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Abstract Co-infections with bacterial or fungal pathogens could be associated with severity and outcome of disease in COVID-19 patients. We, therefore, used a 16S and ITS-based sequencing approach to assess the biomass and composition of the bacterial and fungal communities in endotracheal aspirates of intubated COVID-19 patients. Our method combines information on bacterial and fungal biomass with community profiling, anticipating the likelihood of a co-infection is higher with (1) a high bacterial and/or fungal biomass combined with (2) predominance of potentially pathogenic microorganisms. We tested our methods on 42 samples from 30 patients. We observed a clear association between microbial outgrowth (high biomass) and predominance of individual microbial species. Outgrowth of pathogens was in line with the selective pressure of antibiotics received by the patient. We conclude that our approach may help to monitor the presence and predominance of pathogens and therefore the likelihood of co-infections in ventilated patients, which ultimately, may help to guide treatment.

Output-based standards set a prescribed target to be achieved by a surveillance system, but they leave the selection of surveillance parameters, such as test type and population to be sampled, to the responsible party in the surveillance area. This allows proportionate legislative surveillance specifications to be imposed over a range of unique geographies. This flexibility makes output-based standards useful in the context of zoonotic threat surveillance, particularly where animal pathogens act as risk indicators for human health or where multiple surveillance streams cover human, animal, and food safety sectors. Yet, these systems are also heavily reliant on the appropriate choice of surveillance options to fit the disease context and the constraints of the organization implementing the surveillance system. Here we describe a framework to assist with designing, implementing, and evaluating output-based surveillance systems showing the effectiveness of a diverse range of activities through a case study example. Despite not all activities being relevant to practitioners in every context, this framework aims to provide a useful toolbox to encourage holistic and stakeholder-focused approaches to the establishment and maintenance of productive output-based surveillance systems.

IntroductionPotentially morally injurious events (PMIE) are events that violate one’s deeply held moral values or beliefs, and that have the potential to create significant inner conflict and psychological distress. PMIE have been recognized as an important psychological risk factor in many high-risk occupational groups. However, no study to date has investigated how PMIE relate to the mental health of aid workers. Furthermore, little is known about the mechanisms by which PMIE might be associated with mental health indicators.MethodsParticipants were 243 aid workers (72% female; Mage = 39.31) who had completed at least one aid assignment (M = 8.17). They completed an online questionnaire about their PMIE, trauma history, and mental health. A structural equation model was constructed to examine the roles of negative cognitions and subsequent self-care behaviors in the relationship between PMIE and PTSD symptoms, depression symptoms, and posttraumatic growth, above and beyond the contribution of potentially traumatic events.ResultsWithin the model, the indirect effect through negative cognitions fully accounted for the associations between PMIE and symptoms of PTSD and depression. For the association between PMIE and posttraumatic growth, two indirect effects emerged: the first through negative cognitions and subsequent self-care and, the second, through self-care alone.DiscussionThis study highlighted PMIE as a novel psychological risk factor for aid workers and pointed to two possible mechanisms by which these events may lead to PTSD, depression, and posttraumatic growth. This study adds to the current understanding of how high-risk occupational groups adapt psychologically to PMIE.

Summary: Background: The scale of COVID-19 and its well documented long-term sequelae support a need to understand long-term outcomes including frailty. Methods: This prospective cohort study recruited adults who had survived hospitalisation with clinically diagnosed COVID-19 across 35 sites in the UK (PHOSP-COVID). The burden of frailty was objectively measured using Fried's Frailty Phenotype (FFP). The primary outcome was the prevalence of each FFP group—robust (no FFP criteria), pre-frail (one or two FFP criteria) and frail (three or more FFP criteria)—at 5 months and 1 year after discharge from hospital. For inclusion in the primary analysis, participants required complete outcome data for three of the five FFP criteria. Longitudinal changes across frailty domains are reported at 5 months and 1 year post-hospitalisation, along with risk factors for frailty status. Patient-perceived recovery and health-related quality of life (HRQoL) were retrospectively rated for pre-COVID-19 and prospectively rated at the 5 month and 1 year visits. This study is registered with ISRCTN, number ISRCTN10980107. Findings: Between March 5, 2020, and March 31, 2021, 2419 participants were enrolled with FFP data. Mean age was 57.9 (SD 12.6) years, 933 (38.6%) were female, and 429 (17.7%) had received invasive mechanical ventilation. 1785 had measures at both timepoints, of which 240 (13.4%), 1138 (63.8%) and 407 (22.8%) were frail, pre-frail and robust, respectively, at 5 months compared with 123 (6.9%), 1046 (58.6%) and 616 (34.5%) at 1 year. Factors associated with pre-frailty or frailty were invasive mechanical ventilation, older age, female sex, and greater social deprivation. Frail participants had a larger reduction in HRQoL compared with before their COVID-19 illness and were less likely to describe themselves as recovered. Interpretation: Physical frailty and pre-frailty are common following hospitalisation with COVID-19. Improvement in frailty was seen between 5 and 12 months although two-thirds of the population remained pre-frail or frail. This suggests comprehensive assessment and interventions targeting pre-frailty and frailty beyond the initial illness are required. Funding: UK Research and Innovation and National Institute for Health Research.

Introduction Although previously thought to be a rare occurrence, spontaneous recanalisation is not uncommon, with a growing number of reports describing this phenomenon. However, the frequency, time course and mechanism of spontaneous recanalisation remain unknown. A better characterisation of these events is essential to ensuring adequate identification and proper future trial design for treatment.Objective To describe the current body of literature around spontaneous recanalisation following internal carotid occlusion.Methods and analysis With the assistance of an information specialist, we will search MEDLINE, Embase, Cochrane Central Register for Controlled Trials and Web of Science for studies of adults with spontaneous recanalisation or transient occlusion of the internal carotid artery. Two reviewers will independently collect data on included studies pertaining to publication data, study population information, timepoints of initial presentation, recanalisation and subsequent follow-up.Ethics and dissemination Primary data will not be collected; therefore, formal ethics is not required. The findings of this study will be disseminated through peer-reviewed publications and presentations at academic conferences.

Awake quiescence immediately after encoding is conducive to episodic memory consolidation. Retrieval can render episodic memories labile again, but reconsolidation can modify and restrengthen them. It remained unknown whether awake quiescence after retrieval supports episodic memory reconsolidation. We sought to examine this question via an object-location memory paradigm. We failed to probe the effect of quiescence on reconsolidation, but we did observe an unforeseen "delayed" effect of quiescence on consolidation. Our findings reveal that the beneficial effect of quiescence on episodic memory consolidation is not restricted to immediately following encoding but can be achieved at a delayed stage and even following a period of task engagement.

Many blue-collar jobs, most of which are performed by men, are likely to be displaced by automation. These workers will, therefore, need to be retrained and reskilled, many of them choosing for engineering education as mature students. This paper uses Interpretive Phenomenological Analysis to draw a complex portrait of the experience of blue-collar men studying engineering as mature students in Denmark. We found that the participants faced considerable challenges in their engineering studies: they brought baggage from a challenging youth, from family traumas and educational failures; they felt alienation and cynicism about the world and saw their own possibilities for progress thereby limited; and they experienced difficulties with the contents and the process of the engineering curriculum. However, they persisted with faith in engineering education as a gateway to a better life and a sense of social responsibility as future engineers. The study concludes that more pro-active university support systems would alleviate the difficulties faced by such students.

Abstract Recent evidence shows that deaf signers outperform hearing non-signers in some tests of visual attention and discrimination. Furthermore, they can retain visual information better over short periods, i.e., seconds. However, it is unknown if deaf signers’ retention of detailed visual information is superior following more extended periods. We report a study investigating this possibility. Our data revealed that deaf individuals outperformed hearing people in a visual long-term memory test that probed the fine detail of new memories. Deaf individuals also performed better in a scene-discrimination test, which correlated positively with performance on the long-term memory test. Our findings provide evidence that deaf signers can demonstrate superior visual long-term memory, possibly because of enhanced visual attention during encoding. The relative contributions of factors including sign language fluency, protracted practice, and neural plasticity are still to be established. Our findings add to evidence showing that deaf signers are at an advantage in some respects, including the retention of detailed visual memories over the longer term.

Abstract Microvascular haemodynamic alterations are associated with coronary artery disease (CAD). The conjunctival microcirculation can easily be assessed non-invasively. However, the microcirculation of the conjunctiva has not been previously explored in clinical algorithms aimed at identifying patients with CAD. This case–control study involved 66 patients with post-myocardial infarction and 66 gender-matched healthy controls. Haemodynamic properties of the conjunctival microcirculation were assessed with a validated iPhone and slit lamp-based imaging tool. Haemodynamic properties were extracted with semi-automated software and compared between groups. Biomarkers implicated in the development of CAD were assessed in combination with conjunctival microcirculatory parameters. The conjunctival blood vessel parameters and biomarkers were used to derive an algorithm to aid in the screening of patients for CAD. Conjunctival blood velocity measured in combination with the blood biomarkers (N-terminal pro-brain natriuretic peptide and adiponectin) had an area under receiver operator characteristic curve (AUROC) of 0.967, sensitivity 93.0%, specificity 91.5% for CAD. This study demonstrated that the novel algorithm which included a combination of conjunctival blood vessel haemodynamic properties, and blood-based biomarkers could be used as a potential screening tool for CAD and should be validated for potential utility in asymptomatic individuals.

Juan Mundisugih,1,2 Caroline X Gao,1,3 Jillian F Ikin,1 Michael J Abramson,1 David Brown,1 Sinjini Biswas,1,2 Elizabeth M Dewar,2,4 Danny Liew,1 Dion Stub1,2,4 1School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia; 2Department of Cardiology, Alfred Health, Melbourne, VIC, Australia; 3Centre for Youth Mental Health (Orygen), University of Melbourne, Melbourne, VIC, Australia; 4Baker Heart and Diabetes Institute, Melbourne, VIC, AustraliaCorrespondence: Jillian F Ikin, Tel +61 3 9903 0308, Email jill.blackman@monash.eduBackground and Aims: Mega-wild fires are exposing large communities to weeks or months of high concentration smoke-related fine particulate air pollution (PM). However, little research has examined the long-term vascular responses from exposure to PM of this concentration and duration. We investigated whether level of exposure to 6 weeks of PM from the 2014 Hazelwood coal mine fire was associated with abnormal vascular responses approximately four years later.Methods: A cross-sectional analysis was undertaken of 387 participants (225 exposed, 162 unexposed) aged 55– 89 years, 3.5– 4 years after the mine fire. The primary outcome was flow-mediated dilatation (FMD), with time to reach peak diameter as the secondary outcome. Other secondary markers included high-sensitivity C-reactive protein (hsCRP) and ischaemic Electrocardiogram (ECG) changes.Results: There was no evidence of a difference in FMD between participants with high, medium, low or no mine-fire related PM2.5 exposure (4.09% vs 4.06% vs 4.02% vs 3.98%, respectively, p=0.99). Likewise, there was no difference in hsCRP or ischaemic ECG changes. In contrast, there was evidence of a difference in time to peak diameter (p=0.002) with more unexposed participants reaching peak diameter within 30 seconds (36%) compared to those who had high, medium, or low exposure (23%, 22%, 13%, respectively). Multivariate ordinal logistic regression analysis suggested that township, Morwell (exposed) vs Sale (unexposed), but not level of PM2.5 exposure, was associated with delayed time to peak diameter (OR 2.71; 95% CI 1.56, 4.69). Smokers also had delayed time to peak diameter.Conclusion: There was no association between level of exposure to PM2.5 from the 6-week Hazelwood coal mine fire smoke event and reduced FMD, elevated hsCRP or ischaemic ECG four years later. Evidence of delayed time to peak diameter observed in adults from the exposed town, compared to an unexposed town, requires further investigation.Keywords: vascular responses, flow mediated dilatation, time to peak diameter, particulate matter, epidemiology, air pollution

The outbreak of COVID-19 challenged the sustainability of global agri-food markets. Through this research, the authors have made sincere efforts to recognize and remove/improve the potential factors that contribute towards an inefficient agro-based supply chain. COVID-19 has created much urgency to evaluate the existing supply chain and to propose a valid solution. In this particular research, the involvement of intermediaries is the point of focus. In addition, the profit margins for the farmer are hugely affected due to intermediaries. The current supply chain must be optimized, and this will lead to easier flows between each phase of the supply chain. Surveys were conducted and the farmers’ problems and expected solutions are highlighted in this research. Farmers in the northern states of India experienced more significant disruptions than those in other states because of a decreased availability of foods due to lack of diversity in crops. This research examines the existing supply chain for wheat crops and presents an optimization of the respective supply chain to save farmers more revenue. Through this research, the authors have attempted to observe and explore the problems faced by farmers and consumers due to the inefficient supply chain infrastructure prevalent in India because of the onslaught of COVID-19 and find an efficient solution. Due to the lack of adequate infrastructure, storage facilities, and old food-processing and supply chain technology almost 30–35% of the agricultural produce in India is wasted. A scientific solution to the existing problems is also presented after analyzing the existing supply chain and crop selection of farmers.

Symmetric instability can occur in the ocean interior, and reveals a previously unrecognized route to energy dissipation in the ocean, suggest direct microstructure measurements from the Northwestern Equatorial Pacific Ocean.

Abstract Background The UK Scientific Advisory Group for Emergencies (SAGE) emphasises the need for high levels of engagement with communities and individuals to ensure the effectiveness of any COVID-19 testing programme. A novel pilot health surveillance programme to assess the feasibility of weekly community RT-LAMP (Reverse transcription loop-mediated isothermal amplification) testing for the SARS-CoV-2 virus using saliva samples collected at home was developed and piloted by the University of Southampton and Southampton City Council. Methods Rapid qualitative evaluation was conducted to explore experiences of those who took part in the programme, of those who declined and of those in the educational and healthcare organisations involved in the pilot testing who were responsible for roll-out. This included 77 interviews and 20 focus groups with 223 staff, students, pupils and household members from four schools, one university, and one community healthcare NHS trust. The insights generated and informed the design and modification of the Southampton COVID-19 Saliva Testing Programme and the next phase of community-testing. Results Discussions revealed that high levels of communication, trust and convenience were necessary to ensure people’s engagement with the programme. Participants felt reassured by and pride in taking part in this novel programme. They suggested modifications to reduce the programme’s environmental impact and overcome cultural barriers to participation. Conclusions Participants’ and stakeholders’ motivations, challenges and concerns need to be understood and these insights used to modify the programme in a continuous, real-time process to ensure and sustain engagement with testing over the extended period necessary. Community leaders and stakeholder organisations should be involved throughout programme development and implementation to optimise engagement.

IntroductionUnderstanding how abundance, productivity and distribution of individual species may respond to climate change is a critical first step towards anticipating alterations in marine ecosystem structure and function, as well as developing strategies to adapt to the full range of potential changes.MethodsThis study applies the NOAA (National Oceanic and Atmospheric Administration) Fisheries Climate Vulnerability Assessment method to 64 federally-managed species in the California Current Large Marine Ecosystem to assess their vulnerability to climate change, where vulnerability is a function of a species’ exposure to environmental change and its biological sensitivity to a set of environmental conditions, which includes components of its resiliency and adaptive capacity to respond to these new conditions.ResultsOverall, two-thirds of the species were judged to have Moderate or greater vulnerability to climate change, and only one species was anticipated to have a positive response. Species classified as Highly or Very Highly vulnerable share one or more characteristics including: 1) having complex life histories that utilize a wide range of freshwater and marine habitats; 2) having habitat specialization, particularly for areas that are likely to experience increased hypoxia; 3) having long lifespans and low population growth rates; and/or 4) being of high commercial value combined with impacts from non-climate stressors such as anthropogenic habitat degradation. Species with Low or Moderate vulnerability are either habitat generalists, occupy deep-water habitats or are highly mobile and likely to shift their ranges.DiscussionAs climate-related changes intensify, this work provides key information for both scientists and managers as they address the long-term sustainability of fisheries in the region. This information can inform near-term advice for prioritizing species-level data collection and research on climate impacts, help managers to determine when and where a precautionary approach might be warranted, in harvest or other management decisions, and help identify habitats or life history stages that might be especially effective to protect or restore.

Summary: Topological stress can cause converging replication forks to stall during termination of vertebrate DNA synthesis. However, replication forks ultimately overcome fork stalling, suggesting that alternative mechanisms of termination exist. Using proteomics in Xenopus egg extracts, we show that the helicase RTEL1 and the replisome protein MCM10 are highly enriched on chromatin during fork convergence and are crucially important for fork convergence under conditions of topological stress. RTEL1 and MCM10 cooperate to promote fork convergence and do not impact topoisomerase activity but do promote fork progression through a replication barrier. Thus, RTEL1 and MCM10 play a general role in promoting progression of stalled forks, including when forks stall during termination. Our data reveal an alternate mechanism of termination involving RTEL1 and MCM10 that can be used to complete DNA synthesis under conditions of topological stress.

Objective Advance consent is a recognised method of obtaining informed consent for participation in research, whereby a potential participant provides consent for future involvement in a study contingent on qualifying for the study’s inclusion criteria on a later date. The goal of this study is to map the existing literature on the use of advance consent for enrolment in randomised controlled trials (RCTs) for emergency conditions.Design Scoping review designed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses–Extension for Scoping Reviews guidelines.Data sources We searched electronic databases including MEDLINE, Embase, Web of Science and the Cochrane Register of Clinical Trials from inception to 10 February 2020.Eligibility criteria Eligible studies included articles that discussed or employed the use of advance consent for enrolment in RCTs related to emergency conditions. There were no restrictions on the type of eligible study. Data were extracted directly from included papers using a standardised data charting form. We produced a narrative review including article type and authors’ dispositions towards advance consent.Results Our search yielded 1039 titles with duplicates removed. Six articles met inclusion criteria. Three articles discussed the theoretical use of research advance directives in emergency conditions; one article evaluated stakeholders’ perceptions of advance consent; and one article described a method for patients to document their preferences for participation in future research. Only one study employed advance consent to enrol participants into a clinical trial for an emergency condition.Conclusion Our review demonstrates that there has been minimal exploration of advance consent for enrolment in RCTs for emergency conditions. Future studies could aim to assess the acceptability of advance consent to participants, along with the feasibility of enrolling research participants using this method of consent.Protocol The protocol for this scoping review was published a priori.

Objective. To estimate gastroenteritis disease and its etiological agents in children under the age of 5 years living in South Africa. Methods. A mini literature review of pertinent articles published in ScienceDirect, PubMed, GoogleScholar, and Scopus was conducted using search terms: “Gastroenteritis in children,” “Gastroenteritis in the world,” Gastroenteritis in South Africa,” “Prevalence of gastroenteritis,” “Epidemiological surveillance of gastroenteritis in the world,” and “Causes of gastroenteritis”. Results. A total of 174 published articles were included in this mini review. In the last 20 years, the mortality rate resulting from diarrhea in children under the age of 5 years has declined and this is influenced by improved hygiene practices, awareness programs, an improved water and sanitation supply, and the availability of vaccines. More modern genomic amplification techniques were used to re-analyze stool specimens collected from children in eight low-resource settings in Asia, South America, and Africa reported improved sensitivity of pathogen detection to about 65%, that viruses were the main etiological agents in patients with diarrhea aged from 0 to 11 months but that Shigella, followed by sapovirus and enterotoxigenic Escherichia coli had a high incidence in children aged 12–24 months. In addition, co-infections were noted in nearly 10% of diarrhea cases, with rotavirus and Shigella being the main co-infecting agents together with adenovirus, enteropathogenic E. coli, Clostridium jejuni, or Clostridium coli. Conclusions. This mini review outlines the epidemiology and trends relating to parasitic, viral, and bacterial agents responsible for gastroenteritis in children in South Africa. An increase in sequence-independent diagnostic approaches will improve the identification of pathogens to resolve undiagnosed cases of gastroenteritis. Emerging state and national surveillance systems should focus on improving the identification of gastrointestinal pathogens in children and the development of further vaccines against gastrointestinal pathogens.

School nurses play a crucial role in the prompt, appropriate response to epilepsy-related seizure emergencies among students in the school setting. Two intranasal benzodiazepine rescue therapies are now approved and offer potential benefits of being easy to use and socially acceptable. In July 2021, a survey was sent to 49,314 US school nurses to assess knowledge, perceptions, and practice with seizure rescue therapy. Responses were received from 866 (1.8% response rate). Of respondents, 45.7% had used rectal diazepam gel; 9.3%, midazolam nasal spray; and 6.0%, diazepam nasal spray. The majority (58.7%) had not delegated authority to administer rescue therapy, with state/local regulations and lack of willingness of school personnel being the most common barriers to delegation (37.7% and 20.1%, respectively). Additional training of nurses and school staff and progress on delegation policies may help optimize appropriate use of intranasal rescue therapy for seizures and enhance care of students with epilepsy in schools.

Background Cerebral small vessel disease is associated with higher ratios of soluble‐epoxide hydrolase derived linoleic acid diols (12,13‐dihydroxyoctadecenoic acid [DiHOME] and 9,10‐DiHOME) to their parent epoxides (12(13)‐epoxyoctadecenoic acid [EpOME] and 9(10)‐EpOME); however, the relationship has not yet been examined in stroke. Methods and Results Participants with mild to moderate small vessel stroke or large vessel stroke were selected based on clinical and imaging criteria. Metabolites were quantified by ultra‐high‐performance liquid chromatography–mass spectrometry. Volumes of stroke, lacunes, white matter hyperintensities, magnetic resonance imaging visible perivascular spaces, and free water diffusion were quantified from structural and diffusion magnetic resonance imaging (3 Tesla). Adjusted linear regression models were used for analysis. Compared with participants with large vessel stroke (n=30), participants with small vessel stroke (n=50) had a higher 12,13‐DiHOME/12(13)‐EpOME ratio (β=0.251, P=0.023). The 12,13‐DiHOME/12(13)‐EpOME ratio was associated with more lacunes (β=0.266, P=0.028) but not with large vessel stroke volumes. Ratios of 12,13‐DiHOME/12(13)‐EpOME and 9,10‐DiHOME/9(10)‐EpOME were associated with greater volumes of white matter hyperintensities (β=0.364, P

Human intracranial electroencephalography (iEEG) recordings provide data with much greater spatiotemporal precision than is possible from data obtained using scalp EEG, magnetoencephalography (MEG), or functional MRI. Until recently, the fusion of anatomical data (MRI and computed tomography (CT) images) with electrophysiological data and their subsequent analysis have required the use of technologically and conceptually challenging combinations of software. Here, we describe a comprehensive protocol that enables complex raw human iEEG data to be converted into more readily comprehensible illustrative representations. The protocol uses an open-source toolbox for electrophysiological data analysis (FieldTrip). This allows iEEG researchers to build on a continuously growing body of scriptable and reproducible analysis methods that, over the past decade, have been developed and used by a large research community. In this protocol, we describe how to analyze complex iEEG datasets by providing an intuitive and rapid approach that can handle both neuroanatomical information and large electrophysiological datasets. We provide a worked example using an example dataset. We also explain how to automate the protocol and adjust the settings to enable analysis of iEEG datasets with other characteristics. The protocol can be implemented by a graduate student or postdoctoral fellow with minimal MATLAB experience and takes approximately an hour to execute, excluding the automated cortical surface extraction.

Seafood is an essential source of protein for more than 3 billion people worldwide, yet bycatch of threatened species in capture fisheries remains a major impediment to fisheries sustainability. Management measures designed to reduce bycatch often result in significant economic losses and even fisheries closures. Static spatial management approaches can also be rendered ineffective by environmental variability and climate change, as productive habitats shift and introduce new interactions between human activities and protected species. We introduce a new multispecies and dynamic approach that uses daily satellite data to track ocean features and aligns scales of management, species movement, and fisheries. To accomplish this, we create species distribution models for one target species and three bycatch-sensitive species using both satellite telemetry and fisheries observer data. We then integrate species-specific probabilities of occurrence into a single predictive surface, weighing the contribution of each species by management concern. We find that dynamic closures could be 2 to 10 times smaller than existing static closures while still providing adequate protection of endangered nontarget species. Our results highlight the opportunity to implement near real-time management strategies that would both support economically viable fisheries and meet mandated conservation objectives in the face of changing ocean conditions. With recent advances in eco-informatics, dynamic management provides a new climate-ready approach to support sustainable fisheries.

There are well-known problems associated with the idea of (local) gravitational energy in general relativity. We offer a new perspective on those problems by comparison with Newtonian gravitation, and particularly geometrized Newtonian gravitation (i.e., Newton–Cartan theory). We show that there is a natural candidate for the energy density of a Newtonian gravitational field. But we observe that this quantity is gauge dependent, and that it cannot be defined in the geometrized (gauge-free) theory without introducing further structure. We then address a potential response by showing that there is an analogue to the Weyl tensor in geometrized Newtonian gravitation.

This paper is a study of the topos of the king burning captives in the Assyrian royal inscriptions. This punishment is notable for both its rarity and its cruelty, being the only time that the royal inscriptions describe violence towards children. I approach this topic in terms of Donald Black’s model of social control, in which the form and severity of social control, including violence, varies in relation to the “social geometry” that separates the parties involved in a dispute or conflict. I argue that in the royal inscriptions burning is inflicted on those that the Assyrians saw as “uncivilized”: peoples inhabiting poorer cities in mountain regions who lacked the infrastructure necessary to stockpile prestige goods, such as precious metals, and were separated at a greater distance from Assyria by “social geometry” than other foreigners. These findings provide a useful insight into Assyrian conceptions of the other and give a better understanding of the variations in the severity of punishments inflicted by the Assyrians on their enemies.

By analyzing multitissue gene expression and genome-wide genetic variation data in samples from a vervet monkey pedigree, we generated a transcriptome resource and produced the first catalog of expression quantitative trait loci (eQTLs) in a nonhuman primate model. This catalog contains more genome-wide significant eQTLs per sample than comparable human resources and identifies sex- and age-related expression patterns. Findings include a master regulatory locus that likely has a role in immune function and a locus regulating hippocampal long noncoding RNAs (lncRNAs), whose expression correlates with hippocampal volume. This resource will facilitate genetic investigation of quantitative traits, including brain and behavioral phenotypes relevant to neuropsychiatric disorders.

Vervet monkeys are among the most widely distributed nonhuman primates, show considerable phenotypic diversity, and have long been an important biomedical model for a variety of human diseases and in vaccine research. Using whole-genome sequencing data from 163 vervets sampled from across Africa and the Caribbean, we find high diversity within and between taxa and clear evidence that taxonomic divergence was reticulate rather than following a simple branching pattern. A scan for diversifying selection across taxa identifies strong and highly polygenic selection signals affecting viral processes. Furthermore, selection scores are elevated in genes whose human orthologs interact with HIV and in genes that show a response to experimental simian immunodeficiency virus (SIV) infection in vervet monkeys but not in rhesus macaques, suggesting that part of the signal reflects taxon-specific adaptation to SIV.

While much attention has gone towards ethical, legal, and social implications of direct-to-consumer genetic testing over the past decades, the rise of new forms of consumer omics has largely escaped scrutiny. In this paper, we analyze the product descriptions, promotional messages, terms of service, and privacy policies of five epigenetic and seven microbiomic testing companies. The advent of such tests online represents a significant shift in consumer omics, from a focus on inherited molecules with genetic tests, to broader interest for information about the lives of individuals, such as chronological and biological age, exposures, and lifestyle. Building on previous literature about direct-to-consumer genetic testing, and taking this shift into account, we identify limitations, gaps and inconsistencies in current practices and policies of the new companies. Best practice standards and regulations applicable across different omic sample and data types is a necessary first step in the promotion of responsible consumer omics.

Abstract Background Palliative sedation and analgesia are employed in patients with refractory and intractable symptoms at the end of life to reduce their suffering by lowering their level of consciousness. The doctrine of double effect, a philosophical principle that justifies doing a “good action” with a potentially “bad effect,” is frequently employed to provide an ethical justification for this practice. Main text We argue that palliative sedation and analgesia do not fulfill the conditions required to apply the doctrine of double effect, and therefore its use in this domain is inappropriate. Furthermore, we argue that the frequent application of the doctrine of double effect to palliative sedation and analgesia reflects physicians’ discomfort with the complex moral, intentional, and causal aspects of end-of-life care. Conclusions We are concerned that this misapplication of the doctrine of double effect can consequently impair physicians’ ethical reasoning and relationships with patients at the end of life.