What was interesting to see this year were updates in novel combinations, for example, PD1 antibodies combined with LAG3 antibodies. Antibodies against TIGIT. So I think this will be another exciting space to pay attention to both in the metastatic skin cancer setting and in the adjuvant and neoadjuvant settings. Thank you for your time and attention. That concludes my research roundup for melanoma and skin cancers. Thank you. ASCO: Thank you, Dr. Tsai. Next, Dr. Manali Patel discusses new research in health equity. Dr. Patel is a medical oncologist and Assistant Professor of Medicine at Stanford University. She is also the 2023 Cancer.Net Associate Editor for Health Equity. You can view Dr. Patel's disclosures at Cancer.Net. Dr. Patel: Hi, my name is Manali Patel. I'm the Associate Editor for Health Equity for Cancer.Net, and I'm so incredibly excited to present some really amazing work that was presented at our ASCO Annual Meeting this past June in Chicago. Before I start, I do have one disclosure. I will be talking about studies that were presented relating to patient navigation and one study in particular that my group presented looking at community health workers. And so that is a little bit of a disclosure that I would like to address upfront. And now, just to get right started. I thought what was really interesting was the amount of work this year that was presented on disparities in health equity. As in past years, we actually saw quite an influx, probably more so this year than previously, on studies that looked at differing outcomes, inequities in cancer care delivery, describing disparities in terms of receipt of treatment, so if people were receiving treatment. There tended to be a lot of studies that focused on looking at and describing a lot of these disparities. But what I was really impressed by came out from the pediatric colleagues, individuals who are taking care of younger patients, children who are less than the age of 18, and how many of those particular studies were focused on moving from description to actually intervening and making a difference in health equity. And so I want to highlight a couple. There was one that was done out of Dana-Farber, and actually, a multi-site group of authors. So lots of authors from all over the place, but Emily Jones was the lead author. And they described and actually evaluated how they could collect, in the context of clinical trials for children, which is called Children's Oncology Group Trial-- how they could collect social determinants of health data, meaning data that evaluates people's income, transportation, where people live, what kind of work they may do, if they have food and housing insecurity. And what they were able to show is that, by embedding a lot of these data points-- they actually made these data points optional for patients when they came into the clinical trial. And they found high feasibility, meaning lots of people that were signing up to do clinical trials for the Children's Oncology Group Trial were able to complete this extra data, which is extremely important and is a remarkable willingness of individuals to participate in providing this data which is important for their treatment. Along those same lines, Amy Newman from the Children's Hospital of Philadelphia really did a very nice study looking at the feasibility of what they called PediCARE. And it was this intervention that was focused on trying to ensure that people-- again, children less than the age of 18 across 2 different clinics. They evaluated whether PediCARE would help people to receive necessary and important resources as it relates to social and economic needs. And so they screened for food insecurity, for housing insecurity, for people that had difficulties paying for utilities, and transportation security. And then they randomized individuals to either PediCARE or to just usual cancer care. And what they found was that 100% of the people that were randomized to PediCARE successfully received grocery and transportation resources. They felt that it was easier to buy food for their family, and they reported it was easier to get to and from the hospital and that they would be very likely to report and to recommend this intervention to other individuals. And so it really shows how these interventions can move from just describing that housing, food insecurity or problems-- number 1, it starts with the collection of the data, right? What's really important is making sure that we collect this data because we don't currently do that in cancer care. And then number 2, when we actually do collect the data, what are we going to do about it? And it shows that these interventions really do help people to move past their housing and social and economic issues that they may experience into actually receiving care that's important and necessary to improve outcomes. We did see a lot of data reflecting the importance of health insurance and big policies, what I call Big P, which are these national policies, like the Affordable Care Act. And now we've seen, just year after year and including this year, plethora of studies showing how beneficial the Affordable Care Act has been on reducing disparities and improving cancer outcomes overall. We also saw other studies, such as one presented by Dr. Gladys Rodriguez from Northwestern, which looked at disparities in the intensity of care at the end of life amongst patients with gastrointestinal cancers. And the team revealed, across almost 20 years of data in California, that patients were receiving higher rates of what would be considered low-quality care. Now, this is lower hospice use, which we know helps to actually improve survival, lower rates of palliative care use, and greater rates of burdensome hospitalizations. And now, why I think this is particularly important is because this study evaluated what we know is a problem, that there is low-quality care amongst patients from particular racial and ethnic populations, such as Black and Hispanic patient populations, that aren't receiving the right care when they're diagnosed. And then what this reveals is that, even at the end of life, they're perhaps still receiving low-quality care. Another study looked at screening, which I thought was really impressive. It was by Nicole Anne Gay from the UM Sylvester Comprehensive Cancer Center in Miami. And what they evaluated was essentially a quality improvement program to reduce disparities in lung cancer screening. As a lung cancer doctor myself, it's still shocking that fewer than 6% of people that should receive lung cancer screening, meaning a screening test to help us identify and to treat patients with lung cancer-- they aren't receiving lung cancer screening. And so we know that this is a problem overall. They put into place what's called a multi-level, meaning that there were improvements in the electronic health record that they embedded. They also provided patients with navigation, and they also helped clinicians in the primary care clinics obtain information about who should be eligible and which patients should be receiving screening. And what they found was that they were able to move screening rates from 25% improvement completed during the project period from their baseline, which is actually quite impressive. We also saw an interesting study, and actually, just an interesting evaluation, of childhood leukemia survival on the U.S.-Mexico border. And it was a description of how to implement changes by strengthening care partnerships. And so they evaluated and they described the implementation of this program to achieve what they called sustainable high-quality care for children with leukemia. It was done by Paula Aristizabal and was really in a unique border health setting. It was in partnership between the North American and Mexican institutions. And they used what was called the strengthening model developed by the World Health Organization to evaluate specific domains and to try to improve a sustainable program for children with acute lymphoblastic leukemia at a public referral hospital right on the border region. And I thought that that study was particularly interesting because it shows how to be able to use an approach to improve the staffing of a leukemia service, to implement a sustainable training program as well for other clinicians to learn how to provide leukemia care, and then also to try to improve clinical outcomes and funding for patients to receive medications through local partnerships. I thought it was a really fantastic description of how to begin to do this work that is extremely necessary in low- and middle-income nations but also even on our own U.S.-Mexico border. There were also a lot of studies that evaluated the importance of social and economic factors. We know that financial toxicity, which is an unfortunate side effect of cancer treatment and cancer care and a cancer diagnosis overall, is associated with worse outcomes. Financial toxicity means the burdens and costs that arise with having a cancer diagnosis. And now we've seen studies that were presented at ASCO this past year by Dr. Khan, who showed that, within 2 years of diagnosis, are at higher risk for dying after adjusting for many social and also clinical factors. And Dr. Hu also presented data looking at the implications of having a lot of medical debt and death. And what both of these studies showed is that medical debt is associated with having perhaps a lower likelihood of surviving. It does make sense for Dr. Hu's study that one would have a lot of medical debt if they also have a lot of other conditions, but it does begin to shed some light on the fact that there are worse clinical outcomes, meaning people aren't doing as well, depending on how much other medical care expenses they may have. And then finally, one important piece, which I think is really crucial for what's happening now in the way that oncologists may perhaps be able to advocate for payment for services that are important, is looking at navigation studies. Now, this is patient navigators, and that is a very broad topic. And so there were lots and lots of studies that came out at ASCO that evaluated the importance of navigation, including our own work that looked at what happens to veterans after receiving a lay health worker or a navigator to assist with advanced care planning, meaning helping veterans to understand their goals and preferences. And what these studies have shown is that there's actually not only clinical benefit but also, in our own study, that perhaps there may be a survival benefit even 10 years later. It was very wonderful to be at ASCO this past year, and I really hope that you all can look at some of these studies or take away the important and amazing work that's going on in the health equity space. And I thank you for listening to our podcast. ASCO: Thank you, Dr. Patel. You can find more research from recent scientific meetings at www.cancer.net. Cancer.Net Podcasts feature trusted, timely, and compassionate information for people with cancer, survivors, and their families and loved ones. Subscribe wherever you listen to podcasts for expert information and tips on coping with cancer, recaps of the latest research advances, and thoughtful discussions on cancer care. And check out other ASCO Podcasts to hear the latest interviews and insights from thought leaders, innovators, experts, and pioneers in oncology. Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping people with cancer everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate. [music]

Dr. Michael Atkins and Dr. Vernon Sondak highlight the latest updates to the systemic therapy for melanoma recommendations in this newest guideline. The discussion covers neoadjuvant and adjuvant therapy for resected cutaneous melanoma, options for unresectable and/or metastatic cutaneous melanoma, and therapies for noncutaneous melanoma. They review the importance of this guideline and the most pressing outstanding questions to help inform better treatment strategies for patients with melanoma. Read the full guideline update, "Systemic Therapy for Melanoma: ASCO Guideline Update" at www.asco.org/melanoma-guidelines. TRANSCRIPT This guideline, clinical tools, and resources are available at http://www.asco.org/melanoma-guidelines. Read the full text of the guideline and review authors' disclosures of potential conflicts of interest disclosures in the Journal of Clinical Oncology, https://ascopubs.org/doi/10.1200/JCO. 23.01136 Brittany Harvey: Hello and welcome to the ASCO Guidelines podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all the shows, including this one at asco.org/podcasts. My name is Brittany Harvey, and today I'm interviewing Dr. Michael Atkins from Georgetown Lombardi Comprehensive Cancer Center, and Dr. Vernon Sondak from H. Lee Moffitt Cancer Center and Research Institute, authors on “Systemic Therapy for Melanoma: ASCO Guideline Update.”   Thank you for being here today, Dr. Atkins and Dr. Sondak. Dr. Vernon Sondak: Happy to be here. Dr. Michael Atkins: Yeah, it's a pleasure. Brittany Harvey: Great. Then before we discuss this guideline, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including Dr. Sondak and Dr. Atkins, who have joined us here today, are available online with the publication of the guideline in the Journal of Clinical Oncology, which is linked in the show notes. So then, to dive into the content here, Dr. Sondak, what prompted this full update to the Systemic Therapy for Melanoma Guideline, which was initially published in 2018? Dr. Vernon Sondak: Well, the last 10 years or so have seen enormous advances in the management of metastatic melanoma and localized melanoma with systemic therapy, and the last few years haven't slowed up at all. So since 2018, we've seen new approvals, we've seen key pivotal trials that have shown some amazing results that we'll talk about, and all of these things together weighed into the decision to update the systemic therapy guidelines. Brittany Harvey: Great. Thank you for that background on what prompted the update. So then, this guideline provides updated recommendations across four clinical questions. I'd like to review the key updated recommendations for our listeners. So first, Dr. Sondak, what has changed in the updated recommendations regarding neoadjuvant therapy for adults with resectable cutaneous melanoma? Dr. Vernon Sondak: Neoadjuvant therapy is one of the most rapidly evolving and exciting parts of the management of melanoma with systemic therapy. The updated guidelines now include neoadjuvant pembrolizumab as a new recommendation for patients with resectable stage IIIB to IV cutaneous melanoma. This is based on the SWOG S1801 clinical trial, which was a very simple and yet incredibly influential clinical trial. It took patients with resectable metastatic melanoma, either metastatic to the lymph nodes or beyond, as long as it could be removed surgically, and randomized all of the patients to either get surgery, followed by a year of adjuvant pembrolizumab, which is very standard, or the same exact surgery and the same total amount of pembrolizumab, but with three of the doses given before surgery. So that simplicity, that ability to just compare the effect of neoadjuvant or preoperative pembrolizumab to entirely postoperative adjuvant pembrolizumab, made this trial a really pure assessment of the value of neoadjuvant pembrolizumab.  Impressively, this study showed a significant improvement in event-free survival for patients who got those three doses of pembrolizumab upfront. What's event-free survival? That includes relapse-free survival, but also the kinds of events that you can see happening with neoadjuvant therapy, such as progression of the disease prior to surgery that makes the patient unresectable. And the bottom line is that there was really the same number of issues with neoadjuvant pembrolizumab as with surgery, followed by adjuvant therapy, but there were many fewer recurrences among the patients who got neoadjuvant pembrolizumab. So that's why this was put into the guidelines. Brittany Harvey: Excellent. I appreciate you reviewing the evidence behind those recommendations and what's new for neoadjuvant therapy. So then, Dr. Atkins, moving into adjuvant therapy, for patients with resected cutaneous melanoma, what is new in the recommendations regarding adjuvant systemic therapy options? Dr. Michael Atkins: Sure. In the prior version, adjuvant therapy was recommended for patients with stage IIIB, IIIC, and for some patients with stage IV resected to NED. And those were based on studies with adjuvant pembrolizumab, adjuvant ipilimumab, and adjuvant nivolumab compared to ipilimumab. But what's happened since then is some really important adjuvant studies have been carried out in patients with stage IIB, IIC, and IIIA disease who are at slightly lower risk of recurrence, but still have substantial risk of recurrence, and make up a large percentage of the patients who eventually develop stage IV disease. And in these studies, one with pembrolizumab compared to placebo, there was about a 40% to 50% reduction in relapse-free survival observed, leading to the FDA approval of pembrolizumab in that setting. And then recently we saw the results of a similar study involving nivolumab that showed maybe even a slightly better reduction in the risk of relapse in that same patient population. Ultimately, this will lead to FDA approval as well. And we felt it was important to put in the guidelines the results of these studies so that people can have informed discussions with their patients about whether they want to receive this therapy going forward. It's important to point out that we don't have good data yet on overall survival. We just have data on relapse-free survival. So we don't, for sure, know that treating patients early, rather than waiting until a subset of them relapse and treating those late leads to an improved overall survival. That's an important discussion to have with patients to provide them with this option. In addition, we saw the results of the IMMUNED trial, which looked at nivo-ipi or nivo monotherapy versus placebo or observation in patients with stage IV disease that had been completely resected. And we saw dramatic improvement for the nivo-ipi combination compared to nivo or observation in those patients with stage IV NED. And we felt that, therefore, this was also an important patient population where we should offer guidance Brittany Harvey: Absolutely. That shared patient-clinician decision-making is paramount. And then you've both reviewed the options for resected cutaneous melanoma. But Dr. Atkins, what is new regarding systemic therapy options for patients with unresectable and/or metastatic cutaneous melanoma? Dr. Michael Atkins: Yes. For patients with unresectable metastatic cutaneous melanoma, there was a new drug combination that was approved combining nivolumab with relatlimab, which is an anti-lag-3 antibody that showed benefit compared to nivolumab monotherapy across almost all subgroups. In particular, the benefit was similar regardless of BRAF mutation status, regardless of elevated LDH, and regardless of patient stage. That led to FDA approval, and this is now an available treatment option, which is associated with less toxicity and similar efficacy to the standard of care nivo-ipi. In addition, although nivolumab-ipilimumab had been approved and was in our last recommendation for patients with BRAF-mutated melanoma, we didn't really know whether they should receive BRAF/MEK inhibitors, which were also approved, versus nivolumab-ipilimumab as their initial therapy. And so in the past few years, we saw the results of the DREAMseq trial, which randomized patients with BRAF-mutant melanoma to either nivolumab-ipilimumab, followed by BRAF-MEK inhibitor progression, versus the converse sequence. And we saw that at two years, the starting with a nivolumab-ipilimumab had a 20% improvement in two-year overall survival. This prompted the NCCN to change their guidelines to list nivolumab-ipilimumab or other immunotherapies as a preferred frontline therapy. And we thought that this data was important enough and somewhat validated by a randomized phase II trial, the SECOMBIT, which had a lot smaller numbers to encourage us to change the guidelines. Other minor things that we did were to take T-VEC and no longer recommend that as an option for patients with BRAF-wild type disease who had progressed on anti-PD-1 therapy and that ipilimumab and ipilimumab-containing regimens were no longer recommended for patients with BRAF-mutated disease after progression on other immunotherapy. We felt that those patients probably are best served to get BRAF/MEK inhibitors. Brittany Harvey: It's good to have clarity on some of those sequencing options for patients and also on which treatments are working better for patients in these subpopulations. So then, Dr. Sondak, the last set of recommendations. What has changed regarding options available for patients with noncutaneous melanoma?  Dr. Vernon Sondak: There's no question that our patients with noncutaneous melanomas, such as uveal melanoma or mucosal melanoma, have many fewer options and haven't benefited as much from the revolution in treatment that we've seen with our cutaneous melanoma patients, but there have been definite improvements and progress. The full update incorporates new recommendations for uveal melanoma that were published in 2022 as a rapid recommendation update, specifically a new drug called tebentafusp, which is restricted to HLA-A*02:01-positive patients. It's HLA-type restricted, but it is active in patients with metastatic uveal melanoma. And so the new guideline is that previously untreated patients with metastatic uveal melanoma who are HLA-A*02:01-positive should be offered tebentafusp as a treatment option. So that means all our patients with metastatic uveal melanoma should get HLA typed, so they know if they're a person who is eligible for this treatment and it should be considered early on in the treatment paradigm. Brittany Harvey: Well, thank you both for reviewing the updates to these evidence-based recommendations. There's a lot that's new in this field.  So then, Dr. Atkins, what is the importance of this guideline? And in your view, how will it impact clinicians, and also how will these guideline recommendations affect patients? Dr. Michael Atkins: Sure. Well, we have new treatments such as relatlimab and tebentafusp that are available and should be offered to appropriate patients, and new data on how to optimally apply previously approved treatments such as nivolumab-ipilimumab in patients with BRAF-mutated or resected stage IV melanoma, pembrolizumab use in the neoadjuvant setting, and nivo and pembro in earlier stage disease. And with this new information out there and included in the guidelines, hopefully, this will allow practitioners to give the best possible treatments to their patients, and patients to receive treatments which will improve their outcomes. Brittany Harvey: Absolutely. It's great to have new data to better inform treatment options for patients with melanoma.   So then, finally, Dr. Sondak, what are some of the most pressing outstanding questions regarding systemic therapy for patients with melanoma that may need to be addressed in a future guideline update? Dr. Vernon Sondak: Every advance brings up new questions. In neoadjuvant therapy, we have single-agent pembrolizumab with strong data from the randomized trial I spoke about. We anticipate more data about combination immunotherapy, specifically low-dose ipilimumab and nivolumab in the setting of neoadjuvant therapy. There are some trials going on with that. The best neoadjuvant treatment, the best sequence, how long should we treat, and even should we change the surgery based on the results of neoadjuvant therapy, not just the surgery, but the postoperative adjuvant therapy? Those are all questions that are key in the neoadjuvant side.  In the adjuvant therapy side, we have much more clarity now about BRAF versus immunotherapy in unresectable disease, but we still don't know always what's the best adjuvant therapy for our BRAF-mutated patients. That's an area we hope will eventually get more clarity, but I think it's going to take a while for that.   And finally, we'll learn more about the optimum sequencing of patients with metastatic disease, but especially for the patients who've already failed adjuvant or neoadjuvant therapy. So much of the data that Dr. Atkins and I talked about in metastatic disease, whether cutaneous or noncutaneous, involved previously untreated patients. But so many of our metastatic disease patients today have come to us already with some form of treatment in the adjuvant or neoadjuvant setting. We still have a lot of work to do to define the best treatment strategies for those patients.  Brittany Harvey: Definitely. Well, we'll look forward to learning more as new data comes out and as some of that research comes to fruition. So I want to thank you so much for your work to update this guideline and thank you for your time today, Dr. Sondak and Dr. Atkins. Dr. Vernon Sondak: Thank you. Dr. Michael Atkins: You're very welcome. Thanks a lot. Brittany Harvey: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast. To read the full guideline, go to www.asco.org/melanoma-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app available in the Apple App Store or the Google Play Store. If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. 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 bonus episode of Inside INdiana Business Radio on Demand, IIB reporter Cate Charron takes an extended look at how local festivals throughout the state are supporting their communities and local businesses, including the Harrison County Popcorn Festival and the Strawberry Festival in Crawfordsville. You can read Cate's full story here: https://bit.ly/44toC9i

1:24  Labiotech news3:45  TolerogenixXTolerogenixX GmbH, a biopharmaceutical company developing personalized cellular therapies aimed at achieving sustained immune tolerance to combat organ rejection and autoimmune diseases, has announced that its phase IIb study in renal transplant patients has received the green light to initiate the B arm of the study. MIC treatment is a personalized cell therapy approach modulating the immune system via a novel mode of action to achieve a specific and sustained immune tolerance. It can not only be applied to transplant recipients, but also to patients with autoimmune diseases such as systemic lupus erythematosus and multiple sclerosis. TolerogenixX has already reported positive results from the one- and three-year follow-up of 10 transplant recipients of its TOL-1 phase I trial initiated at Heidelberg University Hospital. All patients who had received MIC infusions prior to kidney transplantation in the TOL-1 clinical trial had a favorable clinical course three years after surgery. 

一、思想問題：罪惡對我的身心靈有什麼影響？我如何呼求主赦罪？ 二、鑰節： 51:10 神啊，求你為我造清潔的心，使我裏面重新有正直（或譯：堅定）的靈。 大衛在先知責備後立即悔改，他在神面前認罪，而他也深知自己無力改變自己，因此他向神要清潔的心，並且能有堅定正直跟隨神的勇敢與魄力，呼求主保守我們的心在神的愛中，在神的聖潔與屬靈的剛強中，使我們能得著主赦罪，並重得救恩之樂。 三、經文結構： 1-12 深切地認罪與懇求主赦罪 →A1-2 呼求神的赦罪I →→B3-6 深切具體地認罪 →A'7-9 呼求神的赦罪II →→B'10-12 懇求聖靈同在 13-19 得主赦罪後的回應 →13-15 開口讚美神，指教有過犯的人 →16-17 獻祭：不是獻牛羊的祭，而是憂傷痛悔的心 →18-19 懇求主重建國家民族：硬體與軟體敬拜 四、結構亮光： 本篇是最有名的一首認罪詩，大衛與烏利亞之妻拔示巴同寢後，使用借刀殺人之計殺了烏利亞，先知拿單清楚指出他的罪惡後，大衛就在神面前真實地認罪悔改。本篇表達了大衛真實認罪的深度，懇求聖靈的寶貴與如何回應赦罪之恩！ vv.1-12深切地在神面前認罪與悔改，這一段採ABAB架構，A是呼求神的赦罪，B是認罪與懇求聖靈同在。 vv.1-2第一次的呼求，清楚地指出所犯的罪，v.1過犯＝背叛；v.2罪孽＝故意偏離；罪＝不中目標、不符合標準、做錯事。可見罪惡就是背叛神，就是故意違背神的律法，大衛求神塗抹、洗淨、潔除，就是完全地除去罪惡，在神在人都看不見。 vv.3-6是深切地認罪，v.3承認自己犯罪，沒有掩蓋、沒有狡辯，就是承認。我們的罪常在我眼前控告我們、引誘我們，也是提醒著我們有多麼需要上帝的救恩。v.4大衛得罪了許多人，為什麼他卻說他惟獨得罪了神？因為上帝是萬有的主宰，我們所做的任何錯誤罪惡，都可說是做在神身上，一切人際關係的問題、身體健康的問題、自我形象的問題，若是沒有回到與神關係的根本，就是在緣木求魚，這是我們應有的看見。 v.5承認自己充滿了罪孽，這也應是所有人應有的自我認識，而且神要求的聖潔不是表面，不是做到了獻祭的表象（詩50:7-15），神要的是內裡，要我們從最深的隱密之處（呂－心底緊密處），做到真實的悔改與聖潔，並因著追求聖潔而有天上的智慧。 vv.7-9第二次大力地呼求，求主用牛膝草潔淨我們，使我們完全乾淨聖潔。v.8經歷真實認罪後重新回到悔改之樂，使壓傷的骨頭可以再次踴躍歡樂；v.9一再地呼求神的赦免，並掩面不看自己的罪惡。 vv.10-12 不只是求神塗抹罪惡，更積極地求神賜下聖靈，使我可以有正直 的靈（呂－更新而堅定），且堅定地遵守神的道，並求神不要收回聖靈，求聖靈繼續感動我們真實深度地悔改尋求主。v.12可以重得救恩之樂，使我們有甘心樂意的靈來扶持我們，繼續走在救恩之路上。大衛深知自己裡面不能沒有聖靈，即便願意悔改，也迫切需要聖靈給我們堅定、樂意的心繼續走天路，否則沒有人可以憑著自己的力量來走，這是大衛智慧的所在。 vv.13-19是大衛在悔改得蒙赦罪後的回應，有四個回應： v.13指教有過犯的人，大衛跌倒的負面見證，使人知道人性罪惡墮落的可怕；卻也成為正面的見證，知道抓住神就得赦罪之福。 vv.14-15開口讚美神，開口讚美神的拯救，憐憫並赦免這麼大的罪惡。 vv.16-17真正的獻祭，大衛明白神要的不是獻牛羊的祭物，與詩50:13-15的對照，神所要的是我們真實痛切悔改的心。 vv.18-19大衛看見自己的悔改非常重要，因為關乎整個國家民族的福祉，大衛是一國之君，一旦君王離開神，整個國家就有麻煩了。而我們也是有權柄、有職分、有屬靈影響力的僕人，我們的悔改事關重大。求主重建耶路撒冷的城牆，不只是物質的，更是聖潔的城牆。我們仍要學習獻祭，並且是獻上神喜悅的祭物，是真心且聖潔的祭物。 五、反省問題： 今天你我的問題是身體的問題？心理的問題？你我與神的關係有什麼問題？ 智慧與聖潔有什麼關係？我是否有聖潔的智慧？還是只有屬地的智慧？ 喜樂與聖潔有什麼關係？我們是否有從主而來聖潔的喜樂？ 我們的家庭幸福，環境的幸福，與聖潔有什麼關係？ －－－－－－－－－－－－－－－－ 講員： 貴格會合一堂 徐坤靖牧師 聖經之鑰-各卷書播放清單： https://thfc.pse.is/3epsdf 【聖經之鑰 相關資源】YouTube： https://thfc.pse.is/3cfams電子書： https://thfc.pse.is/3ccluu Powered by Firstory Hosting

CME credits: 0.25 Valid until: 09-06-2024 Claim your CME credit at https://reachmd.com/programs/cme/preventing-disease-recurrence-adjuvant-therapy-stage-iibiic-melanoma/15392/ The 5-year recurrence rates for stage IIB and IIC melanoma are up to 46%, but now new immunotherapy options are FDA-approved for the adjuvant treatment of stage IIB and IIC melanoma. Find out why this matters and hear Drs. Jason Luke and Tara Mitchell break down the latest data on treating stage IIB and IIC melanoma with adjuvant immunotherapy.=

Host: Jason J. Luke, MD, FACP Guest: Tara Mitchell, MD The 5-year recurrence rates for stage IIB and IIC melanoma are up to 46%, but now new immunotherapy options are FDA-approved for the adjuvant treatment of stage IIB and IIC melanoma. Find out why this matters and hear Drs. Jason Luke and Tara Mitchell break down the latest data on treating stage IIB and IIC melanoma with adjuvant immunotherapy.

Get our free download! Implementing AMA Style – 8 Things to Get Right This episode covers the latest FDA approvals from May 29 to Jun 2, 2023. Here are the key highlights: Pfizer's RSV vaccine, Abrysvo, has received FDA approval for use in adults aged 60 years or older, aimed at preventing lower respiratory tract disease caused by the RSV virus, based on results from the Phase 3 RENOIR clinical trial. Given Memorial day on May 29, it was a light week at the FDA, so we included dome reporting from this week's ASCO annual meeting:  The KEYNOTE-671 Phase 3 study presented at ASCO showed that adding pembrolizumab to neoadjuvant platinum-based chemotherapy, followed by adjuvant therapy after surgery, improved event-free survival in patients with early-stage non-small cell lung cancer, providing strong support for using PD-1/PD-L1 inhibitors in the neoadjuvant and adjuvant settings. The DUO-O Phase 3 trial at ASCO revealed that a combination therapy of bevacizumab, durvalumab, and olaparib showed significantly better progression-free survival compared to bevacizumab monotherapy in newly diagnosed advanced ovarian cancer patients without BRCA mutations. The NATALEE Phase 3 study presented at ASCO found that combining ribociclib, a CDK4/6 inhibitor, with endocrine therapy improved invasive disease-free survival in patients with stage IIB or III HR-positive/HER2-negative early breast cancer compared to endocrine therapy alone. Brought to you by Nichols Reports. Check out our reports to help you get up and running with all the latest therapeutic agents within various medical specialties here. Also brought to you by Nascentmc.com. A group of MD- and PhD-level medical writers serving the continuing medical education industry and meeting medical writing deadlines with excellence and enthusiasm.   Intro and outro musicGarden Of Love by Pk jazz Collective  

Track Listing:1 Nielsen: Symphony No. 1 in G Minor, Op. 7: / I. Allegro orgoglioso 09:202 II. Andante 07:473 III. Allegro comodo 07:494 IV. Allegro con fuoco 08:58 5 Symphony No. 2, Op. 16 The Four Temperaments / I. Allegro collerico 10:066 II. Allegro comodo e flemmatico 04:567 III. Andante malincolico 12:568 IV. Allegro sanguineo 07:02 9 Symphony No. 3, Op. 27 Espansiva / I. Allegro espansivo 11:0910 II. Andante pastorale 10:3811 III. Allegretto un poco 06:4312 IV. Finale. Allegro 10:52 13 Symphony No. 4, Op. 29 The Inextinguishable / I. Allegro 12:2114 II. Poco allegretto 04:3215 III. Poco adagio quasi andante 10:4716 IV. Allegro 08:51 17 Symphony No. 5, Op. 50: Ia. Tempo giusto 10:2918 Ib. Adagio 08:5219 IIa. Allegro 06:1420 IIb. Presto 02:5821 IIc. Andante poco tranquillo 04:2022 IId. Allegro 02:5623 Symphony No. 6 Sinfonia Semplice / I. Tempo giusto 14:2724 II. Humoreske 04:1125 III. Proposta seria 05:2726 IVa. Allegro – Tema. Allegretto un poco 00:5827 IVb. Var. 1 00:3228 IVc. Var. 2. Allegretto quasi andantino 00:2829 IVd. Var. 3. Più vivo – Var. 4. – Var. 5. Brioso 02:1730 IVe. Var. 6. Tempo di Valse – Var. 7 02:1131 IVf. Var. 8. Molto adagio 03:0232 IVg. Var. 9. Tempo di tema 00:2833 IVh. Fanfare 01:44Help support our show by purchasing this album  at:Downloads (classicalmusicdiscoveries.store) Classical Music Discoveries is sponsored by Uber and Apple Classical. @CMDHedgecock#ClassicalMusicDiscoveries #KeepClassicalMusicAlive#CMDGrandOperaCompanyofVenice #CMDParisPhilharmonicinOrléans#CMDGermanOperaCompanyofBerlin#CMDGrandOperaCompanyofBarcelonaSpain#ClassicalMusicLivesOn#Uber#AppleClassical Please consider supporting our show, thank you!Donate (classicalmusicdiscoveries.store) staff@classicalmusicdiscoveries.com This album is broadcasted with the permission of Crossover Media Music Promotion (Zachary Swanson and Amanda Bloom).

EU rejects the bans on Ukrainian grain imports introduced by Poland and Hungary. Hungary and Poland have been on opposite sides of the spectrum of reactions to Russia's war on Ukraine but remain aligned on their internal challenge to EU institutions. Reports mount of a bipartisan US Congress bill being drafted to sanction leading political figures in the Orbán's government. Last week, the US sanctioned three of the IIB's officials, including Russian Chairman Nikolai Kosov and Hungarian Deputy Chairman Imre Laszlocki. In the second part of the podcast, Editorial Director Miles R. Maftean sits down with Filip Konopczyński (Panoptykon Foundation) to discuss the European way to regulate artificial intelligence and emerging technologies and of the amended EU AI Bill aimed at curbing this potentially dangerous revolutionary tool.

The following question refers to Section 3.2 of the 2021 ESC CV Prevention Guidelines. The question is asked by CardioNerds Academy Intern, student Dr. Hirsh Elhence, answered first by Ohio State University Cardiology Fellow Dr. Alli Bigeh, and then by expert faculty Dr. Eugene Yang. Dr. Yang is professor of medicine of the University of Washington where he is medical director of the Eastside Specialty Center and the co-Director of the Cardiovascular Wellness and Prevention Program. Dr. Yang is former Governor of the ACC Washington Chapter and current chair of the ACC Prevention of CVD Section.  The CardioNerds Decipher The Guidelines Series for the 2021 ESC CV Prevention Guidelines represents a collaboration with the ACC Prevention of CVD Section, the National Lipid Association, and Preventive Cardiovascular Nurses Association. Question #19 True or False: A 70-year-old male has an estimated 10-year ASCVD risk (using SCORE2-OP) of 7.5% which confers a very high CVD risk and necessitates treatment with a statin.  TRUE  FALSE  Answer #19 Explanation   FALSE – CVD risk thresholds for risk factor treatment are higher in apparently healthy people 70 years and older in order to prevent overtreatment in the elderly. A 10-year CVD risk ≥15% is considered “very high risk” for individuals ≥70 years of age (compared to a ≥7.5% cut-off for “very high risk” in younger patients 70 years of age, a 10-year CVD risk of 7.5 to 70 years of age, a 10-year CVD risk of

Tune in as IIB's Deputy General Counsel, Michelle Meertens talks with Alma Angotti, a Partner in the Financial Services Segment at Guidehouse Consulting; Kathryn Rock, also a Partner in the Financial Service Segment at Guidehouse; Ari Berman, a Partner at the law firm of Pillsbury Winthrop Shaw Pittman LLP and co-chair of Pillsbury's Securities Litigation & Enforcement Practice and Head of the Israel Team; and David Oliwenstein, formerly with the SEC's Division of Enforcement and now a Partner at the Pillsbury law firm as they discuss ESG frameworks and what are the best practices in governance, internal controls, and disclosure

Zapraszamy Państwa do wysłuchania trzeciego z pięciu wykładów ks. prof. Jerzego Szymika w ramach cyklu „Mozarteum. Synteza teologii Benedykta XVI”. Synteza i interpretacja obejmują tu takie tematy, jak (1) rozumienie teologii, (2) absolutny prymat Boga, (3) chrystocentryzm, (4) konieczność Kościoła, (5) maryjność jako znak firmowy katolicyzmu. Mozart teologii. Jego dzieło jest prawdziwą „summa theologica” na miarę przełomu tysiącleci, kombinacją cech, które rzadko występują razem i jeszcze rzadziej chcą ze sobą współpracować: potęga intelektu, kompetencje analityczne, erudycja na niespotykaną skalę, esencjalność myślenia, zdolności fenomenologiczne, profetyzm, zdolna do zachwytu nuta liryczna, żywa duchowość i duchowe ciepło, pokorna pobożność, precyzyjny i cięty język, niesłychana przenikliwość. Obcując z jego dziełem teologicznym, wchodzimy więc jak do salzburskiego Mozarteum: wirtuozowska forma, najgłębsze treści, emocje godne Sprawy z Bogiem, kultura bawarsko-austriackiego pogranicza. Plan całego cyklu: 1 lutego: Wykład I / Teologia. Czym jest? (Wykład dostępny pod linkiem: https://www.youtube.com/watch?v=KJDrsahV8WE) 2 lutego: Wykład II / Bóg. Kim jest? 3 lutego: Wykład III / Syn jako rozdarta zasłona (Wykład dostępny pod linkiem: https://www.youtube.com/watch?v=N3YnO7tZ4hE) 4 lutego: Wykład IV / Kościół. Kim jest? (Wykład dostępny pod linkiem: https://www.youtube.com/watch?v=-o6wdc8nRJs) 5 lutego: Wykład V / Maryja. Dlaczego właśnie Ona? Jerzy Szymik – ur. 1953 r. w Pszowie na Górnym Śląsku, kapłan Archidiecezji Katowickiej, profesor nauk teologicznych, poeta, publicysta. Specjalizuje się w chrystologii, metodologii teologii, teologii kultury, teologii J. Ratzingera/Benedykta XVI. 1986-2008 związany z Katolickim Uniwersytetem Lubelskim, od 2005 z WTL Uniwersytetu Śląskiego w Katowicach; 2004-2014 członek Międzynarodowej Komisji Teologicznej. Autor 70 książek naukowych, poetyckich i eseistycznych. ___________ Teologia Polityczna to ogólnopolskie środowisko skupiające intelektualistów, naukowców, publicystów, młodzież akademicką, artystów o poglądach konserwatywno-liberalnych. Została założona przez dwóch filozofów Marka A. Cichockiego (wykładowca UW, dyrektor programowy Centrum Europejskiego Natolin) i Dariusza Karłowicza (prezes Fundacji Świętego Mikołaja) jest pierwszym pismem reprezentującym nieznaną w Polsce dziedzinę z pogranicza filozofii, polityki i teologii. „Na sprawy polityczne chcemy spojrzeć z perspektywy spraw ostatecznych” piszą we wstępie pierwszego numeru pisma autorzy. Więcej informacji: https://teologiapolityczna.pl/ Ambitna kultura potrzebuje wsparcia. Nasza działalność jest możliwa dzięki darowiznom od osób prywatnych, o które bardzo prosimy. Każda wpłata ma dla nas ogromne znaczenie. Dziękujemy za Państwa hojność. Wpłat można dokonać na stronie: https://www.teologiapolityczna.pl/mecenas ____________

Zapraszamy Państwa do wysłuchania ostatniego, piątego wykładu ks. prof. Jerzego Szymika w ramach cyklu „Mozarteum. Synteza teologii Benedykta XVI”. Synteza i interpretacja obejmują tu takie tematy, jak (1) rozumienie teologii, (2) absolutny prymat Boga, (3) chrystocentryzm, (4) konieczność Kościoła, (5) maryjność jako znak firmowy katolicyzmu. Mozart teologii. Jego dzieło jest prawdziwą „summa theologica” na miarę przełomu tysiącleci, kombinacją cech, które rzadko występują razem i jeszcze rzadziej chcą ze sobą współpracować: potęga intelektu, kompetencje analityczne, erudycja na niespotykaną skalę, esencjalność myślenia, zdolności fenomenologiczne, profetyzm, zdolna do zachwytu nuta liryczna, żywa duchowość i duchowe ciepło, pokorna pobożność, precyzyjny i cięty język, niesłychana przenikliwość. Obcując z jego dziełem teologicznym, wchodzimy więc jak do salzburskiego Mozarteum: wirtuozowska forma, najgłębsze treści, emocje godne Sprawy z Bogiem, kultura bawarsko-austriackiego pogranicza. Plan całego cyklu: 1 lutego: Wykład I / Teologia. Czym jest? (Wykład dostępny pod linkiem: https://www.youtube.com/watch?v=KJDrsahV8WE) 2 lutego: Wykład II / Bóg. Kim jest? 3 lutego: Wykład III / Syn jako rozdarta zasłona (Wykład dostępny pod linkiem: https://www.youtube.com/watch?v=N3YnO7tZ4hE) 4 lutego: Wykład IV / Kościół. Kim jest? (Wykład dostępny pod linkiem: https://www.youtube.com/watch?v=-o6wdc8nRJs) 5 lutego: Wykład V / Maryja. Dlaczego właśnie Ona? Jerzy Szymik – ur. 1953 r. w Pszowie na Górnym Śląsku, kapłan Archidiecezji Katowickiej, profesor nauk teologicznych, poeta, publicysta. Specjalizuje się w chrystologii, metodologii teologii, teologii kultury, teologii J. Ratzingera/Benedykta XVI. 1986-2008 związany z Katolickim Uniwersytetem Lubelskim, od 2005 z WTL Uniwersytetu Śląskiego w Katowicach; 2004-2014 członek Międzynarodowej Komisji Teologicznej. Autor 70 książek naukowych, poetyckich i eseistycznych. ___________ Teologia Polityczna to ogólnopolskie środowisko skupiające intelektualistów, naukowców, publicystów, młodzież akademicką, artystów o poglądach konserwatywno-liberalnych. Została założona przez dwóch filozofów Marka A. Cichockiego (wykładowca UW, dyrektor programowy Centrum Europejskiego Natolin) i Dariusza Karłowicza (prezes Fundacji Świętego Mikołaja) jest pierwszym pismem reprezentującym nieznaną w Polsce dziedzinę z pogranicza filozofii, polityki i teologii. „Na sprawy polityczne chcemy spojrzeć z perspektywy spraw ostatecznych” piszą we wstępie pierwszego numeru pisma autorzy. Więcej informacji: https://teologiapolityczna.pl/ Ambitna kultura potrzebuje wsparcia. Nasza działalność jest możliwa dzięki darowiznom od osób prywatnych, o które bardzo prosimy. Każda wpłata ma dla nas ogromne znaczenie. Dziękujemy za Państwa hojność. Wpłat można dokonać na stronie: https://www.teologiapolityczna.pl/mecenas ____________

Zapraszamy Państwa do wysłuchania czwartego z pięciu wykładów ks. prof. Jerzego Szymika w ramach cyklu „Mozarteum. Synteza teologii Benedykta XVI”. Mozart teologii. Jego dzieło jest prawdziwą „summa theologica” na miarę przełomu tysiącleci, kombinacją cech, które rzadko występują razem i jeszcze rzadziej chcą ze sobą współpracować: potęga intelektu, kompetencje analityczne, erudycja na niespotykaną skalę, esencjalność myślenia, zdolności fenomenologiczne, profetyzm, zdolna do zachwytu nuta liryczna, żywa duchowość i duchowe ciepło, pokorna pobożność, precyzyjny i cięty język, niesłychana przenikliwość. Obcując z jego dziełem teologicznym, wchodzimy więc jak do salzburskiego Mozarteum: wirtuozowska forma, najgłębsze treści, emocje godne Sprawy z Bogiem, kultura bawarsko-austriackiego pogranicza. Plan całego cyklu: 1 lutego: Wykład I / Teologia. Czym jest? (Wykład dostępny pod linkiem: https://www.youtube.com/watch?v=KJDrsahV8WE) 2 lutego: Wykład II / Bóg. Kim jest? 3 lutego: Wykład III / Syn jako rozdarta zasłona (Wykład dostępny pod linkiem: https://www.youtube.com/watch?v=N3YnO7tZ4hE) 4 lutego: Wykład IV / Kościół. Kim jest? (Wykład dostępny pod linkiem: https://www.youtube.com/watch?v=-o6wdc8nRJs) 5 lutego: Wykład V / Maryja. Dlaczego właśnie Ona? Jerzy Szymik – ur. 1953 r. w Pszowie na Górnym Śląsku, kapłan Archidiecezji Katowickiej, profesor nauk teologicznych, poeta, publicysta. Specjalizuje się w chrystologii, metodologii teologii, teologii kultury, teologii J. Ratzingera/Benedykta XVI. 1986-2008 związany z Katolickim Uniwersytetem Lubelskim, od 2005 z WTL Uniwersytetu Śląskiego w Katowicach; 2004-2014 członek Międzynarodowej Komisji Teologicznej. Autor 70 książek naukowych, poetyckich i eseistycznych. ___________ Teologia Polityczna to ogólnopolskie środowisko skupiające intelektualistów, naukowców, publicystów, młodzież akademicką, artystów o poglądach konserwatywno-liberalnych. Została założona przez dwóch filozofów Marka A. Cichockiego (wykładowca UW, dyrektor programowy Centrum Europejskiego Natolin) i Dariusza Karłowicza (prezes Fundacji Świętego Mikołaja) jest pierwszym pismem reprezentującym nieznaną w Polsce dziedzinę z pogranicza filozofii, polityki i teologii. „Na sprawy polityczne chcemy spojrzeć z perspektywy spraw ostatecznych” piszą we wstępie pierwszego numeru pisma autorzy. Więcej informacji: https://teologiapolityczna.pl/ Ambitna kultura potrzebuje wsparcia. Nasza działalność jest możliwa dzięki darowiznom od osób prywatnych, o które bardzo prosimy. Każda wpłata ma dla nas ogromne znaczenie. Dziękujemy za Państwa hojność. Wpłat można dokonać na stronie: https://www.teologiapolityczna.pl/mecenas ____________

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Welcome to Episode 106 Sponsored by CultTVMan, Sean's Custom Model Tools and Return To Kit FormHostsStuart ClarkGeoff HeylandTerry MiesleChris Wallace Modelairplanemaker.comThanks to our latest Patreon Supporters:***************************************LATEST NEWSModel Airplane Maker - Let's Get Pacific! Group BuildMaschinen Krieger Competition 2022 Gallery WinnersAirfix 1/24 Spitfire Behind the sceneshttps://www.youtube.com/watch?v=QW1EaiPpbWU&ab_channel=MOS6510ModelsChris Doll Space Art holiday sale - and get the 2023 calendar while they last!***************************************MAILBAGWe want to hear from you! Let us know if you have any comments or suggestions scalemodelpodcast@gmail.com. ***************************************LATEST HOBBY ANNOUNCEMENTSRevell Hurricane Mk.IIB in 1/32nd scaleM8 Howitzer Motor Carriage in 1/48th scale.Trumpeter Jan announcementsTamiya's 1/48th F-35A Lightning II1972 Ford F-250 Ranger XLT With SnowplowBoeing E-7A Wedgetail in 1/72Wildcat & Airacobra over Guadalcanal Double ReleaseModel Monkey new releases.A Pershing launcher & Gun truckBelcher BitsWhat's new at Scalemates.com***************************************SPONSOR AD #1Cult TV ManBox Art for November***************************************Interview This Episode's Special Guest:Chris Wallace Modelairplanemaker.com***************************************SPONSOR AD #2Seans Custom Model Tools***************************************WHAT'S ON THE BENCHStuart - Finishing the 1/144 Bandai X-Wing, getting ready for the group build with a 1/48 Tamiya Beaufighter.Geoff - focused on finishing the construction of a new guest room/sewing room for my wife, so not much time on the bench. Picking away at finishing the Bachem Natter. Also getting back to the CL52!Chris - Recently finished the massive Revell SR-71. No regrets! Aside from some tedious filling and re-scribing around the nacelles, it went well. My review is at: http://modelairplanemaker.com/2022/11/10/1-48-revell-sr-71-blackbird-americas-middle-finger/ and my painting video is at https://youtu.be/zNuUQ2o0vfg. Next up is the Tamiya F4U-1D Corsair for the Group Build starting December 1:Terry - Finishing up the Dora Wings P-43 and Cavalier Mustang. Now I'm just waiting on a brass pitot for the Mustang, then they're done! The Christmas birds are essentially done, I did start building the Bandai V-33 Stork mech carrier to do a quick paint job but have been convinced to do a very challenging paint scheme, for which I've cut some vinyl masks. So…holiday time maybe? Pacific group build choices are two Mitshubishi C5M2 “Babs” aircraft.The sewer line was repaired, the leaking shower was repaired, which needs to be replaced, and solar panels were installed, Kiowa departed and missed. ☹️***************************************THINGS WE'VE SEENClick2Detail parts for several items, notably B-52s and Space Shuttles. 3D printed parts.  Chris: https://www.usni.org/magazines/proceedings for more ‘nuts and bolts' explanations of how things were done in the US Navy and Marineshttps://warfarehistorynetwork.com/article/heroic-airacobras-of-the-cactus-air-force/ will give anyone a new appreciation of the P-400USAF Museum displays its newly-refurbished A-1H.Warbird News coverage with more pictures.***************************************THE LAST WORDSMP Ep. 106 is also sponsored by Return To Kit Form (R2KF). Check out their web store!For more modelling podcast goodness, check out other modelling podcasts at modelpodcasts.comPlease leave us a positive review if you enjoy what we're doing!Check us out: FaceBook, YouTube, and our very own website 

Welcome to Episode 106 Sponsored by CultTVMan, Sean's Custom Model Tools and Return To Kit FormHostsStuart ClarkGeoff HeylandTerry MiesleChris Wallace Modelairplanemaker.comThanks to our latest Patreon Supporters:***************************************LATEST NEWSModel Airplane Maker - Let's Get Pacific! Group BuildMaschinen Krieger Competition 2022 Gallery WinnersAirfix 1/24 Spitfire Behind the sceneshttps://www.youtube.com/watch?v=QW1EaiPpbWU&ab_channel=MOS6510ModelsChris Doll Space Art holiday sale - and get the 2023 calendar while they last!***************************************MAILBAGWe want to hear from you! Let us know if you have any comments or suggestions scalemodelpodcast@gmail.com. ***************************************LATEST HOBBY ANNOUNCEMENTSRevell Hurricane Mk.IIB in 1/32nd scaleM8 Howitzer Motor Carriage in 1/48th scale.Trumpeter Jan announcementsTamiya's 1/48th F-35A Lightning II1972 Ford F-250 Ranger XLT With SnowplowBoeing E-7A Wedgetail in 1/72Wildcat & Airacobra over Guadalcanal Double ReleaseModel Monkey new releases.A Pershing launcher & Gun truckBelcher BitsWhat's new at Scalemates.com***************************************SPONSOR AD #1Cult TV ManBox Art for November***************************************Interview This Episode's Special Guest:Chris Wallace Modelairplanemaker.com***************************************SPONSOR AD #2Seans Custom Model Tools***************************************WHAT'S ON THE BENCHStuart - Finishing the 1/144 Bandai X-Wing, getting ready for the group build with a 1/48 Tamiya Beaufighter.Geoff - focused on finishing the construction of a new guest room/sewing room for my wife, so not much time on the bench. Picking away at finishing the Bachem Natter. Also getting back to the CL52!Chris - Recently finished the massive Revell SR-71. No regrets! Aside from some tedious filling and re-scribing around the nacelles, it went well. My review is at: http://modelairplanemaker.com/2022/11/10/1-48-revell-sr-71-blackbird-americas-middle-finger/ and my painting video is at https://youtu.be/zNuUQ2o0vfg. Next up is the Tamiya F4U-1D Corsair for the Group Build starting December 1:Terry - Finishing up the Dora Wings P-43 and Cavalier Mustang. Now I'm just waiting on a brass pitot for the Mustang, then they're done! The Christmas birds are essentially done, I did start building the Bandai V-33 Stork mech carrier to do a quick paint job but have been convinced to do a very challenging paint scheme, for which I've cut some vinyl masks. So…holiday time maybe? Pacific group build choices are two Mitshubishi C5M2 “Babs” aircraft.The sewer line was repaired, the leaking shower was repaired, which needs to be replaced, and solar panels were installed, Kiowa departed and missed. ☹️***************************************THINGS WE'VE SEENClick2Detail parts for several items, notably B-52s and Space Shuttles. 3D printed parts.  Chris: https://www.usni.org/magazines/proceedings for more ‘nuts and bolts' explanations of how things were done in the US Navy and Marineshttps://warfarehistorynetwork.com/article/heroic-airacobras-of-the-cactus-air-force/ will give anyone a new appreciation of the P-400USAF Museum displays its newly-refurbished A-1H.Warbird News coverage with more pictures.***************************************THE LAST WORDSMP Ep. 106 is also sponsored by Return To Kit Form (R2KF). Check out their web store!For more modelling podcast goodness, check out other modelling podcasts at modelpodcasts.comPlease leave us a positive review if you enjoy what we're doing!Check us out: FaceBook, YouTube, and our very own website 

Tune in as Andrew Olmem, partner in Mayer Brown's Washington DC office and a member of the Public Policy, Regulatory & Political Law, and Financial Services Regulatory & Enforcement practices and former Deputy Assistant to the President for Economic Policy and Deputy Director of the US National Economic Council, joins IIB's CEO Briget Polichene to discuss West Virginia vs. EPA and its implications for future regulatory challenges, financial institutions, and more.

In episode 3 of Exploration Science, Professor Ingrid Dijkgraaf and Dr. Amine Jmel discuss the potential of tick salivary proteins as lead molecules to develop therapeutics, vaccines, and imaging agents for applications ranging from cardiac disease to livestock immunization. DOI Links: Inhibition of platelet adhesion, thrombus formation, and fibrin formation by a potent αIIbβ3 integrin inhibitor from ticks: 10.1002/rth2.12466 Immunomodulatory Proteins in Tick Saliva from a Structural Perspective: 10.3389/fcimb.2021.769574 Exogenous Integrin αIIbβ3 Inhibitors Revisited: Past, Present and Future Applications: 10.3390/ijms22073366 Structural characterization of anti-CCL5 activity of the tick salivary protein evasin-4: 10.1074/jbc.RA120.013891 Tick Saliva Protein Evasin-3 Allows for Visualization of Inflammation in Arteries through Interactions with CXC-Type Chemokines Deposited on Activated Endothelium: 10.1021/acs.bioconjchem.0c00095 Tick saliva protein Evasin-3 modulates chemotaxis by disrupting CXCL8 interactions with glycosaminoglycans and CXCR2: 10.1074/jbc.RA119.008902 Watch on YouTube: https://youtu.be/EZBAt7Sw-e4

Sabe-se que o Pembrolizumabe prolonga a tanto a SG quanto a SLPem pacientes com melanoma avançado. Neste episódio, os Drs. Allan Pereira e Rodrigo Munhoz (Sírio Libanês SP) discutiram o KEYNOTE-716 que avaliou o uso do pembrolizumabe como terapia adjuvante em pacientes com melanoma de estágio II de alto risco completamente ressecado. Estudo importante, fase 3, randomizado que envolveu 160 Centros em várias partes do mundo, incluindo o Brasil. Nele foram recrutados pacientes com melanoma completamente ressecado estágios IIB ou IIC (TNM T3b ou T4 com biópsia de linfonodo sentinela negativa). Entre 2018 e 2020, quase 1.200 pacientes foram recrutados. Com um tempo de follow-up de cerca de 14 meses, 54 (11%) de 487 pacientes no grupo pembrolizumab e 82 (17%) de 489 no grupo placebo recaíram ou foram a óbito: HR 0,65 (IC 0·46–0·92), (p=0·0066). Uma segunda análise com tempo médio de follow-up de 21 meses, 72 (15%) pacientes no grupo pembrolizumab e 115 (24%) no grupo placebo recaíram ou foram a óbito: HR 0,61 (IC 0.45-0.82). Sejam bem-vindos a mais um episódio do Clinical Papers Podcast! Para saber mais sobre o paper, acesse: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)00562-1/fulltext

The IIB head honcho reacts to the Big Ten's massive new media deal, discusses what the future of major college sports means for Indianapolis sporting events and the NCAA, and looks back on his path from television to building his own business brand over the past quarter-century.

Dr. Diwakar Davar and Dr. Jason Luke, both of the University of Pittsburgh's Hillman Cancer Center, highlight key advances in early phase therapeutics and immunotherapy that were featured at the 2022 ASCO Annual Meeting and also address toxicities, including immune checkpoint inhibitor-associated myocarditis. TRANSCRIPT Dr. Diwakar Davar: Hello, and welcome to the ASCO Daily News Podcast. My name is Dr. Diwakar Davar, and I'm an assistant professor of Medical Oncology, specializing in melanoma and phase 1 therapeutics at the University of Pittsburgh's Hillman Cancer Center. I am the guest host of today's podcast. My guest today is Dr. Jason Luke, a colleague and the director of the Cancer Immunotherapeutics Center at the UPMC Hillman Cancer Center here.  Today, we'll be discussing advances in early-phase therapeutics and immunotherapy that were featured at the 2022 ASCO Annual Meeting.   You'll find our full disclosures in the show notes, and the disclosures of all guests on the podcast are available on our transcripts at asco.org/podcasts.  Jason, thank you for coming on the podcast today.  Dr. Jason Luke: Thanks so much for the invitation. It was a great ASCO, and I hope everyone had a good time.  Dr. Diwakar Davar: So, onto our abstracts. So, the first one that we'll be discussing, and Jason as you know we've done this before. We'll be rapidly transitioning between phase 1 therapeutics, melanoma, and advanced phase 2 and 3 trials, but you know this is something you do very well. So Abstract 2504, it's a phase 1 trial of TIM-3 inhibitor cobomilab immunotherapy and in combination with PD-1 inhibitors nivolumab and dostarlimab. The AMBER Trial that was presented recently, and in full disclosure, both you and I actually are on this abstract. So, what do you think of this abstract? What do you think of the data that is discussed, and how do we contextualize this in relation to what needs to be done in this space?  Dr. Jason Luke: So, I think this is an exciting abstract because it brings forward what may be the next high-priority immune checkpoint to try to target in clinical oncology. To level-set, I think everybody listening will know about PD-1 and CTLA-4 as immune checkpoints. In the last year, we've had LAG-3 come forward as now a standard of care element of armamentarium in melanoma, and we look forward to further studies of LAG-3 and other tumor types as we think it should be a good partner where PD-1 is otherwise approved.  So here now, we hear about TIM-3, which is another negative regulatory checkpoint on a number of different immune subsets. And in this abstract, the antibody targeting TIM-3 was cobolimab. So, TIM-3 is a very interesting molecule. It has, what you might call, pleiotropic effects in the immune system. So, while in the context of this abstract, it was being targeted as another immune checkpoint on T cells, it's important to point out that TIM-3 has other regulatory roles in other immune subsets such as myeloid cells and very particularly dendritic cells, and that's important because it might bring in another element of the innate immune system to try to drive anti-tumor responses. So, it's an exciting target because it might be able to expand the groups of patients who could benefit from immune checkpoint blockade.  So, in this abstract, we see initially the phase 1 data of combining cobolimab, anti-TIM-3 with anti-PD-1 of a couple of different flavors. And what you could take from this abstract is that in the phase 1 setting, the drug was well-tolerated and combined well, and had pharmacokinetic properties that would be consistent with what we'd expect for this kind of a monoclonal antibody. I think we have to marry this abstract, which is really the phase 1 data about safety in pharmacokinetic (PK) to another abstract presented in the melanoma session, which showed an expansion cohort of patients who got cobolimab plus nivolumab or dostarlimab.  And there we did see a 50% response rate, albeit that there was heterogeneity of patients being treatment naïve versus treatment-experienced. So, what I would say to this on a high level is that I think these data are preliminarily exciting, suggesting that further investigation into TIM-3 may be valuable in terms of expanding the population of patients initially in melanoma, but there will data coming soon in lung cancer and in other tumor types with another novel checkpoint. And I think if we think ahead into the future, the question is probably going to end up being, which combinations of checkpoints for which patients. That's pretty exciting to think about. We've seen a lot of data of PD-1 plus other molecules, and I think some future biomarker stratification really will be necessary to know which patient would benefit the most from which of these combos, but for the time being, this is exciting data to see where the field is going to go over the next couple of years.  Dr. Diwakar Davar: Great. And I guess, to your point, one important thing to highlight from the abstract is your point about the role of the different compartments. There was actually a very interesting dose-response relationship with the highest dose of the drug not necessarily being the most effective dose, suggesting that yes, as you escalate, you may have different effects in different compartments, and maybe therefore a broad selection of doses might be required to ensure that you have optimal engagement of the optimal target.  So, the next abstract is Abstract 3007. This is the tumor-agnostic efficacy and safety of erdafitinib. So, we now know that FGFR pathway aberrations are found from 77% of all malignancies, FGFR targets are now U.S. Food and Drug Administration (FDA) approved in cholangiocarcinoma with pemigatinib, infigratinib, and as well with erdafitinib metastatic urothelial cancer. We know that these agents are not necessarily effective tests in 1 tumor type because these alterations have risen in multiple tumor types. So, the RAGNAR trial, looking at this across multiple tumor types, what do you make of the interim analysis result presented by Dr. Loriot?  Dr. Jason Luke: So, I'd say that this is probably the future of targeted therapy. And so, I think that where we have activity in 1 disease, it's very likely we would have activity in others. So, the author has described this as the largest basket trial of a molecularly defined subset that's been pursued to date. There are upwards of more than 200 patients in the study. I think it's really important, as we think about the data, to realize, though, that all FGFR alterations are not exactly the same thing. And so, in this study, they gave erdafitinib to patients with solid tumors of any FGFR altered status. And so that's FGFR1, 2, 3, 4 mutations or gene fusions. And that's a lot of heterogeneity in there actually.  And in this study, there were two-thirds fusions and one-third mutations, mostly in FGFR2 and 3. That will become relevant as we start to think about the results. On a high level, I have to say that it is impressive in pan-cancer fashion, just selecting by FGFR alteration, there's about a 30% response rate observed. I think that no matter what, that's going to be valuable considering these were patients with refractory tumors with 3 lines of prior therapy on median. I think what we need to know more is the breakdown of which specific molecular alteration and FGFR in which tumor types drove most of the benefit.  So, for example, in bladder cancer where erdafitinib is already approved, that's almost entirely an FGFR3 fusion setting. So we know the drug is effective there. And so I think there will be a further breakdown of the data. As it matures more, you really start to tease out, is it really the case that any FGFR alteration can be treated or there are some that really ought to be the high priorities that we really ought to be going after. I think it would be remiss not to also note, however, that while there's excitement about this sort of pan-cancer approach, the current generation of FGFR inhibitors are not exactly the easiest drugs to take.  And so, the in-class, hypophosphatemia and stomatitis really does lead to dose reductions in a lot of the patients. And I think that that's probably really important to emphasize is that despite the pan-tumor activity, there's still a lot of potential in this field to refine further because it's almost certainly the case that if we had less off-target toxicity, so to say, we could improve the efficacy beyond that 30% that we saw here.  All the same, I think this is exciting for the concept of a pan-cancer tumor agnostic sort of approach, and we'll really look forward to more data to come from this study over the next, hopefully, few months.  Dr. Diwakar Davar: And I guess 1 corollary to that is that we now need to start looking for FGFR alterations in multiple tumor types. So, tests, tests, tests. All right, Abstract 3004, phase 1a/1b dose escalation and expansion study of the MDM2-p53 antagonist BI 907828 in patients with multiple solid tumors including advanced, metastatic, liposarcoma. So, we've recently had data of the previously undruggable KRAS, and now we've got previously undruggable p53, for which we now have targets. So, Jason, what do you make of the p53 targeting approach, in this case, using MDM2 and this particular drug from Boehringer Ingelheim?  Dr. Jason Luke: So, I think that this is an exciting abstract exactly for the reason that you mentioned, which is that p53 has been, and unfortunately, to some degree, still remains, one of those holy grails but undruggable targets in oncology. So MDM2, for those who are listening but might not be aware, is a negative regulator of p53. So, the concept here then is if you drug it, you might release p53 to reactivate activity in that pathway, and then p53 being the guardian of the genome, so to say, potentially leading to apoptosis of cancer cells.  And so, this drug binds MDM2 and MDM2 can be amplified as a resistance mechanism in p53 and several tumor types. And so here, they showed data for the early part of a clinical trial investigating the small molecule, BI 907828, but then they focus specifically in liposarcoma, which is a disease known to be an MDM2 amplified. And so, the results were pretty interesting. The toxicity of this kind of an approach, just to note, is really in class. It leads to some gastrointestinal (GI) toxicities as well as hematologic problems, and this goes again for most regulators of the cell cycle will have these effects, whether they're CDK inhibitors or MDM2 or p53 modulators.  But I think what was very interesting, this is a disease liposarcoma where chemotherapy, functionally speaking, has no role. We, unfortunately, give it to some patients sometimes, but it has almost no activity, and they observe that in poorly differentiated liposarcomas, the response rate was about 12%, but the stable disease was quite durable. And so, I think that really is potentially a big deal because this is an orphan disease. It really lacks any other treatment. But as you zoom out from that, if you start to think about targeting amplified MDM2 in other settings, I think the activity that we see here is intriguing, and potentially suggests that we may be coming to a future where we'll have multiple, sort of, orthogonal approaches after reactivating p53. There were actually other abstracts at ASCO Annual Meeting of other molecules that were less mature also along this line.  So, I think, very exciting to take away from this, one, a potential treatment for liposarcoma for all of those patients that anybody listening actually sees, but secondarily this concept of targeting p53, which I think we'll see a lot more of over the next couple of years.  Dr. Diwakar Davar: Excellent. Moving on to the Abstract 3002, this is a phase 1, two-part multicenter, first-in-human study of DS-6000a of an antibody-drug conjugate comprising the anti-CDH6 IgG1 monoclonal antibody that is attached to a topoisomerase I inhibitor payload via a cleavable linker. And so basically, a way in which you can give topoisomerase: (1) TOP1 inhibitor, (2) CDH6-expressing cells. This was studied in advanced renal cell carcinoma (RCC) and advanced ovarian cancer in this abstract presented by Dr. Hamilton. Jason, what do you think of the results and what do you think of this approach in general, this antibody-drug conjugate (ADC) approach using novel targets as well as novel payloads?  Dr. Jason Luke: I think this is one of those that you can't help but be pretty excited about, and I think in the context of the data shown at the plenary session in breast cancer for antibody-drug conjugates (LBA3), I think this is really where the field is going to start to go. So, you mentioned that this is an antibody-drug conjugate that targets cadherin 6 or CDH6, which people will remember from biochemistry class and medical school, or something is a cell-cell adhesion molecule, really a basement membrane protein. So, the concept of targeting it really is just to go after a latch mechanism to get the molecule into the tumor where you want. And CDH expression is very high in renal cell carcinoma, upwards of 80% of samples, also high in ovarian cancer, which is why they chose those 2 tumors to go after.  So, the ADCC, and you described its structure just a little bit, but it's essentially the same backbone as trastuzumab deruxtecan, which we saw this outstanding activity for HER2 and breast cancer on the plenary, with these 8 chemotherapies moieties attached to it, but here now, targeting it instead to HER2, with this molecule now to CDH6. And I think, again, you can't help but be impressed. There were treatment responses on almost every dose level of the dose escalation in this study. There's in fact only 1 patient whose tumor was not, at least, stable disease or a PR, and I think that that just goes to show the power of truly bringing the chemotherapy in a targeted manner into the tumor microenvironment. Responses were heterogeneous. They were not super deep responses per se, but the stable disease was quite durable in the study, and the patients were going out more than 7 months. And again, realizing this is at the lower dose levels as we're increasing the dose and move this in their earlier lives of therapy is likely to be even more effective.  They did show a waterfall plot of the reduction in CA 125 for the patients with ovarian cancer that really looked quite impressive. And given that that's our clinical biomarker that we commonly follow, it may actually even more indicative of the benefit we would see as opposed to resist.  Now, again, there is some toxicity. It is a chemotherapy moiety that's conjugated to the ADCs. So, the most common toxicities were nausea, vomiting, and low platelet counts, but these are kind of toxicities that we're quite accustomed to with chemotherapy. Just to summarize, I think there's a lot of promise for this kind of antibody-drug conjugate targeting, and I think it can only be impressive that they had this amount of activity in the dose escalation of the study. [I] very much look forward to the expansion cohorts in renal and ovarian, which we'll presumably expect to see later this year, early in the next year.  Dr. Diwakar Davar: And as you alluded to, this really was parallel that ASCO, by the standing ovation given to Dr. Modi when she presented the DESTINY04 data of trastuzumab deruxtecan in HER2-low breast cancer, basically now redefining breast cancer from 4 camps, now we have to think of not just HER2 amplified or HER2-high, but also HER2-low. So yes, really have to now rethink how we classify these diseases (LBA3).  So Abstract 2509, the efficacy of anti-PD-1/PD-L1 immunotherapy in non–small cell lung cancer dependent based on CD8 and PD-L1 status. So really Dr. Galon taking us into what he has now described as the immunoscore—really a way of characterizing tumors. A way of thinking about tumors that you've also championed, Jason, in terms of this T cell-inflamed and uninflamed hypothesis. So, tell us a little bit about how these jives with your work and how you would think about lung cancer patients responding and not responding to immune checkpoint inhibitors (ICI) therapy in this context?  Dr. Jason Luke: Yeah. I think the focus quickly here on the immunoscore, so the people are aware of that, I think is really important for diving into these specific results. You have to realize our fundamental underlying predicate for immune checkpoint blockade inhibitor response is that patients have mounted an adaptive immune response. So, CD8 T-cells have gone into the tumor where they elaborate chemokines and cytokines like interferon gamma, which upregulates the expression of PD-L1 in the tumor but also in the surrounding immune cells.  So, you realize that even though antibodies are targeting PD-1, it's really that we're targeting that tumor microenvironment. So, the more robustly we can measure that, and we understand it, the more likely we are to know whether or not the patient is going to benefit. So, this is where the immunoscore comes in. The immunoscore is actually a fairly simple test. It's one slide, immunohistochemistry slide where they can stain jointly for CD8 and PD-L1 on the same slide. And that allows them to do a number of different things beyond just testing the total level of PD-L1. They can test the CD8 density, the PD-L1 expression, but then also the interaction between CD8 T-cells, their distance from each other, from PD-L1 expressing cells, and so on and so forth.  And so really [this] can give us a much more robust analysis of what all is going on in the tumor microenvironment again, off of a single slide. So here then, in this abstract, for patients with non–small cell lung cancer receiving anti-PD-1, they then compared the utility of only PD-L1 testing versus doing the immunoscore. And so, it was actually quite a large set. They had about 250 patients in their analytical set and then split about 150 or 180 or something into the training and validation sets, and they compared the immunoscore against 2 different standard PD-L1 antibodies, the 22C3 as well as the SP263. And what they saw was a high concordance for expression between PD-L1 and the immunoscore.  That's good, because, again, they're measuring PD-L1 in both of those. And so that was a good, sort of, level set. The immunoscore, however, allows them to look to 7 different parameters, again, beyond just PD-L1, as I mentioned. So, CD8 density, interaction, distance, and this kind of thing. Then in these test and training cohorts, they were able to actually split out patients who are PD-L1 positive into further groups, those that were immunoscore low and that were high. And in so doing, they were actually able to sort of dramatically predict the likely progression-free survival on PD-1 checkpoint blockade in those different non–small cell lung cancer groups.  So why is this important? Selection of patients by PD-1 has been very useful in the field of non–small cell lung cancer, but it's hardly a panacea. You're not at all assured your patient is going to do well just because they're PD-L1. And here comes a second assay that can be done in a standard of care setting. So, the immunoscore is a test. You could just order it, and that really does give you much more predictive power about who's likely to do well and who isn't. And I think this test and more broadly multi-spectral imaging is really going to become a core component to how we risk stratify and predict outcomes to checkpoint blockade and lung cancer, but broadly in other tumor types over the next couple of years.  Dr. Diwakar Davar: Okay. Now, moving on from a biomarker for PD-L1 and PD-1 to a setting in which PD-1 was just recently U.S. Food and Drug Administration (FDA)-approved, so I'll give a brief background to the trial that you've actually developed and led. And so, this is KEYNOTE-716, the abstract in question is LBA9500 (late-breaking abstract) 9500, but this is the distant metastasis-free survival (DMFS) data readout. The DMFS, distant metastasis-free survival with pembrolizumab versus placebo in the adjuvant setting for patients with stage IIB or IIC, that is high-risk node-negative melanoma and the data from the phase 3 KEYNOTE-716 study.  So, this data, at least the recurrence-free survival (RFS) data was actually earlier published, you had presented it earlier last year and also more recently this year, but it was published recently in Lancet. And we know that 716 is a study in which, for the first time ever, we have an immune checkpoint inhibitor PD-1 that was studied against placebo with the high-risk node-negative setting in stage IIB and C melanoma, demonstrated a significant RFS benefit in the setting against placebo. And now we have the DMFS readout.  Maybe you could tell us a little bit about both the RFS and the DMFS data, and why this is such an important advance for these patients.  Dr. Jason Luke: Thanks. And I agree this really is a sea change in how we thought about stratification of patients with melanoma, but I think this broadly has implications for other tumor types as well. So, in melanoma, we've historically thought of its involvement of the lymph nodes—stage III as being the high-risk disease, but we also, if you look at the outcomes from the AJCC, we see the patients with stage IIB and IIC, so deep primary lesions, actually have similar bad outcomes as those patients with stage IIIA and IIIB. And so anti-PD1 and adjuvant therapy and melanoma were originally proved for stage III, but having understood that about 5 years ago actually, started to think, well, why not also treat the patients with stage II if they're at similar risk.  And we pursued KEYNOTE-716 as you mentioned, and it read out last year as a positive trial for recurrence-free survival. And the abstract here then was to look at the impact on distant metastasis-free survival. So, while the regulatory consideration for approval, and it is approved and it's available for patients now, was based on relapse, what we really want to be preventing is the development of metastatic disease because presumably that would correlate with the eventual death of the patient from cancer.  So, in the abstract here, we see the first update for DMFS, which also was positive on its first analysis, the hazard ratio at 0.64. And so, again, very similar to the RFS benefit, showing about a 35-36% reduction in distant metastasis-free survival. And this is a theme that we've seen across adjuvant studies in melanoma, all the adjuvant studies in fact, is that the RFS improvement, the relapse-free survival hazard ratio mirrors very closely the distant metastasis-free survival ratio. We saw that again here. I think it just emphasizes that anti-PD-1 immunotherapy is highly effective in melanoma no matter what stage it's in, but rather related to the risk of death for melanoma.  And so this really has a practice changing in the field of melanoma oncology. Patients need to be referred to medical oncology early for discussion around risk stratification and consideration of adjuvant therapy—I think even at the same time that they're having resection of their primary lesion, and it even calls into  question of whether or not we should even fully be doing procedures like sentinel lymph node biopsies any longer, considering we can make the decision to give adjuvant therapy now based on the primary—albeit that's a controversial area of discussion.  And I would just love for this to start to penetrate into other disease settings. We've seen more recently, approval for neoadjuvant therapy in lung cancer and we see in kidney cancer, bladder cancer. We see adjuvant therapy in—I think we're going to see immunotherapy starting to become an important part of the armamentarium in these hard-to-treat cancers, even at the time that perioperatively before or after surgery.  So definitely a major change in the way we're thinking about stratifying patients and emphasizes that you need to get those patients with melanoma in to have that discussion around adjuvant therapy probably at the time of the primary lesion resection.  Dr. Diwakar Davar: And finally, Abstract 2507, single-cell profiling of human heart and blood in patients with checkpoint inhibitor-associated myocarditis. So, this is data from the NGH Group, Dr. Villani and colleagues are presented by Dr. Blum. We know that myocarditis is an uncommon but very serious immune related adverse event (irAE), and here in this particular dataset, this group which has done a lot of underlying work to really uncover the role of certain key phenotypes, cellular phenotypes, in the development of myocarditis it's presenting the data in the context of ICI-related myocarditis. So, what do you think of this data, what do you think of the use of checkpoint inhibitors are now, as you've said, migrated linear in the lifecycle of the patient, what do we need to be thinking about and how does this improve our understanding of both the use of the drug and what we need to be worried about?  Dr. Jason Luke: I think the toxicities of immunotherapy, while, less frequent than, say, chemotherapy, can actually be more disastrous. In the rare patients, we have extreme immune-related adverse events, there is an incidence of actually life-threatening and fatal events. And so, myocarditis, associated with checkpoint blockade, is one of those things that could be seen, and here at ASCO Annual Meeting, we saw a couple of abstracts summarizing the experience from the National Cancer Institute following myocarditis events, and then this abstract in a translational level trying to better understand what is actually going on in terms of the immune response in those myocarditis cases.  And so, I thought this was actually a very interesting abstract. There was only a small number of patients. They had 13 samples from patients who had had endomyocardial biopsies in the context of immune-related myocarditis, and you might say, well, only 13 samples, but fortunately, this is quite a rare event, less than 1% of patients who get immune checkpoint inhibitors. And what they saw was relatively unsurprising, which is that in patients who were having myocarditis, they saw an increase in T cells and in K-cells, as well as activated CD8 and CD4 T-cells.  I think what was very interesting was when they started to dig into what were the phenotypes of the cells and what were the pathways that were turned on. Again, it was not especially surprising to see that they saw increased levels of interferon signaling and immune-receptor signaling as well as motility and adhesion, but this really, I think emphasizes that there are potentially interventions beyond just the general immune-suppression approaches that we give. They could be more nuanced but perhaps more efficacious because sadly, patients do pass away when they develop this. And in their cohort of 13 patients, 3 of those patients died. And specifically, in looking in those 3 patients, they actually saw that all 3 patients had a shared T cell cluster. And they can't exactly say what it is exactly yet, but I think it's very interesting to see that because it suggests that there's probably something about the T cell response in those patients that disproportionately triggered a fatal event.  And if we can understand that better, we then may be able to really tailor our interventions in a way that is more useful. Because, frankly, the way these patients usually present is they show up in the emergency room (ER), and they're seen by an ER doctor who thinks they're having acute coronary. They ship them off to the catheterization (cath) lab. They open him up, and then they get in there, and there's nothing going on. There's no plaque. And so now, all of a sudden, everyone is quite confused. And so, if we had better ways to search for that ahead of time to be aware of it, we might have better interventions because usually what happens right at that moment is everybody gets very confused and starts calling the oncologist, and we start slapping on steroids and other immunomodulatory agents, but sometimes it's late.  So, I think this is a great abstract. It's really starting to preliminary give us an idea of what is the actual biology that underpins these terrible events, and we can hope that we can build off that over time hopefully to eventually come up with better predictors and then obviously better interventions to try to avoid these outcomes in a small but real number of patients.  Dr. Diwakar Davar: Excellent. One other point is you and I are both involved in drug development, and as we start thinking of side effects. Side effects are really on the flip side of responses in drug development. So really 1 point to make of this is that when people start developing side effects rather than, as you say, putting your hands up in the air and waving them around, 1 of the things that we should be doing in drug development is possibly biopsying these patients because we could get new PD insights into how these drugs work, why they work, and particularly which sub-populations themselves they work on, particularly in the early-drug development setting when you oftentimes don't have that many responses.  With that, thank you, Jason, for sharing your insights with us today.  Dr. Jason Luke: Thank you.  Dr. Diwakar Davar: And thank you to our listeners for your time today. If you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts. So, thank you for your attention, and we will sign out.      Disclosures:  Dr. Diwakar Davar:   Honoraria: Merck, Tesaro, Array BioPharma, Immunocore, Instil Bio, Vedanta Biosciences  Consulting or Advisory Role: Instil Bio, Vedanta Biosciences  Consulting or Advisory Role (Immediate family member): Shionogi  Research Funding: Merck, Checkmate Pharmaceuticals, CellSight Technologies, GSK, Merck, Arvus Biosciences, Arcus Biosciences  Research Funding (Inst.): Zucero Therapeutics  Patents, Royalties, Other Intellectual Property: Application No.: 63/124,231 Title: COMPOSITIONS AND METHODS FOR TREATING CANCER Applicant: University of Pittsburgh–Of the Commonwealth System of Higher Education Inventors: Diwakar Davar Filing Date: December 11, 2020 Country: United States MCC Reference: 10504-059PV1 Your Reference: 05545; and Application No.: 63/208,719 Enteric Microbiotype Signatures of Immune-related Adverse Events and Response in Relation to Anti-PD-1 Immunotherapy  Dr. Jason Luke:   Stock and Other Ownership Interests: Actym Therapeutics, Mavu Pharmaceutical , Pyxis, Alphamab Oncology, Tempest Therapeutics, Kanaph Therapeutics, Onc.AI, Arch Oncology, Stipe, NeoTX  Consulting or Advisory Role: Bristol-Myers Squibb, Merck, EMD Serono, Novartis, 7 Hills Pharma, Janssen, Reflexion Medical, Tempest Therapeutics, Alphamab Oncology, Spring Bank, Abbvie, Astellas Pharma, Bayer, Incyte, Mersana, Partner Therapeutics, Synlogic, Eisai, Werewolf, Ribon Therapeutics, Checkmate Pharmaceuticals, CStone Pharmaceuticals, Nektar, Regeneron, Rubius, Tesaro, Xilio, Xencor, Alnylam, Crown Bioscience, Flame Biosciences, Genentech, Kadmon, KSQ Therapeutics, Immunocore, Inzen, Pfizer, Silicon Therapeutics, TRex Bio, Bright Peak, Onc.AI, STipe, Codiak Biosciences, Day One Therapeutics, Endeavor, Gilead Sciences, Hotspot Therapeutics, SERVIER, STINGthera, Synthekine  Research Funding (Inst.): Merck , Bristol-Myers Squibb, Incyte, Corvus Pharmaceuticals, Abbvie, Macrogenics, Xencor, Array BioPharma, Agios, Astellas Pharma , EMD Serono, Immatics, Kadmon, Moderna Therapeutics, Nektar, Spring bank, Trishula, KAHR Medical, Fstar, Genmab, Ikena Oncology, Numab, Replimmune, Rubius Therapeutics, Synlogic, Takeda, Tizona Therapeutics, Inc., BioNTech AG, Scholar Rock, Next Cure  Patents, Royalties, Other Intellectual Property: Serial #15/612,657 (Cancer Immunotherapy), and Serial #PCT/US18/36052 (Microbiome Biomarkers for Anti-PD-1/PD-L1 Responsiveness: Diagnostic, Prognostic and Therapeutic Uses Thereof)  Travel, Accommodations, Expenses: Bristol-Myers Squibb, Array BioPharma, EMD Serono, Janssen, Merck, Novartis, Reflexion Medical, Mersana, Pyxis, Xilio  Disclaimer: 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.     

CardioNerds (Amit and Dan) join Dr. Omid Amidi (CardioNerds Academy Graduate) and Dr. Marwah Shahid from the UCLA Cardiology Fellowship program along with Dr. Evelyn Song (CardioNerds Academy House Faculty and Heart Failure Hospitalist at UCSF) to discuss a complex case focused on management of severe coronary artery disease in a patient with Glanzmann thrombasthenia. Dr. Rushi Parikh (Interventional cardiologist, UCLA) provides the ECPR for this episode. Audio editing by CardioNerds Academy Intern, student doctor Akiva Rosenzveig. Glanzmann Thrombasthenia is a bleeding disorder due to impairment of platelet aggregation secondary to a mutation in the GPIIB/IIIA receptor. This case is focused on work up of stable coronary artery disease followed by a discussion on duration of dual antiplatelet therapy post percutaneous coronary intervention in a patient with Glanzmann thrombasthenia.   Check out this published case in JACC: Case Reports Jump to: Case media - Case teaching - References CardioNerds Case Reports PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Case Media See the published case in JACC: Case Reports Episode Schematics & Teaching Pearls 1. Patients with Glanzmann thrombocytopenia (GT) may have a higher risk of bleeding, depending on their disease phenotype. 2. It is unclear whether the mechanism of GT protects patient against stent thrombosis in the setting of PCI. Additionally, there is little data on the use of antiplatelet agents in patients with GT. 3. Short-term DAPT may be a reasonably safe option for patients with GT undergoing PCI. 4. We report a successful case of percutaneous coronary intervention in a patient with GT with no complications at a 1 year follow up. Notes 1. What is Glanzmann thrombasthenia? GT is an inherited platelet disorder that is characterized by spontaneous bleeding with phenotypic variability ranging from minimal bruising to potentially fatal hemorrhaging.  GT is caused by autosomal recessive inheritance of quantitative or qualitative deficiencies of functional αIIbβ3 integrin coded by ITGA2B or ITGB3 genes for αIIb and β3, respectively. As a result, platelets may be stimulated, but the platelet glycoprotein IIb/IIIa receptor is unable to bind fibrinogen to cross-link platelets, rending them potentially ineffective. In platelet aggregation studies, there is lack of response to collagen, epinephrine, arachidonic acid, and ADP stimulation. Thus, platelet aggregation is impaired.  2. What is known about PCI and antiplatelet therapy in the setting of Glanzmann thrombasthenia? To the best of our knowledge, this is the first case report of percutaneous coronary intervention in the setting of GT. It is unclear if the mechanism of GT alone provides sufficient antiplatelet activity and whether antiplatelet therapy leads to significantly increased bleeding risk. The use of antiplatelet therapy is not well studied in the GT population. What we do know is that the mechanism of GT prevents platelet aggregation—the final step in platelet-related thrombosis—while oral antiplatelet therapy affects platelet activation, thus, in our patient we felt that short term DAPT was reasonable. It is important to note that in the event of an active bleed requiring platelet transfusion, donor platelets possess functional glycoprotein IIb/IIIa receptors and thus exponentially increase the risk of stent thrombosis. Therefore, unlike our case, if a patient is not maintained on chronic oral antiplatelet therapy, initiation of oral or intravenous antiplatelet therapy should be considered to prevent stent thrombosis at the time of platelet transfusion. Like any other patient with a high bleeding risk, it is important to have clear indications to conduct a coronary angiogram in patient...

Tune in as IIB's CEO Briget Polichene joins John Carey, a Senior Managing Director at IIB Gold APM Treliant as they discuss his role, as well as a recent three part series he authored on monitorship, including how to select a monitor, how to drive success under a monitorship, and what to do when facing a potential enforcement action.

Monday's College Football National Championship was a big win for Indy. We talked about it with leaders from Visit Indy, the playoff and the planning committee as well as the volunteers that made it happen. Also, Indiana embraces the next generation of technology; a new pediatric burn care center opens in Indianapolis, we learn what's next for University High School and talk about the week's biggest stories with our partners at the IBJ.

Yoda comes bearing delicious Neapolitan and Lydian gifts! Joining me today is Star Wars Minute host Alex Robinson. We explore the harmony in this infamous scene, compare it to themes from other franchises, talk about digital technology's impact on film scoring, and discuss the artistic process. Discussion topics/Highlights: The Force theme with a Neapolitan chord replacing the Major IV chord. Neapolitan chord may also be called IIb, flat two, flat II, Neapolitan 6th Neapolitan chords in Yoda's theme, Indiana Jones theme, Superman theme Marvel vs. Star Wars film scores trash compactor music from A New Hope Music as a manipulative narrative device The effects of digital technology on filmmaking, including film scoring Author's intent vs. audience interpretation The Imperial March within Young Anakin's theme The difficulty in defining artistic inspiration/process Puppets, Muppets, Miss Piggy, Dark Crystal Shoutouts to Pete the Retailer, Tony Thaxton, and the past week on Star Wars Minute Themes Referenced (in order of appearance): Rey's theme, Force theme, Yoda's theme Where we are in the soundtrack: 13. The Sacred Jedi Texts Links Mentioned: YouTube playlist of Star Wars Minute's corresponding episodes talking about the same minutes: Last Jedi Minutes 81-85: https://youtube.com/playlist?list=PLE4n8ygyS0MKwlklsCBX18zZRJDlvDa6R Star Wars Minute Rogue One Minute 101: Three Mountains: https://www.starwarsminute.com/2020/04/06/rogue-one-minute-101-three-mountains Trouble in the Trash Compactor with Unused Score: https://youtu.be/gtRD2Vfsigg I couldn't find a supercut of all the Luke/Ben flashbacks as they appear in the movie, but here's one with different music: https://youtu.be/LqPEPPytDzI (If anyone finds one with John Williams' music included, please send it my way!) Alex Robinson: Twitter: https://twitter.com/ARobTwit Instagram: https://www.instagram.com/arobtwit/ Website: https://alexrobinson.fun Star Wars Minute: https://www.starwarsminute.com/ Godfather Minute: https://godfatherminute.tumblr.com/ Alphabeatical: https://www.alphabeatical.com/ Connect with Star Wars Music Minute: Watch us on YouTube: youtube.com/starwarsmusicminute Twitter: @StarWarsMusMin and @chrysanthetan Instagram: @starwarsmusicminute and @chrysanthetan Email podcast@starwarsmusicminute.com Submit anonymous questions/comments for the show with this quick form. Want more? Check out Chrysanthe's Patreon for weekly practice/composing/music analysis livestreams.

A Journey from Dentistry to Entrepreneurship with Dr. Rui Coelho Dr. Rui Coelho is a Leader of a group investigation of Medical Device Class III. He is the founder of BoneEasy, a Portugal based company that manufactures Patient-specific Implants across the world only for the craniomaxillofacial region. Learn more about 3D Printing on www.surgeonsin3dprinting.com.   Subscribe    Apple I  Google I  Amazon Music I Spotify I Gaana   Resources:   Join the Facebook community Surgeons in 3D Printing!   Visit the website: www.surgeonsin3dprinting.com.   Three Takeaways Basics of Anatomy & Physiology are the foundation for designing. The team approach makes life easy while large-scale implementation. Spread and use technology for patient benefit.   Sponsors: Reconstructive Healthcare Solutions Private Ltd.   Show Notes   Today's AudioTraining: A Journey from Dentistry to Entrepreneurship.   [1.09] -  Dr. Rui Coelho shares his journey from being a dentist to entrepreneurship.   His reason to develop individualized bone graft. Beginning of printing Titanium using basic principles of Facial Anatomy.   [2:45] He shares the beginning of his journey which started with a literature study. He also shares how they first started with chrome-cobalt printing and then took over Titanium as printing material. He also discusses the problems accompanied by Metal Printing.     [5.47] Dr. Rui shares his transitioning phase when he visited various manufacturing units to learn what was available and then transitioned to his own company.   [7.28] Dr. Rui shares key points on :   Creating a design to match muscle attachments. Getting completely versed with software to start innovation and team building. Keeping the anatomic principles as a basis to create designs.   [10:32] Dr. Rui did not find software as a difficulty and found a team-based approach that worked better for him. He shares the presence of his company in various parts of the world and says that Bone Easy is a company that makes medical devices of class II B, implantable medical devices.    [15:06] Dr. Rui shares various materials that can be used for printing metal. He also describes the importance of a clinical picture and then tracing the result forward to find the final result.     [16:50]   Dr. Rui shares insights on his team-building approach which involves engineers working as per the principles of anatomy and physiology.     [17:28]   Dr. Rui shares his expertise as a professional. He shares his role where at times he advised fat grafting to create a place for the implant.His clinical experience has added a lot to the designing of anatomically structured designs.   [19:41]  Dr. Rui shares the difficulties experienced while planning patient-specific implants. He also shares how designs can vary according to the surgeons involved and the time involved for validation of the implant designs.   [20:42]  Dr. Rui discusses the complex face, its thin bones, and the difficulties like the thickness of mucosa and soft tissue coverage of the defect etc.faced while fixing this entire structure back to original form.   [22:27]: Dr. Rui shares the turnaround time of his company after the clinical decision on the implant is made. He elaborates on time for different processes.   [23:15] Dr. Rui gives insights on sterilization protocols for Class IIB devices.   [24:36] Dr. Rui elaborated about the customized & Sterilised boxes for transporting the implants boxes and the validation process their company follows.   [27:08] Dr. Rui talks about spreading this technology as it serves amazing benefits for patients. He also talks about the radiological issues involved.   [29:30] Dr. Rui discusses Research being carried out and the difficulties with research due to different designs for each case. He also shared about the research they have been doing and its release in early 2021. [32:25] Dr. Rui emphasizes spreading the technology and using it due to its benefits to patients.   Killer Resources   Take the first step to your 3D Printing journey.   Register for the upcoming course on Introduction to 3D Printing.   Connect with us on a zoom call for 20 minutes of free consultation.