Search

Surf zones are highly dynamic marine ecosystems that are subject to increasing anthropogenic and climatic pressures, posing multiple challenges for biomonitoring. Traditional methods such as seines and hook and line surveys are often labor intensive, taxonomically biased, and can be physically hazardous. Emerging techniques, such as baited remote underwater video (BRUV) and environmental DNA (eDNA) are promising nondestructive tools for assessing marine biodiversity in surf zones of sandy beaches. Here we compare the relative performance of beach seines, BRUV, and eDNA in characterizing community composition of bony (teleost) and cartilaginous (elasmobranch) fishes of surf zones at 18 open coast sandy beaches in southern California. Seine and BRUV surveys captured overlapping, but distinct fish communities with 50% (18/36) of detected species shared. BRUV surveys more frequently detected larger species (e.g. sharks and rays) while seines more frequently detected one of the most abundant species, barred surfperch (Amphistichus argenteus). In contrast, eDNA metabarcoding captured 88.9% (32/36) of all fishes observed in seine and BRUV surveys plus 57 additional species, including 15 that frequent surf zone habitats. On average, eDNA detected over 5 times more species than BRUVs and 8 times more species than seine surveys at a given site. eDNA approaches also showed significantly higher sensitivity than seine and BRUV methods and more consistently detected 31 of the 32 (96.9%) jointly observed species across beaches. The four species detected by BRUV/seines, but not eDNA were only resolved at higher taxonomic ranks (e.g. Embiotocidae surfperches and Sygnathidae pipefishes). In frequent co-detection of species between methods limited comparisons of richness and abundance estimates, highlighting the challenge of comparing biomonitoring approaches. Despite potential for improvement, results overall demonstrate that eDNA can provide a cost-effective tool for long-term surf zone monitoring that complements data from seine and BRUV surveys, allowing more comprehensive surveys of vertebrate diversity in surf zone habitats.

ImportanceSARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or other health effects after the acute phase of infection; termed post-acute sequelae of SARS-CoV-2 infection (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are ill-defined. The objectives of the Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC in Adults (RECOVER-Adult) are to: (1) characterize PASC prevalence; (2) characterize the symptoms, organ dysfunction, natural history, and distinct phenotypes of PASC; (3) identify demographic, social and clinical risk factors for PASC onset and recovery; and (4) define the biological mechanisms underlying PASC pathogenesis.MethodsRECOVER-Adult is a combined prospective/retrospective cohort currently planned to enroll 14,880 adults aged ≥18 years. Eligible participants either must meet WHO criteria for suspected, probable, or confirmed infection; or must have evidence of no prior infection. Recruitment occurs at 86 sites in 33 U.S. states, Washington, DC and Puerto Rico, via facility- and community-based outreach. Participants complete quarterly questionnaires about symptoms, social determinants, vaccination status, and interim SARS-CoV-2 infections. In addition, participants contribute biospecimens and undergo physical and laboratory examinations at approximately 0, 90 and 180 days from infection or negative test date, and yearly thereafter. Some participants undergo additional testing based on specific criteria or random sampling. Patient representatives provide input on all study processes. The primary study outcome is onset of PASC, measured by signs and symptoms. A paradigm for identifying PASC cases will be defined and updated using supervised and unsupervised learning approaches with cross-validation. Logistic regression and proportional hazards regression will be conducted to investigate associations between risk factors, onset, and resolution of PASC symptoms.DiscussionRECOVER-Adult is the first national, prospective, longitudinal cohort of PASC among US adults. Results of this study are intended to inform public health, spur clinical trials, and expand treatment options.RegistrationNCT05172024.

BackgroundLife course factors may be associated with pre-pregnancy body mass index and gestational weight gain; however, collecting information on pre-pregnancy exposures and pregnancy health in the same cohort is challenging.ObjectivesThe Life-course Experiences And Pregnancy (LEAP) study aims to identify adolescent and young adult risk factors for pre-pregnancy weight and gestational weight gain (GWG). We built upon an existing cohort study to overcome challenges inherent to studying life course determinants of pregnancy health.PopulationParticipants in an ongoing prospective cohort study of weight-related health who identified as women.DesignRetrospective cohort study.MethodsIn 2019-2020, 1,252 women participating since adolescence in a cohort study of weight-related health were invited to complete an online reproductive history survey. Participants who reported a live birth were invited to release their prenatal, delivery, and postpartum medical records for validation of survey reports. Descriptive analyses were conducted to assess the characteristics of the overall cohort and the medical record validation subsample, and to describe adolescent and young adult characteristics of those with high (>80th percentile), moderate (20th-80th percentile), and low (Preliminary resultsNine hundred seventy-seven women (78%) completed the LEAP survey and 656 reported a live birth. Of these, 379 (58%) agreed to release medical records, and 250 records were abstracted (66% of the 379). Of the 977 survey respondents 769 (79%) reported attempting a pregnancy, and 656 (67%) reported at least one live birth. The validation subsample was similar to the overall cohort. Women with a high GWG had a higher adolescent BMI percentile and prevalence of unhealthy weight control behaviors than those with moderate or low GWG.ConclusionsLEAP offers a valuable resource for identifying life course factors that may influence the health of pregnant people and their offspring.

BackgroundDespite the widespread use of humor in social interactions and the considerable literature on humor in multiple fields of study, the use of humor in parenting has received very little formal study. The purpose of this pilot study was to gather preliminary data on the use of humor in the raising of children.Materials and methodsWe developed and administered a 10-item survey to measure people's experiences being raised with humor and their views regarding humor as a parenting tool. Responses were aggregated into Disagree, Indeterminate, and Agree, and analyzed using standard statistical methods.ResultsRespondents (n = 312) predominantly identified as male (63.6%) and white (76.6%) and were (by selection) between the ages of 18-45 years old. The majority of participants reported that they: were raised by people who used humor in their parenting (55.2%); believe humor can be an effective parenting tool (71.8%) and in that capacity has more potential benefit than harm (63.3%); either use (or plan to use) humor in parenting their own children (61.8%); and would value a course on how to utilize humor in parenting (69.7%). Significant correlations were found between the use of humor and both i) the quality of respondents' relationships with their parents and ii) assessments of how good a job their parents had done.ConclusionsIn this pilot study, respondents of childbearing/rearing age reported positive views about humor as a parenting tool.

Compassion towards oneself and towards others has been associated with positive psychological outcomes, however, research is limited by the availability of valid psychometric measures, particularly in languages other than English. The current study translated (English to French) and validated the following measures: the Compassionate Engagement and Action Scales (CEAS), assessing self-compassion (CEAS-SC), compassion to others (CEAS-TO), and compassion from others (CEAS-FROM); the Compassion Scale (CS); and the Sussex-Oxford Compassion Scales for Self (SOCS-S) and Others (SOCS-O). French-speaking participants were recruited online (N = 384) and completed the translated measures as well as questionnaires assessing self-compassion, depression, anxiety, stress, insecure attachment, mindfulness, and well-being. Confirmatory Factor Analysis supports the original factor structures proposed for the CEAS-FROM (two-factor hierarchical), CS (four-factor hierarchical), SOCS-S and SOCS-O (five-factor hierarchical), with alternate factor structures proposed for CEAS-SC (three-factor) and CEAS-TO (two-factor). Results showed good internal consistency and convergent validity for all scales, supporting the use of total scores for the translated measures.

Negative emotion evoked in listeners of music can produce intense pleasure, but we do not fully understand why. The present study addressed the question by asking participants (n = 50) to self-select a piece of sadness-evoking music that was loved. The key part of the study asked participants to imagine that the felt sadness could be removed. Overall participants reported performing the task successfully. They also indicated that the removal of the sadness reduced their liking of the music, and 82% of participants reported that the evoked sadness also adds to the enjoyment of the music. The study provided evidence for a "Direct effect hypothesis", which draws on the multicomponent model of emotion, where a component of the negative emotion is experienced as positive during music (and other aesthetic) experiences. Earlier evidence of a mediator, such as 'being moved', as the source of enjoyment was reinterpreted in light of the new findings. Instead, the present study applied a semantic overlap explanation, arguing that sadness primes emotions that share meaning with sadness, such as being-moved. The priming occurs if the overlap in meaning is sufficient. The degree of semantic overlap was defined empirically. The present study therefore suggests that mediator-based explanations need to be treated with caution both as a finding of the study, and because of analytic limitations in earlier research that are discussed in the paper.

The coastal zone provides foraging opportunities for insular populations of terrestrial mammals, allowing for expanded habitat use, increased dietary breadth, and locally higher population densities. We examined the use of sandy beach resources by the threatened island fox (Urocyon littoralis) on the California Channel Islands using scat analysis, surveys of potential prey, beach habitat attributes, and stable isotope analysis. Consumption of beach invertebrates, primarily intertidal talitrid amphipods (Megalorchestia spp.) by island fox varied with abundance of these prey across sites. Distance-based linear modeling revealed that abundance of giant kelp (Macrocystis pyrifera) wrack, rather than beach physical attributes, explained the largest amount of variation in talitrid amphipod abundance and biomass across beaches. δ13C and δ15N values of fox whisker (vibrissae) segments suggested individualism in diet, with generally low δ13C and δ15N values of some foxes consistent with specializing on primarily terrestrial foods, contrasting with the higher isotope values of other individuals that suggested a sustained use of sandy beach resources, the importance of which varied over time. Abundant allochthonous marine resources on beaches, including inputs of giant kelp, may expand habitat use and diet breadth of the island fox, increasing population resilience during declines in terrestrial resources associated with climate variability and long-term climate change.

Spinocerebellar ataxia 2 (SCA2) is a neurodegenerative disorder caused by the expansion of the poly-glutamine (polyQ) tract of Ataxin-2 (ATXN2). Other polyQ-containing proteins such as ATXN7 and huntingtin are associated with the development of neurodegenerative diseases when their N-terminal polyQ domains are expanded. Furthermore, they undergo proteolytic processing events that produce N-terminal fragments that include the polyQ stretch, which are implicated in pathogenesis. Interestingly, N-terminal ATXN2 fragments were reported in a brain extract from a SCA2 patient, but it is currently unknown whether an expanded polyQ domain contributes to ATXN2 proteolytic susceptibility. Here, we used transient expression in HEK293 cells to determine whether ATXN2 is a target for specific N-terminal proteolysis. We found that ATXN2 proteins with either normal or expanded polyQ stretches undergo proteolytic cleavage releasing an N-terminal polyQ-containing fragment. We identified a short amino acid sequence downstream of the polyQ domain that is necessary for N-terminal cleavage of full-length ATXN2 and sufficient to induce proteolysis of a heterologous protein. However, this sequence is not required for cleavage of a short ATXN2 isoform produced from an alternative start codon located just upstream of the CAG repeats encoding the polyQ domain. Our study extends our understanding of ATXN2 posttranslational regulation by revealing that this protein can be the target of specific proteolytic cleavage events releasing polyQ-containing products that are modulated by the N-terminal domain of ATXN2. N-terminal ATXN2 proteolysis of expanded polyQ domains might contribute to SCA2 pathology, as observed in other neurodegenerative disorders caused by polyQ domain expansion.

Pathogen surveillance for great ape health monitoring has typically been performed on non-invasive samples, primarily feces, in wild apes and blood in sanctuary-housed apes. However, many important primate pathogens, including known zoonoses, are shed in saliva and transmitted via oral fluids. Using metagenomic methods, we identified viruses in saliva samples from 46 wild-born, sanctuary-housed chimpanzees at two African sanctuaries in Republic of Congo and Uganda. In total, we identified 20 viruses. All but one, an unclassified CRESS DNA virus, are classified in five families: Circoviridae, Herpesviridae, Papillomaviridae, Picobirnaviridae, and Retroviridae. Overall, viral prevalence ranged from 4.2% to 87.5%. Many of these viruses are ubiquitous in primates and known to replicate in the oral cavity (simian foamy viruses, Retroviridae; a cytomegalovirus and lymphocryptovirus; Herpesviridae; and alpha and gamma papillomaviruses, Papillomaviridae). None of the viruses identified have been shown to cause disease in chimpanzees or, to our knowledge, in humans. These data suggest that the risk of zoonotic viral disease from chimpanzee oral fluids in sanctuaries may be lower than commonly assumed.

China has low birth rates at higher parities and intensive grandparental childcare. Despite this, there has been little empirical research into the role of intergenerational support in the transition to second birth. This study examines whether grandparental childcare increases the likelihood and speed of a transition to second birth in the context of relaxations in Chinese family planning policy and whether this differs for working and non-working mothers. Using data from the China Family Panel Studies (2010-2016), the association between grandparental childcare, mother's working status and second childbirth are explored using split-population survival models to distinguish between the impact on the timing of fertility and ultimate parity progression. The odds of having a second child are four times higher for those who use grandparental childcare than those that don't. Amongst those who have a second child, grandparental childcare leads to 30% lower odds of transition to second birth than those without grandparental care, each month. Grandparental childcare is also associated with maternal employment, which is itself associated with a sharp decrease in the transition to second birth. At the micro-level, grandparental childcare helps mothers continue working, which in turn defers a second birth. The results emphasise the importance of work-life balance strategies, such as grandparental care, in enabling women of childbearing age to realize their fertility intentions in combination with work.

ImportanceSARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or other health effects after the acute phase of infection; termed post-acute sequelae of SARS-CoV-2 infection (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are ill-defined. The objectives of the Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC in Adults (RECOVER-Adult) are to: (1) characterize PASC prevalence; (2) characterize the symptoms, organ dysfunction, natural history, and distinct phenotypes of PASC; (3) identify demographic, social and clinical risk factors for PASC onset and recovery; and (4) define the biological mechanisms underlying PASC pathogenesis.MethodsRECOVER-Adult is a combined prospective/retrospective cohort currently planned to enroll 14,880 adults aged ≥18 years. Eligible participants either must meet WHO criteria for suspected, probable, or confirmed infection; or must have evidence of no prior infection. Recruitment occurs at 86 sites in 33 U.S. states, Washington, DC and Puerto Rico, via facility- and community-based outreach. Participants complete quarterly questionnaires about symptoms, social determinants, vaccination status, and interim SARS-CoV-2 infections. In addition, participants contribute biospecimens and undergo physical and laboratory examinations at approximately 0, 90 and 180 days from infection or negative test date, and yearly thereafter. Some participants undergo additional testing based on specific criteria or random sampling. Patient representatives provide input on all study processes. The primary study outcome is onset of PASC, measured by signs and symptoms. A paradigm for identifying PASC cases will be defined and updated using supervised and unsupervised learning approaches with cross-validation. Logistic regression and proportional hazards regression will be conducted to investigate associations between risk factors, onset, and resolution of PASC symptoms.DiscussionRECOVER-Adult is the first national, prospective, longitudinal cohort of PASC among US adults. Results of this study are intended to inform public health, spur clinical trials, and expand treatment options.RegistrationNCT05172024.

Surf zones are highly dynamic marine ecosystems that are subject to increasing anthropogenic and climatic pressures, posing multiple challenges for biomonitoring. Traditional methods such as seines and hook and line surveys are often labor intensive, taxonomically biased, and can be physically hazardous. Emerging techniques, such as baited remote underwater video (BRUV) and environmental DNA (eDNA) are promising nondestructive tools for assessing marine biodiversity in surf zones of sandy beaches. Here we compare the relative performance of beach seines, BRUV, and eDNA in characterizing community composition of bony (teleost) and cartilaginous (elasmobranch) fishes of surf zones at 18 open coast sandy beaches in southern California. Seine and BRUV surveys captured overlapping, but distinct fish communities with 50% (18/36) of detected species shared. BRUV surveys more frequently detected larger species (e.g. sharks and rays) while seines more frequently detected one of the most abundant species, barred surfperch (Amphistichus argenteus). In contrast, eDNA metabarcoding captured 88.9% (32/36) of all fishes observed in seine and BRUV surveys plus 57 additional species, including 15 that frequent surf zone habitats. On average, eDNA detected over 5 times more species than BRUVs and 8 times more species than seine surveys at a given site. eDNA approaches also showed significantly higher sensitivity than seine and BRUV methods and more consistently detected 31 of the 32 (96.9%) jointly observed species across beaches. The four species detected by BRUV/seines, but not eDNA were only resolved at higher taxonomic ranks (e.g. Embiotocidae surfperches and Sygnathidae pipefishes). In frequent co-detection of species between methods limited comparisons of richness and abundance estimates, highlighting the challenge of comparing biomonitoring approaches. Despite potential for improvement, results overall demonstrate that eDNA can provide a cost-effective tool for long-term surf zone monitoring that complements data from seine and BRUV surveys, allowing more comprehensive surveys of vertebrate diversity in surf zone habitats.

IntroductionMany countries recommend Nicotine Replacement Therapy (NRT) for smoking cessation in pregnancy. Preclinical studies of nicotine exposure to pregnant mammals could indicate how nicotine may adversely affect the developing fetus. As a first step towards summarising this literature, we undertook a systematic scoping review to determine the number and nature of offspring outcomes studied.MethodsWe searched MEDLINE and EMBASE databases for papers reporting empirical data on offspring outcomes following nicotine exposure to pregnant non-human mammals. We excluded studies that investigated exposure to only smoking, e-cigarettes, nicotine vaccines, or studies with no 'nicotine only' group. We developed a draft taxonomy and using this, described and quantified outcomes reported.ResultsWe identified 476 studies, which reported 729 offspring outcomes. The draft taxonomy classified outcomes as being measured in i) whole animals, ii) body systems and iii) 'other'. Body system outcomes were further categorised as being functional changes, or changes at macroscopic or cellular levels. The most frequently used outcomes were those detecting changes in the brain (n = 265), physical parameters measured in whole animals (n = 122) and any respiratory system changes (n = 97).ConclusionsThis scoping review quantifies the nature and frequency of outcomes used in preclinical studies investigating the potential impacts of nicotine administration in pregnancy on offspring. Systematic reviews of studies investigating outcomes involving animal brains, respiratory system, or 'whole animal' outcomes may have greatest potential for further advancing knowledge regarding impacts of gestational nicotine exposure on offspring.Protocol and registrationProtocol for this review can be found on Open Science Framework (https://osf.io/ptmzc/).

Background: Despite the widespread use of humor in social interactions and the considerable literature on humor in multiple fields of study, the use of humor in parenting has received very little formal study. The purpose of this pilot study was to gather preliminary data on the use of humor in the raising of children. Materials and methods: We developed and administered a 10-item survey to measure people's experiences being raised with humor and their views regarding humor as a parenting tool. Responses were aggregated into Disagree, Indeterminate, and Agree, and analyzed using standard statistical methods. Results: Respondents (n = 312) predominantly identified as male (63.6%) and white (76.6%) and were (by selection) between the ages of 18–45 years old. The majority of participants reported that they: were raised by people who used humor in their parenting (55.2%); believe humor can be an effective parenting tool (71.8%) and in that capacity has more potential benefit than harm (63.3%); either use (or plan to use) humor in parenting their own children (61.8%); and would value a course on how to utilize humor in parenting (69.7%). Significant correlations were found between the use of humor and both i) the quality of respondents' relationships with their parents and ii) assessments of how good a job their parents had done. Conclusions: In this pilot study, respondents of childbearing/rearing age reported positive views about humor as a parenting tool. [ABSTRACT FROM AUTHOR]

Compassion towards oneself and towards others has been associated with positive psychological outcomes, however, research is limited by the availability of valid psychometric measures, particularly in languages other than English. The current study translated (English to French) and validated the following measures: the Compassionate Engagement and Action Scales (CEAS), assessing self-compassion (CEAS-SC), compassion to others (CEAS-TO), and compassion from others (CEAS-FROM); the Compassion Scale (CS); and the Sussex-Oxford Compassion Scales for Self (SOCS-S) and Others (SOCS-O). French-speaking participants were recruited online (N = 384) and completed the translated measures as well as questionnaires assessing self-compassion, depression, anxiety, stress, insecure attachment, mindfulness, and well-being. Confirmatory Factor Analysis supports the original factor structures proposed for the CEAS-FROM (two-factor hierarchical), CS (four-factor hierarchical), SOCS-S and SOCS-O (five-factor hierarchical), with alternate factor structures proposed for CEAS-SC (three-factor) and CEAS-TO (two-factor). Results showed good internal consistency and convergent validity for all scales, supporting the use of total scores for the translated measures. [ABSTRACT FROM AUTHOR]

New immune checkpoints are emerging in a bid to improve response rates to immunotherapeutic drugs. The adenosine A2A receptor (A2AR) has been proposed as a target for immunotherapeutic development due to its participation in immunosuppression of the tumor microenvironment. Blockade of A2AR could restore tumor immunity and, consequently, improve patient outcomes. Here, we describe the discovery of a potent, selective, and tumor-suppressing antibody antagonist of human A2AR (hA2AR) by phage display. We constructed and screened four single-chain variable fragment (scFv) libraries—two synthetic and two immunized—against hA2AR and antagonist-stabilized hA2AR. After biopanning and ELISA screening, scFv hits were reformatted to human IgG and triaged in a series of cellular binding and functional assays to identify a lead candidate. Lead candidate TB206-001 displayed nanomolar binding of hA2AR-overexpressing HEK293 cells; cross-reactivity with mouse and cynomolgus A2AR but not human A1, A2B, or A3 receptors; functional antagonism of hA2AR in hA2AR-overexpressing HEK293 cells and peripheral blood mononuclear cells (PBMCs); and tumor-suppressing activity in colon tumor-bearing HuCD34-NCG mice. Given its therapeutic properties, TB206-001 is a good candidate for incorporation into next-generation bispecific immunotherapeutics. [ABSTRACT FROM AUTHOR]

Competitive fitness assays in liquid culture have been a mainstay for characterizing experimental evolution of microbial populations. Growth of microbial strains has also been extensively characterized by colony size and could serve as a useful alternative if translated to per generation measurements of relative fitness. To examine fitness based on colony size, we established a relationship between cell number and colony size for strains of Saccharomyces cerevisiae robotically pinned onto solid agar plates in a high-density format. This was used to measure growth rates and estimate relative fitness differences between evolved strains and their ancestors. After controlling for edge effects through both normalization and agar-trimming, we found that colony size is a sensitive measure of fitness, capable of detecting 1% differences. While fitnesses determined from liquid and solid mediums were not equivalent, our results demonstrate that colony size provides a sensitive means of measuring fitness that is particularly well suited to measurements across many environments.

Non-invasive Gamma ENtrainment Using Sensory stimulation (GENUS) at 40Hz reduces Alzheimer's disease (AD) pathology such as amyloid and tau levels, prevents cerebral atrophy, and improves behavioral testing performance in mouse models of AD. Here, we report data from (1) a Phase 1 feasibility study (NCT04042922, ClinicalTrials.gov) in cognitively normal volunteers (n = 25), patients with mild AD dementia (n = 16), and patients with epilepsy who underwent intracranial electrode monitoring (n = 2) to assess safety and feasibility of a single brief GENUS session to induce entrainment and (2) a single-blinded, randomized, placebo-controlled Phase 2A pilot study (NCT04055376) in patients with mild probable AD dementia (n = 15) to assess safety, compliance, entrainment, and exploratory clinical outcomes after chronic daily 40Hz sensory stimulation for 3 months. Our Phase 1 study showed that 40Hz GENUS was safe and effectively induced entrainment in both cortical regions and other cortical and subcortical structures such as the hippocampus, amygdala, insula, and gyrus rectus. Our Phase 2A study demonstrated that chronic daily 40Hz light and sound GENUS was well-tolerated and that compliance was equally high in both the control and active groups, with participants equally inaccurate in guessing their group assignments prior to unblinding. Electroencephalography recordings show that our 40Hz GENUS device safely and effectively induced 40Hz entrainment in participants with mild AD dementia. After 3 months of daily stimulation, the group receiving 40Hz stimulation showed (i) lesser ventricular dilation and hippocampal atrophy, (ii) increased functional connectivity in the default mode network as well as with the medial visual network, (iii) better performance on the face-name association delayed recall test, and (iv) improved measures of daily activity rhythmicity compared to the control group. These results support further evaluation of GENUS in a pivotal clinical trial to evaluate its potential as a novel disease-modifying therapeutic for patients with AD.

Darwin Core, the data standard used for sharing modern biodiversity and paleodiversity occurrence records, has previously lacked proper mechanisms for reporting what is known about the estimated age range of specimens from deep time. This has led to data providers putting these data in fields where they cannot easily be found by users, which impedes the reuse and improvement of these data by other researchers. Here we describe the development of the Chronometric Age Extension to Darwin Core, a ratified, community-developed extension that enables the reporting of ages of specimens from deeper time and the evidence supporting these estimates. The extension standardizes reporting about the methods or assays used to determine an age and other critical information like uncertainty. It gives data providers flexibility about the level of detail reported, focusing on the minimum information needed for reuse while still allowing for significant detail if providers have it. Providing a standardized format for reporting these data will make them easier to find and search and enable researchers to pinpoint specimens of interest for data improvement or accumulate more data for broad temporal studies. The Chronometric Age Extension was also the first community-managed vocabulary to undergo the new Biodiversity Informatics Standards (TDWG) review and ratification process, thus providing a blueprint for future Darwin Core extension development.

Cannabis is commonly used among people who drink alcohol, yet evidence on acute effects of co-use is conflicting. Two important variables that may influence the effects of cannabis and alcohol are cannabinoid content (i.e., the ratio of cannabidiol [CBD] and 9-tetrahydrocannabinol [THC]) as well as the order of use (i.e., cannabis before alcohol vs. alcohol before cannabis). Research is mixed regarding the acute imapct of cannabis on alcohol consumption and intoxication, with some studies suggesting additive effects of alcohol and cannabis, and others demonstrating negligible effects of combining these substances. Further complicating this, high-THC-content cannabis concentrates are increasingly popular on the legal-market, but to our knowledge, no studies have explored concentrate and alcohol co-use. In addition to cannabinoid content, order of use may influence intoxication and other acute effects, but is also understudied. Co-use studies typically administer a fixed dose of alcohol before cannabis, and there is a lack of data on the acute effects of cannabis before alcohol. Thus, there is a need for experimental co-use studies exploring the impact of cannabinoid content (particularly of highly potent cannabis concentrates) and order effects on intoxication. This study uses a federally-compliant mobile laboratory procedure to explore the effects of co-administration of legal-market cannabis concentrates with a moderate alcohol dose (.8g/kg) in a sample of community participants who regularly use alcohol and cannabis. The study will also explore alcohol and cannabis order effects (cannabis before alcohol vs. alcohol before cannabis). Outcomes are objective intoxication (measured using blood cannabinoid level, heart rate, psychomotor performance and breath alcohol level [BrAC]) and subjective intoxication (assessed via self-report measures). Overall, this study may influence harm-reduction recommendations for individuals who drink alcohol and use cannabis.

Unlike other European domesticates introduced in the Americas after the European invasion, equids (Equidae) were previously in the Western Hemisphere but were extinct by the late Holocene era. The return of equids to the Americas through the introduction of the domestic horse (Equus caballus) is documented in the historical literature but is not explored fully either archaeologically or genetically. Historical documents suggest that the first domestic horses were brought from the Iberian Peninsula to the Caribbean in the late 15th century CE, but archaeological remains of these early introductions are rare. This paper presents the mitochondrial genome of a late 16th century horse from the Spanish colonial site of Puerto Real (northern Haiti). It represents the earliest complete mitogenome of a post-Columbian domestic horse in the Western Hemisphere offering a unique opportunity to clarify the phylogeographic history of this species in the Americas. Our data supports the hypothesis of an Iberian origin for this early translocated individual and clarifies its phylogenetic relationship with modern breeds in the Americas.

Background Tuberculosis (TB) remains the leading cause of death among human immunodeficiency virus (HIV) infected individuals in South Africa. Despite the implementation of HIV/TB integration services at primary healthcare facility level, the effect of HIV on TB treatment outcomes has not been well investigated. To provide evidence base for TB treatment outcome improvement to meet End TB Strategy goal, we assessed the effect of HIV status on treatment outcomes of TB patients at a rural clinic in the Ugu Health District, South Africa. Methods We reviewed medical records involving a cohort of 508 TB patients registered for treatment between 1 January 2013 and 31 December 2015 at rural public sector clinic in KwaZulu-Natal province, South Africa. Data were extracted from National TB Programme clinic cards and the TB case registers routinely maintained at study sites. The effect of HIV status on TB treatment outcomes was determined by using multinomial logistic regression. Estimates used were relative risk ratio (RRR) at 95% confidence intervals (95%CI). Results A total of 506 patients were included in the analysis. Majority of the patients (88%) were new TB cases, 70% had pulmonary TB and 59% were co-infected with HIV. Most of HIV positive patients were on antiretroviral therapy (ART) (90% (n = 268)). About 82% had successful treatment outcome (cured 39.1% (n = 198) and completed treatment (42.9% (n = 217)), 7% (n = 39) died 0.6% (n = 3) failed treatment, 3.9% (n = 20) defaulted treatment and the rest (6.6% (n = 33)) were transferred out of the facility. Furthermore, HIV positive patients had a higher mortality rate (9.67%) than HIV negative patients (2.91%)”. Using completed treatment as reference, HIV positive patients not on ART relative to negative patients were more likely to have unsuccessful outcomes [RRR, 5.41; 95%CI, 2.11–13.86]. Conclusions When compared between HIV status, HIV positive TB patients were more likely to have unsuccessful treatment outcome in rural primary care. Antiretroviral treatment seems to have had no effect on the likelihood of TB treatment success in rural primary care. The TB mortality rate in HIV positive patients, on the other hand, was higher than in HIV negative patients emphasizing the need for enhanced integrated management of HIV/TB in rural South Africa through active screening of TB among HIV positive individuals and early access to ART among HIV positive TB cases.

The COVID Pandemic may affect fertility behaviour and intentions in many ways. Restrictions on service provision reduce access to family planning services and increase fertility in the short term. By contrast, the economic uncertainty brought about by the pandemic and its impact on mental health and well-being may reduce fertility. These various pathways have been explored in the context of high income countries such as the United States and Western Europe, but little is known about middle income countries. In this paper we asses the impact of the COVID pandemic on fertility intentions and behaviour in the Republic of Moldova, a middle income country in Eastern Europe, using the Generations and Gender Survey. This survey was conducted partially before and partially after the onset of the pandemic in 2020, allowing for detailed comparisons of individual circumstances. The results indicate that the pandemic reduced the used of intrauterine devices, and increased the use of male condoms, but with no overall decrease in contraceptive use. Conversely individuals interviewed after the onset of the pandemic were 34.5% less likely to be trying to conceive, although medium term fertility intentions were unchanged. Indicators therefore suggest that in the medium term fertility intentions may not be affected by the pandemic but restricted access to contraception requiring medical consultation and a decrease in short-term fertility intentions could disrupt short term family planning.

Background Frailty has emerged as an important prognostic marker of adverse outcomes after cardiac surgery, but evidence regarding its ability to predict quality of life after cardiac surgery is currently lacking. Whether frail patients derive the same quality of life benefit after cardiac surgery as patients without frailty remains unclear. Methods This systematic review will include interventional studies (RCT and others) and observational studies evaluating the effect of preoperative frailty on quality-of-life outcomes after cardiac surgery amongst patients 65 years and older. Studies will be retrieved from major databases including the Cochrane Central Register of Controlled Trials, Embase, and Medline. The primary exposure will be frailty status, independent of the tool used. The primary outcome will be change in quality of life, independent of the tool used. Secondary outcomes will include readmission during the year following the index intervention, discharge to a long-term care facility and living in a long-term care facility at one year. Screening, inclusion, data extraction and quality assessment will be performed independently by two reviewers. Meta-analysis based on the random-effects model will be conducted to compare the outcomes between frail and non-frail patients. The evidential quality of the findings will be assessed with the GRADE profiler. Conclusion The findings of this systematic review will be important to clinicians, patients and health policy-makers regarding the use of preoperative frailty as a screening and assessment tool before cardiac surgery. Study registration OSF registries (https://osf.io/vm2p8).

For patients affected by Facioscapulohumeral dystrophy (FSHD), alternate methods for increasing physical activity engagement that may benefit shoulder function and wider health are needed. Arm cycling has been proposed as a potential method for achieving this although dosage parameters and evidence is limited. The aim of this study was to conduct a pilot study evaluating the effect of a single intermittent arm cycling exercise programme on people affected by FSHD. People with confirmed genetic diagnosis of FSHD between the ages 18-60 years were recruited to attend a single session for the exercise intervention (5 exercise efforts lasting 2 minutes each with 30 seconds of rest between each effort). Prior to exercise, measures of shoulder function (Oxford shoulder score), strength and range of movement were recorded. During the exercise participants were video recorded to quantify range of movement and extract movement profile features. Participants comments were recorded and followed up four days later to check for adverse events. Fifteen participants, (6F:9M) were recruited with median (IQR) Oxford Shoulder Scores of 25 (18 to 39). All participants successfully completed the exercise intervention with only transient symptoms consistent with exercise being reported and achieving a median (IQR) rate of perceived exertion scores of 13 (12 to 13). Movement profile data was available for 12 out of 15 participants and suggests that exercise intensity did not compromise movement. An association between strength and shoulder function (R2 = 0.5147), Rate of perceived exertion (RPE) of the final effort against shoulder function and strength (R2 = 0.2344 and 0.1743 respectively) was identified. Participant comments were positive regarding the exercise intervention. Our study demonstrates that an intermittent arm cycling programme is feasible for people affected by FSHD. Further work is needed to evaluate physiological responses to exercise across variations in programme variables and equipment set up in a larger sample of people affected by FSHD.

IntroductionThe use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals.Materials and methodsA set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed.ResultsNone of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR-145 correlated with nadir CD4+ T cell count.DiscussionNo associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection.

During general anesthesia, both behavioral and autonomic changes are caused by the administration of anesthetics such as propofol. Propofol produces unconsciousness by creating highly structured oscillations in brain circuits. The anesthetic also has autonomic effects due to its actions as a vasodilator and myocardial depressant. Understanding how autonomic dynamics change in relation to propofol-induced unconsciousness is an important scientific and clinical question since anesthesiologists often infer changes in level of unconsciousness from changes in autonomic dynamics. Therefore, we present a framework combining physiology-based statistical models that have been developed specifically for heart rate variability and electrodermal activity with a robust statistical tool to compare behavioral and multimodal autonomic changes before, during, and after propofol-induced unconsciousness. We tested this framework on physiological data recorded from nine healthy volunteers during computer-controlled administration of propofol. We studied how autonomic dynamics related to behavioral markers of unconsciousness: 1) overall, 2) during the transitions of loss and recovery of consciousness, and 3) before and after anesthesia as a whole. Our results show a strong relationship between behavioral state of consciousness and autonomic dynamics. All of our prediction models showed areas under the curve greater than 0.75 despite the presence of non-monotonic relationships among the variables during the transition periods. Our analysis highlighted the specific roles played by fast versus slow changes, parasympathetic vs sympathetic activity, heart rate variability vs electrodermal activity, and even pulse rate vs pulse amplitude information within electrodermal activity. Further advancement upon this work can quantify the complex and subject-specific relationship between behavioral changes and autonomic dynamics before, during, and after anesthesia. However, this work demonstrates the potential of a multimodal, physiologically-informed, statistical approach to characterize autonomic dynamics.

In current anesthesiology practice, anesthesiologists infer the state of unconsciousness without directly monitoring the brain. Drug- and patient-specific electroencephalographic (EEG) signatures of anesthesia-induced unconsciousness have been identified previously. We applied machine learning approaches to construct classification models for real-time tracking of unconscious state during anesthesia-induced unconsciousness. We used cross-validation to select and train the best performing models using 33,159 2s segments of EEG data recorded from 7 healthy volunteers who received increasing infusions of propofol while responding to stimuli to directly assess unconsciousness. Cross-validated models of unconsciousness performed very well when tested on 13,929 2s EEG segments from 3 left-out volunteers collected under the same conditions (median volunteer AUCs 0.99-0.99). Models showed strong generalization when tested on a cohort of 27 surgical patients receiving solely propofol collected in a separate clinical dataset under different circumstances and using different hardware (median patient AUCs 0.95-0.98), with model predictions corresponding with actions taken by the anesthesiologist during the cases. Performance was also strong for 17 patients receiving sevoflurane (alone or in addition to propofol) (median AUCs 0.88-0.92). These results indicate that EEG spectral features can predict unconsciousness, even when tested on a different anesthetic that acts with a similar neural mechanism. With high performance predictions of unconsciousness, we can accurately monitor anesthetic state, and this approach may be used to engineer infusion pumps to intelligibly respond to patients' neural activity.

The coastal zone provides foraging opportunities for insular populations of terrestrial mammals, allowing for expanded habitat use, increased dietary breadth, and locally higher population densities. We examined the use of sandy beach resources by the threatened island fox (Urocyon littoralis) on the California Channel Islands using scat analysis, surveys of potential prey, beach habitat attributes, and stable isotope analysis. Consumption of beach invertebrates, primarily intertidal talitrid amphipods (Megalorchestia spp.) by island fox varied with abundance of these prey across sites. Distance-based linear modeling revealed that abundance of giant kelp (Macrocystis pyrifera) wrack, rather than beach physical attributes, explained the largest amount of variation in talitrid amphipod abundance and biomass across beaches. δ13C and δ15N values of fox whisker (vibrissae) segments suggested individualism in diet, with generally low δ13C and δ15N values of some foxes consistent with specializing on primarily terrestrial foods, contrasting with the higher isotope values of other individuals that suggested a sustained use of sandy beach resources, the importance of which varied over time. Abundant allochthonous marine resources on beaches, including inputs of giant kelp, may expand habitat use and diet breadth of the island fox, increasing population resilience during declines in terrestrial resources associated with climate variability and long-term climate change.

IntroductionThe objective of this study was to describe interruptions in the pediatric ambulatory setting and to assess their impact on perceived physician communication, patient satisfaction and recall of provided physician instructions.MethodsAn observational study was performed at the Children's Hospital of Philadelphia, Pediatric Gastroenterology clinic. Participation consisted of video recording the clinic visit and the caregiver completed post-visit surveys on communication and satisfaction. Video recordings were coded for interruptions, which were divided into 3 main categories: Visit Associated, Pediatric Associated, and Unanticipated. An interruption rate was calculated and correlated with the following outcome variables to assess the impact of interruptions: caregiver satisfaction, caregiver perception on the quality of physician communication, and caregiver instruction recall.ResultsThere were 675 interruptions noted in the 81 clinic visits, with an average of 7.96 (σ = 7.68) interruptions per visit. Six visits had no interruptions. The Patient was the most frequent interrupter. Significantly higher interruption rates occurred in clinic visits with younger patients (ConclusionThe effect of interruptions on the pediatric visit remains unclear. Interruptions may be part of the communication process to ensure alignment of the patient's agenda. Additional studies are needed to help determine the impact of interruptions and guide medical education on patient communication.

In September 2017, Hurricane Maria made landfall across the Caribbean region as a category 4 storm. In the aftermath, many residents of Puerto Rico were without power or clean running water for nearly a year. Using both English and Spanish tweets from September 16 to October 15 2017, we investigate discussion of Maria both on and off the island, constructing a proxy for the temporal network of communication between victims of the hurricane and others. We use information theoretic tools to compare the lexical divergence of different subgroups within the network. Lastly, we quantify temporal changes in user prominence throughout the event. We find at the global level that Spanish tweets more often contained messages of hope and a focus on those helping. At the local level, we find that information propagating among Puerto Ricans most often originated from sources local to the island, such as journalists and politicians. Critically, content from these accounts overshadows content from celebrities, global news networks, and the like for the large majority of the time period studied. Our findings reveal insight into ways social media campaigns could be deployed to disseminate relief information during similar events in the future.

Research-based teaching practices can improve student learning outcomes in a variety of complex educational environments. The implementation of learner-centered teaching practices in STEM can both benefit from or be constrained by different factors related to individual instructors and the teaching environment. Additionally, we know little of how the instructional climate varies across institutions and how this climate affects teaching practices. Our study sought to examine the relative importance of environmental influences and individual characteristics on learner-centered teaching practices across institutions. We also assessed differences in our study population and departmental climate for 35 US higher education institutions across the country. We found that self-efficacy in teaching and professional development exert a strong influence on faculty teaching practices in biology. While departmental climate did not emerge as a significant predictor of teaching practices, there was consistently low support for teaching, and institution size was negatively correlated with leadership and evaluation of effective teaching. We also found that intensive professional development programs, such as the Faculty Institutes for Reforming Science Teaching IV program, may prepare instructors to teach learner-centered courses in different collegial teaching climates. Our results suggest that through cultivating self-efficacy and participating in iterative professional development, instructors can implement effective teaching practices in a variety of institutional environments.

ObjectiveTo develop and assess a novel guidance technique and instrumentation system for minimally invasive short-stemmed total shoulder arthroplasty that will help to reduce the complications associated with traditional open replacement such as poor muscle healing and neurovascular injury. We have answered key questions about the developed system including (1) can novel patient-specific guides be accurately registered and used within a minimally invasive environment?; (2) can accuracy similar to traditional techniques be achieved?MethodsA novel intra-articular patient-specific guide was developed for use with a new minimally invasive posterior surgical approach that guides bone preparation without requiring muscle resection or joint dislocation. Additionally, a novel set of instruments were developed to enable bone preparation within the minimally invasive environment. The full procedure was evaluated in six cadaveric shoulders, using digitizations to assess accuracy of each step.ResultsPatient-specific guide registration accuracy in 3D translation was 2.2±1.2mm (RMSE±1 SD; p = 0.007) for the humeral component and 2.7±0.7mm (pConclusionThis system achieves minimally invasive shoulder replacement with accuracy similar to traditional open techniques while avoiding common causes of complications.SignificanceThis novel technique could lead to a paradigm shift in shoulder arthroplasty for patients with moderate arthritis, which could significantly improve rehabilitation and functional outcomes.

IntroductionE-cigarette advertising has been shown to increase e-cigarette awareness and use. Although e-cigarette marketing in the early 2010s has been well-documented, little is known about how it has changed in recent years in response to the regulatory scrutiny from the FDA and the Congress to combat youth vaping epidemic. This study aims to examine the exposure to e-cigarette TV advertising among youth and adults in the U.S. from 2013 to 2019, overall and by media market and brand.MethodsQuarterly data on e-cigarette TV advertising exposure, measured by target rating points (TRPs), and expenditures from 2013 to 2019 were compiled from the StradegyTM of Kantar Media. Trends of quarterly e-cigarette advertising TRPs were reported by age group, market, and brand.ResultsOver the study period, overall exposure to e-cigarette TV advertising was higher among adults than among youth. E-cigarette advertising TRPs and expenditures were relatively stable, despite intermittent fluctuations, between 2013 Q1 and 2017 Q1 except for a one-time dip in 2015 Q3, followed by a sharp decline in 2017 Q2 and stayed low till the end of 2018. A resurgence of e-cigarette advertising TRPs occurred in 2019 Q1, led by the advertising from JUUL, Blu, and Vuse, which peaked in the third quarter of 2019, with quarterly TRPs reaching 316.8 for youth and 1,701.9 for adults, and quarterly advertising expenditure totaling $31 million.ConclusionsSignificant variations, both over time and across media markets and brands, were observed for e-cigarette televised advertising between 2013 and 2019. Following a lull in TV advertising in 2017/18, major e-cigarette companies have substantially increased advertising of their products on American television since early 2019, resulting in a surge in exposure to e-cigarette advertising among both youth and adults. Our findings highlighted the importance of continued monitoring of e-cigarette advertising in the U.S.

In this paper, we describe a population of mothers who are opioid dependent at the time of giving birth and neonates exposed to opioids in utero who experience withdrawal following birth. While there have been studies of national trends in this population, there remains a gap in studies of regional trends. Using data from the Arizona Department of Health Services Hospital Discharge Database, this study aimed to characterize the population of neonates with neonatal opioid withdrawal syndrome (NOWS) and mothers who were opioid dependent at the time of giving birth, in Arizona. We analyzed approximately 1.2 million electronic medical records from the Arizona Department of Health Services Hospital Discharge Database to identify patterns and disparities across socioeconomic, ethnic, racial, and/or geographic groupings. In addition, we identified comorbid conditions that are differentially associated with NOWS in neonates or opioid dependence in mothers. Our analysis was designed to assess whether indicators such as race/ethnicity, insurance payer, marital status, and comorbidities are related to the use of opioids while pregnant. Our findings suggest that women and neonates who are non-Hispanic White and economically disadvantaged, tend be part of our populations of interest more frequently than expected. Additionally, women who are opioid dependent at the time of giving birth are unmarried more often than expected, and we suggest that marital status could be a proxy for support. Finally, we identified comorbidities associated with neonates who have NOWS and mothers who are opioid dependent not previously reported.

Social organisms rank among the most abundant and ecologically dominant species on Earth, in part due to exclusive recognition systems that allow cooperators to be distinguished from exploiters. Exploiters, such as social parasites, manipulate their hosts recognition systems, whereas cooperators are expected to minimize interference with their partners recognition abilities. Despite our wealth of knowledge about recognition in single-species social nests, less is known of the recognition systems in multi-species nests, particularly involving cooperators. One uncommon type of nesting symbiosis, called parabiosis, involves two species of ants sharing a nest and foraging trails in ostensible cooperation. Here, we investigated recognition cues (cuticular hydrocarbons) and recognition behaviors in the parabiotic mixed-species ant nests of Camponotus femoratus and Crematogaster levior in North-Eastern Amazonia. We found two sympatric, cryptic Cr. levior chemotypes in the population, with one type in each parabiotic colony. Although they share a nest, very few hydrocarbons were shared between Ca. femoratus and either Cr. levior chemotype. The Ca. femoratus hydrocarbons were also unusually long-chained branched alkenes and dienes, compounds not commonly found amongst ants. Despite minimal overlap in hydrocarbon profile, there was evidence of potential interspecific nestmate recognition -Cr. levior ants were more aggressive toward Ca. femoratus non-nestmates than Ca. femoratus nestmates. In contrast to the prediction that sharing a nest could weaken conspecific recognition, each parabiotic species also maintains its own aggressive recognition behaviors to exclude conspecific non-nestmates. This suggests that, despite cohabitation, parabiotic ants maintain their own species-specific colony odors and recognition mechanisms. It is possible that such social symbioses are enabled by the two species each using their own separate recognition cues, and that interspecific nestmate recognition may enable this multi-species cooperative nesting.

Data from morphology, linguistics, history, and archaeology have all been used to trace the dispersal of chickens from Asian domestication centers to their current global distribution. Each provides a unique perspective which can aid in the reconstruction of prehistory. This study expands on previous investigations by adding a temporal component from ancient DNA and, in some cases, direct dating of bones of individual chickens from a variety of sites in Europe, the Pacific, and the Americas. The results from the ancient DNA analyses of forty-eight archaeologically derived chicken bones provide support for archaeological hypotheses about the prehistoric human transport of chickens. Haplogroup E mtDNA signatures have been amplified from directly dated samples originating in Europe at 1000 B.P. and in the Pacific at 3000 B.P. indicating multiple prehistoric dispersals from a single Asian centre. These two dispersal pathways converged in the Americas where chickens were introduced both by Polynesians and later by Europeans. The results of this study also highlight the inappropriate application of the small stretch of D-loop, traditionally amplified for use in phylogenetic studies, to understanding discrete episodes of chicken translocation in the past. The results of this study lead to the proposal of four hypotheses which will require further scrutiny and rigorous future testing.

BACKGROUND:There is a growing focus on the development of multi-factorial cancer risk prediction algorithms alongside tools that operationalise them for clinical use. BOADICEA is a breast and ovarian cancer risk prediction model incorporating genetic and other risk factors. A new user-friendly Web-based tool (CanRisk.org) has been developed to apply BOADICEA. This study aimed to explore the acceptability of the prototype CanRisk tool among two healthcare professional groups to inform further development, evaluation and implementation. METHOD:A multi-methods approach was used. Clinicians from primary care and specialist genetics clinics in England, France and Germany were invited to use the CanRisk prototype with two test cases (either face-to-face with a simulated patient or via a written vignette). Their views about the tool were examined via a semi-structured interview or equivalent open-ended questionnaire. Qualitative data were subjected to thematic analysis and organised around Sekhon's Theoretical Framework of Acceptability. RESULTS:Seventy-five clinicians participated, 21 from primary care and 54 from specialist genetics clinics. Participants were from England (n = 37), France (n = 23) and Germany (n = 15). The prototype CanRisk tool was generally acceptable to most participants due to its intuitive design. Primary care clinicians were concerned about the amount of time needed to complete, interpret and communicate risk information. Clinicians from both settings were apprehensive about the impact of the CanRisk tool on their consultations and lack of opportunities to interpret risk scores before sharing them with their patients. CONCLUSIONS:The findings highlight the challenges associated with developing a complex tool for use in different clinical settings; they also helped refine the tool. This prototype may not have been versatile enough for clinical use in both primary care and specialist genetics clinics where the needs of clinicians are different, emphasising the importance of understanding the clinical context when developing cancer risk assessment tools.

BACKGROUND:Intensive care unit (ICU) patients with the most severe forms of acute coronary syndrome (ACS) require invasive therapies such as extracorporeal life support. The risk of bleeding in ICU patients with ACS treated with a dual antiplatelet therapy of aspirin and ticagrelor is unknown. The primary objective of this study was to compare the bleeding risk of ticagrelor and clopidogrel in ICU patients with ACS. METHODS AND FINDINGS:We conducted a retrospective study based on a propensity score and a proportional hazards model. All patients with ACS hospitalized in the ICU of a French university hospital between January 2013 and January 2017 were included in the study. Bleeding during ICU stay was defined as all Thrombolysis in myocardial infarction (TIMI) major or minor events. A total of 155 patients were included in the study. According to propensity score matching, 57 patients treated with aspirin and ticagrelor were matched with 57 patients treated with aspirin and clopidogrel. Median (first-third quartile) Simplified Acute Physiology Score II was 61.5 (41.0-85.0). Bleeding during ICU stay occurred in 12 patients (21.1%) treated with clopidogrel and in 35 patients (61.4%) treated with ticagrelor (p

Childhood sexual abuse (CSA) has been shown to predict the coupling of depression and inflammation in adulthood. Trust within intimate relationships, a core element in marital relations, has been shown to predict positive physical and mental health outcomes, but the mediating role of trust in partners in the association between CSA and inflammation in adulthood requires further study. The present study aimed to examine the impact of CSA on inflammatory biomarkers (IL-6 and IL-1β) in adults with depression and the mediating role of trust. A cross-sectional survey data set of adults presenting with mood and sleep disturbance was used in the analysis. CSA demonstrated a significant negative correlation with IL-6 level (r = -0.28, p

INTRODUCTION:Digital e-cigarette marketing is largely unregulated and remains easily accessible to young people. The growing public concern around youth JUUL use and its viral presence on social media led the company to engage in several voluntary actions to remove and reduce JUUL-related content on Instagram in May 2018. The current study examined how JUUL-related Instagram content changed in the US following JUUL Labs' wave of voluntary actions in May 2018. METHODS:In 2019, we collected a total of 50,817 JUUL-relevant posts by 16,323 unique users on Instagram from March 1-May 15, 2018 (Phase 1) and May 16-November 11, 2018 (Phase II) using the application programming interface. We conducted a semantic network analysis to identify major topic clusters over time. RESULTS:Approximately 14,838 JUUL-related posts were made by 5,201 accounts in Phase I and 35,979 posts were made by 11,122 accounts in Phase II. Major content clusters remained unchanged over time-key topics were JUUL-related product characteristics and JUUL-communities; the general vape community; and cannabis-related behavior. Of note, cannabis-related content grew in Phase II, particularly use of the term CBD. CONCLUSIONS:Our results reflect the limits of voluntary industry actions to reduce or change vaping-related content on social media. Rather, strong federal restriction on commercial tobacco marketing is the optimal pathway to reduce initial product marketing exposure among youth. These limits would make the emergence and viral contagion of brand-related social media content less likely and reduce its influence on youth behavior.

Research in music and emotion has long acknowledged the importance of extra-musical cues, yet has been unable to measure their effect on emotion communication in music. The aim of this research was to understand how extra-musical cues affect emotion responses to music in two distinguishable cultures. Australian and Cuban participants (N = 276) were instructed to name an emotion in response to written lyric excerpts from eight distinct music genres, using genre labels as cues. Lyrics were presented primed with genre labels (original priming and a false, lured genre label) or unprimed. For some genres, emotion responses to the same lyrics changed based on the primed genre label. We explain these results as emotion expectations induced by extra-musical cues. This suggests that prior knowledge elicited by lyrics and music genre labels are able to affect the musical emotion responses that music can communicate, independent of the emotion contribution made by psychoacoustic features. For example, the results show a lyric excerpt that is believed to belong to the Heavy Metal genre triggers high valence/high arousal emotions compared to the same excerpt primed as Japanese Gagaku, without the need of playing any music. The present study provides novel empirical evidence of extra-musical effects on emotion and music, and supports this interpretation from a multi-genre, cross-cultural perspective. Further findings were noted in relation to fandom that also supported the emotion expectation account. Participants with high levels of fandom for a genre reported a wider range of emotions in response to the lyrics labelled as being a song from that same specific genre, compared to lower levels of fandom. Both within and across culture differences were observed, and the importance of a culture effect discussed.

BackgroundWomen involved in repetitive, fatiguing, jobs develop more neck and/or shoulder musculoskeletal disorders than men. Sex differences in the pain response to exercise could contribute to the higher prevalence of neck/shoulder musculoskeletal disorders in women. The objective of this study was to assess sex differences in pain sensitivity following a fatiguing upper limb task. Relationships between measures of fatigue and of the sensitivity to nociceptive and to non-nociceptive stimulations were also explored.MethodsThirty healthy adults (15 women) performed a fatiguing repetitive pointing task with their dominant arm. Upper limb electromyography was recorded from the dominant upper trapezius, anterior deltoid and bicep brachii and from the contralateral tibialis anterior. Before and immediately after the repetitive pointing task, pressure pain and light touch sensitivity thresholds were measured over the same muscles.ResultsElectromyographic signs of fatigue were observed only in the anterior deltoid and biceps brachii muscles. Pressure pain thresholds over both muscles increased slightly (effect size ≤ 0.34), but no changes occurred over the upper trapezius and the tibialis anterior. Light touch thresholds increased moderately to importantly after the repetitive pointing task over all four muscles (effect sizes = 0.58 to 0.87). No sex differences were observed in any sensory variable. Moreover, no or weak correlations (r = -0.27 to 0.39) were observed between electromyographical signs of fatigue, light touch threshold and pressure pain threshold variables.ConclusionsWe observed sex-independent effects of a repetitive upper limb task on the sensitivity to painful and to nonpainful stimuli. Moreover, the hypoalgesia induced by the repetitive pointing task was weak and localized, and did not directly correlate with the induced muscle fatigue. Results suggest that fatigue-related changes in the sensitivity to noxious and innocuous stimuli could not explain women's greater prevalence of neck/shoulder musculoskeletal disorders.

Oxidative stress (OS) plays a marked role in aging and results from a variety of stressors, making it a powerful measure of health and a way to examine costs associated with life history investments within and across species. However, few urinary OS markers have been examined under field conditions, particularly in primates, and their utility to non-invasively monitor the costs of acute stressors versus the long-term damage associated with aging is poorly understood. In this study, we examined variation in 5 urinary markers of oxidative damage and protection under 5 validation paradigms for 37 wild, chimpanzees living in the Kibale National Park, Uganda. We used 924 urine samples to examine responses to acute immune challenge (respiratory illness or severe wounding), as well as mixed-longitudinal and intra-individual variation with age. DNA damage (8-OHdG) correlated positively with all other markers of damage (F-isoprostanes, MDA-TBARS, and neopterin) but did not correlate with protection (total antioxidant capacity). Within individuals, all markers of damage responded to at least one if not both types of acute infection. While OS is expected to increase with age, this was not generally true in chimpanzees. However, significant changes in oxidative damage were detected within past-prime individuals and those close to death. Our results indicate that OS can be measured using field-collected urine and integrates short- and long-term aspects of health. They further suggest that more data are needed from long-lived, wild animals to illuminate if common age-related increases in inflammation and OS damage are typical or recently aberrant in humans.