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BACKGROUND: International data on anogenital HPV infection incidence among men are limited. METHODS: Incidence of incident-persistent (IP) anogenital HPV infections was evaluated among 295 men who have sex with men (MSM) and 1576 heterosexual men (HM) aged 16-27 years in the placebo arm of a global, multicenter 4-valent (4v) HPV vaccine trial. We estimated IP incidence (penile/scrotal, perineal/perianal, anal) for 4vHPV and 9-valent (9v) HPV vaccine types and cumulative IP incidence over 36 months. RESULTS: IP infection incidence per 100 person-years (95% CI) among HM for 4vHPV and 9vHPV types was 4.1 (3.5-4.9) and 6.8 (5.9-7.6) at penile/scrotal, and 1.2 (.8-1.6) and 1.9 (1.5-2.4) at perineal/perianal sites, respectively; and among MSM, IP infection incidence was 2.3 (1.3-3.8) and 3.2 (2.0-4.9) at penile/scrotal, 6.8 (4.9-9.2) and 9.0 (6.9-11.6) at perineal/perianal, and 12.0 (9.4-15.1) and 16.8 (13.7-20.2) at anal sites, respectively. Cumulative IP incidence over 36 months (excluding anal canal; any 9vHPV type) was higher among MSM versus HM (24.1% vs 18.4%). CONCLUSIONS: A substantial proportion of unvaccinated men of catch-up vaccination age developed IP 9vHPV-related infections. Gender-neutral vaccination could decrease male HPV infection, contribute to herd protection, and reduce disease burden. Clinical Trials Registration. NCT00090285.

Please, see the workshop's website here: https://sites.google.com/view/cogconceptsThe goal of this workshop is to initiate an interdisciplinary conversation about reconceptualizing cognitive science disciplines. This workshop will bring together researchers proposing new conceptualizations in their disciplines, cognitive scientists investigating the mechanisms of concept learning and the role of concepts in human cognition, researchers building infrastructures to study and improve cognitive concepts, and philosophers analyzing scientific conceptualizations. The workshop will include activities which will prompt the audience to think about the conceptual foundations of their respective areas, and about ways to improve these foundations. These activities are designed to maximize audience participation and include panel discussions, as well as mind-matching sessions. One of the outcomes of the workshop is identifying the diversity of approaches for improving cognitive science concepts that could be relevant to both discipline-wide and more specific efforts.

This study explores how scientific conceptualizations, such as partitioning of the brain into distinct regions, shape investigation. One hundred fifty-six undergraduate psychology students (novices) completed a science learning task in which they explored the behavioral functions of a fictional brain segment by conducting simplified neuroimaging and lesioning experiments on it. We investigated how the partitioning of the segment into regions influenced participants' experimental choices and learning outcomes by randomly seeding the brain regions for each participant. The participants exhibited conceptual influences on their experimentation: they preferred to explore the boundaries and prototypical--or "skeletal"--locations of the delineated regions. These conceptual biases significantly shaped learning outcomes; for example, participants were more successful at identifying signals near region boundaries. Additionally, participants demonstrated conceptual expectations that led them to associate a discovered signal with locations within one region rather than locations that straddled region boundaries. This research contributes to our understanding of how the scientific concepts affect scientific investigation.

We analyze the visual perception task that home plate umpires (N = 121) perform calling balls and strikes (N = 3,001,019) in baseball games, focusing on the topics of perceptual learning and bias in decision-making. In the context of perceptual learning, our results show that monitoring, training, and feedback improve skill over time. In addition, we document two other aspects of umpires' improvement that are revealing with respect to the nature of their perceptual expertise. First, we show that biases in umpires' decision-making persist even as their overall accuracy improves. This suggests that bias and accuracy are orthogonal and that reduction of bias in decision-making requires interventions aimed specifically at this goal. Second, we measure a distinct difference in the rate of skill improvement between older and younger umpires. Younger umpires improve more quickly, suggesting that the decision task umpires engage in becomes routinized over time.

Abstract Mollusks are the second most diverse animal phylum, yet little is known about their endocrinology or how they respond to endocrine disrupting compound (EDC) pollution. Characteristic effects of endocrine disruption are reproductive impairment, skewed sex ratios, development of opposite sex characteristics, and population decline. However, whether classical vertebrate EDCs, such as steroid hormone-like chemicals and inhibitors of steroidogenesis, exert effects on mollusks is controversial. In the blue mussel, Mytilus edulis, EDC exposure is correlated with feminized sex ratios in wild and laboratory mussels, but sex reversal has not been confirmed. Here, we describe a non-destructive qPCR assay to identify the sex of M. edulis allowing identification of males and females prior to experimentation. We exposed male mussels to 17α-ethinylestradiol and female mussels to ketoconazole, EDCs that mimic vertebrate steroid hormones or inhibit their biosynthesis. Both chemicals changed the sex of individual mussels, interfered with gonadal development, and disrupted gene expression of the sex differentiation pathway. Impacts from ketoconazole treatment, including changes in steroid levels, confirmed a role for steroidogenesis and steroid-like hormones in mollusk endocrinology. The present study expands the possibilities for laboratory and field monitoring of mollusk species and provides key insights into endocrine disruption and sexual differentiation in bivalves.

Abstract Background Nurses contribute to the largest demographic of the healthcare workforce. However, given current global shortages of workforce capacity, this often leads to limited capacity to engage in extracurricular educational developments beyond their immediate role. Consequently, this significantly limits the range of workforce training and development opportunities that are available to them, which could enhance the variety of skills that are brought to the National Health Service (NHS). Objective We aimed to understand prior, current, and future participation in global health activities such as global health conferences, networks, and placements, among National Health Service (NHS) staff. Furthermore, we investigated the barriers and facilitators to participation in global health activities for nurses in our sample. Method Qualitative and quantitative data was gathered from an online survey conducted in England from July to November 2021. Thematic analysis was used to examine the qualitative data collected from one open-ended question, whereas statistical analysis was used to examine the remaining quantitative data. Results Most (84%) nurses in our sample had not participated in a global health activity. Our results highlighted three barriers to participation, including insufficient communication, a lack of awareness, and capacity issues. Conclusion This study showed that, despite low levels of prior participation, there is a strong desire among surveyed nurses to be involved in global health activities and education. Our findings also suggest that enhanced communication of opportunities available is needed, in addition to organisational support which incorporates strategies to overcome capacity constraints.

Interactive computer simulations are commonly used as pedagogical tools to support students' statistical reasoning. This paper examines whether and how these simulations enable their intended effects. We begin by contrasting two theoretical frameworks--"dual processes" and "grounded cognition"--in the context of people's conceptions about statistical sampling, setting the stage for the potential benefits of simulations in learning such conceptions. Then, we continue with reviewing the educational literature on statistical sampling simulations. Our review tentatively suggests benefits of the simulations for building "statistical habits of mind." However, challenges seem to persist when more specific concepts and skills are investigated. With and without simulations, students have difficulty forming an aggregate view of data, interpreting sampling distributions, showing a process-based understanding of the law of large numbers, making statistical inferences, and context-independent reasoning. We propose that grounded cognition offers a framework for understanding these findings, highlighting the bidirectional relationship between perception and conception, perceptual design features, and guided perceptual routines for supporting students' meaning making from simulations. Finally, we propose testable instructional strategies for using simulations in statistics education.

This article provides a short overview of how to communicate about the purposes of educational assessments. The authors address the assessments that may be required at the state or district level, including summative assessments, interim assessments, and formative assessment practices. The article describes the needs of various audiences and the implications of those audience needs when talking with each of them about assessments. The authors conclude by describing communication strategies and how they might be used to communicate about statewide and districtwide assessments.

Abstract Mutant selective drugs targeting the inactive, GDP-bound form of KRASG12C have been approved for use in lung cancer, but resistance develops rapidly. Here we use an inhibitor, (RMC-4998) that targets RASG12C in its active, GTP-bound form, to treat KRAS mutant lung cancer in various immune competent mouse models. RAS pathway reactivation after RMC-4998 treatment could be delayed using combined treatment with a SHP2 inhibitor, which not only impacts tumour cell RAS signalling but also remodels the tumour microenvironment to be less immunosuppressive. In an immune inflamed model, RAS and SHP2 inhibitors in combination drive durable responses by suppressing tumour relapse and inducing development of immune memory. In an immune excluded model, combined RAS and SHP2 inhibition sensitises tumours to immune checkpoint blockade, leading to efficient tumour immune rejection. These preclinical results demonstrate the potential of the combination of RAS(ON) G12C-selective inhibitors with SHP2 inhibitors to sensitize tumours to immune checkpoint blockade.

Prader–Willi syndrome (PWS) is a rare orphan disease and complex genetic neurodevelopmental disorder, with a birth incidence of approximately 1 in 10,000–30,000. Management of people with PWS requires a multi-disciplinary approach, ideally through a multi-disciplinary team (MDT) clinic with community support. Hypotonia, poor feeding and faltering growth are characteristic features in the neonatal period, followed by hyperphagia and risk of rapid weight gain later in childhood. Children and adolescents (CA) with PWS usually display developmental delay and mild learning disability and can develop endocrinopathies, scoliosis, respiratory difficulties (both central and obstructive sleep apnoea), challenging behaviours, skin picking, and mental health issues, especially into adulthood. This consensus statement is intended to be a reference document for clinicians managing children and adolescents (up to 18 years of age) with PWS. It considers the bio-psycho-social domains of diagnosis, clinical assessment, and management in the paediatric setting as well as during and after transition to adult services. The guidance has been developed from information gathered from peer-reviewed scientific reports and from the expertise of a range of experienced clinicians in the United Kingdom and Ireland involved in the care of patients with PWS.

Abstract Autologous(auto-) and allogeneic(allo-) hematopoietic stem cell transplantation (HSCT) are key treatments for relapsed/refractory diffuse large B-cell lymphoma (DLBCL), although their roles are challenged by CAR-T-cells and other immunotherapies. We examined the transplantation trends and outcomes for DLBCL patients undergoing auto-/allo-HSCT between 1990 and 2021 reported to EBMT. Over this period, 41,148 patients underwent auto-HSCT, peaking at 1911 cases in 2016, while allo-HSCT saw a maximum of 294 cases in 2018. The recent decline in transplants corresponds to increased CAR-T treatments (1117 cases in 2021). Median age for auto-HSCT rose from 42 (1990–1994) to 58 years (2015–2021), with peripheral blood becoming the primary stem cell source post-1994. Allo-HSCT median age increased from 36 (1990–1994) to 54 (2015–2021) years, with mobilized blood as the primary source post-1998 and reduced intensity conditioning post-2000. Unrelated and mismatched allo-HSCT accounted for 50% and 19% of allo-HSCT in 2015–2021. Three-year overall survival (OS) after auto-HSCT improved from 56% (1990–1994) to 70% (2015–2021), p 40,000 transplants, providing insights for evaluating emerging DLBCL therapies.

Study objectivesAdolescence is characterized by significant brain development, accompanied by changes in sleep timing and architecture. It also is a period of profound psychosocial changes, including the initiation of alcohol use; however, it is unknown how alcohol use affects sleep architecture in the context of adolescent development. We tracked developmental changes in polysomnographic (PSG) and electroencephalographic (EEG) sleep measures and their relationship with emergent alcohol use in adolescents considering confounding effects (e.g. cannabis use).MethodsAdolescents (n = 94, 43% female, age: 12-21 years) in the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) study had annual laboratory PSG recordings across 4-years. Participants were no/low drinkers at baseline.ResultsLinear mixed effect models showed developmental changes in sleep macrostructure and EEG, including a decrease in slow wave sleep and slow wave (delta) EEG activity with advancing age. Emergent moderate/heavy alcohol use across three follow-up years was associated with a decline in percentage rapid eye movement (REM) sleep over time, a longer sleep onset latency (SOL) and shorter total sleep time (TST) in older adolescents, and lower non-REM delta and theta power in males.ConclusionsThese longitudinal data show substantial developmental changes in sleep architecture. Emergent alcohol use during this period was associated with altered sleep continuity, architecture, and EEG measures, with some effects dependent on age and sex. These effects, in part, could be attributed to the effects of alcohol on underlying brain maturation processes involved in sleep-wake regulation.

The Heart Valve Collaboratory is a multidisciplinary, patient-centered community of stakeholders addressing complex problems and embracing innovation to help patients with heart valve disease achieve their fullest potential for health. The Scientific Council is composed of cardiologists, surgeons, ex-officio representatives of the Food and Drug Administration and Centers for Medicare and Medicaid Services, National Heart Lung Blood Institute, and representatives from industry partners. In October 2022, this group convened a workshop that included experts from stakeholder groups to address the unmet and clinical needs of patients with pediatric and congenital heart valve disease. The following document includes the discussion and summary of the current state of valve therapy and the needs being addressed for valve development.

Objective: Bicuspid aortic valve (AV) patients with aortic regurgitation (AR) differ from tricuspid AV patients given younger age, greater left ventricle (LV) compliance, and more prevalent aortic stenosis (AS). Bicuspid AV-specific data to guide timing of AV replacement or repair are lacking. Methods: Adults with bicuspid AV and moderate or greater AR who underwent aortic valve replacement or repair at our center were studied. The presurgical echocardiogram, and echocardiograms within 3 years postoperatively were evaluated for LV geometry/function, and AV function. Semiquantitative AS/AR assessment was performed in all patients with adequate imaging. Results: One hundred thirty-five patients (85% men, aged 44.5 ± 15.9 years) were studied (63% pure AR, 37% mixed AS/AR). Following aortic valve replacement or repair, change in LV end-diastolic dimension and change in LV end-diastolic volume were associated with preoperative LV end-diastolic dimension (β = 0.62 Δcm/cm; 95% CI, 0.43-0.73 Δcm/cm; P

Objective: Congenital heart disease is a risk factor for mortality after orthotopic heart transplantation; however, the impact of preoperative circulation type and primary congenital heart disease diagnosis remains poorly delineated. Methods: We retrospectively reviewed patients with adult congenital heart disease aged 16 years or more who underwent orthotopic heart transplantation at our institution between 2008 and 2022. Patients were categorized as having single-ventricle or biventricular circulation. The primary end point was 5-year post-transplant survival. Results: Sixty-one patients with adult congenital heart disease (single-ventricle: n = 26 [42.6%], biventricular: n = 35 [57.4%]) underwent orthotopic heart transplantation at 33.7 [interquartile range, 19.1-48.7] years. The most common congenital heart disease diagnosis was hypoplastic left heart syndrome (n = 11, 42.3%) in the single-ventricle group and congenitally corrected transposition of the great arteries (n = 7, 20.0%) in the biventricular group. Twenty-four patients previously underwent Fontan palliation. At transplant, patients in the single-ventricle group were younger (18.5 [interquartile range, 17.6-32.3] years vs 45.0 [interquartile range, 33.0-52.2] years, P

We develop a conceptual framework for studying collective adaptation in complex socio-cognitive systems, driven by dynamic interactions of social integration strategies, social environments and problem structures. Going beyond searching for 'intelligent' collectives, we integrate research from different disciplines and outline modelling approaches that can be used to begin answering questions such as why collectives sometimes fail to reach seemingly obvious solutions, how they change their strategies and network structures in response to different problems and how we can anticipate and perhaps change future harmful societal trajectories. We discuss the importance of considering path dependence, lack of optimization and collective myopia to understand the sometimes counterintuitive outcomes of collective adaptation. We call for a transdisciplinary, quantitative and societally useful social science that can help us to understand our rapidly changing and ever more complex societies, avoid collective disasters and reach the full potential of our ability to organize in adaptive collectives.

In End Times, Peter Turchin takes us on three journeys: One is his personal history of the discovery of patterns in history, which form the basis for his development of cliodyamics; a second is his tracing of the primary pattern, namely how elite overproduction and popular immiseration have repeatedly led to state breakdowns across history; and third is the history of the United States, reprising and updating his findings in Age of Discord (Turchin 2017). The journeys converge on a rather distressing endpoint, however: Turchin has found that the pattern of state breakdown that recurs across history is now unfolding in the United States; and in 75% of the times this pattern has been seen in past societies, it led to some form of convulsive state breakdown, including revolution or civil war.

Abstract We analyze the visual perception task that home plate umpires (N = 121) perform calling balls and strikes (N = 3,001,019) in baseball games, focusing on the topics of perceptual learning and bias in decision-making. In the context of perceptual learning, our results show that monitoring, training, and feedback improve skill over time. In addition, we document two other aspects of umpires’ improvement that are revealing with respect to the nature of their perceptual expertise. First, we show that biases in umpires’ decision-making persist even as their overall accuracy improves. This suggests that bias and accuracy are orthogonal and that reduction of bias in decision-making requires interventions aimed specifically at this goal. Second, we measure a distinct difference in the rate of skill improvement between older and younger umpires. Younger umpires improve more quickly, suggesting that the decision task umpires engage in becomes routinized over time.

Abstract Mass spectrometry (MS) is an analytical technique for molecule identification that can be used for investigating protein-metal complex interactions. Once the MS data is collected, the mass spectra are usually interpreted manually to identify the adducts formed as a result of the interactions between proteins and metal-based species. However, with increasing resolution, dataset size, and species complexity, the time required to identify adducts and the error-prone nature of manual assignment have become limiting factors in MS analysis. AdductHunter is a open-source web-based analysis tool that automates the peak identification process using constraint integer optimization to find feasible combinations of protein and fragments, and dynamic time warping to calculate the dissimilarity between the theoretical isotope pattern of a species and its experimental isotope peak distribution. Empirical evaluation on a collection of 22 unique MS datasetsshows fast and accurate identification of protein-metal complex adducts in deconvoluted mass spectra.

Abstract Background Prader-Willi syndrome (PWS) is a complex genetic neurodevelopmental condition characterised by a range of debilitating and lifelong symptoms. The many physical and behavioural challenges that arise with adults with PWS often necessitate full-time (i.e., 24-hour) professional care support. However, despite the fact that many clinicians regard full-time PWS-specific care to represent best practice, relatively few studies have directly examined the benefits of such services. The purpose of this paper is to use archival data to investigate the impact of full-time care services on people with PWS, and to assemble a large statistical dataset on which robust analyses of improvements in weight, BMI, and behavioural outcomes can be based. Methods Information collated by the International PWS Organisation (IPWSO), an international non-profit membership organisation supporting national PWS associations around the world, was combined into a single anonymised dataset for statistical analysis. Data were supplied by service-providers from several countries who provide full-time support to people with PWS. The dataset included details on the specific services provided, basic demographic information on service recipients, including weight, body mass index (BMI), and observational records relating to behaviours of concern (BOC; consisting of temper outbursts, skin-picking, egocentrism, inflexibility, and striving for dominance). Results A total of 193 people with PWS (ranging in age from 50 yrs; 93% of whom were > 18 yrs), residing in 11 services across 6 countries, were represented in the dataset. On average, people with PWS showed significant reductions in weight and BMI after joining a full-time care service, with improvements within one year of entering, which were cumulative over time and independent of age or initial weight at entry. Similar cumulative improvements over time were seen for BOC within one year and were unrelated to age or severity of BOC at entry. The degree to which services are specialised for residents with PWS appeared to confer particular benefits, with people living in PWS-exclusive services showing the greatest improvements in weight, BMI, and BOC. Reductions in BOC were associated with greater, rather than less, social contact, suggesting that these improvements were not achieved at the expense of broader freedoms, such as the opportunity to meet with families and friends. Conclusions We conclude that full-time care services have a high likelihood of enhancing the lives of people with PWS within one year with long-lasting benefits, especially if those services are exclusive and specialised around the particular needs of PWS.

In the present exploratory study we investigate whether cognitive flexibility is a unitary mechanism underlying flexible behaviours across many domains or a domain-specific capacity. The literature on cognitive flexibility is divided into several research lines that do not converge. The most prominent one considers flexibility an executive function that represents the ability to switch among rules or tasks. In other research traditions it is associated with distinct components, such as the capacity to place an item into many categories (in creativity tests) or a characteristic of different cognitive or perceptual processes (e.g., flexible language use, flexibility in mathematics, perceptual flexibility). To determine whether flexibility in different domains relies on a general shared mechanism, 221 subjects from two countries (The United States and Romania, mean age 19.52 years) were tested online with several measurements from four different domains of investigation: language, mathematics, perception, and executive functions (specifically, set shifting). All tasks required some form of cognitive flexibility. In addition, we measured math anxiety to see how this relates to mathematical flexibility. The results show very few and small significant partial correlations among the tasks. They also highlight that there is no unitary overarching “executive” factor. The most prominent common factor was speed of processing for mathematical and language response times. Shifting does not seem to be a mechanism that underlies flexibility in all the investigated domains. While we acknowledge the need for replication of this study, the data suggest that the construct of shifting does not exhaust the notion of flexibility as it arises across cognitive domains.

The goal of this paper is to extend research on parental involvement in education and its relationship to social class and inequalities. We do so by developing a new theoretical framework that helps us to better understand and explain cross-national and cross-cultural differences in how parental involvement in education differs across socio-economic groups. We propose that giving greater analytical attention to the role of institutional factors, cultural processes, and the underlying class and economic structures of particular countries is important for understanding the social mechanisms underpinning patterns of parental involvement in education. Once this framework has been developed, we identify promising directions for future research.