Evolution of Black Holes in the Galaxy

In this article we consider the formation and evolution of black holes, especially those in binary stars where radiation from the matter falling on them can be seen. We consider a number of effects introduced by some of us, which are not traditionally included in binary evolution of massive stars. These are (i) hypercritical accretion, which allows neutron stars to accrete enough matter to collapse to a black hole during their spiral-in into another star. (ii) the strong mass loss of helium stars, which causes their evolution to differ from that of the helium core of a massive star. (iii) The direct formation of low-mass black holes (M\sim2\msun) from single stars, a consequence of a significant strange-matter content of the nuclear-matter equation of state at high density. We discuss these processes here, and then review how they affect various populations of binaries with black holes and neutron stars.Comment: 46 pages, 1 figure, to be published in Physics Repor

Establishment of a standard operating procedure for predicting the time of calving in cattle

Precise calving monitoring is essential for minimizing the effects of dystocia in cows and calves. We conducted two studies in healthy cows that compared seven clinical signs (broad pelvic ligaments relaxation, vaginal secretion, udder hyperplasia, udder edema, teat filling, tail relaxation, and vulva edema) alone and in combination in order to predict the time of parturition. The relaxation of the broad pelvic ligaments combined with teat filling gave the best values for predicting either calving or no calving within 12 h. For the proposed parturition score (PS), a threshold of 4 PS points was identified below which calving within the next 12 h could be ruled out with a probability of 99.3% in cows (95.5% in heifers). Above this threshold, intermitted calving monitoring every 3 h and a progesterone rapid blood test (PRBT) would be recommended. By combining the PS and PRBT (if PS ≥ 4), the prediction of calving within the next 12 h improved from 14.9% to 53.1%, and the probability of ruling out calving was 96.8%. The PRBT was compared to the results of an enzyme immunoassay (sensitivity, 90.2%; specificity, 74.9%). The standard operating procedure developed in this study that combines the PS and PRBT will enable veterinarians to rule out or predict calving within a 12 h period in cows with high accuracy under field conditions

Disrupting malaria parasite AMA1-RON2 interaction with a small molecule prevents erythrocyte invasion

Plasmodium falciparumresistance to artemisinin derivatives, the first-line anti-malarial drug, drives the search for new classes of chemotherapeutic agents. Current discovery is primarily directed against the intracellular forms of the parasite. However, late schizont-infected red blood cells (RBCs) may still rupture and cause disease by sequestration; consequently targeting invasion may reduce disease severity. Merozoite invasion of RBCs requires interaction between two parasite proteins AMA1 and RON2. Here we identify the first inhibitor of this interaction that also blocks merozoite invasion in genetically distinct parasites by screening a library of over 21,000 compounds. We demonstrate that this inhibition is mediated by the small molecule binding to AMA1 and blocking the formation of AMA1-RON complex. Electron microscopy confirms that the inhibitor prevents junction formation, a critical step in invasion that results from AMA1-RON2 binding. This study uncovers a strategy that will allow for highly effective combination therapies alongside existing anti-malarial drugs

Neuropsychiatric manifestation of confusional psychosis due to Cryptococcus neoformans var. grubii in an apparently immunocompetent host: a case report

Cognitive disorders like dementia, delirium, depression, anxiety, psychosis and mania are the commonest neuropsychiatric manifestations. We discuss here a case of an adult women presenting with neuropsychiatric manifestations of confusional psychosis owing to Cryptococcosis. The principal cause was consequently established by culturing Cryptococcus neoformans from the cerebrospinal fluid confirmed as C. neoformans var. grubii (Serotype A) by genotypic methods. Antifungal therapy with IV Amphotericin B lead to sustained improvement and recovery of the patient from behavioural disorders. The case discussed here invokes the need for the vigilance it demands in delineating organic brain syndromes for a favourable treatment outcome

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

Proposal of early CT morphological criteria for response of liver metastases to systemic treatments in gastroenteropancreatic neuroendocrine tumors:Alternatives to RECIST

RECIST 1.1 criteria are commonly used with computed tomography (CT) to evaluate the efficacy of systemic treatments in patients with neuroendocrine tumors (NETs) and liver metastases (LMs), but their relevance is questioned in this setting. We aimed to explore alternative criteria using different numbers of measured LMs and thresholds of size and density variation. We retrospectively studied patients with advanced pancreatic or small intestine NETs with LMs, treated with systemic treatment in the first-and/or second-line, without early progression, in 14 European expert centers. We compared time to treatment failure (TTF) between responders and non-responders according to various criteria defined by 0%, 10%, 20% or 30% decrease in the sum of LM size, and/or by 10%, 15% or 20% decrease in LM density, measured on two, three or five LMs, on baseline (≤1 month before treatment initiation) and first revaluation (≤6 months) contrast-enhanced CT scans. Multivariable Cox proportional hazard models were performed to adjust the association between response criteria and TTF on prognostic factors. We included 129 systemic treatments (long-acting somatostatin analogs 41.9%, chemotherapy 26.4%, targeted therapies 31.8%), administered as first-line (53.5%) or second-line therapies (46.5%) in 91 patients. A decrease ≥10% in the size of three LMs was the response criterion that best predicted prolonged TTF, with significance at multivariable analysis (HR 1.90; 95% CI: 1.06–3.40; p =.03). Conversely, response defined by RECIST 1.1 did not predict prolonged TTF (p =.91), and neither did criteria based on changes in LM density. A ≥10% decrease in size of three LMs could be a more clinically relevant criterion than the current 30% threshold utilized by RECIST 1.1 for the evaluation of treatment efficacy in patients with advanced NETs. Its implementation in clinical trials is mandatory for prospective validation. Criteria based on changes in LM density were not predictive of treatment efficacy. Clinical Trial Registration: Registered at CNIL-CERB, Assistance publique hopitaux de Paris as “E-NETNET-L-E-CT” July 2018. No number was assigned. Approved by the Medical Ethics Review Board of University Medical Center Groningen.</p

Solar geoengineering: The case for an international non-use agreement

Solar geoengineering is gaining prominence in climate change debates as an issue worth studying; for some it is even a potential future policy option. We argue here against this increasing normalization of solar geoengineering as a speculative part of the climate policy portfolio. We contend, in particular, that solar geoengineering at planetary scale is not governable in a globally inclusive and just manner within the current international political system. We therefore call upon governments and the United Nations to take immediate and effective political control over the development of solar geoengineering technologies.Specifically, we advocate for an International Non-Use Agreement on Solar Geoengineering and outline the core elements of this proposal

The full value of vaccine assessments concept - current opportunities and recommendations

For vaccine development and adoption decisions, the ‘Full Value of Vaccine Assessment’ (FVVA) framework has been proposed by the WHO to expand the range of evidence available to support the prioritization of candidate vaccines for investment and eventual uptake by low- and middle-income countries. Recent applications of the FVVA framework have already shown benefits. Building on the success of these applications, we see important new opportunities to maximize the future utility of FVVAs to country and global stakeholders and provide a proof-of-concept for analyses in other areas of disease control and prevention. These opportunities include the following: (1) FVVA producers should aim to create evidence that explicitly meets the needs of multiple key FVVA consumers, (2) the WHO and other key stakeholders should develop standardized methodologies for FVVAs, as well as guidance for how different stakeholders can explicitly reflect their values within the FVVA framework, and (3) the WHO should convene experts to further develop and prioritize the research agenda for outcomes and benefits relevant to the FVVA and elucidate methodological approaches and opportunities for standardization not only for less well-established benefits, but also for any relevant research gaps. We encourage FVVA stakeholders to engage with these opportunities

The Full Value of Vaccine Assessments Concept—Current Opportunities and Recommendations

For vaccine development and adoption decisions, the ‘Full Value of Vaccine Assessment’ (FVVA) framework has been proposed by the WHO to expand the range of evidence available to support the prioritization of candidate vaccines for investment and eventual uptake by low- and middle-income countries. Recent applications of the FVVA framework have already shown benefits. Building on the success of these applications, we see important new opportunities to maximize the future utility of FVVAs to country and global stakeholders and provide a proof-of-concept for analyses in other areas of disease control and prevention. These opportunities include the following: (1) FVVA producers should aim to create evidence that explicitly meets the needs of multiple key FVVA consumers, (2) the WHO and other key stakeholders should develop standardized methodologies for FVVAs, as well as guidance for how different stakeholders can explicitly reflect their values within the FVVA framework, and (3) the WHO should convene experts to further develop and prioritize the research agenda for outcomes and benefits relevant to the FVVA and elucidate methodological approaches and opportunities for standardization not only for less well-established benefits, but also for any relevant research gaps. We encourage FVVA stakeholders to engage with these opportunities