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. ...
Gopalan et al. describe multi CUT&Tag, a method for simultaneous mapping of multiple chromatin epitopes in the same cells. Multi CUT&Tag can directly detect co association of chromatin proteins in pools of cells or single cells, enabling studies of combinatorial gene regulatory inputs and cellular heterogeneity from small populations of cells.
While often deleterious, hybridization can also be a key source of genetic variation and pre-adapted haplotypes, enabling rapid evolution and niche expansion. Here we evaluate these opposing selection forces on introgressed ancestry between maize (Zea mays ssp. mays) and its wild teosinte relative, mexicana (Zea mays ssp. mexicana). Introgression from ecologically diverse teosinte may have facilitated maize’s global range expansion, in particular to challenging high elevation regions (> 1500 m). We generated low-coverage genome sequencing data for 348 maize and mexicana individuals to evaluate patterns of introgression in 14 sympatric population pairs, spanning the elevational range of mexicana, a teosinte endemic to the mountains of Mexico. While recent hybrids are commonly observed in sympatric populations and mexicana demonstrates fine-scale local adaptation, we find that the majority of mexicana ancestry tracts introgressed into maize over 1000 generations ago. This mexicana ancestry seems to have maintained much of its diversity and likely came from a common ancestral source, rather than contemporary sympatric populations, resulting in relatively low FST between mexicana ancestry tracts sampled from geographically distant maize populations.Introgressed mexicana ancestry in maize is reduced in lower-recombination rate quintiles of the genome and around domestication genes, consistent with pervasive selection against introgression. However, we also find mexicana ancestry increases across the sampled elevational gradient and that high introgression peaks are most commonly shared among high-elevation maize populations, consistent with introgression from mexicana facilitating adaptation to the highland environment. In the other direction, we find patterns consistent with adaptive and clinal introgression of maize ancestry into sympatric mexicana at many loci across the genome, suggesting that maize also contributes to adaptation in mexicana, especially at the lower end of its elevational range. In sympatric maize, in addition to high introgression regions we find many genomic regions where selection for local adaptation maintains steep gradients in introgressed mexicana ancestry across elevation, including at least two inversions: the well-characterized 14 Mb Inv4m on chromosome 4 and a novel 3 Mb inversion Inv9f surrounding the macrohairless1 locus on chromosome 9. Most outlier loci with high mexicana introgression show no signals of sweeps or local sourcing from sympatric populations and so likely represent ancestral introgression sorted by selection, resulting in correlated but distinct outcomes of introgression in different contemporary maize populations.
The exponential rise of information available means we can now, in theory, access knowledge on almost any question we ask. However, as the amount of unverified information increases, so too does the challenge in deciding which information to trust. Farmers, when learning about agricultural innovations, have historically relied on in person advice from traditional ‘experts’, such as agricultural advisers, to inform farm management. As more farmers go online for information, it is not clear whether they are now using digital information to corroborate in person advice from traditional ‘experts’, or if they are foregoing ‘expert’ advice in preference for peer generated information. To fill this knowledge gap, we sought to understand how farmers in two contrasting European countries (Hungary and the UK) learnt about sustainable soil innovations and who influenced them to innovate. Through interviews with 82 respondents, we found farmers in both countries regularly used online sources to access soil information; some were prompted to change their soil management by farmer social media ‘influencers’. However, online information and interactions were not usually the main factor influencing farmers to change their practices. Farmers placed most trust in other farmers to learn about new soil practices and were less trusting of traditional ‘experts’, particularly agricultural researchers from academic and government institutions, who they believed were not empathetic towards farmers’ needs. We suggest that some farmers may indeed have had enough of traditional ‘experts’, instead relying more on their own peer networks to learn and innovate. We discuss ways to improve trustworthy knowledge exchange between agricultural stakeholders to increase uptake of sustainable soil management practices, while acknowledging the value of peer influence and online interactions for innovation and trust building.
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.
Leaves and flowers are colonized by diverse bacteria that impact plant fitness and evolution. Although the structure of these microbial communities is becoming well-characterized, various aspects of their environmental origin and selection by plants remain uncertain, such as the relative proportion of soilborne bacteria in phyllosphere communities. Here, to address this issue and to provide experimental support for bacteria being filtered by flowers, we conducted common-garden experiments outside and under gnotobiotic conditions. We grew Arabidopsis thaliana in a soil substitute and added two microbial communities from natural soils. We estimated that at least 25% of the phyllosphere bacteria collected from the plants grown in the open environment were also detected in the controlled conditions, in which bacteria could reach leaves and flowers only from the soil. These taxa represented more than 40% of the communities based on amplicon sequencing. Unsupervised hierarchical clustering approaches supported the convergence of all floral microbiota, and 24 of the 28 bacteria responsible for this pattern belonged to the Burkholderiaceae family, which includes known plant pathogens and plant growth-promoting members. We anticipate that our study will foster future investigations regarding the routes used by soil microbes to reach leaves and flowers, the ubiquity of the environmental filtering of Burkholderiaceae across plant species and environments, and the potential functional effects of the accumulation of these bacteria in the reproductive organs of flowering plants.
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.
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.
Early and accurate identification of cognitive and functional decline in bilingual Latino/a older adults with Alzheimer’s disease and related dementias continues to be a substantial public health concern. This paper highlights the heterogeneity in the clinical expression of Alzheimer’s disease among bilingual Latino/as, the clinical decisions leading to a culturally and linguistically congruent neuropsychological assessment, and the interdisciplinary, multi setting partnerships needed to ensure a healthy longevity post diagnosis for the patient, the caregiver, and the family. Psychologists play an important role in advocating for the best standard of care, as the patients and families endure the long journey of care with dignity and respect.
Background There are currently no recommendations guiding when best to perform coronary artery calcium (CAC) scanning among young adults to identify those susceptible for developing premature atherosclerosis.Objective The purpose of this study was to determine the ideal age at which a first CAC scan has the highest utility according to atherosclerotic cardiovascular disease (ASCVD) risk factor profile.Method We included 22,346 CAC Consortium participants aged 30-50 years who underwent noncontrast computed tomography. Sex-specific equations were derived from multivariable logistic modeling to estimate the expected probability of CAC >0 according to age and the presence of ASCVD risk factors.Result Participants were on average 43.5 years of age, 25% were women, and 34% had CAC >0, in whom the median CAC score was 20. Compared with individuals without risk factors, those with diabetes developed CAC 6.4 years earlier on average, whereas smoking, hypertension, dyslipidemia, and a family history of coronary heart disease were individually associated with developing CAC 3.3-4.3 years earlier. Using a testing yield of 25% for detecting CAC >0, the optimal age for a potential first scan would be at 36.8 years (95% CI: 35.5-38.4 years) in men and 50.3 years (95% CI: 48.7-52.1 years) in women with diabetes, and 42.3 years (95% CI: 41.0-43.9 years) in men and 57.6 years (95% CI: 56.0-59.5 years) in women without risk factors.Conclusion Our derived risk equations among health-seeking young adults enriched in ASCVD risk factors inform the expected prevalence of CAC >0 and can be used to determine an appropriate age to initiate clinical CAC testing to identify individuals most susceptible for early/premature atherosclerosis.
Background . Low levels of physical activity (PA) in adolescents highlight the necessity for effective intervention. During adolescence, peer relationships can be a fundamental aspect of adopting and maintaining positive health behaviors. Aim. This review aims to determine peer-led strategies that showed promise to improve PA levels of adolescents. It will also identify patterns across these interventions, including training provided and the behavior change techniques (BCTs) employed. Method . Adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, PubMed, PsychINFO, and Scopus were searched using key concepts of peer, PA and adolescent for articles that examined interventions that had a peer-led component and reported on at least one PA outcome in 12- to 19-year-olds. Following title and abstract screening of 1,509 studies, and full text review stage, 18 progressed to data synthesis. Methodological quality was assessed using an adapted scale. Result . Quality assessment identified 11 studies as high quality. Half of the included studies (n = 9) reported improved PA outcomes in the school setting. The most prominent behavioral change techniques were social support, information about health consequences, and demonstration of the behavior. Older adolescents leading younger peers and younger adolescents leading those of the same age showed potential. Seldom have older adolescents been targeted. Gender-specific interventions showed the most promise. Conclusion . Peer leadership requires careful planning and in the school setting can be a resourceful way of promoting adolescent PA.
RNA molecules can fold into complex structures and interact with trans-acting factors to control their biology. Recent methods have been focused on developing novel tools to measure RNA structure transcriptome-wide, but their utility to study and predict RNA-protein interactions or RNA processing has been limited thus far. Here, we extend these studies with the first transcriptome-wide mapping method for cataloging RNA solvent accessibility, icLASER. By combining solvent accessibility (icLASER) with RNA flexibility (icSHAPE) data, we efficiently predict RNA-protein interactions transcriptome-wide and catalog RNA polyadenylation sites by RNA structure alone. These studies showcase the power of designing novel chemical approaches to studying RNA biology. Further, our study exemplifies merging complementary methods to measure RNA structure inside cells and its utility for predicting transcriptome-wide interactions that are critical for control of and regulation by RNA structure. We envision such approaches can be applied to studying different cell types or cells under varying conditions, using RNA structure and footprinting to characterize cellular interactions and processing involving RNA.
In the crucible of the pandemic, it has never before been clearer that, to ensure the relevance and even the survival of the discipline, nursing must cultivate a radical imagination. In the paper that follows, I trace the imperative for conjuring a radical imagination for nursing. In this fever dream for nursing futures, built on speculative visions of what could be, I draw on anarchist, abolitionist, posthuman, Black feminist, new materialist and other big ideas to plant seeds of generative insurrection and creative resistance. In thinking through a radical imagination, I unpack the significance of reparatory history for nursing, a discipline founded on normative whiteness. From there, I consider what it would take to shift the capitalist frame of healthcare to one of mutual aid, which requires the deep work of abolition. With a radical imagination that breaks down the enclosures that contain us through reparatory history, mutual aid and abolition, kinship becomes urgently possible.
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.