The Polypeptide Structure of Immunoglobulin: Experimental Studies on the Recombination of Radiolabelled Myeloma Polypeptide Chains

Peer Reviewe

Risk Tradeoffs and Equitable Decision-Making in the COVID-19 Pandemic

Since the start of the Covid-19 pandemic, societies have faced agonizing decisions about whether to close schools, shutter businesses, delay nonemergency health care, restrict travel, and authorize the use of emergency Covid-19 countermeasures under limited scientific understanding. Measures to control the spread of COVID-19 have disrupted our health, educational, and economic systems, tarnished our mental health, and took away our cherished time with family and friends. Conflicting advice from health agencies on the utility of public health measures left us wondering, was it all worth it? We still do not have all the answers to guide us through difficult risk-risk tradeoff decisions during a health emergency. When both action and inaction can result in significant harm and irreversible damage, decisions surrounding infection control measures become complicated, and there is no single correct answer. Yet ethics can help us think about hard trade-offs that weigh competing values and have deep consequences for society and particularly the most disadvantaged. This essay discusses the challenges of making policy trade-offs amid scientific uncertainty. While there may be no perfect formula for deciding what to do and when, we propose four key considerations for assessing risk-risk trade-offs, involving effectiveness, less-restrictive means, harm identification and amelioration, and equitable distribution. We then and apply those four considerations to the areas of education, economies, health care, travel and migration, social engagement, and medical countermeasures, examining governments’ response to the COVID-19 pandemic, and assessing how responses to the next major outbreak can be improved

Using COVID-19 to Strengthen the WHO: Promoting Health and Science Above Politics

On April 14, 2020, President Trump announced the suspension of funding for the World Health Organization (WHO) to investigate WHO’s handling of the COVID-19 pandemic—citing WHO’s “disastrous decision” to oppose a travel ban on China, and for being slow and “China-centric.” Certainly, China failed in its international duty to respond rapidly and transparently to the novel coronavirus, and it suppressed truthful information, propelling a localized outbreak into a pandemic now in over 210 countries. Yet close examination of WHO’s COVID-19 response reveals that the Organization acted in line with its authority under the International Health Regulations, and using the available scientific evidence. Still, WHO’s response has been constrained by its limited funding and authority, and its need to maintain diplomacy among member states. We are facing a once-in-a-century health emergency, with WHO under attack as never before. But out of a crisis can come an historic opportunity to strengthen WHO to become the health agency the world desperately needs. What might WHO reform look like if we truly want to empower the Organization, as we should? That reform should address the structural problems that put WHO in the crossfires of geopolitical disputes and force it to appeal to countries’ political interests instead of the best scientific evidence. We propose an emboldened WHO Director-General, sustainable funding, strengthened authority to use unofficial data, and incentives for states’ compliance with global health norms

How the Biden Administration Can Reinvigorate Global Health Security, Institutions, and Governance

The tragedy of COVID-19 can be fertile soil for deep structural reforms. President Biden can both bolster the immediate responses to COVID-19 and its vast ramifications, and spearhead lasting changes to create a healthier and safer world, from which the United States would richly benefit. The agenda we propose for President Biden is ambitious, yet US. bold leadership on global health will benefit all people, including Americans, and is in the U.S. national interest Along with responding to the COVID-19 domestically, the Biden administration should enhance U.S.-initiatives home, expanding the Global Health Security Agenda and restoring and reinvigorating the PREDICT animal virus identification and tracking project, while ensuring that the U.S. Strategic National Stockpile is fully stocked with critical medical supplies and expanding research and development of antimicrobials. To enable the world to benefit from U.S. science – and to benefit from it – the administration should support the Open Science movement. And the administration should work with Congress to use devote 2% of past and future U.S. domestic COVID-19 spending to the global response, extend a debt moratorium, and enhance debt cancellation. The United States should lead strengthened global governance for health security, beginning with proposing a doubling of mandatory WHO contributions, WHO reform including enhanced civil society participation, and strengthening the International Health Regulations (2005). Meanwhile, along with joining and funding the global vaccine distribution mechanism, COVAX, the Biden administration should propose creating a permanent facility for distributing PPE and other medical supplies and equipment, diagnostics, therapies, and vaccines during epidemics and pandemics. And by supporting use of TRIPS-flexibilities and, going further, supporting suspending intellectual property rights related to COVID-19 technologies, expanding production and increasing access, the administration would enable expanded global production, enhanced access, and lower prices. Finally, the Biden administration should lead a collaborative global effort to ensure that the global health architecture is firmly based in human rights, which would enhance equity and accountability and elevate the voices and priorities of marginalized populations. At its foundation would be the Framework Convention on Global Health, a proposed treaty that, if adopted, would strengthen implementation of the right to health and promote global health equity, while a Right to Health Capacity Fund could support right-to-health advocacy, accountability, and participation mechanisms

The Global Health and Care Worker Compact: Evidence Base and Policy Considerations

Background During the COVID-19 pandemic, and recognising the sacrifice of health and care workers alongside discrimination, violence, poor working conditions and other violations of their rights, health and safety, in 2021 the World Health Assembly requested WHO to develop a global health and care worker compact, building on existing normative documentation, to provide guidance to ‘protect health and care workers and safeguard their rights’. Methods A review of existing international law and other normative documents was conducted. We manually searched five main sets of international instruments: (1) International Labour Organization conventions and recommendations; (2) WHO documents; (3) United Nations (UN) human rights treaties and related documents; (4) UN Security Council and General Assembly resolutions and (5) the Geneva Conventions and Additional Protocols. We included only legal or other normative documents with a global or regional focus directly addressing or relevant to health and care workers or workers overall. Results More than 70 documents met our search criteria. Collectively, they fell into four domains, within which we identified 10 distinct areas: (1) preventing harm, encompassing (A) occupational hazards, (B) violence and harassment and (C) attacks in situations of fragility, conflict and violence; (2) inclusivity, encompassing (A) non-discrimination and equality; (3) providing support, encompassing (A) fair and equitable remuneration, (B) social protection and (C) enabling work environments and (4) safeguarding rights, encompassing (A) freedom of association and collective bargaining and (B) whistle-blower protections and freedom from retaliation. Discussion A robust legal and policy framework exists for supporting health and care workers and safeguarding their rights. Specific human rights, the right to health overall, and other binding and non-binding legal documents provide firm grounding for the compact. However, these existing commitments are not being fully met. Implementing the compact will require more effective governance mechanisms and new policies, in partnership with health and care workers themselves

Inspiratory muscle training reduces blood lactate concentration during volitional hyperpnoea

Although reduced blood lactate concentrations ([lac−]B) have been observed during whole-body exercise following inspiratory muscle training (IMT), it remains unknown whether the inspiratory muscles are the source of at least part of this reduction. To investigate this, we tested the hypothesis that IMT would attenuate the increase in [lac−]B caused by mimicking, at rest, the breathing pattern observed during high-intensity exercise. Twenty-two physically active males were matched for 85% maximal exercise minute ventilation (V˙Emax) and divided equally into an IMT or a control group. Prior to and following a 6 week intervention, participants performed 10 min of volitional hyperpnoea at the breathing pattern commensurate with 85% V˙Emax

Absence of repellents in Ustilago maydis induces genes encoding small secreted proteins

The rep1 gene of the maize pathogen Ustilago maydis encodes a pre-pro-protein that is processed in the secretory pathway into 11 peptides. These so-called repellents form amphipathic amyloid fibrils at the surface of aerial hyphae. A SG200 strain in which the rep1 gene is inactivated (∆rep1 strain) is affected in aerial hyphae formation. We here assessed changes in global gene expression as a consequence of the inactivation of the rep1 gene. Microarray analysis revealed that only 31 genes in the ∆rep1 SG200 strain had a fold change in expression of ≥2. Twenty-two of these genes were up-regulated and half of them encode small secreted proteins (SSPs) with unknown functions. Seven of the SSP genes and two other genes that are over-expressed in the ∆rep1 SG200 strain encode proteins that can be classified as secreted cysteine-rich proteins (SCRPs). Interestingly, most of the SCRPs are predicted to form amyloids. The SCRP gene um00792 showed the highest up-regulation in the ∆rep1 strain. Using GFP as a reporter, it was shown that this gene is over-expressed in the layer of hyphae at the medium-air interface. Taken together, it is concluded that inactivation of rep1 hardly affects the expression profile of U. maydis, despite the fact that the mutant strain has a strong reduced ability to form aerial hyphae

European summer temperatures since Roman times

The spatial context is critical when assessing present-day climate anomalies, attributing them to potential forcings and making statements regarding frequency and severity in the long-term perspective. Recent initiatives have expanded the number of high-quality proxy-records and developed new reconstruction methods. These advances allow more rigorous regional past temperature reconstructions and the possibility of evaluating climate models on policy-relevant, spatio-temporal scales. We provide a new proxy-based, annually-resolved, spatial reconstruction of the European summer temperature fields back to 755 CE based on a Bayesian hierarchical modelling (BHM), together with estimates of the European mean temperature variation since 138 BCE based on Composite-plus-Scaling. Our reconstructions compare well with independent instrumental and proxy-based temperature estimates, but suggest a larger amplitude in summer temperature variability than previously reported. Temperature differences between the medieval period, the recent period and Little Ice Age are larger in reconstructions than simulations. This may indicate either inflated variability of the reconstructions, a lack of sensitivity to external forcing on sub-hemispheric scales in the climate models and/or an underestimation of internal variability on centennial and longer time scales including the representation of internal feedback mechanisms

Measurements of fiducial and differential cross sections for Higgs boson production in the diphoton decay channel at s√=8 TeV with ATLAS

Measurements of fiducial and differential cross sections are presented for Higgs boson production in proton-proton collisions at a centre-of-mass energy of s√=8 TeV. The analysis is performed in the H → γγ decay channel using 20.3 fb−1 of data recorded by the ATLAS experiment at the CERN Large Hadron Collider. The signal is extracted using a fit to the diphoton invariant mass spectrum assuming that the width of the resonance is much smaller than the experimental resolution. The signal yields are corrected for the effects of detector inefficiency and resolution. The pp → H → γγ fiducial cross section is measured to be 43.2 ±9.4(stat.) − 2.9 + 3.2 (syst.) ±1.2(lumi)fb for a Higgs boson of mass 125.4GeV decaying to two isolated photons that have transverse momentum greater than 35% and 25% of the diphoton invariant mass and each with absolute pseudorapidity less than 2.37. Four additional fiducial cross sections and two cross-section limits are presented in phase space regions that test the theoretical modelling of different Higgs boson production mechanisms, or are sensitive to physics beyond the Standard Model. Differential cross sections are also presented, as a function of variables related to the diphoton kinematics and the jet activity produced in the Higgs boson events. The observed spectra are statistically limited but broadly in line with the theoretical expectations