id 18F-Fluorocholine PET/CT in Primary Hyperparathyroidism: Superior Diagnostic Performance to Conventional Scintigraphic Imaging for Localization of Hyperfunctioning Parathyroid Glands By jnm.snmjournals.org Published On :: 2020-04-01T06:00:28-07:00 Primary hyperparathyroidism (PHPT) is a common endocrine disorder, definitive treatment usually requiring surgical removal of the offending parathyroid glands. To perform focused surgical approaches, it is necessary to localize all hyperfunctioning glands. The aim of the study was to compare the efficiency of established conventional scintigraphic imaging modalities with emerging 18F-fluorocholine PET/CT imaging in preoperative localization of hyperfunctioning parathyroid glands in a larger series of PHPT patients. Methods: In total, 103 patients with PHPT were imaged preoperatively with 18F-fluorocholine PET/CT and conventional scintigraphic imaging methods, consisting of 99mTc-sestamibi SPECT/CT, 99mTc-sestamibi/pertechnetate subtraction imaging, and 99mTc-sestamibi dual-phase imaging. The results of histologic analysis, as well as intact parathyroid hormone and serum calcium values obtained 1 d after surgery and on follow-up, served as the standard of truth for evaluation of imaging results. Results: Diagnostic performance of 18F-fluorocholine PET/CT surpassed conventional scintigraphic methods (separately or combined), with calculated sensitivity of 92% for PET/CT and 39%–56% for conventional imaging (65% for conventional methods combined) in the entire patient group. Subgroup analysis, differentiating single and multiple hyperfunctioning parathyroid glands, showed PET/CT to be most valuable in the group with multiple hyperfunctioning glands, with sensitivity of 88%, whereas conventional imaging was significantly inferior, with sensitivity of 22%–34% (44% combined). Conclusion: 18F-fluorocholine PET/CT is a diagnostic modality superior to conventional imaging methods in patients with PHPT, allowing for accurate preoperative localization. Full Article
id Cholecystokinin 2 Receptor Agonist 177Lu-PP-F11N for Radionuclide Therapy of Medullary Thyroid Carcinoma: Results of the Lumed Phase 0a Study By jnm.snmjournals.org Published On :: 2020-04-01T06:00:28-07:00 Treatment of patients with advanced medullary thyroid carcinoma (MTC) is still a challenge. For more than 2 decades, it has been known that the cholecystokinin 2 receptor is a promising target for the treatment of MTC with radiolabeled minigastrin analogs. Unfortunately, kidney toxicity has precluded their therapeutic application so far. In 6 consecutive patients, we evaluated with advanced 3-dimensional dosimetry whether improved minigastrin analog 177Lu-DOTA-(d-Glu)6-Ala-Tyr-Gly-Trp-Nle-Asp-PheNH2 (177Lu-PP-F11N) is a suitable agent for the treatment of MTC. Methods: Patients received 2 injections of about 1 GBq (~80 μg) of 177Lu-PP-F11N with and without a solution of succinylated gelatin (SG, a plasma expander used for nephroprotection) in a random crossover sequence to evaluate biodistribution, pharmacokinetics, and tumor and organ dosimetry. An electrocardiogram was obtained and blood count and blood chemistry were measured up to 12 wk after the administration of 177Lu-PP-F11N to assess safety. Results: In all patients, 177Lu-PP-F11N accumulation was visible in tumor tissue, stomach, and kidneys. Altogether, 13 tumors were eligible for dosimetry. The median absorbed doses for tumors, stomach, kidneys, and bone marrow were 0.88 (interquartile range [IQR]: 0.85–1.04), 0.42 (IQR: 0.25–1.01), 0.11 (IQR: 0.07–0.13), and 0.028 (IQR: 0.026–0.034) Gy/GBq, respectively. These doses resulted in median tumor-to-kidney dose ratios of 11.6 (IQR: 8.11–14.4) without SG and 13.0 (IQR: 10.2–18.6) with SG; these values were not significantly different (P = 1.0). The median tumor-to-stomach dose ratio was 3.34 (IQR: 1.14–4.70). Adverse reactions (mainly hypotension, flushing, and hypokalemia) were self-limiting and not higher than grade 1. Conclusion: 177Lu-PP-F11N accumulates specifically in MTC at a dose that is sufficient for a therapeutic approach. With a low kidney and bone marrow radiation dose, 177Lu-PP-F11N shows a promising biodistribution. The dose-limiting organ is most likely the stomach. Further clinical studies are necessary to evaluate the maximum tolerated dose and the efficacy of 177Lu-PP-F11N. Full Article
id First-in-Humans Imaging with 89Zr-Df-IAB22M2C Anti-CD8 Minibody in Patients with Solid Malignancies: Preliminary Pharmacokinetics, Biodistribution, and Lesion Targeting By jnm.snmjournals.org Published On :: 2020-04-01T06:00:28-07:00 Immunotherapy is becoming the mainstay for treatment of a variety of malignancies, but only a subset of patients responds to treatment. Tumor-infiltrating CD8-positive (CD8+) T lymphocytes play a central role in antitumor immune responses. Noninvasive imaging of CD8+ T cells may provide new insights into the mechanisms of immunotherapy and potentially predict treatment response. We are studying the safety and utility of 89Zr-IAB22M2C, a radiolabeled minibody against CD8+ T cells, for targeted imaging of CD8+ T cells in patients with cancer. Methods: The initial dose escalation phase of this first-in-humans prospective study included 6 patients (melanoma, 1; lung, 4; hepatocellular carcinoma, 1). Patients received approximately 111 MBq (3 mCi) of 89Zr-IAB22M2C (at minibody mass doses of 0.2, 0.5, 1.0, 1.5, 5, or 10 mg) as a single dose, followed by PET/CT scans at approximately 1–2, 6–8, 24, 48, and 96–144 h after injection. Biodistribution in normal organs, lymph nodes, and lesions was evaluated. In addition, serum samples were obtained at approximately 5, 30, and 60 min and later at the times of imaging. Patients were monitored for safety during infusion and up to the last imaging time point. Results: 89Zr-IAB22M2C infusion was well tolerated, with no immediate or delayed side effects observed after injection. Serum clearance was typically biexponential and dependent on the mass of minibody administered. Areas under the serum time–activity curve, normalized to administered activity, ranged from 1.3 h/L for 0.2 mg to 8.9 h/L for 10 mg. Biodistribution was dependent on the minibody mass administered. The highest uptake was always in spleen, followed by bone marrow. Liver uptake was more pronounced with higher minibody masses. Kidney uptake was typically low. Prominent uptake was seen in multiple normal lymph nodes as early as 2 h after injection, peaking by 24–48 h after injection. Uptake in tumor lesions was seen on imaging as early as 2 h after injection, with most 89Zr-IAB22M2C–positive lesions detectable by 24 h. Lesions were visualized early in patients receiving treatment, with SUV ranging from 5.85 to 22.8 in 6 target lesions. Conclusion: 89Zr-IAB22M2C imaging is safe and has favorable kinetics for early imaging. Biodistribution suggests successful targeting of CD8+ T-cell–rich tissues. The observed targeting of tumor lesions suggests this may be informative for CD8+ T-cell accumulation within tumors. Further evaluation is under way. Full Article
id Evidence of Tissue Repair in Human Donor Pancreas After Prolonged Duration of Stay in Intensive Care By diabetes.diabetesjournals.org Published On :: 2020-02-20T11:55:30-08:00 M2 macrophages play an important role in tissue repair and regeneration. They have also been found to modulate β-cell replication in mouse models of pancreatic injury and disease. We previously reported that β-cell replication is strongly increased in a subgroup of human organ donors characterized by prolonged duration of stay in an intensive care unit (ICU) and increased number of leukocytes in the pancreatic tissue. In the present study we investigated the relationship between duration of stay in the ICU, M2 macrophages, vascularization, and pancreatic cell replication. Pancreatic organs from 50 donors without diabetes with different durations of stay in the ICU were analyzed by immunostaining and digital image analysis. The number of CD68+CD206+ M2 macrophages increased three- to sixfold from ≥6 days’ duration of stay in the ICU onwards. This was accompanied by a threefold increased vascular density and a four- to ninefold increase in pancreatic cells positive for the replication marker Ki67. A strong correlation was observed between the number of M2 macrophages and β-cell replication. These results show that a prolonged duration of stay in the ICU is associated with an increased M2 macrophage number, increased vascular density, and an overall increase in replication of all pancreatic cell types. Our data show evidence of marked levels of tissue repair in the human donor pancreas. Full Article
id A Critical Insulin TCR Contact Residue Selects High-Affinity and Pathogenic Insulin-Specific T Cells By diabetes.diabetesjournals.org Published On :: 2020-02-20T11:55:30-08:00 Type 1 diabetes is an autoimmune-mediated disease that culminates in the targeted destruction of insulin-producing β-cells. CD4 responses in NOD mice are dominated by insulin epitope B:9-23 (InsB9-23) specificity, and mutation of the key T-cell receptor (TCR) contact residue within the epitope prevents diabetes development. However, it is not clear how insulin self-antigen controls the selection of autoimmune and regulatory T cells (Tregs). Here we demonstrate that mutation of insulin epitope results in escape of highly pathogenic T cells. We observe an increase in antigen reactivity, clonality, and pathogenicity of insulin-specific T cells that develop in the absence of cognate antigen. Using a single TCR system, we demonstrate that Treg development is greatly diminished in mice with the Y16A mutant epitope. Collectively, these results suggest that the tyrosine residue at position 16 is necessary to constrain TCR reactivity for InsB9-23 by both limiting the development of pathogenic T cells and supporting the selection of Tregs. Full Article
id A Hybrid Insulin Epitope Maintains High 2D Affinity for Diabetogenic T Cells in the Periphery By diabetes.diabetesjournals.org Published On :: 2020-02-20T11:55:30-08:00 β-Cell antigen recognition by autoreactive T cells is essential in type 1 diabetes (T1D) pathogenesis. Recently, insulin hybrid peptides (HIPs) were identified as strong agonists for CD4 diabetogenic T cells. Here, using BDC2.5 transgenic and NOD mice, we investigated T-cell recognition of the HIP2.5 epitope, which is a fusion of insulin C-peptide and chromogranin A (ChgA) fragments, and compared it with the WE14 and ChgA29–42 epitopes. We measured in situ two-dimensional affinity on individual live T cells from thymus, spleen, pancreatic lymph nodes, and islets before and after diabetes. Although preselection BDC2.5 thymocytes possess higher affinity than splenic BDC2.5 T cells for all three epitopes, peripheral splenic T cells maintained high affinity only to the HIP2.5 epitope. In polyclonal NOD mice, a high frequency (~40%) of HIP2.5-specific islet T cells were identified at both prediabetic and diabetic stages comprising two distinct high- and low-affinity populations that differed in affinity by 100-fold. This high frequency of high- and low-affinity HIP2.5 T cells in the islets potentially represents a major risk factor in diabetes pathogenesis. Full Article
id {beta}-Cell Stress Shapes CTL Immune Recognition of Preproinsulin Signal Peptide by Posttranscriptional Regulation of Endoplasmic Reticulum Aminopeptidase 1 By diabetes.diabetesjournals.org Published On :: 2020-03-20T11:50:28-07:00 The signal peptide of preproinsulin is a major source for HLA class I autoantigen epitopes implicated in CD8 T cell (CTL)–mediated β-cell destruction in type 1 diabetes (T1D). Among them, the 10-mer epitope located at the C-terminal end of the signal peptide was found to be the most prevalent in patients with recent-onset T1D. While the combined action of signal peptide peptidase and endoplasmic reticulum (ER) aminopeptidase 1 (ERAP1) is required for processing of the signal peptide, the mechanisms controlling signal peptide trimming and the contribution of the T1D inflammatory milieu on these mechanisms are unknown. Here, we show in human β-cells that ER stress regulates ERAP1 gene expression at posttranscriptional level via the IRE1α/miR-17-5p axis and demonstrate that inhibition of the IRE1α activity impairs processing of preproinsulin signal peptide antigen and its recognition by specific autoreactive CTLs during inflammation. These results underscore the impact of ER stress in the increased visibility of β-cells to the immune system and position the IRE1α/miR-17 pathway as a central component in β-cell destruction processes and as a potential target for the treatment of autoimmune T1D. Full Article
id Opioid agonist treatment and risk of mortality during opioid overdose public health emergency: population based retrospective cohort study By feeds.bmj.com Published On :: Tuesday, March 31, 2020 - 09:36 Full Article
id Prediction models for diagnosis and prognosis of covid-19 infection: systematic review and critical appraisal By feeds.bmj.com Published On :: Tuesday, April 7, 2020 - 09:01 Full Article
id Use of electronic medical records in development and validation of risk prediction models of hospital readmission: systematic review By feeds.bmj.com Published On :: Wednesday, April 8, 2020 - 09:41 Full Article
id Association between maternal and paternal mental illness and risk of injuries in children and adolescents: nationwide register based cohort study in Sweden By feeds.bmj.com Published On :: Wednesday, April 8, 2020 - 22:31 Full Article
id Estimated population wide benefits and risks in China of lowering sodium through potassium enriched salt substitution: modelling study By feeds.bmj.com Published On :: Wednesday, April 22, 2020 - 17:00 Full Article
id Occurrence, prevention, and management of the psychological effects of emerging virus outbreaks on healthcare workers: rapid review and meta-analysis By feeds.bmj.com Published On :: Tuesday, May 5, 2020 - 12:46 Full Article
id Don’t Be Afraid of Political Fragmentation By feedproxy.google.com Published On :: Mon, 16 Dec 2019 11:00:17 +0000 16 December 2019 Pepijn Bergsen Research Fellow, Europe Programme @pbergsen LinkedIn If managed correctly, splintering and more volatile political systems – so-called ‘Dutchification’ – need not be a ticket to political and policy paralysis. 2019-12-16-Dutch-Election.jpg Voters cast their vote as part of the Dutch general elections on March 15, 2017 at a polling station in a mill in Oisterwijk. Photo by ROB ENGELAAR/AFP via Getty Images. In recent decades, political party systems across Europe have fragmented and electoral volatility has increased. The number of parties represented in parliaments across the continent has grown and the formerly dominant mainstream parties have seen their support base collapse, forcing parties into often uncomfortable and unstable coalitions.From the United Kingdom to Germany, politicians and commentators talk of such scenarios in often apocalyptic terms and associate it with political instability and policy paralysis.They shouldn’t. Instead they should focus their energy on making these increasingly competitive political markets work.The Netherlands is frequently held up as a prime example of this process, which is therefore sometimes referred to as ‘Dutchification’. Its highly proportional political system has created the opportunity for new parties and specific interest groups to win parliamentary representation, ranging from an animal rights party and a party catering specifically to the interests of the elderly.This has been accompanied by increased electoral volatility. In the 1970s, less than 15% of seats in the Dutch parliament would change party at any election, but in the last election in 2017, this was just over a quarter. The system also created space for the relatively early rise of populist far-right parties, though it was not the cause of their rise.Nevertheless, despite the regularly difficult coalition politics, it remains one of the most well-governed countries in the world.A short history of fragmentationLooking at the effective number of parties represented in parliaments, the number of parties, corrected for their size, provides a good measure of the extent of fragmentation. In the Netherlands this steadily increased from around four in the 1980s to over eight following the election in 2017. Even the populist far-right vote has fragmented, with two parties partly competing for the same electorate. In other countries it has been a more recent phenomenon. Spain remained a de facto two-party system until the financial crisis. Dissatisfaction with both mainstream parties has seen challenger parties on both the left and the right attract significant support, making it harder to form stable coalitions. Political fragmentation decreased slightly in Italy in recent years, but that was from a high base as it shot up in the early 1990s when the post-war political settlement crumbled.German politics, long a hallmark of stability, is struggling with the decrease in support for the parties that dominated its political scene in the post-war period. The Christian Democrats and Social Democrats only barely managed to win a majority together in the election in 2017, at 53.4% of the vote compared with the 81.3% achieved 30 years earlier. The latest polls suggest they would only get to 40% together if an election were held today.A similar trend is visible within the European Parliament. Whereas the two largest groups in the European Parliament, the Christian Democrats and the Social Democrats, together won 66% of the vote in the election in 1999, they did not even manage to win a majority together in 2019, taking just 39.5% of the vote.No crisis of democracyIf electoral volatility and political fragmentation does indeed constitute some sort of crisis of democracy, we should expect to see voters become unhappy about how their national democracy functions. Largely, the opposite seems to be the case.In the Netherlands, satisfaction with its democracy went up at the same time as Dutchification did its work. Similar trends are visible in other highly fragmented European political systems, often those with very proportional systems. Despite regular minority governments, satisfaction with democracy is above 90% in Denmark and at 80% in Sweden, according to the latest Eurobarometer data.In comparison, it stood at 52% in the United Kingdom and 53% in France, where the electoral system has, at least on the surface, prevented the kind of fragmentation supposedly plaguing proportional systems.Satisfaction with democracy seems to be affected by a number of factors. This includes the state of the economy, particularly in countries that were hit the hardest by the global financial and euro zone crises. Nevertheless, the data suggests that, even if we can’t say that Dutchification by definition leads to more satisfaction with democracy, it is clearly not associated with falling faith in the system.A competitive political marketDutchification should be seen as accompanying a more competitive political marketplace. A more emancipated, demanding and politically engaged electorate than in the post-war decades is willing to shop around instead of merely vote according to socioeconomic class or other dividing lines, such as religious ones. The fragmented parliaments that emerge as a result provide better representation of different groups within European societies.This makes life harder for Europe’s political parties and politicians, as they juggle large coalitions, or changing coalitions under minority governments, but provides voters with more choice and democratic renewal. If handled correctly this would also allow more responsiveness to shifts in public opinion.Such democratic creative destruction in competitive political markets is to be celebrated in a well-functioning democracy. Just as companies prefer to operate in an oligopoly, political parties prefer the stability of limited political competition. But wishing for this kind of stability comes perilously close to preferring stability over proper representation.Worrying about Dutchification risks confusing a crisis of the traditional mainstream parties with a crisis of democracy. For some countries, particularly those like the Netherlands and Denmark which have longer histories of consensus-based politics and coalition building, this is an easier adjustment. But this should not be an excuse to not attempt to make politics work better as they were forced to go through, arguably still ongoing, adjustment processes too.Instead of investing in futile attempts to get back to how things were in the old days, or hoping this will somehow magically happen, political leaders and parties across Europe need to reassess how they deal with the new reality of Dutchification. Full Article
id Webinar: European Union – The Economic and Political Implications of COVID-19 By feedproxy.google.com Published On :: Tue, 24 Mar 2020 12:25:01 +0000 Corporate Members Event Webinar 26 March 2020 - 5:00pm to 5:45pm Online Event participants Colin Ellis, Chief Credit Officer, Head of UK, Moody’s Investors ServiceSusi Dennison, Director, Europe Power Programme, European Council of Foreign RelationsShahin Vallée, Senior Fellow, German Council of Foreign Relations (DGAP)Pepijn Bergsen, Research Fellow, Europe Programme, Chatham HouseChair: Hans Kundnani, Senior Research Fellow, Europe Programme, Chatham House In the past few weeks, European Union member states have implemented measures such as social distancing, school and border closures and the cancellation of major cultural and sporting events in an effort to curb the spread of COVID-19. Such measures are expected to have significant economic and political consequences, threatening near or total collapse of certain sectors. Moreover, the management of the health and economic crises within the EU architecture has exposed tensions and impasses in the extent to which the EU is willing to collaborate to mitigate pressures on fellow member states.The panellists will examine the European Union's response to a series of cascading crises and the likely impact of the pandemic on individual member states. Can the EU prevent an economic hit from developing into a financial crisis? Are the steps taken by the European Central Bank to protect the euro enough? And are member states expected to manage the crisis as best they can or will there be a united effort to mitigate some of the damage caused? This event is part of a fortnightly series of 'Business in Focus' webinars reflecting on the impact of COVID-19 on areas of particular professional interest for our corporate members. Not a corporate member? Find out more. Full Article
id Virtual Breakfast: Engaging with the EU From the Outside: A Perspective From Norway By feedproxy.google.com Published On :: Tue, 07 Apr 2020 14:45:01 +0000 Invitation Only Research Event 24 April 2020 - 8:30am to 9:30am Event participants Niels Engelschiøn, Director-General, Department for European Affairs, Norwegian Ministry of Foreign AffairsChair: Dr Robin Niblett, Director; Chief Executive, Chatham House Please note this an online-only event.Norway is one of the few European countries that remains outside of the European Union. After the country’s population rejected the prospect of joining the EU twice, Norway’s relationship with the Union has been based on its membership of the European Economic Area (EEA), alongside Iceland and Liechtenstein.The ‘Norway Model’ was often mentioned in the run up to the Brexit vote as a possible basis for Britain’s future relationship with the bloc, not least because it offers the least disruption to the current arrangement. Equally, Norway is not subject to the EU fisheries policy - an anticipated major issue in the next phase of Brexit talks. Nor is it part of the EU Customs Union.Even though Prime Minister Johnson has now ruled out the type of deep economic and regulatory integration with the EU that Norway enjoys through its EEA membership, the country’s experience can still offer valuable lessons for the UK as it prepares to exit the transition period at the end of 2020.In this session, the speaker will share Norway’s experience as a long-standing EEA member and discuss the challenges of engaging with the EU from the outside. What lessons can Norway offer the UK ahead of the negotiations on the future of UK-EU relations? What are the limits of its current arrangement with the EU? And is there any appetite among the Norwegian population to revisit it? Department/project Europe Programme, Britain and Europe: The Post-Referendum Agenda Alina Lyadova Europe Programme Coordinator Email Full Article
id Belarusians Left Facing COVID-19 Alone By feedproxy.google.com Published On :: Thu, 16 Apr 2020 15:19:10 +0000 16 April 2020 Ryhor Astapenia Robert Bosch Stiftung Academy Fellow, Russia and Eurasia Programme @ryhorastapenia LinkedIn Anaïs Marin Associate Fellow, Russia and Eurasia Programme LinkedIn The way the epidemic is being mismanaged creates a risk of political destabilisation and leaves the country exposed to external influence. 2020-04-16-Belarus-COVID-Football Playing accordion in front of dummy football fans in Brest, Belarus as the country's championship continues despite the COVID-19 outbreak. Photo by SERGEI GAPON/AFP via Getty Images. Since the World Health Organisation (WHO) declared COVID-19 a pandemic, few countries have chosen to ignore social distancing recommendations. But, even among those states which have, the Belarusian official response to its epidemic remains unique.President Aliaksandr Lukashenka’s statements that vodka, sauna and tractors are protecting Belarusians from coronavirus attracted amused attention in international media. Lukashenka also described other societies’ response to COVID-19 as ‘a massive psychosis’.Although Lukashenka is notorious for his awkward style of public communication, the fact that Belarus is refusing to impose comprehensive confinement measures is of concern. Belarusians continue to work, play football and socialise.Lukashenka, himself playing ice hockey in front of state cameras, claims it is the best way to stay healthy. Belarusian authorities clearly appear to be in denial – and this could have dire humanitarian consequences.From denial to half measuresBelarus actually has one of the largest numbers of hospital beds in the world per 1,000 of the population. But in the absence of quarantine measures its health system, already crippled by corruption and embezzlement, is likely to be overwhelmed.Patients being treated for pneumonia in hospitals have suggested medical staff are uninformed and inadequately equipped. It is claimed doctors are not reporting COVID-19 as the suspected cause of death, either through a lack of testing or for fear of reprisals.Observers believe the real mortality rate is already well above official figures (40 deaths as of 16 April). Based on an Imperial College London model, between 15,000 and 32,000 people could die under the current mild confinement regime – and such a high death toll would hugely impact the country’s political stability. Citing personal data protection, the Ministry of Health has imposed a total news blackout; the only cluster officially acknowledged so far is the city of Vitsebsk.Although specific Belarusian cities and some individuals started changing their approach – by extending school vacations or cancelling weddings – such measures remain half-hearted.Clearly a major reason for such an apparently irresponsible reaction is that Belarus cannot afford a massive lockdown that would freeze its already underdeveloped economy and drive it deeper into recession. Unlike many other nations, Belarus lacks budgetary resources for a sizable stimulus package. But a delayed response might backfire on the economy.Economic recession has been forecast to amount to at least 10% of GDP. For Lukashenka, who openly challenged conventional wisdom regarding the need for quarantine and isolation, such an economic downturn would harm his confidence rating in the eyes of Belarusian voters, mindful of the state’s mismanagement of the crisis. And it could create doubt within the ruling elite itself, with Lukashenka seeking re-election for a sixth mandate in late August.Against this backdrop, a radicalization of the opposition-minded part of society is also to be expected, with greater reliance on social networks in the face of official secrecy and disinformation. The expected response of the regime is then likely to be pre-emptive repression. Evidence is emerging that law enforcement agencies have already stepped up judicial and paralegal harassment of dissenters, notably independent journalists and bloggers.Russia’s initial reluctance to address the coronavirus crisis may also have influenced Belarus. Lukashenka and his administration often react to public health challenges by the Soviet rulebook, reminiscent of the Soviet authorities’ mismanagement of the Chernobyl disaster in 1986.Russia has unilaterally closed its borders with Belarus and, as bilateral relations continue to deteriorate, this casts further doubt on the viability of the Union State of Belarus and Russia. Pro-Russian media forecast Moscow will be unwilling to alleviate the expected socio-economic crisis, as it continues to reject Minsk’s demands regarding subsidised oil deliveries. Yet the Kremlin might use the crisis as an opportunity to resume its integrationist pressure on Belarus.China, with which Belarus engaged in a seemingly privileged strategic partnership in the 2010s, was actually the first country to dispatch humanitarian aid to beef up Belarusian capacity to fight the virus.But Minsk should not expect Beijing to rescue its economy and, unless it commits to more internal reforms, Belarus is not likely to receive much from the EU either. The regime has already applied to the IMF for emergency financial support, but conditions are attached and, even if successful, the funds would amount to no more than $900m.The government’s decision to take only half measures so far is rooted in the hope COVID-19 is not as bad as foreign experts fear. But, unless the leadership acknowledges the public health crisis and mitigates its economic impact, COVID-19 will accelerate Belarus’s slide back into international self-isolation. If combined with a humanitarian crisis, this will put the Belarusian regime under considerable stress.This crisis does risk a new ‘Chernobyl moment’ for the authorities, but the population could react more vocally this time. As volunteers self-organise to fight the epidemic, it might become more difficult for the authorities to say that it is efficient in running the country. But the bottom line is Belarus desperately needs money. Whoever steps up to support Belarus financially will also be able to heavily influence its politics. Full Article
id Webinar: Turkey’s Challenging Post-COVID 19 Outlook By feedproxy.google.com Published On :: Fri, 17 Apr 2020 13:05:01 +0000 Invitation Only Research Event 7 May 2020 - 1:00pm to 2:00pm Event participants Dr Murat Ucer, Turkey Country Analyst, GlobalSource Partners Chair: Fadi Hakura, Manager, Turkey Project, Europe Programme, Chatham House Turkish President Recep Tayyip Erdogan has so far refused to impose a nation-wide lockdown to suppress the spread of coronavirus in the country. In late March, Turkish health officials announced that they expect the virus to peak in three weeks' time and for Turkey to overcome it quickly. At the same time, Turkey has ruled out turning to the IMF for help in dealing with the crisis despite growing pressures on the Lira and the wider economy. The country's relations with its traditional allies, the US and Europe, remain thorny. This event will focus on the likely impact of the epidemic on Turkey's economy and politics. What are the reasons behind Erdogan’s reluctance to implement a comprehensive lockdown to break the chain of virus transmission? Why is Turkey resolutely opposed to agreeing a funding package with the IMF? What is the macro outlook for 2020 and beyond for the country's economy? And how may the government's long-term popularity be affected? Event attributes Chatham House Rule Department/project Europe Programme, Turkey Project Alina Lyadova Europe Programme Coordinator Email Full Article
id Avoiding a Virus-Induced Cold War with China By feedproxy.google.com Published On :: Fri, 17 Apr 2020 16:05:40 +0000 17 April 2020 Robin Niblett Director and Chief Executive, Chatham House @RobinNiblett Managing relations with China once the COVID-19 crisis abates will be one of the biggest challenges facing political leaders in the United States and Europe – two of the areas worst-hit by the virus that originated in China. 2020-04-17-Trump-Xi Chinese president Xi Jinping and US president Donald Trump in Beijing, China. Photo by Thomas Peter-Pool/Getty Images. So far, there has been a noticeable worsening of relations that had already soured in recent years – the latest step being President Donald Trump’s suspension of US funding for the World Health Organization (WHO) in response to accusations of Chinese interference in its operations.Should the world now simply prepare for a period of intense and extended hostility? As director of a policy institute founded 100 years ago in the shadow of the First World War, I believe we must do all in our power to avoid a return of the global strategic rivalries that blighted the 20th century.Deepening suspicionsOf course, the outcome does not lie only in the hands of the US and Europe. In the 1930s, as much as they wanted to avoid another great war, British and French leaders were forced to respond to Germany’s aggression in central Europe. In the late 1940s, America’s instinct to disentangle itself from war-ravaged Europe was quickly tempered by the realization that the Soviet Union would impose or infiltrate Communist control as far into Europe as possible.Today, those who warned that China - a one-party, surveillance state with a power-centralising leader - could never be treated as a global stakeholder feel vindicated. They see in COVID-19 an opportunity to harden policies towards China, starting by blocking all Chinese investment into 5G infrastructure and breaking international dependence on Chinese supply chains.They can point to the fact that Chinese Communist Party officials in Wuhan initially prioritised sustaining economic growth and supressed reports about COVID-19’s capacity for human-to-human transmission, epitomised by their treatment of Dr Li Wenliang. They can highlight how Beijing’s obsession with denying Taiwan a voice in the WHO prevented Taiwanese input into the early analysis of the crisis. They can highlight the ways in which Beijing has instrumentalised its medical support for coronavirus-afflicted countries for diplomatic gain.For their part, those in China who believed the US and Europe would never allow China’s return as a regional and world power see this criticism as further evidence. They can point to comments about this being the ‘Chinese virus’, a leaked biological weapon or China’s ‘Chernobyl moment’. ‘Wolf warrior’ Chinese diplomats have sought to outdo each other by challenging narratives about COVID-19, while propagating disinformation about the origins of the virus.There are major risks if this blame game escalates, as it could in the lead-up to a fraught US presidential election. First, consciously uncoupling the US economically from China will make the post-coronavirus recovery that much harder. China already accounts for nearly 20% of world GDP but, unlike after the global financial crisis in 2008, it is fast becoming the world’s leading consumer market. Its financial stimulus measures need to be closely coordinated with the G7 and through the G20.Second, Chinese scientists were the first to uncover the genetic code of the virus and shared it with the WHO as early as January 12, enabling the roll-out of effective testing around the world. They are now involved in the global search for a vaccine alongside American and European counterparts. While the Chinese government will remain a legitimate target for criticism, Chinese citizens and companies will contribute to many of the most important technical breakthroughs this century.Third, if COVID-19 creates a long-term schism between China and the US, with Europeans caught on its edge, this could do deep damage to world order. China may become a less willing partner in lowering global greenhouse gas emissions and sharing renewable energy technologies; in helping African and other developing countries grow sustainably; and in helping to build a more resilient global health infrastructure.Getting the balance rightBut the COVID-19 crisis can also be the hinge point to a more coherent and self-interested transatlantic approach to China, one whose motto should be ‘beware but engage’. There should indeed be limits on state-backed Chinese investment in strategic US and European economic sectors, just as China limits Western access to its market. But the goal should be to lower barriers to trade and investment over time on a mutually beneficial and transparent basis, not to recreate an economic Cold War.Chinese human rights violations, at home and abroad, should be called out. The dissemination of Chinese systems of citizen surveillance, which will be more popular in a post-coronavirus world, should be monitored and contested with US and European alternatives. And the extent of Chinese exports’ access to international markets should be conditional on China improving its phytosanitary standards - which protect humans, animals, and plants from diseases, pests, or contaminants - and strictly regulating unhygienic wet markets.But to go further and try to make disengagement the dominant transatlantic policy as COVID-19 subsides will not only divide Europe and America. It will also contribute to a self-fulfilling prophecy; in which a resentful China grows apart from the US and Europe during a period where they must work together.Given that it will likely be the world’s largest economy in 2030, how the US and Europe manage their relations with China after this crisis is a question at least as seminal as the one they faced after 1945 with the Soviet Union. In the ensuing years, the Soviet Union became a military superpower and competitor, but not an economic one. Containment was a viable, correct and, ultimately, successful strategy. The same options are not available this time. There will be no winners from a new Cold War with China. Full Article
id Virtual Breakfast: Europe in the Age of COVID-19: Priorities and Debates By feedproxy.google.com Published On :: Tue, 21 Apr 2020 12:15:01 +0000 Invitation Only Research Event 6 May 2020 - 9:00am to 10:00am Event participants Duncan Robinson, Charlemagne Columnist; Brussels Bureau Chief, the EconomistChair: Pepijn Bergsen, Research Fellow, Europe Programme, Chatham House The new European Commission had a bold new agenda when it began its work in December 2019, with climate change, digital transformation and strengthening European democracy among its priorities. Less than six months later, the European continent is in the midst of the worst crisis since the second World War and business as usual has been taken over by crisis management.Has COVID-19 monopolized the agenda in Brussels? What priorities are still on the table and what debates have fallen victim to the coronavirus? Is the current crisis reigniting and exacerbating existing faultlines in the EU or creating new ones?Reflecting on his first four months as the Economist’s Charlemagne columnist, the speaker will share what decision-making in Brussels looks like during a pandemic and what debates are dominating conversations in the EU capital today. Event attributes Chatham House Rule Department/project Europe Programme, Britain and Europe: The Post-Referendum Agenda Alina Lyadova Europe Programme Coordinator Email Full Article
id The multilevel identity politics of the 2019 Eurovision Song Contest By feedproxy.google.com Published On :: Thu, 07 May 2020 09:28:22 +0000 7 May 2020 , Volume 96, Number 3 Galia Press-Barnathan and Naama Lutz Read online This article uses the 2019 Eurovision Song Contest (ESC) that took place in Tel Aviv to explore how cultural mega-events serve both as political arenas and as tools for identity construction, negotiation and contestation. These processes of identity politics are all conducted across national–subnational–international–transnational levels. The hosting of mega-events fleshes out these multiple processes in a very strong manner. We first discuss the politics of hosting mega-events in general. We then examine the identity politics associated more specifically with the Eurovision Song Contest, before examining in depth the complex forms of identity politics emerging around the competition following the 2018 Israeli victory. We suggest that it is important to study together the multiple processes—domestic, international and transnational—of identity politics that take place around the competition, as they interact with each other. Consequently, we follow the various stakeholders involved at these different levels and their interactions. We examine the internal identity negotiation process in Israel surrounding the event, the critical actors debating how to use the stage to challenge the liberal, western, ‘normal’ identity Israel hoped to project in the contest and how other stakeholders (participating states, national broadcasting agencies, participating artists) reacted to them, and finally we examine the behaviour of the institution in charge, the European Broadcasting Union, and national governments. We contribute to the study of mega-events as fields of contestation, to the understanding of the complex, multilevel nature of national identity construction, negotiation and contestation in the current era, and more broadly to the role that popular culture plays in this context. Full Article
id The prospects of carbon dioxide removal in climate policymaking within the United States By feedproxy.google.com Published On :: Fri, 14 Feb 2020 10:40:01 +0000 Research Event 19 November 2019 - 9:00am to 5:00pm School of Law, University of California, Davis Agendapdf | 158.8 KB Meeting Summarypdf | 207.92 KB This meeting formed part of a programme of work which investigates the role of negative emissions technologies (NETs) in achieving the Paris Agreement climate targets. Previous meetings held in London and Brussels have looked at integrating negative emissions into EU policy-making, the implications and degree to which NETs, and in particular bioenergy with carbon capture storage (BECCS), can be an effective climate mitigation tool. This meeting focused on the possible deployment pathways of NETs and alternatives to BECCS for the US in particular, in the context of geographical constraints and socioenvironmental implications, the role of the private sector, and appropriate governance and finance mechanisms. Department/project Energy, Environment and Resources Programme, Bioenergy, Carbon Capture and Storage (BECCS) Melissa MacEwen Project Manager, Energy, Environment and Resources Programme Email Full Article
id Lack of evidence for interventions offered in UK fertility centres By feeds.bmj.com Published On :: Monday, November 28, 2016 - 00:06 Full Article
id Overdiagnosis of thyroid cancer By feeds.bmj.com Published On :: Wednesday, November 30, 2016 - 23:30 Full Article
id Covid-19: Home testing programme across England aims to help define way out of lockdown By feeds.bmj.com Published On :: Friday, May 1, 2020 - 12:17 Full Article
id Covid-19’s impact on US medical research—shifting money, easing rules By feeds.bmj.com Published On :: Friday, May 1, 2020 - 13:37 Full Article
id Covid-19 is no worse in immunocompromised children, says NICE By feeds.bmj.com Published On :: Friday, May 1, 2020 - 14:22 Full Article
id Covid-19: Coroners needn’t investigate PPE policy failures in deaths of NHS staff, new guidance says By feeds.bmj.com Published On :: Monday, May 4, 2020 - 10:35 Full Article
id Covid-19: NHS bosses told to assess risk to ethnic minority staff who may be at greater risk By feeds.bmj.com Published On :: Monday, May 4, 2020 - 14:16 Full Article
id Covid-19: GPs have a fortnight to start organising weekly care home reviews, says NHS By feeds.bmj.com Published On :: Tuesday, May 5, 2020 - 11:01 Full Article
id Partha Kar: Covid-19 and ethnicity—why are all our angels white? By feeds.bmj.com Published On :: Tuesday, May 5, 2020 - 11:31 Full Article
id Covid-19: UK advisory panel members are revealed after experts set up new group By feeds.bmj.com Published On :: Tuesday, May 5, 2020 - 12:31 Full Article
id David Oliver: Is abuse towards doctors in government roles unfair? By feeds.bmj.com Published On :: Wednesday, May 6, 2020 - 09:26 Full Article
id Emergency departments must not return to pre-covid days of overcrowding and lack of safety, says college By feeds.bmj.com Published On :: Wednesday, May 6, 2020 - 11:01 Full Article
id Covid-19: Lack of capacity led to halting of community testing in March, admits deputy chief medical officer By feeds.bmj.com Published On :: Wednesday, May 6, 2020 - 12:25 Full Article
id Covid-19: the challenge of patient rehabilitation after intensive care By feeds.bmj.com Published On :: Wednesday, May 6, 2020 - 12:36 Full Article
id Covid-19: UK death toll overtakes Italy’s to become worst in Europe By feeds.bmj.com Published On :: Wednesday, May 6, 2020 - 13:37 Full Article
id Covid-19: Woman with terminal cancer should be released from care home to die with family, says judge By feeds.bmj.com Published On :: Wednesday, May 6, 2020 - 15:01 Full Article
id Covid-19: Surviving the long road ahead By feeds.bmj.com Published On :: Thursday, May 7, 2020 - 11:51 Full Article
id Covid-19: Trump says added deaths are necessary price for reopening US businesses By feeds.bmj.com Published On :: Thursday, May 7, 2020 - 14:10 Full Article
id CRISPR-Cas12a has widespread off-target and dsDNA-nicking effects [DNA and Chromosomes] By feedproxy.google.com Published On :: 2020-04-24T06:08:45-07:00 Cas12a (Cpf1) is an RNA-guided endonuclease in the bacterial type V-A CRISPR-Cas anti-phage immune system that can be repurposed for genome editing. Cas12a can bind and cut dsDNA targets with high specificity in vivo, making it an ideal candidate for expanding the arsenal of enzymes used in precise genome editing. However, this reported high specificity contradicts Cas12a's natural role as an immune effector against rapidly evolving phages. Here, we employed high-throughput in vitro cleavage assays to determine and compare the native cleavage specificities and activities of three different natural Cas12a orthologs (FnCas12a, LbCas12a, and AsCas12a). Surprisingly, we observed pervasive sequence-specific nicking of randomized target libraries, with strong nicking of DNA sequences containing up to four mismatches in the Cas12a-targeted DNA-RNA hybrid sequences. We also found that these nicking and cleavage activities depend on mismatch type and position and vary with Cas12a ortholog and CRISPR RNA sequence. Our analysis further revealed robust nonspecific nicking of dsDNA when Cas12a is activated by binding to a target DNA. Together, our findings reveal that Cas12a has multiple nicking activities against dsDNA substrates and that these activities vary among different Cas12a orthologs. Full Article
id Impact of 1,N6-ethenoadenosine, a damaged ribonucleotide in DNA, on translesion synthesis and repair [Enzymology] By feedproxy.google.com Published On :: 2020-05-01T00:06:09-07:00 Incorporation of ribonucleotides into DNA can severely diminish genome integrity. However, how ribonucleotides instigate DNA damage is poorly understood. In DNA, they can promote replication stress and genomic instability and have been implicated in several diseases. We report here the impact of the ribonucleotide rATP and of its naturally occurring damaged analog 1,N6-ethenoadenosine (1,N6-ϵrA) on translesion synthesis (TLS), mediated by human DNA polymerase η (hpol η), and on RNase H2–mediated incision. Mass spectral analysis revealed that 1,N6-ϵrA in DNA generates extensive frameshifts during TLS, which can lead to genomic instability. Moreover, steady-state kinetic analysis of the TLS process indicated that deoxypurines (i.e. dATP and dGTP) are inserted predominantly opposite 1,N6-ϵrA. We also show that hpol η acts as a reverse transcriptase in the presence of damaged ribonucleotide 1,N6-ϵrA but has poor RNA primer extension activities. Steady-state kinetic analysis of reverse transcription and RNA primer extension showed that hpol η favors the addition of dATP and dGTP opposite 1,N6-ϵrA. We also found that RNase H2 recognizes 1,N6-ϵrA but has limited incision activity across from this lesion, which can lead to the persistence of this detrimental DNA adduct. We conclude that the damaged and unrepaired ribonucleotide 1,N6-ϵrA in DNA exhibits mutagenic potential and can also alter the reading frame in an mRNA transcript because 1,N6-ϵrA is incompletely incised by RNase H2. Full Article
id Genetic evidence for reconfiguration of DNA polymerase {theta} active site for error-free translesion synthesis in human cells [DNA and Chromosomes] By feedproxy.google.com Published On :: 2020-05-01T00:06:09-07:00 The action mechanisms revealed by the biochemical and structural analyses of replicative and translesion synthesis (TLS) DNA polymerases (Pols) are retained in their cellular roles. In this regard, DNA polymerase θ differs from other Pols in that whereas purified Polθ misincorporates an A opposite 1,N6-ethenodeoxyadenosine (ϵdA) using an abasic-like mode, Polθ performs predominantly error-free TLS in human cells. To test the hypothesis that Polθ adopts a different mechanism for replicating through ϵdA in human cells than in the purified Pol, here we analyze the effects of mutations in the two highly conserved tyrosine residues, Tyr-2387 and Tyr-2391, in the Polθ active site. Our findings that these residues are indispensable for TLS by the purified Pol but are not required in human cells, as well as other findings, provide strong evidence that the Polθ active site is reconfigured in human cells to stabilize ϵdA in the syn conformation for Hoogsteen base pairing with the correct nucleotide. The evidence that a DNA polymerase can configure its active site entirely differently in human cells than in the purified Pol establishes a new paradigm for DNA polymerase function. Full Article
id The Trump Immigration Plan: A Lopsided Proposal By www.migrationpolicy.org Published On :: Fri, 26 Jan 2018 18:11:15 -0500 The White House immigration plan offered as a solution to resolve the fate of DREAMers seeks legal immigration cuts unlike any seen since 1924. In addition to a decrease of up to 40 percent in family-sponsored immigration, the proposal demands vast increases in enforcement and a retrenchment in protections for those seeking humanitarian relief. In exchange, one-sixth of the unauthorized population could gain legal status. Full Article
id Creatividad Dentro de la Crisis: Opciones Legales para Inmigrantes Venezolanos en América Latina By www.migrationpolicy.org Published On :: Mon, 04 Feb 2019 17:43:58 -0500 Convocamos un seminario en línea (webinar) en español en la ocasión del lanzamiento del informe, Creatividad dentro de la crisis: opciones legales para inmigrantes venezolanos en América Latina, que describe donde se han radicado los migrantes venezolanos; las medidas que han utilizado los gobiernos latinoamericanos para regularizar el estatus legal de los migrantes venezolanos; y los esfuerzos por integrar a los recién llegados en sus nuevas comunidades de residencia. Full Article
id Making the Global Compact on Migration a Reality: Ideas for Enhancing Regular Migration Pathways at All Skill Levels By www.migrationpolicy.org Published On :: Thu, 30 Aug 2018 19:11:37 -0400 As the final phase of preparations for the historic adoption of a Global Compact for Safe, Orderly, and Regular Migration approaches, this webinar explores two central objectives of the compact: enhancing the availability and flexibility of pathways for regular migration, and investing in skills development. Full Article
id Making the Global Compact on Migration a Reality: Ideas for Enhancing Regular Migration Pathways at All Skill Levels By www.migrationpolicy.org Published On :: Wed, 12 Sep 2018 17:30:25 -0400 As the final phase of preparations for the historic adoption of a Global Compact for Safe, Orderly, and Regular Migration approaches, this webinar explores two central objectives of the compact: enhancing the availability and flexibility of pathways for regular migration, and investing in skills development. Full Article
id Many Psychology Experiments Lack Evidence of Validity, Says Report By feeds.socialpsychology.org Published On :: 2020-05-01T04:05:06-04:00 Source: Science Daily - Top SocietyAn examination of nearly 350 published psychological experiments found that nearly half failed to show that they were based on a valid foundation of empirical evidence, suggesting that a wide swath of psychological science may be based on an "untested foundation." Full Article
id How One Woman Fled Domestic Violence During COVID-19 Pandemic By feeds.socialpsychology.org Published On :: 2020-05-01T06:47:43-04:00 Source: USA Today - Top StoriesWhen the coronavirus initially hit Colorado in early March, many flocked to grocery stores and cleared shelves, preparing to hunker down in their homes. But for Jeara and her four young children, those first days of the pandemic were different: They were settling into a domestic violence shelter after an incident involving her husband days earlier. Full Article
id Often Overlooked Learning Disorder May Affect Millions of Kids By feeds.socialpsychology.org Published On :: 2020-05-04T04:27:46-04:00 Source: Psych CentralNew research suggests nonverbal learning disability, a poorly understood and often-overlooked disorder that causes problems with visual-spatial processing, may affect nearly 3 million children in the United States alone. Full Article