BACKGROUND Vaccination using severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein antigen has been effective in the prevention of coronavirus disease 2019 (Covid-19). NVX-CoV2373 is an adjuvanted, recombinant S protein nanoparticle vaccine that demonstrated clinical efficacy for prevention of Covid-19 in phase 2b/3 trials in the United Kingdom and South Africa.
METHODS This phase 3, randomized, observer-blinded, placebo-controlled trial evaluated the efficacy and safety of NVX-CoV2373 in adults [≥]18 years of age in the United States and Mexico during the first quarter of 2021. Participants were randomized in a 2:1 ratio to receive two doses of NVX-CoV2373 or placebo 21 days apart. The primary end point was vaccine efficacy (VE) against reverse transcriptase-polymerase chain reaction-confirmed Covid-19 in SARS-CoV-2-naive participants [≥]7 days after the second dose administration.
RESULTS Of the 29,949 participants randomized between December 27, 2020, and February 18, 2021, 29,582 (median age: 47 years, 12.6% [≥]65 years) received [≥]1 dose: 19,714 received vaccine and 9868 placebo. In the per-protocol population, there were 77 Covid-19 cases; 14 among vaccine and 63 among placebo recipients (VE: 90.4%, 95% confidence interval [CI] 82.9 to 94.6, P90%) for prevention of Covid-19, with most cases due to variant strains. ...
This commentary responds to Stephen Cave and Kanta Dihal’s (2020) call for further investigations of the whiteness of AI. My response focuses on three overlapping projects needed to more fully understand racial bias in the construction of AI and its representations in pop culture: (1) unpacking the intersections of gender and other variables with whiteness in AI’s construction, marketing, and intended functions; (2) observing the many different ways in which whiteness is scripted, and (3) noting how white racial framing exceeds white casting and thus cannot be undone by more diverse and inclusive hiring (or engineering). Our techno utopian fantasies, I conclude, are morally suspect in ways that go beneath and beyond the white plastic covering on robotic bodies.
Background : Worldwide, neurological disorders are the leading cause of disability adjusted life years lost and the second leading cause of death. Despite global health capacity building efforts, each year, 22.6 million individuals worldwide require neurosurgeon"s care due to diseases such as traumatic brain injury and hydrocephalus, and 13.8 million of these individuals require surgery. It is clear that neurosurgical care is indispensable in both national and international public health discussions. This study highlights the role neurosurgeons can play in supporting the global health agenda, national surgical plans, and health strengthening systems (HSS) interventions.
Method : Guided by a literature review, the authors discuss key topics such as the global burden of neurosurgical diseases, the current state of neurosurgical care around the world and the inherent benefits of strong neurosurgical capability for health systems.
Result : Neurosurgical diseases make up an important part of the global burden of diseases. Many neurosurgeons possess the sustained passion, resilience, and leadership needed to advocate for improved neurosurgical care worldwide. Neurosurgical care has been linked to 14 of the 17 Sustainable Development Goals (SDGs), thus highlighting the tremendous impact neurosurgeons can have upon HSS initiatives.
Conclusion : We recommend policymakers and global health actors to: (i) increase the involvement of neurosurgeons within the global health dialogue; (ii) involve neurosurgeons in the national surgical system strengthening process; (iii) integrate neurosurgical care within the global surgery movement; and (iv) promote the training and education of neurosurgeons, especially those residing in Low and middle income countries, in the field of global public health.
Adaptive optics (AO) is a technique that corrects for optical aberrations. It was originally proposed to correct for the blurring effect of atmospheric turbulence on images in ground-based telescopes and was instrumental in the work that resulted in the Nobel prize-winning discovery of a supermassive compact object at the centre of our galaxy. When AO is used to correct for the eye’s imperfect optics, retinal changes at the cellular level can be detected, allowing us to study the operation of the visual system and to assess ocular health in the microscopic domain. By correcting for sample-induced blur in microscopy, AO has pushed the boundaries of imaging in thick tissue specimens, such as when observing neuronal processes in the brain. In this primer, we focus on the application of AO for high-resolution imaging in astronomy, vision science and microscopy. We begin with an overview of the general principles of AO and its main components, which include methods to measure the aberrations, devices for aberration correction, and how these components are linked in operation. We present results and applications from each field along with reproducibility considerations and limitations. Finally, we discuss future directions.
Untargeted metabolomics experiments rely on spectral libraries for structure annotation, but, typically, only a small fraction of spectra can be matched. Previous in silico methods search in structure databases but cannot distinguish between correct and incorrect annotations. Here we introduce the COSMIC workflow that combines in silico structure database generation and annotation with a confidence score consisting of kernel density P value estimation and a support vector machine with enforced directionality of features. On diverse datasets, COSMIC annotates a substantial number of hits at low false discovery rates and outperforms spectral library search. To demonstrate that COSMIC can annotate structures never reported before, we annotated 12 natural bile acids. The annotation of nine structures was confirmed by manual evaluation and two structures using synthetic standards. In human samples, we annotated and manually validated 315 molecular structures currently absent from the Human Metabolome Database. Application of COSMIC to data from 17,400 metabolomics experiments led to 1,715 high-confidence structural annotations that were absent from spectral libraries.
Stroke, Ahead of Print. Background and Purpose:Poststroke/transient ischemic attack obstructive sleep apnea (OSA) is prevalent, linked with numerous unfavorable health consequences, but remains underdiagnosed. Reasons include patient inconvenience and costs associated with use of in laboratory polysomnography (iPSG), the current standard tool. Fortunately, home sleep apnea testing (HSAT) can accurately diagnose OSA and is potentially more convenient and cost effective compared with iPSG. Our objective was to assess whether screening for OSA in patients with stroke/transient ischemic attack using HSAT, compared with standard of care using iPSG, increased diagnosis and treatment of OSA, improved clinical outcomes and patient experiences with sleep testing, and was a cost effective approach.
Method :We consecutively recruited 250 patients who had sustained a stroke/transient ischemic attack within the past 6 months. Patients were randomized (1:1) to use of (1) HSAT versus (2) iPSG. Patients completed assessments and questionnaires at baseline and 6 month follow up appointments. Patients diagnosed with OSA were offered continuous positive airway pressure. The primary outcome was compared between study arms via an intention to treat analysis.
Result :At 6 months, 94 patients completed HSAT and 71 patients completed iPSG. A significantly greater proportion of patients in the HSAT arm were diagnosed with OSA (48.8% versus 35.2%,P=0.04) compared with the iPSG arm. Furthermore, patients assigned to HSAT, compared with iPSG, were more likely to be prescribed continuous positive airway pressure (40.0% versus 27.2%), report significantly reduced sleepiness, and a greater ability to perform daily activities. Moreover, a significantly greater proportion of patients reported a positive experience with sleep testing in the HSAT arm compared with the iPSG arm (89.4% versus 31.1%). Finally, a cost effectiveness analysis revealed that HSAT was economically attractive for the detection of OSA compared with iPSG.
Conclusion :In patients with stroke/transient ischemic attack, use of HSAT compared with iPSG increases the rate of OSA diagnosis and treatment, reduces daytime sleepiness, improves functional outcomes and experiences with sleep testing, and could be an economically attractive approach.REGISTRATION:URL:https://www.clinicaltrials.gov; Unique identifier: NCT02454023.
Modern linkages among magmatic, geochemical, and geobiological processes provide clues about the importance of thermophiles in the origin of biogeochemical cycles. The aim of this study was to identify the primary chemoautotrophs and host–virus interactions involved in microbial colonization and biogeochemical cycling at sublacustrine, vapor-dominated vents that represent the hottest measured ecosystems in Yellowstone National Park (~140 °C). Filamentous microbial communities exposed to extreme thermal and geochemical gradients were sampled using a remotely operated vehicle and subjected to random metagenome sequencing and microscopic analyses. Sulfurihydrogenibium (phylum Aquificae) was the predominant lineage (up to 84% relative abundance) detected at vents that discharged high levels of dissolved H2, H2S, and CO2. Metabolic analyses indicated carbon fixation by Sulfurihydrogenibium spp. was powered by the oxidation of reduced sulfur and H2, which provides organic carbon for heterotrophic community members. Highly variable Sulfurihydrogenibium genomes suggested the importance of intra-population diversity under extreme environmental and viral pressures. Numerous lytic viruses (primarily unclassified taxa) were associated with diverse archaea and bacteria in the vent community. Five circular dsDNA uncultivated virus genomes (UViGs) of ~40 kbp length were linked to the Sulfurihydrogenibium metagenome-assembled genome (MAG) by CRISPR spacer matches. Four UViGs contained consistent genome architecture and formed a monophyletic cluster with the recently proposed Pyrovirus genus within the Caudovirales. Sulfurihydrogenibium spp. also contained CRISPR arrays linked to plasmid DNA with genes for a novel type IV filament system and a highly expressed β-barrel porin. A diverse suite of transcribed secretion systems was consistent with direct microscopic analyses, which revealed an extensive extracellular matrix likely critical to community structure and function. We hypothesize these attributes are fundamental to the establishment and survival of microbial communities in highly turbulent, extreme-gradient environments.
Major negative life events, such as trauma exposure, can play a key role in igniting or exacerbating psychopathology. However, few disorders are diagnosed with respect to precipitating events, and the role of these events in the unfolding of new psychopathology is not well understood. The authors conducted a multisite transdiagnostic longitudinal study of trauma exposure and related mental health outcomes to identify neurobiological predictors of risk, resilience, and different symptom presentations. A total of 146 participants (discovery cohort: N=69; internal replication cohort: N=77) were recruited from emergency departments within 72 hours of a trauma and followed for the next 6 months with a survey, MRI, and physiological assessments. Task-based functional MRI 2 weeks after a motor vehicle collision identified four clusters of individuals based on profiles of neural activity reflecting threat reactivity, reward reactivity, and inhibitory engagement. Three clusters were replicated in an independent sample with a variety of trauma types. The clusters showed different longitudinal patterns of posttrauma symptoms. These findings provide a novel characterization of heterogeneous stress responses shortly after trauma exposure, identifying potential neuroimaging-based biotypes of trauma resilience and psychopathology.
Volume 46, Issue 4, December 2021.
Tumour necrosis factor (TNF) is a classical, pleiotropic pro-inflammatory cytokine. It is also the first ‘adipokine’ described to be produced from adipose tissue, regulated in obesity and proposed to contribute to obesity-associated metabolic disease. In this review, we provide an overview of TNF in the context of metabolic inflammation or metaflammation, its discovery as a metabolic messenger, its sites and mechanisms of action and some critical considerations for future research. Although we focus on TNF and the studies that elucidated its immunometabolic actions, we highlight a conceptual framework, generated by these studies, that is equally applicable to the complex network of pro-inflammatory signals, their biological activity and their integration with metabolic regulation, and to the field of immunometabolism more broadly.
Objective : The provision of high quality personal protective equipment (PPE) has been a critical challenge during the COVID 19 pandemic. We evaluated an alternative strategy, mass deployment of a powered air purifying respirator (PeRSo), in a large university hospital.
Method : We performed prospective user feedback via questionnaires sent to healthcare workers (HCWs) issued PeRSos, economic analysis, and evaluated the real world impact.
Result : Where paired responses were available, PeRSo was preferred over droplet precautions for comfort, patient response, overall experience, and subjective feeling of safety. For all responses, more participants reported the overall experience being rated “Very good” more frequently for PeRSo. The primary limitation identified was impairment of hearing. Economic simulation exercises revealed that the adoption of PeRSo within ICU is associated with net cost savings in the majority of scenarios and savings increased progressively with greater ITU occupancy. In evaluation during the second UK wave, over 3,600 respirators were deployed, all requested by staff, which were associated with a low staff absence relative to most comparator hospitals.
Conclusion : Health services should consider a widespread implementation of powered reusable respirators as a safe and sustainable solution for the protection of HCWs as SARS CoV 2 becomes an endemic viral illness.
Secondary contact between species often results in the formation of a hybrid zone, with the eventual fates of the hybridizing species dependent on evolutionary and ecological forces. We examine this process in the Amazon Basin by conducting the first genomic and phenotypic characterization of the hybrid zone formed after secondary contact between two obligate army‐ant‐followers: the White‐breasted Antbird (Rhegmatorhina hoffmannsi) and the Harlequin Antbird (R. berlepschi). We found a major geographic displacement (∼120 km) between the mitochondrial and nuclear clines, and we explore potential hypotheses for the displacement, including sampling error, genetic drift, and asymmetric cytonuclear incompatibilities. We cannot exclude roles for sampling error and genetic drift in contributing to the discordance; however, the data suggest expansion and unidirectional introgression of hoffmannsi into the distribution of berlepschi. This article is protected by copyright. ...
For centuries, both scientists and philosophers have discussed the nature of species resulting in ca 35 species concepts proposed to date. However, in our opinion, none of them incorporated neither recent advances in evolutionary genomics nor dimensionality of species in befitting depth. Our attempt to do so resulted in following conclusions. Due to the continuous nature of evolution (regardless of its rate and constancy), species are inevitably undefinable as natural discontinuous units (except those originating in saltatory speciation) whenever the time dimension is taken into consideration. Therefore, the very existence of species as a natural discontinuous entity is relative to its dimensionality. A direct consequence of the relativity of species is the duality of speciators (e.g., incipient species) meaning that, in a given time, they may be perceived as both being and not being a species. Finally, the most accurate way to reflect both the relativity of species and the duality of speciators in species delimitation is probabilistic. While the novelty of these ideas may be questionable, they still deserve more extensive attention from the biological community. Here, we hope to draw such attention by outlining one of the possible pathways towards a new kind of probabilistic species delimitation methods based on the probability of irreversible divergence of evolutionary lineages. We anticipate that our probabilistic view of speciation has the potential to facilitate some of the most serious and universal issues of current taxonomy and to ensure unity of the species‐level taxonomy across the tree of life.
Bayes factors allow researchers to test the effects of experimental manipulations in within subjects designs using mixed effects models. van Doorn et al. (2021) showed that such hypothesis tests can be performed by comparing different pairs of models which vary in the specification of the fixed and random effect structure for the within subjects factor. To discuss the question of which model comparison is most appropriate, van Doorn et al. compared three corresponding Bayes factors using a case study. We argue that researchers should not only focus on pairwise comparisons of two nested models but rather use Bayesian model selection for the direct comparison of a larger set of mixed models reflecting different auxiliary assumptions regarding the heterogeneity of effect sizes across individuals. In a standard one factorial, repeated measures design, the comparison should include four mixed effects models: fixed effects H0, fixed effects H1, random effects H0, and random effects H1. Thereby, one can test both the average effect of condition and the heterogeneity of effect sizes across individuals. Bayesian model averaging provides an inclusion Bayes factor which quantifies the evidence for or against the presence of an average effect of condition while taking model selection uncertainty about the heterogeneity of individual effects into account. We present a simulation study showing that model averaging among a larger set of mixed models performs well in recovering the true, data generating model.
Mounting evidence suggests that publications and citations of scholars in the STEM fields (Science, Technology, Engineering and Mathematics) suffer from gender biases. In this paper, we study the physics community, a core STEM field in which women are still largely under represented and where these gender disparities persist. To reveal such inequalities, we compare the citations received by papers led by men and women that cover the same topics in a comparable way. To do that, we devise a robust statistical measure of similarity between publications that enables us to detect pairs of similar papers. Our findings indicate that although papers written by women tend to have lower visibility in the citation network, pairs of similar papers written by men and women receive comparable attention when corrected for the time of publication. These analyses suggest that gender disparity is closely related to the first mover and cumulative advantage that men have in physics and is not an intentional act of discrimination towards women.
Music and movement occur together across the world. Sievers et al. show a basis for this link: human auditory and visual cortex share a representational structure, putting music and movement in comparable terms. Shared crossmodal representations may arise to identify environmentally relevant feature combinations, such as those expressing emotion.