University settings have demonstrated potential for coronavirus disease (COVID-19) outbreaks; they combine congregate living, substantial social activity, and a young population predisposed to mild ...illness. Using genomic and epidemiologic data, we describe a COVID-19 outbreak at the University of Wisconsin-Madison, Madison, Wisconsin, USA. During August-October 2020, a total of 3,485 students, including 856/6,162 students living in dormitories, tested positive. Case counts began rising during move-in week, August 25-31, 2020, then rose rapidly during September 1-11, 2020. The university initiated multiple prevention efforts, including quarantining 2 dormitories; a subsequent decline in cases was observed. Genomic surveillance of cases from Dane County, in which the university is located, did not find evidence of transmission from a large cluster of cases in the 2 quarantined dorms during the outbreak. Coordinated implementation of prevention measures can reduce COVID-19 spread in university settings and may limit spillover to the surrounding community.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Good decision-making is a complex endeavor, and particularly so in a health context. The possibilities for day-to-day clinical practice opened up by AI-driven clinical decision support systems ...(AI-CDSS) give rise to fundamental questions around responsibility. In causal, moral and legal terms the application of AI-CDSS is challenging existing attributions of responsibility. In this context, responsibility gaps are often identified as main problem. Mapping out the changing dynamics and levels of attributing responsibility, we argue in this article that the application of AI-CDSS causes diffusions of responsibility with respect to a causal, moral, and legal dimension. Responsibility diffusion describes the situation where multiple options and several agents can be considered for attributing responsibility. Using the example of an AI-driven ‘digital tumor board’, we illustrate how clinical decision-making is changed and diffusions of responsibility take place. Not denying or attempting to bridge responsibility gaps, we argue that dynamics and ambivalences are inherent in responsibility, which is based on normative considerations such as avoiding experiences of disregard and vulnerability of human life, which are inherently accompanied by a moment of uncertainty, and is characterized by revision openness. Against this background and to avoid responsibility gaps, the article concludes with suggestions for managing responsibility diffusions in clinical decision-making with AI-CDSS.
What is story completion? How come I've never heard of it? Can it be useful for me as a qualitative researcher? A relatively unknown method for qualitative data collection, story completion has a ...long history of use in psychotherapy practice and (quantitative) developmental psychology research. We believe it has untapped, exciting potential as a qualitative technique in and beyond psychology, offering something quite different to many of the popular methods (e.g., interviews, focus groups). In this article, an introduction to an exciting Special Issue that discusses and demonstrates the potential of story completion, we provide a brief history of the development of story completion as a qualitative technique and an overview of design, sampling, and data analysis in story completion research. We finish by highlighting potential pitfalls of story completion, alongside a discussion of the possibilities it offers, and briefly introduce the empirical papers in the Special Issue.
Mutations in SCN2A, a gene encoding the voltage-gated sodium channel Nav1.2, have been associated with a spectrum of epilepsies and neurodevelopmental disorders. Here, we report the phenotypes of 71 ...patients and review 130 previously reported patients. We found that (i) encephalopathies with infantile/childhood onset epilepsies (≥3 months of age) occur almost as often as those with an early infantile onset (<3 months), and are thus more frequent than previously reported; (ii) distinct phenotypes can be seen within the late onset group, including myoclonic-atonic epilepsy (two patients), Lennox-Gastaut not emerging from West syndrome (two patients), and focal epilepsies with an electrical status epilepticus during slow sleep-like EEG pattern (six patients); and (iii) West syndrome constitutes a common phenotype with a major recurring mutation (p.Arg853Gln: two new and four previously reported children). Other known phenotypes include Ohtahara syndrome, epilepsy of infancy with migrating focal seizures, and intellectual disability or autism without epilepsy. To assess the response to antiepileptic therapy, we retrospectively reviewed the treatment regimen and the course of the epilepsy in 66 patients for which well-documented medical information was available. We find that the use of sodium channel blockers was often associated with clinically relevant seizure reduction or seizure freedom in children with early infantile epilepsies (<3 months), whereas other antiepileptic drugs were less effective. In contrast, sodium channel blockers were rarely effective in epilepsies with later onset (≥3 months) and sometimes induced seizure worsening. Regarding the genetic findings, truncating mutations were exclusively seen in patients with late onset epilepsies and lack of response to sodium channel blockers. Functional characterization of four selected missense mutations using whole cell patch-clamping in tsA201 cells-together with data from the literature-suggest that mutations associated with early infantile epilepsy result in increased sodium channel activity with gain-of-function, characterized by slowing of fast inactivation, acceleration of its recovery or increased persistent sodium current. Further, a good response to sodium channel blockers clinically was found to be associated with a relatively small gain-of-function. In contrast, mutations in patients with late-onset forms and an insufficient response to sodium channel blockers were associated with loss-of-function effects, including a depolarizing shift of voltage-dependent activation or a hyperpolarizing shift of channel availability (steady-state inactivation). Our clinical and experimental data suggest a correlation between age at disease onset, response to sodium channel blockers and the functional properties of mutations in children with SCN2A-related epilepsy.
Abstract
Background
High-frequency, rapid-turnaround severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing continues to be proposed as a way of efficiently identifying and mitigating ...transmission in congregate settings. However, 2 SARS-CoV-2 outbreaks occurred among intercollegiate university athletic programs during the fall 2020 semester, despite mandatory directly observed daily antigen testing.
Methods
During the fall 2020 semester, athletes and staff in both programs were tested daily using Quidel’s Sofia SARS Antigen Fluorescent Immunoassay, with positive antigen results requiring confirmatory testing with real-time reverse-transcription polymerase chain reaction. We used genomic sequencing to investigate transmission dynamics in these 2 outbreaks.
Results
In the first outbreak, 32 confirmed cases occurred within a university athletics program after the index patient attended a meeting while infectious, despite a negative antigen test on the day of the meeting. Among isolates sequenced from that outbreak, 24 (92%) of 26 were closely related, suggesting sustained transmission following an initial introduction event. In the second outbreak, 12 confirmed cases occurred among athletes from 2 university programs that faced each other in an athletic competition, despite receipt of negative antigen test results on the day of the competition. Sequences from both teams were closely related and distinct from viruses circulating in the community for team 1, suggesting transmission during intercollegiate competition in the community for team 2.
Conclusions
These findings suggest that antigen testing alone, even when mandated and directly observed, may not be sufficient as an intervention to prevent SARS-CoV-2 outbreaks in congregate settings, and they highlight the importance of vaccination to prevent SARS-CoV-2 outbreak in congregate settings.
Growth factors of the gp130 family promote oligodendrocyte differentiation, and viability, and myelination, but their mechanisms of action are incompletely understood. Here, we show that these ...effects are coordinated, in part, by the transcriptional activator Krüppel-like factor-6 (Klf6). Klf6 is rapidly induced in oligodendrocyte progenitors (OLP) by gp130 factors, and promotes differentiation. Conversely, in mice with lineage-selective Klf6 inactivation, OLP undergo maturation arrest followed by apoptosis, and CNS myelination fails. Overlapping transcriptional and chromatin occupancy analyses place Klf6 at the nexus of a novel gp130-Klf-importin axis, which promotes differentiation and viability in part via control of nuclear trafficking. Klf6 acts as a gp130-sensitive transactivator of the nuclear import factor importin-α5 (Impα5), and interfering with this mechanism interrupts step-wise differentiation. Underscoring the significance of this axis in vivo, mice with conditional inactivation of gp130 signaling display defective Klf6 and Impα5 expression, OLP maturation arrest and apoptosis, and failure of CNS myelination.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Acute Myeloid Leukemia (AML) develops due to the acquisition of mutations from multiple functional classes. Here, we demonstrate that activating mutations in the granulocyte colony stimulating factor ...receptor (CSF3R), cooperate with loss of function mutations in the transcription factor CEBPA to promote acute leukemia development. The interaction between these distinct classes of mutations occurs at the level of myeloid lineage enhancers where mutant CEBPA prevents activation of a subset of differentiation associated enhancers. To confirm this enhancer-dependent mechanism, we demonstrate that CEBPA mutations must occur as the initial event in AML initiation. This improved mechanistic understanding will facilitate therapeutic development targeting the intersection of oncogene cooperativity.
Asbestos-related diseases are often considered a ‘thing of the past’ in the global North. Yet, asbestos products remain widely used in the global South, especially in low cost housing. Like many ...occupational diseases, the history of asbestos is fraught with scientific controversy. The role of the asbestos industry in fostering uncertainty has been investigated for decades. But, less is known about the ways in which publicly-funded, not industry-funded, science has produced ignorance about the health consequences of exposure. To explore the contribution of publicly-funded science to the construction of ignorance, we examine the continuities and discontinuities among three hypotheses of mesothelioma causality: the amphibole hypothesis, the SV40 hypothesis, and the genetic hypothesis. Placing our analysis of scientific controversy in the context of asbestos mining in South Africa, we summarize the key features of the long-standing amphibole hypothesis, track in detail the emergence of SV40 as a causal agent, and outline the ongoing debate over genes as causes of mesothelioma. Regardless of the source of funding, we argue that by operating within conceptually closed biomedical frameworks, each hypothesis generated scientific controversy that made the political, social, and economic context of asbestos mining, milling, and manufacture in South Africa and other regions of the global South invisible, thereby limiting causal understanding.
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