(SCALE Nanotech) ESA-backed researchers demonstrate the laser-propulsion of graphene sails in microgravity. The light sails use a scalable micro-membrane design that minimizes their mass and hence increases their thrust upon light irradiation. To demonstrate the new sail concept, the scientists gained access to ZARM Drop Tower. There, the sail prototypes were set in vacuum and microgravity, and 1W-lasers caused their acceleration up to 1 m/s2.

(American Association for the Advancement of Science) High-resolution images and video were taken by the Japanese space agency's Hayabusa2 spacecraft as it briefly landed to collect samples from Ryugu -- a nearby asteroid that orbits mostly between Earth and Mars -- allowing researchers to get an up-close look at its rocky surface, according to a new report.

(NASA/Goddard Space Flight Center) NASA has selected a new pathfinding CubeSat mission to gather data not collected since the agency flew the Dynamics Explorer in the early 1980s.

(Aarhus University) An international team of researchers has put together a new image of Neanderthals based on the genes Neanderthals left in the DNA of modern humans when they had children with them about 50,000 years ago. The researchers found the new information by trawling the genomes of more than 27,000 Icelanders. Among other things, they discovered that Neanderthal children had older mothers and younger fathers than the Homo-Sapien children in Africa did at the time.

(University of Helsinki) A multidisciplinary research group coordinated by the University of Helsinki dated the bones of dozens of Iron Age residents of the Levänluhta site in Finland, and studied the carbon and nitrogen stable isotope ratios. The results provide an overview of the dietary habits based on terrestrial, marine and freshwater ecosystems, as well as of sources of livelihoods throughout the Levänluhta era.

(American Friends of Tel Aviv University) The research reveals that hunter-gatherer societies expressed a deep emotional and psychological connection with the animal species they hunted, especially after their disappearance. The study will help anthropologists and others understand the profound environmental changes taking place in our own lifetimes.

(Perot Museum of Nature and Science) Published in PLOS ONE today, a study by an international team from the Perot Museum of Nature and Science in Dallas and Hokkaido University in Japan further explores the proliferation of the most commonly occurring duck-billed dinosaur of the ancient Arctic as the genus Edmontosaurus. The findings reinforce that the hadrosaurs -- dubbed 'caribou of the Cretaceous' -- had a geographical distribution of approximately 60 degrees of latitude, spanning the North American West from Alaska to Colorado.

(University of Washington) By comparing new measurements from NASA's ICESat-2 mission with the original ICESat mission, which operated from 2003 to 2009, scientists were able to measure precisely how the Greenland and Antarctic ice sheets have changed over 16 years.

Palestinian officials said Friday that Israel is forcing banks in the occupied West Bank to close accounts held by the families of prisoners in Israeli jails to prevent the Palestinian Authority from providing stipends to them. Israel has long objected to the Palestinian Authority's payments to the families of prisoners and those killed in the conflict, including militants, saying it rewards terrorism. The Palestinians view the payments as a social safety net for those living under decades of military occupation.

Mikheil Saakashvili, the former president of Georgia, vowed on Friday to help his new boss, Ukrainian President Volodymyr Zelenskiy, clean out a political "swamp" of oligarchs' interests that he said were preventing Ukraine prospering. Twice president of Georgia, Saakashvili had a brief but stormy spell in Ukrainian politics five years ago under Zelenskiy's predecessor Petro Poroshenko in which he once clambered onto a roof to avoid law enforcement.

It may not be a pardon. But the Justice Department has dropped charges against Donald Trump’s former national security adviser Michael Flynn, who pleaded guilty to lying to the FBI.Retired Army Lt. Gen. Flynn, an important figure in the war on terror who gave Trump’s 2016 run military validation, will avoid prison time after the Justice Department provided a deliverance on Thursday that Flynn had long sought. It is also the second redemption that Trump has provided the general, who served as his first national security adviser for less than a month. “The Government has determined, pursuant to the Principles of Federal Prosecution and based on an extensive review and careful consideration of the circumstances, that continued prosecution of this case would not serve the interests of justice,” wrote Timothy Shea, the interim U.S. attorney for the District of Columbia and a former senior aide to Attorney General William Barr. Shortly before the filing, lead prosecutor Brandon Von Grack abruptly withdrew from the case.The Justice Department filing, in essence, portrays Flynn as the victim of an FBI frame-up job, and his lies to the FBI as legally marginal. Shea wrote that Flynn’s lies needed to have been “not simply false, but ‘materially’ false with respect to a matter under investigation.” Later in the filing, Shea referred to those lies as “gaps in [Flynn’s] memory,” rather than deliberate falsehoods Flynn conceded. “Even if he told the truth, Mr. Flynn’s statements could not have conceivably ‘influenced’ an investigation that had neither a legitimate counterintelligence nor criminal purpose,” Shea wrote.It was an astonishing turnaround since 2018, when a federal judge said to Flynn in a sentencing hearing, “arguably, you sold your country out.” That judge, Emmet Sullivan, could still decide to reject Shea’s filing and continue with Flynn’ sentencing. Michael Bromwich, a former federal prosecutor and Justice Department inspector general, tweeted that the extraordinary move represented “a pardon by another name” and called it a “black day in DOJ history.”Rep. Jerrold Nadler (D-NY), chairman of the House Judiciary Committee, said the decision to drop charges was “outrageous” and revealed “a politicized and thoroughly corrupt Department of Justice.” Sen. Ron Wyden (D-OR) added, “If Barr’s Justice Department will drop charges against someone who twice pleaded guilty to lying to the FBI and who the White House publicly fired for lying to the vice president, there’s nothing it won’t do, no investigation it won’t taint.”Neither Flynn nor his attorney, Sidney Powell, responded immediately to requests for comment.Speaking to reports on Thursday afternoon, Trump said he had no prior knowledge of the Justice Department’s decision. “He was an innocent man,” Trump said, of Flynn. “Now in my book he’s an even greater warrior.”The dropped charges follow a years-long groundswell from Trump’s base, and particularly Fox News, to clear Flynn. His advocates claim that Flynn was set up by the same disreputable FBI figures who they believe persecuted Trump over phantom collusion with Russia.Flynn’s guilty plea, in December, 2017, has been no obstacle to the narrative, particularly since Flynn sought afterwards, unsuccessfully, to withdraw his plea. His sentencing, initially set for February, had also been delayed.Last month, agitation for a Flynn pardon intensified after documents emerged from two of Trump’s most hated ex-FBI figures, counterintelligence official Peter Strzok and attorney Lisa Page, discussing Flynn’s fateful January 2017 interview with the FBI. Page asked when and how to “slip it in” to Flynn that lying to an FBI agent is a crime, something that Flynn’s advocates believed showed the general being railroaded from the start. But veteran FBI agents and prosecutors have pointed out that the FBI is not legally obligated to inform an interview subject that lying to them is illegal. “Michael Flynn was very familiar with the FBI,” said Stephanie Douglas, a former executive assistant director of the FBI’s National Security Branch. “He would certainly have been aware of his obligation to provide candid and truthful information. His claim he was tricked and manipulated doesn’t sound valid to me.” Shea, in his Thursday court filing, suggested the FBI officials were “fishing for falsehoods merely to manufacture jurisdiction over any statement.” In Shea’s view, Flynn’s lies were less germane to the prosecution than the FBI “lack[ing] sufficient basis to sustain its initial counterintelligence investigation,” and its pre-interview position that it ought to close the investigation before speaking with the then national security adviser.Former FBI deputy head Andrew McCabe said on Thursday that the suggestion there was no reason to interview Flynn was “patently false, and ignores the considerable national security risk his contacts raised.” He said Flynn’s lies added to the FBI’s concerns about his relationship with Russia. “Today’s move... is pure politics designed to please the president,” he added.U.S. Attorney Jeff Jensen, who was appointed by Barr to review Flynn’s and other high-profile cases, said on Thursday that he concluded “the proper and just course” was to dismiss the case. “I briefed Attorney General Barr on my findings, advised him on these conclusions, and he agreed,” he said.The FBI Didn’t Frame Michael Flynn. That’s Just Trump’s Excuse for a Prospective Pardon.While serving as national security adviser, Flynn misled FBI interviewers about conversations he had with the then-Russian ambassador, Sergei Kislyak. In one of those late 2016 conversations, according to court filings, Flynn asked the Russians to avoid escalatory actions in response to sanctions and diplomatic expulsions then President Barack Obama enacted as reprisal for Russian electoral interference. Shea, in his filing, called Flynn’s Kislyak calls “entirely appropriate on their face.”The national security adviser’s lies prompted the holdover attorney general, Sally Yates, to warn the White House that Flynn had given the Russians leverage to blackmail him. But it would take weeks before Trump fired Flynn over “an eroding level of trust” concerning misleading Vice President Mike Pence on the Kislyak contacts. By May, Trump was said to have regretted dismissing the general.  Flynn in 2017 agreed to cooperate with Special Counsel Robert Mueller’s investigation. The general avoided charges for taking $530,000 in unregistered money from interests connected to the Turkish government—something he only declared with the Justice Department after his downfall as national security adviser. During a sentencing hearing in 2018, a federal judge castigated Flynn for disgracing the uniform Flynn wore for three decades. “Arguably, you sold your country out,” Judge Emmet Sullivan said. Two years earlier, on stage at the Republican national convention, Flynn had led a chant of “lock her up” about Hillary Clinton. Protesters outside Flynn’s courtroom did not let the general forget it. Trump’s enduring bond with Flynn is a testament to the importance of the role the general played in 2016.A host of national security officials, many aligned with the Republican Party, rejected Trump in 2016 as unfit to be president owing to his nativism, his penchant for brutality and his benign view of dictators like Russia’s Vladimir Putin. Flynn was the exception. And the general was an exceptional figure. As the intelligence chief for the Joint Special Operations Command during the mid-2000s, Flynn is one of a select few people who can be said to have personally prosecuted the most sensitive missions of the war on terror. Michael Flynn Putting Mueller Deal at Risk in ‘Dangerous’ New TrialIt was a pivotal credential in another way. Flynn emerged from the war on terror endorsing Trump’s view that the security apparatus, abetted by hidebound liberals and cowardly conservatives, had neutered the war on terror by refusing to see it was a civilizational conflict with Islam. “Islam is a political ideology” that “hides behind this notion of being a religion,” Flynn told the Islamophobic group ACT for America shortly after the 2016 convention. His hostility to Islam informed his sanguine view of Russia, which both Flynn and Trump saw as naturally aligned with the U.S. against what they called “Radical Islamic Terror.”It also meant that Trump and Flynn shared a common bureaucratic enemy. James Clapper, then the director of national intelligence, was a lead architect of an intelligence assessment finding Russia intervened in the election on Trump’s behalf. In 2014, Clapper fired Flynn as director of the Defense Intelligence Agency. It was deeply embittering. Just four years earlier, Flynn had been hailed as an innovator after claiming U.S. military intelligence had misunderstood the Afghanistan war. While Flynn portrayed himself as a martyr, victimized by the ‘Deep State’ for daring to warn about radical Islam, Clapper and other intelligence leaders had fallen out with Flynn over what they considered an incompetent management style and an iffy relationship with the truth. Reportedly, Flynn believed Iran was involved in the 2012 assault on a CIA compound in Benghazi that killed four Americans, and claimed incorrectly that Iran was responsible for more American deaths than al-Qaeda. Aides referred to such untruths as “Flynn facts.” Flynn facts did not disturb Trump. They validated his instincts on national security. Trump rewarded Flynn by making him national security adviser, one of the most important positions in the U.S. security apparatus. It was the first time Trump redeemed Flynn. Thursday’s dropped charges represent the second. Read more at The Daily Beast.Get our top stories in your inbox every day. Sign up now!Daily Beast Membership: Beast Inside goes deeper on the stories that matter to you. Learn more.

As businesses slowly reopen, experts warn that social distancing may need to be dialed back up: ‘It’s not an on-off switch’ * Coronavirus – latest US updates * Coronavirus – latest global updatesSome California businesses on Friday began opening their doors for business – at least partially.As states and counties across the nation contend with pressure to lift the stay-at-home measures that have destroyed local economies, California is taking an especially cautious approach, walking a fine line between political and economic pressure to reopen and the public health imperative to stop the spread of disease.Public health experts told the Guardian that while no US state was equipped with enough coronavirus testing and surveillance to feel fully confident reopening, California’s slow, piecemeal recovery plan – though far from perfect – seemed like the least risky option. The planSeven weeks after the governor, Gavin Newsom, ordered his 40 million constituents to shelter in place and all non-essential businesses to close, California on Friday entered phase two of its grand reopening plan.Some retail stores, including bookshops, florists, music stores, clothing and sporting goods retailers, can reopen if they organize curbside pickup. Some manufacturing and logistics in the retail supply chain can restart as well, as long as they follow safety and hygiene protocols. And local authorities are allowed to ease regulations further than the state guidelines if they meet certain testing and sanitation requirements.Phase three of the plan – potentially months away – could see salons, gyms, movie theaters and in-person church services resume. Phase four would end all restrictions. The timingFriday’s reopenings come as California has avoided the surge of infections states like New York have seen. And although California has seen more than 61,000 cases and 2,500 deaths, its hospitals have not been overwhelmed.Last week, state officials reported the first week-over-week decline in Covid-19 deaths.The new guidelines also follow small but sustained protests across the state to demand a relaxation of regulations to revive the state’s crippled economy, and some rural counties have partially reopened in defiance of the lockdown measures. The caveatsHowever, California still hasn’t seen the two weeks of declining cases that the White House suggested as a criterion for easing restrictions and that several European countries have used as a benchmark.The state also lacks the robust testing and tracking systems that countries such as Germany and South Korea have used.The state has ramped up its ability to administer and process tests, although for now, its rate of 29,414 tests a day is below the figure required by some analyses.Authorities are working to put a robust contact tracing effort in place to make sure those who test positive get the care they need and are able to isolate themselves until they recover. Although some counties and communities have spearheaded community-wide testing and tracing programs, overall, the state isn’t at the point where its system is as widespread or efficient as a country like Germany’s.Experts say California should also have a system in place to make sure vulnerable, unhoused populations have access to shelter and medical care – to prevent infection flare-ups in homeless shelters and encampments. Progress on those measures heavily varies county by county.And ideally, there would be a treatment or a vaccine before reopening, said Dr Richard Jackson, a professor emeritus at the UCLA Fielding School of Public Health and the former head of the California department of public health. While we await a cure, Jackson cautioned, “no one should feel completely safe as we remove restrictions.” The trade-offsCalifornia’s reopening strategy stands in sharp contrast to the approach of states like Georgia, which suddenly allowed gyms, barber shops, hair salons, tattoo parlors and bowling alleys to welcome customers last week.“What certain places have done, where they’ve just thrown open the doors and said, ‘OK, we don’t have to keep our distance any more,’ is a colossal mistake,” Jackson said. Reopening businesses that put lots of people into close contact and speed the spread of disease will reverse the success of shelter-in-place rules, he noted, and overwhelm hospitals as cases surge. “Doing it very cautiously and carefully does make sense at this point in time,” he said.“I get that governors have to balance the public health goals with the economic goals,” said Dr Robert Tsai, surgeon and health policy researcher at Brigham and Women’s hospital in Boston and the Harvard TH Chan School of Public Health. “But this stage of the pandemic is really all about trade-offs,” he noted. The weeks aheadIn the coming weeks, state and local leaders will have to watch closely and prepare to dial the distancing back up if the number of cases surges, said Tsai.“Social distancing isn’t an on-off switch. What it needs to be is a dial, which can be turned up or down depending on what the data show on the ground in terms of how the Covid-19 epidemic is progressing.“Reopening is going to be a very complicated process, and it should be complicated,” he added. “Because this is about making sure that people don’t end up in the hospital or dying.”That California’s plan allows for counties to maintain stricter distancing guidelines or ease up measures could be both a strength and a liability.The flexibility has allowed hotspots like the Bay Area and Los Angeles to take a more cautious approach, but it has also already caused confusion. In San Diego, where curbside shopping has already begun, business owners were unsure what, if anything, would change on Friday. In Bakersfield, restaurants allowed patrons to dine in on Monday and Tuesday, in defiance of the state’s guidelines.A hodgepodge reopening could cause surges in cases; Californians who travel between more lax and more strict counties could spread infections. Moreover, a rush to reopen fast in some areas could be counterproductive to economic recovery, said Alessandro Rebucci, an economist at the Johns Hopkins Carey School of Business.“If you reopen when the pandemic is still out there, people and businesses will not just go back to normal,” Rebucci noted. Based on research from China, it seems clear that fear of contracting the illness will keep businesses owners and patrons home until they feel it’s safe enough, he said.

Disposable masks can be used more than once, but it's important to make sure the mask isn't carrying coronavirus.

(Rutgers University) Rutgers' RUCDR Infinite Biologics received an amended emergency use authorization from the FDA late Thursday for the first SARS-CoV-2 coronavirus test that will allow people to collect their own saliva at home and send to a lab for results. The decision follows the FDA's recent emergency approval to RUCDR Infinite Biologics for the first saliva-based test, which involves health care workers collecting saliva from individuals at testing sites.

(American Geriatrics Society) The American Geriatrics Society (AGS) and the AGS Health in Aging Foundation today conferred one of their newest honors, the Arti Hurria Memorial Award for Emerging Investigators in Internal Medicine Focused on the Care of Older Adults, on two experts: Rasheeda Hall, MD, a board-certified nephrologist and assistant professor of medicine at Duke University; and Kah Poh (Melissa) Loh, MBBCh, BAO, a board-certified internist, hematologist, and oncologist at the University of Rochester Medical Center.

(Kessler Foundation) Andrew Houtenville, Ph.D., research director of the University of New Hampshire's Institute on Disability: 'Unlike the Great Recession and the Great Depression, many workers in the COVID Recession may be 'on temporary layoff' (aka furloughed) and may be recalled, rather than losing their jobs completely. To further investigate this issue, we plan to release a Special nTIDE Report on May 15.'

(American Association for the Advancement of Science) While an effective vaccine for the SARS-CoV-2 virus is likely many months away, development could be accelerated by conducting controlled human infection (CHI) studies -- which are increasingly being considered by the scientific community due to the urgent need.

(University of Huddersfield) A team of researchers received funding of almost £130,000 to work with a group of women in Zambia and create songs that warn against the dangers of the coronavirus -- and now New York wants to hear them.

Korey Capozza
May 1, 2015; 28:83-91
Feature Articles

Omar D. Fernandes
Jul 1, 2010; 23:194-198
Care Innovations

Hours after he was released from police lock-up last week, dancehall artiste Dexta Daps dropped some new music on his eager fans. The track, Breaking News, explores an all-too-familiar domestic violence storyline, but incorporates a controversial...

Her voice cracked as she related the story of a man with disabilities who lost his wife and whose child has had to drop out of school because he has no money. All he has is Bridgette Johnson, a fellow disabled person who has dedicated her life...

A Conversation with John Faraci, executive chairman of the Carrier Corporation, and former CEO of International Paper

The Sanford C. Bernstein & Co. Center for Leadership and Ethics spoke with Anna Houseman '21 about her daily routine, personal ethics, and staying productive during the pandemic. 

Earthquake: 2020-05-06 21:54HKT M6.7 [7.0S, 130.0E] in Tanimbar Islands Region, Indonesia http://openstreetmap.org/?mlat=-7&mlon=130.

Gary Lichtenstein Editions has partnered with Urban Pathways to increase awareness and safety in the homeless community.

Research Event

Event participants

Professor Dapo Akande, Co-Director, Oxford Institute for Ethics, Law and Armed Conflict 
Emanuela-Chiara Gillard, Associate Fellow, International Law Programme, Chatham House
Ahila Sornarajah, Senior Lawyer, International and EU Law
Chair: Elizabeth Wilmshurst, Distinguished Fellow, International Law Programme, Chatham House

Research Event

Event participants

Phil Bloomer, Executive Director, Business & Human Rights Resource Centre
Julie Broome, Director, Ariadne Network
Allison Corkery, Director of Rights Claiming and Accountability Program, Centre for Economic and Social Rights; Atlantic Fellow for Social and Economic Equity, London School of Economics
Chair: Sonya Sceats, Associate Fellow, International Law Programme

Members Event

Event participants

Professor Sarah Cleveland, Louis Henkin Professor of Human and Constitutional Rights; Faculty Co-Director, Human Rights Institute, Columbia Law School

Amal Clooney, Barrister, Doughty Street Chambers

The Honourable Irwin Cotler, Chair, Raoul Wallenberg Centre for Human Rights; Minister of Justice and Attorney-General of Canada (2003-06)

Baroness Helena Kennedy QC, Director, International Bar Association’s Human Rights Institute

Lord Neuberger, President, Supreme Court of the United Kingdom (2012-17)

Maria Ressa, CEO, Rappler Online News Network

Chair: Elizabeth Wilmshurst CMG, Distinguished Fellow, International Law Programme, Chatham House

The canonical pathway of eicosanoid production in most mammalian cells is initiated by phospholipase A2-mediated release of arachidonic acid, followed by its enzymatic oxidation resulting in a vast array of eicosanoid products. However, recent work has demonstrated that the major phospholipase in mitochondria, iPLA2γ (patatin-like phospholipase domain containing 8 (PNPLA8)), possesses sn-1 specificity, with polyunsaturated fatty acids at the sn-2 position generating polyunsaturated sn-2-acyl lysophospholipids. Through strategic chemical derivatization, chiral chromatographic separation, and multistage tandem MS, here we first demonstrate that human platelet-type 12-lipoxygenase (12-LOX) can directly catalyze the regioselective and stereospecific oxidation of 2-arachidonoyl-lysophosphatidylcholine (2-AA-LPC) and 2-arachidonoyl-lysophosphatidylethanolamine (2-AA-LPE). Next, we identified these two eicosanoid-lysophospholipids in murine myocardium and in isolated platelets. Moreover, we observed robust increases in 2-AA-LPC, 2-AA-LPE, and their downstream 12-LOX oxidation products, 12(S)-HETE-LPC and 12(S)-HETE-LPE, in calcium ionophore (A23187)-stimulated murine platelets. Mechanistically, genetic ablation of iPLA2γ markedly decreased the calcium-stimulated production of 2-AA-LPC, 2-AA-LPE, and 12-HETE-lysophospholipids in mouse platelets. Importantly, a potent and selective 12-LOX inhibitor, ML355, significantly inhibited the production of 12-HETE-LPC and 12-HETE-LPE in activated platelets. Furthermore, we found that aging is accompanied by significant changes in 12-HETE-LPC in murine serum that were also markedly attenuated by iPLA2γ genetic ablation. Collectively, these results identify previously unknown iPLA2γ-initiated signaling pathways mediated by direct 12-LOX oxidation of 2-AA-LPC and 2-AA-LPE. This oxidation generates previously unrecognized eicosanoid-lysophospholipids that may serve as biomarkers for age-related diseases and could potentially be used as targets in therapeutic interventions.

Lucía Trilla-Fuertes
Apr 1, 2020; 19:690-700
Research

Quentin Perraud
Apr 1, 2020; 19:589-607
Research

Nora Linscheid
Apr 14, 2020; 0:RA119.001878v1-mcp.RA119.001878
Research

Taewook Kang
Apr 7, 2020; 0:RA119.001882v1-mcp.RA119.001882
Research

Research Event

Event participants

Andrew Sullivan, President and CEO Internet Society
Chair: Emily Taylor, Associate Fellow, International Security Department, Chatham House; Editor, Journal of Cyber Policy

Invitation Only Research Event

15 April 2020

Research Event

Event participants

Ahmed Tabaqchali, Chief Investment Officer, Asia Frontier Capital Iraq Fund; Adjunct Assistant Professor, American University of Iraq Sulaimani
Moderator: Renad Mansour, Senior Research Fellow, Middle East and North Africa Programme, Chatham House

Introduction: The aim of this study was to analyze patterns of persistent versus recurrent or new PET lesions in a selected patient cohort with PSA persistence following salvage lymph node dissection (SLND) and pre/post procedure prostate-specific membrane antigen ligand positron emission tomography (PSMA-PET). Material and Methods: 16 patients were included in this multicenter study. Inclusion criteria were: a) PSMA-PET performed for biochemical recurrence before SLND (pre-SLND PET) and b) repeat PSMA-PET performed for persistently elevated PSA level (≥0.1 ng/mL) ≥6 weeks after SLND (post-SLND PET). Image analysis was performed by three independent nuclear medicine physicians applying the molecular imaging TNM system PROMISE. Lesions were confirmed by histopathology, presence on correlative CT/MRI/bone scan or PSA response after focal therapy. Results: post-SLND PET identified PCa-lesions in 88% (14/16) of patients with PSA persistence after SLND. Median PSA was 1.2 ng/mL (IQR, 0.6-2.8 ng/mL). Disease was confined to the pelvis in 56% of patients (9/16) and most of these men had common iliac (6/16, 38%) and internal iliac lymph node metastases (6/16, 38%). Extrapelvic disease was detected in 31% of patients (5/16). In pre- and post-SLND PET comparison, 10/16 had at least one lesion already detected at baseline (63% PET persistence); 4/16 had new lesions only (25% PET recurrence); 2 had no disease on post-SLND PET. All validated regions (11 regions in 9 patients) were true positive. 9/14 (64%) patients underwent repeat local therapies after SLND (7/14 radiotherapy, 2/14 surgery). Conclusion: SLND of pelvic nodal metastases was often not complete according to PSMA-PET. About two thirds of patients had PET positive nodal disease after SLND already seen on pre-SLND PSMA-PET. Notably, about one quarter of patients had new lesions, not detected by pre-surgical PSMA-PET.

Objective: To develop a novel approach to generate individual maps of white matter (WM) innate immune cell activation using ¹⁸F-DPA-714 translocator protein (TSPO) positron emission tomography (PET), and to explore the relationship between these maps and individual trajectories of disability worsening in patients with multiple sclerosis (MS). Methods: Patients with MS (n = 37), whose trajectories of disability worsening over the 2 years preceding study entry were calculated, and healthy controls (n = 19) underwent magnetic resonance magnetic and ¹⁸F-DPA-714 PET. A threshold of significant activation of ¹⁸F-DPA-714 binding was calculated with a voxel-wise randomized permutation-based comparison between patients and controls, and used to classify each WM voxel in patients as characterized by a significant activation of innate immune cells (DPA+) or not. Individual maps of innate immune cell activation in the WM were employed to calculate the extent of activation in WM regions-of-interests and to classify each WM lesion as "DPA-active", "DPA-inactive" or "unclassified". Results: Compared with the WM of healthy controls, patients with MS had a significantly higher percentage of DPA+ voxels in the normal-appearing WM, (NAWM in patients=24.9±9.7%; WM in controls=14.0±7.8%, p<0.001). In patients with MS, the percentage of DPA+ voxels showed a significant increase from NAWM, to perilesional areas, T2 hyperintense lesions and T1 hypointense lesions (38.1±13.5%, 45.0±17.9%, and 51.9±22.9%, respectively, p<0.001). Among the 1379 T2 lesions identified, 512 were defined as DPA-active and 258 as DPA-inactive. A higher number of lesions classified as DPA-active (OR=1.13, P = 0.009), a higher percentage of DPA+ voxels in the NAWM (OR=1.16, P = 0.009) and in T1-spin-echo lesions (OR=1.06, P = 0.036), were significantly associated with a retrospective more severe clinical trajectory in patients with MS. Conclusion: A more severe trajectory of disability worsening in MS is associated with an innate immune cells activation inside and around WM lesions. ¹⁸F-DPA-714 PET may provide a promising biomarker to identify patients at risk of severe clinical trajectory.

Purpose: The main objective of this prospective study was to determine the impact of multi-phasic acquisition of ⁶⁸Ga-PSMA PET/CT in the detection of recurrent prostate cancer (PCa) in the early stage of biochemical recurrence (BR) with prostate-serum-antigen (PSA) level <1ng/ml. Also, ⁶⁸Ga-PSMA PET/CT positivity was correlated with clinical parameters for the assessment of predictive markers. Methods: A prospective monocentric study was conducted on 135 PCa patients with BR and PSA<1ng/ml. All patients have undergone initial prostatectomy with additional radiation therapy in 19.3% and androgen-deprivation therapy (ADT) in 7.4% of patients. Dynamic acquisition [1–8min. post-injection (p.i.)] from the prostate bed, standard whole-body (60min. p.i.) and limited bed positions of delayed studies (120-150min. p.i.), were performed. Studies were reviewed by two board-certified nuclear medicine specialists, independently. A combination of visual and semi-quantitative analyses and correlation with morphological (e.g. MRI) and/or clinical follow-up findings was used for the final interpretation of abnormal lesions as benign or malignant. ⁶⁸Ga-PSMA PET/CT positivity was also correlated with primary clinical findings. Results: Incorporating the information of all phases, 116 lesions were detected in 49.6% of patients (22 local recurrences, 63 lymph nodes, and 31 distant metastases). The detection rates were 31.8%, 44.9%, and 71.4% for PSA<0.2ng/ml, 0.2≤PSA<0.5, and 0.5≤PSA<1, respectively. Additional dynamic and/or delayed phases resulted in better determination of equivocal lesions and a higher diagnostic performance in 25.9% of patients. Stand-alone dynamic and delayed images led to better interpretation of equivocal findings in the prostate bed (31.4%) and other (lymph node/bone) lesions (20%), respectively. Conclusion: ⁶⁸Ga-PSMA PET/CT revealed promising results for the early detection of recurrent disease in patients with PSA level of 0.5-1.0ng/ml. However, it showed limited value in cases with PSA<0.5ng/ml. Multi-phasic ⁶⁸Ga-PSMA PET/CT led to better determination of equivocal findings. Although, dynamic images may provide helpful information in assessment of the prostate bed; however, delayed acquisitions seem to have higher impact in clarifying of the equivocal findings.

We developed a first-of-kind dasatinib-derivative imaging agent, ¹⁸F-SKI-249380 (¹⁸F-SKI), and validated its use for noninvasive in vivo tyrosine kinase-targeted tumor detection in preclinical models. In this study, we assess the feasibility of using ¹⁸F-SKI for PET imaging in patients with malignancies. Methods: Five patients with a prior diagnosis of breast cancer, renal cell cancer, or leukemia underwent whole-body PET/CT imaging 90 min post-injection of ¹⁸F-SKI (mean: 241.24 ± 116.36 MBq) as part of a prospective study. In addition, patients underwent either a 30-min dynamic scan of the upper abdomen including, at least partly, cardiac left ventricle, liver, spleen, and kidney (n = 2) or three 10-min whole-body PET/CT scans (n = 3) immediately post-injection and blood-based radioactivity measurements to determine the time course of tracer distribution and facilitate radiation dose estimates. A subset of three patients had a delayed whole-body PET/CT scan at 180 min. Biodistribution, dosimetry, and tumor uptake were quantified. Absorbed doses were calculated using OLINDA/EXM 1.0. Results: No adverse events occurred after injection of ¹⁸F-SKI. A total of 27 tumor lesions were analyzed with median SUVpeak 1.4 (range, 0.7–2.3) and tumor-to-blood ratios of 1.6 (range, 0.8–2.5) at 90 min post-injection. Intratumoral drug concentrations calculated for four reference lesions ranged from 0.03–0.07 nM. In all reference lesions, constant tracer accumulation was observed between 30–90 min post-injection. Blood radio-assay indicated that radiotracer clearance from blood and plasma was initially rapid (blood half-time 1.31 ± 0.81 min, plasma 1.07 ± 0.66 min; n = 4), followed variably by either a prolonged terminal phase (blood half-time 285 ± 148.49 min, plasma 240 ± 84.85 min; n = 2) or a small rise to plateau (n = 2). Like dasatinib, ¹⁸F-SKI underwent extensive metabolism post-administration, as evidenced by metabolite analysis. Radioactivity was predominantly cleared via the hepatobiliary route. The highest absorbed dose estimates (mGy/MBq) in normal tissues were to the right colon (0.167 ± 0.04) and small intestine (0.153 ± 0.03). The effective dose was 0.0258 (SD 0.0034) mSv/MBq. Conclusion: ¹⁸F-SKI demonstrated significant tumor uptake, distinct image contrast despite low injected doses, and rapid clearance from blood.

Background: Patients with NHL who are treated with rituximab may develop resistant disease, often associated with changes in expression of CD20. The next generation β-particle emitting radioimmunoconjugate ¹⁷⁷Lu-lilotomab-satetraxetan (Betalutin®) was shown to up-regulate CD20 expression in different rituximab-sensitive NHL cell lines and to act synergistically with rituximab in a rituximab-sensitive NHL animal model. We hypothesized that ¹⁷⁷Lu-lilotomab-satetraxetan may be used to reverse rituximab-resistance in NHL. Methods: The rituximab-resistant Raji2R and the parental Raji cell lines were used. CD20 expression was measured by flow cytometry. ADCC was measured by a bioluminescence reporter assay. The efficacies of combined treatments with ¹⁷⁷Lu-lilotomab-satetraxetan (150MBq/kg or 350MBq/kg) and rituximab (4x10mg/kg) were compared with those of single agents or saline in a Raji2R-xenograft model. Cox-regression and the Bliss independence model were used to assess synergism. Results: Rituximab-binding in Raji2R cells was 36±5% of that in the rituximab-sensitive Raji cells. ¹⁷⁷Lu-lilotomab-satetraxetan treatment of Raji2R cells increased the binding to 53±3% of the parental cell line. Rituximab ADCC-induction in Raji2R cells was 20±2% of that induced in Raji cells, while treatment with ¹⁷⁷Lu-lilotomab-satetraxetan increased the ADCC-induction to 30±3% of the Raji cells, representing a 50% increase (p<0.05). The combination of rituximab with 350MBq/kg ¹⁷⁷Lu-lilotomab-satetraxetan synergistically suppressed Raji2R tumor growth in athymic Foxn1^nu mice. Conclusion: ¹⁷⁷Lu-lilotomab-satetraxetan has the potential to reverse rituximab-resistance; it increases binding and ADCC-activity in-vitro and can synergistically improve anti-tumor efficacy in-vivo.

McCune-Albright syndrome (MAS) is a mosaic disorder arising from gain-of-function mutations in the GNAS gene, which encodes the 3', 5'-cyclic adenosine monophosphate (cAMP) pathway-associated G-protein, Gsα. Clinical manifestations of MAS in a given individual, including fibrous dysplasia, are determined by the timing and location of the GNAS mutation during embryogenesis, the tissues involved, and the role of Gsα in the affected tissues. The Gsα mutation results in dysregulation of the cAMP signaling cascade, leading to upregulation of phosphodiesterase type 4 (PDE4), which catalyzes the hydrolysis of cAMP. Increased cAMP levels have been found in vitro in both animal models of fibrous dysplasia and in cultured cells from individuals with MAS, but not in humans with fibrous dysplasia. Positron emission tomography (PET) imaging of PDE4 with ¹¹C-(R)-rolipram has been used successfully to study the in vivo activity of the cAMP cascade. To date, it remains unknown whether fibrous dysplasia and other symptoms of MAS, including neuropsychiatric impairments, are associated with increased PDE4 activity in humans. Methods: ¹¹C-(R)-rolipram whole-body and brain PET scans were performed in six individuals with MAS (three for brain scans and six for whole-body scans) and nine healthy controls (seven for brain scans and six for whole-body scans). Results: ¹¹C-(R)-rolipram binding correlated with known locations of fibrous dysplasia in the periphery of individuals with MAS; no uptake was observed in the bones of healthy controls. In peripheral organs and the brain, no difference in ¹¹C-(R)-rolipram uptake was noted between participants with MAS and healthy controls. Conclusion: This study is the first to find evidence for increased cAMP activity in areas of fibrous dysplasia in vivo. No differences in brain uptake between MAS participants and controls were detected, which could be due to several reasons, including the limited anatomic resolution of PET. Nevertheless, the results confirm the usefulness of PET scans with ¹¹C-(R)-rolipram to indirectly measure increased cAMP pathway activation in human disease.

Introduction: Gastrin Releasing peptide receptors (GRPRs) are potential molecular imaging targets in a variety of tumors. Recently, a ⁶⁸Ga-labelled antagonist to GRPRs, NeoBOMB1, was developed for PET. We report on the outcome of a Phase I/IIa clinical trial (EudraCT 2016-002053-38) within the EU-FP7 project Closed-loop Molecular Environment for Minimally Invasive Treatment of Patients with Metastatic Gastrointestinal Stromal Tumours (‘MITIGATE’) (grant agreement number 602306) in patients with oligometastatic gastrointestinal stromal tumors (GIST). Materials and Methods: The main objectives were evaluation of safety, biodistribution, dosimetry and preliminary tumor targeting of ⁶⁸Ga-NeoBOMB1 in patients with advanced TKI-treated GIST using PET/CT. Six patients with histologically confirmed GIST and unresectable primary or metastases undergoing an extended protocol for detailed pharmacokinetic analysis were included. ⁶⁸Ga-NeoBOMB1 was prepared using a kit procedure with a licensed ⁶⁸Ge/⁶⁸Ga generator. 3 MBq/kg body-weight were injected intravenously and safety parameters were assessed. PET/CT included dynamic imaging at 5 min, 11 min and 19 min as well as static imaging at 1, 2 and 3-4 h p.i. for dosimetry calculations. Venous blood samples and urine were collected for pharmacokinetics. Tumor targeting was assessed on a per-lesion and per-patient basis. Results: ⁶⁸Ga-NeoBOMB1 (50 µg) was prepared with high radiochemical purity (yield >97%). Patients received 174 ± 28 MBq of the radiotracer, which was well tolerated in all patients over a follow-up period of 4 weeks. Dosimetry calculations revealed a mean adsorbed effective dose of 0.029 ± 0.06 mSv/MBq with highest organ dose to the pancreas (0.274 ± 0.099 mSv/MBq). Mean plasma half-life was 27.3 min with primarily renal clearance (mean 25.7 ± 5.4% of injected dose 4h p.i.). Plasma metabolite analyses revealed high stability, metabolites were only detected in the urine. In three patients a significant uptake with increasing maximum standard uptake values (SUV_max at 2h p.i.: 4.3 to 25.9) over time was found in tumor lesions. Conclusion: This Phase I/IIa study provides safety data for ⁶⁸Ga-NeoBOMB1, a promising radiopharmaceutical for targeting GRPR-expressing tumors. Safety profiles and pharmacokinetics are suitable for PET imaging and absorbed dose estimates are comparable to other ⁶⁸Ga-labelled radiopharmaceuticals used in clinical routine.

31 October 2019

Trade between Central and Eastern Europe and sub-Saharan Africa has increased significantly in the last decade and a half. There is a strong case to be made for greater economic re-engagement, especially in terms of investment, that has the potential to support inclusive growth in both regions.

6 November 2019 , Volume 95, Number 6

3 January 2020