Coronavirus disease 2019 (Covid-19) disproportionately results in hospitalization or death in older patients and those with underlying conditions. Sotrovimab is a pan-sarbecovirus monoclonal antibody ...that was designed to prevent progression of Covid-19 in high-risk patients early in the course of disease.
In this ongoing, multicenter, double-blind, phase 3 trial, we randomly assigned, in a 1:1 ratio, nonhospitalized patients with symptomatic Covid-19 (≤5 days after the onset of symptoms) and at least one risk factor for disease progression to receive a single infusion of sotrovimab at a dose of 500 mg or placebo. The primary efficacy outcome was hospitalization (for >24 hours) for any cause or death within 29 days after randomization.
In this prespecified interim analysis, which included an intention-to-treat population of 583 patients (291 in the sotrovimab group and 292 in the placebo group), 3 patients (1%) in the sotrovimab group, as compared with 21 patients (7%) in the placebo group, had disease progression leading to hospitalization or death (relative risk reduction, 85%; 97.24% confidence interval, 44 to 96; P = 0.002). In the placebo group, 5 patients were admitted to the intensive care unit, including 1 who died by day 29. Safety was assessed in 868 patients (430 in the sotrovimab group and 438 in the placebo group). Adverse events were reported by 17% of the patients in the sotrovimab group and 19% of those in the placebo group; serious adverse events were less common with sotrovimab than with placebo (in 2% and 6% of the patients, respectively).
Among high-risk patients with mild-to-moderate Covid-19, sotrovimab reduced the risk of disease progression. No safety signals were identified. (Funded by Vir Biotechnology and GlaxoSmithKline; COMET-ICE ClinicalTrials.gov number, NCT04545060.).
Criminal courts are often required, in the course of implementing existing doctrines of constitutional criminal law, to regulate other institutional actors within the criminal justice system — most ...notably, prosecutors and police officers. The one-off nature of constitutional criminal adjudication, however, often impedes such regulation, in part by denying courts an opportunity to "see" the systemic features of law enforcement behavior. This mismatch between criminal courts' institutional task and their institutional capacity has inspired efforts to identify other means of addressing systemic failings of American criminal justice — including calls for a pivot to law enforcement self-regulation as a primary means of constraining state power in the criminal justice arena. The true capacity of criminal courts, however, has thus far been significantly underappreciated. For at an institutional level, criminal courts are not only deeply and serially engaged with the very governmental entities that constitutional criminal law seeks to regulate, but are also constantly collecting — often in a digital format readily amenable to organization, search, and analysis — valuable and detailed systemic facts about how other criminal justice actors operate. This information extends far beyond the truncated transactional horizon of a given case, and thus could allow courts to access a deep internal well of institutional knowledge about their local criminal justice systems. Uncovering the hidden potential of this latent institutional knowledge raises important questions about the opportunities for — and the responsibilities of — criminal courts to collect systemic facts, to analyze them, to make them transparent to litigants and to the public, and to integrate them into the process of constitutional criminal adjudication.
Probable Cause Pluralism CRESPO, ANDREW MANUEL
The Yale law journal,
03/2020, Letnik:
129, Številka:
5
Journal Article
The constitutionality of a search or seizure typically depends upon the connection between the target of that search or seizure and some allegation of illegal behavior — a connection assessed by ...asking whether the search or seizure is supported by probable cause. But as central as probable cause is to the Fourth Amendment's administration, no one seems to know what it means or how it operates. Indeed, the Supreme Court insists it is "not possible" to define the term, holding instead that the probable-cause inquiry entails no more than the application of "common sense" to "the totality of the circumstances." Viewed charitably, this refusal to elaborate on the meaning of probable cause stems from an understandable desire for doctrinal flexibility in the face of weighty and competing law-enforcement demands. But the Court's doctrinal approach is also routinely criticized as an "I know it when I see it" jurisprudence that is ill equipped to safeguard civil liberties in the numerous interactions between civilians and law-enforcement actors. This tension between doctrinal flexibility and structure is the animating dilemma of probable-cause jurisprudence — a dilemma that this Article attempts to navigate and, ultimately, to resolve. To do so, it urges a rejection of an often invoked — if not always followed — tenet of Supreme Court doctrine: probable cause unitarianism. That dominant idea, expressly endorsed in many of the Court's leading precedents, holds that whatever probable cause means, it ought to entail the same basic analytic method and be judged by the same substantive standard, from one case to another. But on close inspection, the Supreme Court's existing jurisprudence contains seeds of an alternative — and superior — conception of probable cause, which this Article terms probable cause pluralism. On this view, probable cause is an open-textured and capacious idea that can comfortably encompass distinct analytic frameworks and substantive standards, each of which can be tailored to the unique epistemological and normative challenges posed by different types of Fourth Amendment events. Probable-cause analysis can be statistically driven or intuitively assessed; it can demand compelling evidence of illegal behavior or only an occasionally satisfied profile; it can presume the credibility of some types of witnesses while treating others with deserved skepticism or disbelief. It can, in short, come to mean something — if it gives up on meaning any one thing in all cases. In its current form, probable cause's pluralism is nascent, implicit, and undertheorized — and is thus at best a stunted and haphazard collection of disparate ideas. This Article's central contribution is to bring those ideas together, refining and synthesizing them into a comprehensive account of what a pluralist theory of probable cause could and should look like. Specifically, by organizing probable cause around three central analytic axes — which in turn ask how to assess evidentiary claims, how to assess proponents of such claims, and how to determine the certainty thresholds for those two assessments — this Article constructs a universally applicable framework for determining the constitutionality of any given search or seizure. With that framework in hand, scholars and jurists will be better equipped to reason through the many and varied cases to come and better able to assess the many cases that have come before.
Iris L. s.l. is one of the most diverse and well-known genera in the Asparagales, with approximately 250-300 circumscribed species and significant economic impact. The taxonomy of the genus has ...suffered dramatic changes in the last century, particularly in the last decades after the application of molecular techniques. As a result several contrasting systematic arrangements are currently available to taxonomists. Many genera that were split from Iris s.str. in the past, on the basis of morphology (e.g., Hermodactylus, Iridodictyum, Juno, Pardanthopsis, and Xiphion, among others), are now a priori re-included in a very widely circumscribed Iris s.l. (incl. Belamcanda). This resulted in a more heterogeneous genus that is more difficult to define on morphological grounds. Testing congruence between taxonomic treatments and the results of recent molecular studies of Iris has never been performed, mostly due to the lack of proper taxonomic context.
We generated several conventional phylogenies for Iris & outgroups using extensive sampling of taxa (187) and characters (10 plastid loci). We demonstrate that the natural history of Iris, written either as conventional molecular phylogenies or, if viewing in the context of the comparative approach, as a nested most parsimonious hierarchy of patterns, appear to be fully congruent with the narrow taxonomical treatment of the genus, restricted to the rhizomatous "bearded" taxa. The resulting topologies place Belamcanda, Pardanthopsis, and Gattenhofia as sisters to Iris s.str. and genus Siphonostylis as sister to Iris s.l.
The present study clearly justifies the splitting of Iris s.l. into at least 23 genera, 18 of which have already been accepted in the past by numerous authorities. These genera are characterized by unique combinations of partly overlapping morphological characters and biogeography. Moreover, nearly the same entities, which we here recognize at a generic rank, were for centuries frequently referred to by horticulturists as "working-name" groups.
The American criminal justice system is a system of pleas. Few who know it well think it is working. And yet, identifying plausible strategies for law reform proves challenging, given the widely held ...scholarly assumption that plea bargaining operates “beyond the shadow of the law.” That assumption holds true with respect to substantive and constitutional criminal law—the two most studied bodies of law in the criminal justice system—neither of which significantly regulates prosecutorial power. The assumption is misguided, however, insofar as it fails to account for a third body of law—the subconstitutional law of criminal procedure—that regulates and often establishes the very mechanisms by which prosecutorial plea bargaining power is both generated and deployed.
These hidden regulatory levers are neither theoretical nor abstract. Rather, they exist in strikingly varied forms across our pluralist criminal justice system. This Article excavates these unexamined legal frameworks, conceptualizes their regulatory potential, highlights their heterogeneity across jurisdictions, and exposes the institutional actors most frequently responsible for their content. In so doing, it opens up not only new scholarly terrain but also new potential pathways to criminal justice reform.
Context
Continuing professional development (CPD) activities for healthcare professionals are central to the optimisation of patient safety and person‐centred care. Although there is some evidence on ...the economics of healthcare professionals training, very little is known about the costs and benefits of CPD.
Methods
This study aimed to review the research evidence on economic evaluations of CPD activities for healthcare professionals. CINAHL, MEDLINE/PubMed, Scopus, Econlit and Web of Science databases were used to identify articles published between 2010 and 2021.
Results
Of the 6791 titles identified, 119 articles met the inclusion criteria and were included in this scoping review. The majority of articles were partial economic evaluations of CPD programmes (n = 70); half were from the USA. Studies that included multiple professions were most prevalent (n = 54), followed by nurses (n = 34) and doctors (n = 23). Patient outcomes were the most commonly reported outcome (n = 51), followed by change in clinical practice (n = 38) and healthcare professionals' knowledge gain (n = 19).
Conclusions
There is an urgent call for more evidence regarding the economic evaluations of CPD. This is particularly important in view of the rising costs of healthcare globally. The majority of studies included in this review did not provide detailed information on the evaluations and many focused exclusively on the cost of CPD activities rather than outcomes.
In view of the rising costs of healthcare globally, Witold et al. demonstrate an urgent need for stronger economic evaluations of CPD programmes.
Abstract
Macroptilium gracile (Phaseolinae, Fabaceae) sensu lato is an extremely diverse species distributed from Mexico to Argentina. The taxonomic and nomenclatural history of the species is ...confusing, due to existing contrasting treatments. All 15 names corresponding to 12 taxa that have often been considered akin to M. gracile were selected here to clarify the identity of this taxonomic aggregate, using morphological, molecular and biogeographical analyses. Univariate and multivariate statistical analyses (nMDS and cluster) of 67 morphological traits were performed on a sample of 109 herbarium sheets. Maximum parsimony and Bayesian inference analyses were conducted using plastid (rpl32-trnL(UAG), trnK-matK-trnK) and nuclear (ITS/5.8S) DNA sequence data on a sample of 31 accessions belonging to taxa of the M. gracile complex and other Macroptilium spp., using three members of related genera (Phaseolus and Vigna) as outgroups. A database with plant locations per taxa was used to elaborate a distribution map, and the potential habitats were estimated through nMDS analysis. Our morphological, molecular and biogeographic results suggest that members of the M. gracile complex belong to three taxonomic entities, for which a new arrangement is proposed accepting Macroptilium gracile (with two varieties) and M. campestre, including two new nomenclatural combinations (M. gracile var. subcoriaceum and M. campestre). Types for all cited names are indicated where available (with a new lectotype designation). Morphological, ecological and distributional data are reported for each accepted taxon.
Survivors to COVID-19 have described long-term symptoms after acute disease. These signs constitute a heterogeneous group named long COVID or persistent COVID. The aim of this study is to describe ...persisting symptoms 6 months after COVID-19 diagnosis in a prospective cohort in the Northwest Spain. This is a prospective cohort study performed in the COHVID-GS. This cohort includes patients in clinical follow-up in a health area of 569,534 inhabitants after SARS-CoV-2/COVID-19 diagnosis. Clinical and epidemiological characteristics were collected during the follow up. A total of 248 patients completed 6 months follow-up, 176 (69.4%) required hospitalization and 29 (10.2%) of them needed critical care. At 6 months, 119 (48.0%) patients described one or more persisting symptoms. The most prevalent were: extra-thoracic symptoms (39.1%), chest symptoms (27%), dyspnoea (20.6%), and fatigue (16.1%). These symptoms were more common in hospitalized patients (52.3% vs. 38.2%) and in women (59.0% vs. 40.5%). The multivariate analysis identified COPD, women gender and tobacco consumption as risk factors for long COVID. Persisting symptoms are common after COVID-19 especially in hospitalized patients compared to outpatients (52.3% vs. 38.2%). Based on these findings, special attention and clinical follow-up after acute SARS-CoV-2 infection should be provided for hospitalized patients with previous lung diseases, tobacco consumption, and women.
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•Phylogenies based on plastid and nuclear DNA revealed morphologically solid clades.•A time-calibrated tree allowed reappraisal of evolutionary and biogeographic relations.•The ...evolution of the section matches Mediterranean major geological and climate events.•Mediterranean glacial refuges acted as genetic reservoirs for lineage diversification.
Biscutella ser. Biscutella (= ser. Lyratae Malin.) is a group of mostly annual or short-lived perennial plants, with petals gradually tapering at the base and lateral intrastaminal nectaries, endemic to the Mediterranean basin and the Middle East. Recent taxonomic work has revealed that a relative morphological homogeneity occurs in Europe and Asia, but a high plasticity is found in N Africa for most of the characters traditionally used for taxonomic arrangements. This fact had generally led to overestimation of the number of taxa, which currently is reduced to ten (namely 7 species and 3 additional varieties), some of them being narrow endemics. In the present contribution, on the basis of a previous detailed morphological study carried out by the authors, the first comprehensive phylogeny based on 47 DNA sequence data including concatenation of two plastid (rpl32-trnL and trnV) and one nuclear (ITS) regions, together with the first time-calibrated phylogenetic tree, allows reappraisal of evolutionary and biogeographic relationships among the accepted taxa in the series. According to all evidence gathered in the present study, the current distribution of B. ser. Biscutella, mostly centred in the southern parts of the Mediterranean basin and the Middle East, suggests that it evolved in relation with the major geological and climatic events occurred in the Mediterranean basin and Eurasia within the last 20 million years. The origin of Biscutella is dated ca 18.75 Mya, and the radiation of the series triggered ca 5.87 Mya with the Messinian Salinity Crisis. Rapid diversification occurred coetaneously to the Intensification of Northern Hemisphere Glaciation (ca 2.86 Mya) onwards, with parallel large-amplitude aridity cycles in Africa and southwestern Asia. In recent times, the divergence of lineages became faster in the W Mediterranean (ca 1.54 to 0.43 Mya), mostly related to geographical and ecological patterns of specialisation. In many cases, the distribution of the current species is apparently linked to ancient glacial refuges in S Mediterranean basin.
The use of convolutional neuronal networks (CNN) for the treatment of interferometric fringes has been introduced in recent years. In this paper, we optimize and build a CNN model, based U-NET ...architecture, to maximize its performance processing electronic speckle interferometry fringes (ESPI). The proposed approach is based on quick and light trainings to select the architecture parameters (network depth and kernel sizes) to maximize the performance of the neural network improving the visibility of ESPI images. To measure the performance, the structural similarity index (SSMI) will be the lead indicator, and the need for large datasets to train neural networks, unavailable for ESPI images, forces the use of a simulated ESPI image dataset along the process. This dataset is computed using Zernike polynomials to simulate local surface deformations in the specimen under test and simulated true speckle fields for the reference and object field involved in ESPI techniques.
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