Search

Asthma is a heterogeneous disease, with multiple underlying inflammatory pathways and structural airway abnormalities that impact disease persistence and severity. Recent progress has been made in developing targeted asthma therapeutics, especially for subjects with eosinophilic asthma. However, there is an unmet need for new approaches to treat patients with severe and exacerbation-prone asthma, who contribute disproportionately to disease burden. Extensive deep phenotyping has revealed the heterogeneous nature of severe asthma and identified distinct disease subtypes. A current challenge in the field is to translate new and emerging knowledge about different pathobiologic mechanisms in asthma into patient-specific therapies, with the ultimate goal of modifying the natural history of disease. Here, we describe the Precision Interventions for Severe and/or Exacerbation-Prone Asthma (PrecISE) Network, a groundbreaking collaborative effort of asthma researchers and biostatisticians from around the United States. The PrecISE Network was designed to conduct phase II/proof-of-concept clinical trials of precision interventions in the population with severe asthma, and is supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health. Using an innovative adaptive platform trial design, the PrecISE Network will evaluate up to 6 interventions simultaneously in biomarker-defined subgroups of subjects. We review the development and organizational structure of the PrecISE Network, and choice of interventions being studied. We hope that the PrecISE Network will enhance our understanding of asthma subtypes and accelerate the development of therapeutics for severe asthma.

Common bean (Phaseolus vulgaris) is one of the major legume crops cultivated worldwide. Bacterial wilt (BW) of common bean (Curtobacterium flaccumfaciens pv. flaccumfaciens), being a seed-borne disease, has been a challenge in common bean producing regions. A genome-wide association study (GWAS) was conducted to identify SNP markers associated with BW resistance in the USDA common bean core collection. A total of 168 accessions were evaluated for resistance against three different isolates of BW. Our study identified a total of 14 single nucleotide polymorphism (SNP) markers associated with the resistance to BW isolates 528, 557, and 597 using mixed linear models (MLMs) in BLINK, FarmCPU, GAPIT, and TASSEL 5. These SNPs were located on chromosomes Phaseolus vulgaris [Pv]02, Pv04, Pv08, and Pv09 for isolate 528; Pv07, Pv10, and Pv11 for isolate 557; and Pv04, Pv08, and Pv10 for isolate 597. The genomic prediction accuracy was assessed by utilizing seven GP models with 1) all the 4,568 SNPs and 2) the 14 SNP markers. The overall prediction accuracy (PA) ranged from 0.30 to 0.56 for resistance against the three BW isolates. A total of 14 candidate genes were discovered for BW resistance located on chromosomes Pv02, Pv04, Pv07, Pv08, and Pv09. This study revealed vital information for developing genetic resistance against the BW pathogen in common bean. Accordingly, the identified SNP markers and candidate genes can be utilized in common bean molecular breeding programs to develop novel resistant cultivars.

In psychological science, replicability—repeating a study with a new sample achieving consistent results (Parsons et al., 2022)—is critical for affirming the validity of scientific findings. Despite its importance, replication efforts are few and far between in psychological science with many attempts failing to corroborate past findings. This scarcity, compounded by the difficulty in accessing replication data, jeopardizes the efficient allocation of research resources and impedes scientific advancement. Addressing this crucial gap, we present the Replication Database (https://forrt-replications.shinyapps.io/fred_explorer), a novel platform hosting 1,239 original findings paired with replication findings. The infrastructure of this database allows researchers to submit, access, and engage with replication findings. The database makes replications visible, easily findable via a graphical user interface, and tracks replication rates across various factors, such as publication year or journal. This will facilitate future efforts to evaluate the robustness of psychological research.

Abstract Background Critically unwell babies in intensive care units may develop acute renal failure. Options for renal replacement therapy are limited by their small size and available technology. Objectives To determine the clinical efficacy, outcomes and safety profile of the NIDUS® (a novel infant haemodialysis device) for babies under 8 kg, compared with current renal replacement therapy. Design A clinical investigation using a non-blinded cluster stepped wedge design with paediatric intensive care units randomised to sequences. Setting Paediatric intensive care units in six UK hospitals. Participants Children under 8 kg who required renal replacement therapy for fluid overload or biochemical disturbance. Interventions Continuous renal replacement therapy was provided by the usual methods: peritoneal dialysis and continuous haemofiltration (during control periods) and by the NIDUS (during intervention periods), a novel device designed for babies with a smaller circuit and filter and volumetric control of ultrafiltration. Main outcome measures Primary outcome was precision of ultrafiltration compared with prescription; secondary outcomes included biochemical clearances, accuracy of reported ultrafiltration and mortality. Data sources Bedside study data collected by weighing bags of fluid entering and leaving the device were entered into the study database along with case descriptors. Some secondary outcome data was collected via the Paediatric Intensive Care Audit Network. Results Ninety-seven participants were recruited by study closure, 62 to control and 35 to intervention. The primary outcome was obtained from 62 control but only 21 intervention patients, largely because of technical difficulties using NIDUS. The analysis comparing the available primary outcomes showed that ultrafiltration with NIDUS was closer to that prescribed than with control: standard deviations controls 18.75, intervention 2.95 (ml/hour), adjusted ratio 0.13, 95% confidence interval (0.03 to 0.71); p = 0.018. The mean clearances for creatinine, urea and phosphate were lower on peritoneal dialysis than NIDUS, which were in turn lower than continuous veno-venous haemofiltration. The variability in the clearances was in the same order. Of the 62 control patients, 10 died (2/62 on peritoneal dialysis; 7/13 on continuous haemofiltration) before discharge from paediatric intensive care unit (16%), compared with 12 out of 35 (34%) in the NIDUS group: p = 0.04, 95% confidence interval for difference (0 to 36%). Harms No important adverse events occurred and the NIDUS has an acceptable safety profile compared with other renal replacement therapies in this critically ill population with multi-organ failure. Mortality was lowest for Peritoneal Dialysis, highest for continuous haemofiltration, with the NIDUS in-between. Only one serious adverse device event which was reported to the Medicines and Healthcare products Regulatory Agency. Conclusions NIDUS works effectively, delivering appropriate blood clearances and accurate, controllable fluid removal (ultrafiltration), indicating that it has an important place alongside other dialysis modalities for infant renal replacement therapy. Future work Findings from this study indicate some modifications are required to NIDUS to improve usability. Further studies on use of the NIDUS device in other populations of babies for example those with chronic renal failure, and long-term outcomes are required. Trial registration This trial is registered as ISRCTN 13787486. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation Programme (NIHR award ref: 14/23/26) and is published in full in Efficacy and Mechanism Evaluation; Vol. 11, No. 1. See the NIHR Funding and Awards website for further award information. Plain language summary Why do this study? Some children in intensive care are so poorly that their kidneys do not work well, and they need help, called dialysis, to get rid of fluid and chemicals from their blood. For babies, we currently use peritoneal dialysis, where fluid is cycled in and out of the tummy, or adapted machines designed for bigger children (continuous veno-venous haemofiltration). A new machine, the NIDUS® (Allmed, www.allmedgroup.com), was developed specifically for babies weighing under 8 kg with much smaller tubing. NIDUS worked well when studied in Newcastle but needed testing elsewhere. What was the question? How well does NIDUS work compared to other dialysis methods? What are the problems? What did we do? The study was done in six paediatric intensive care units who used their usual dialysis methods (=control) in the first part of the study and then later swapped to using the NIDUS (=intervention). What did we find? We recruited 97 participants, 62 to control (49 peritoneal dialysis, 13 continuous veno-venous haemofiltration) and 35 intervention (NIDUS). We found NIDUS provided much better control of fluid removal. The CVVH machines were more efficient at blood cleaning than NIDUS, which was better than peritoneal dialysis. What does this mean? We learnt a lot about babies needing kidney support in paediatric intensive care units and that all methods have advantages and disadvantages. We showed that NIDUS could be very useful for some participants because it cleans blood effectively and gives accurate, controllable fluid removal. We have gathered important information to help us improve NIDUS to make it easier to use and run. Many parents responded to our questionnaire and most told us they felt it was acceptable to be approached about taking part in research despite the circumstances. This is very important for future research studies. We are very grateful to families for their generosity in becoming involved in this study. Scientific summary Background Critically unwell babies in paediatric intensive care units (PICUs) may develop acute renal failure and require management with renal replacement therapy. Although mortality and morbidity vary and are related to the underlying diagnosis, survival of babies in paediatric intensive care is worse for those with fluid overload. Babies requiring renal replacement treatment present specific therapeutic challenges because of their small size and the current technology available. Difficulties with vascular access and blood flows, fluid balance, loss of circuits, filter clotting and hypotensive episodes at initiation are all described in the literature. The need for new solutions and improved technology is well recognised. Continuous veno-venous haemofiltration (CVVH) machines in use in the UK at the time of this study are not approved for use in babies weighing 80%) were similar. The median (IQR) age in controls 10.5 (7, 38) days was similar to that in the intervention group 11 (7, 61) days; the range of age of participants was between 1 and 477 days (approximately 15 months). The median (IQR) weights 3.2 (2.9, 3.9) and 3.7 (3.1, 5.6) kg were similar between control and intervention. Availability of primary outcome The primary outcome was available on all 62 control patients but only 21 of the 35 intervention patients. This was due to a range of reasons including difficulties in obtaining the information needed to compute the UF rate (accurate timing and weighing data) and technical difficulties using the NIDUS: full details are in the report. Precision of UF Analysis comparing the 62 control patients with the 21 intervention patients with a primary outcome showed that UF with the NIDUS was closer to that prescribed than with control: standard deviations (SDs) controls 18.75, intervention 2.95 (ml/hour), adjusted ratio 0.13, 95% confidence interval (0.03 to 0.71); p = 0.018. For the NIDUS and CVVH devices, an important measure was to compare the difference between the actual fluid removal measured and that reported by the device. This had a mean closer to zero for the NIDUS than CVVH (means −0.44 vs. 11.6 ml/hour, respectively), with less variation in NIDUS than CVVH (SDs 3.2 vs. 28.4 ml/hour). Biochemical clearances The initial intention was to compare clearance rate on NIDUS with the control group. However, for these variables combining PD and CVVH in this way proved to be misleading because NIDUS clearances rates were intermediate between those of PD and CVVH. The clearance for creatinine on PD was smaller and less variable (mean 0.08, SD 0.03 ml/min/kg) than on the NIDUS (mean 0.46, SD 0.30 ml/min/kg), which was in turn smaller and less variable than for CVVH (mean 1.20, SD 0.72 ml/min/kg). The pattern was repeated for urea: PD (0.12, 0.06), NIDUS (0.48, 0.30) and CVVH (1.15, 0.67), all in ml/min/kg, and also for phosphate: PD (0.07, 0.04), NIDUS (0.44, 0.27) and CVVH (1.16, 0.71), all in ml/min/kg. All pairwise treatment comparisons of means and of SDs gave p

Background: Adolescents with intellectual disabilities are insufficiently physically active. Where interventions have been developed and delivered, these have had limited effectiveness, and often lack a theoretical underpinning. Aim: Through application of the COM-B model, our aim is to explore the factors influencing adolescent physical activity within schools. Methods: A qualitative methodology, using focus groups with students who have mild/moderate intellectual disabilities, their parents'/carers' and teachers'. The COM-B model provided the lens through which the data were collected and analysed. Results: We identified of a range of individual, interpersonal, and environmental factors influencing physical activity, across all six COM-B constructs, within the context of the 'school-system'. Conclusion: This is the first study to use the COM-B model to explore school-based physical activity behaviour, for adolescents with intellectual disabilities. Identification of such physical activity behavioural determinants can support the development of effective and sustainable interventions.

During the immediate period following psychiatric hospitalization, adolescents are at increased risk for suicide attempts and rehospitalization. Because most adolescents return to school during this time, school-related experiences are important considerations during the transition from inpatient hospitalization. This study sought to understand how adolescent perceptions of school may change following hospitalization, and how these changes may predict recovery from a suicide-related crisis. Participants included 155 adolescents (M[subscript]age = 15.2 years; 68.6% female, 65.4% White; 14.7% Hispanic/Latinx; grades 7-12) hospitalized for a suicide-related crisis assessed 3 weeks and 6 months following discharge. Results from Latent Change Score models indicated a worsening of perceptions of teacher relationships (mean change ([delta]) = 1.52), connectedness to learning ([delta] = 1.55), parent involvement ([delta] = 1.82), and academic satisfaction ([delta] = 1.34), as well as higher frequency of perceived bullying victimization ([delta] = 0.71) following hospitalization. Poorer perceptions of teacher relationships and higher frequency of perceived bullying victimization during hospitalization ([beta] = 0.31 and 0.34), as well as worsening changes of teacher relationships and increased frequency of perceived bullying victimization following hospitalization ([beta] = 0.48 and 0.41) were associated with higher levels of suicidal ideation severity 3 weeks following discharge. Poorer and worsening perceptions of teacher relationships were associated with higher levels of suicidal ideation intensity at 3 weeks ([beta] = 0.37 and 0.54). Poorer perceptions of connectedness to learning during hospitalization emerged as a significant predictor of higher levels of suicidal ideation intensity 6 months following hospitalization ([beta] = 0.20). Results reinforce the importance of fostering positive adult relationships and preventing bullying both prior to and immediately following psychiatric hospitalization.

Humanitarian research with Syrian refugees can be difficult to conduct in-person, due to COVID-19 containment, security, and logistics issues. We assessed whether the online implementation of a brief, culturally grounded resilience measure would yield reliable responses for use with children and adolescents in the Middle East region. We implemented an online survey screening for socio-economic status, insecurity, prosocial behaviour, and resilience (using the Child Youth Resilience Measure, CYRM) with 119 Syrian refugees (14-18 years old; 74 male, 45 female) living in Jordan. Responses were compared with in-person data, available for a separate cohort of 324 Syrian refugees, previously sampled in Jordan with the same survey instruments. The online CYRM produced reliable and valid responses, as shown by analyses of internal reliability, convergent and divergent validity, and 7-day test-retest consistency. We reflect on logistic, ethical, and methodological challenges of online surveys, and suggest ways to plan and execute online research with hard-to-reach, crisis-affected communities.

The transitional years of early adulthood, with key tasks of identity and intimacy development, engender both opportunities and risks for well-being. We propose that the conceptualization and measurement of early adults' well-being can be improved through (a) an integration of ideas from developmental and psychological science on well-being, (b) the use of short, daily momentary assessments of well-being, and (c) a developmentally-informed examination of the structure of well-being within (and not just across) time. We developed a daily assessment of well-being based on the PERMA model (Seligman, 2011) and used network analysis to gain understanding from this data. Using Ecological Momentary Assessments, we assessed the five PERMA elements in college students' daily life and their network properties. Consistent with the PERMA model, network analysis showed items clustered around theorized elements and formed a unitary network of well-being. Consistent with developmental theory, we found that having positive relationships and positive emotion were most central to early adults' daily well-being.

The venom-containing barb attached to their ‘whip-like’ tail provides stingrays a defensive mechanism for evading predators such as sharks. From human encounters, dermal stingray envenomation is characterized by intense pain often followed by tissue necrosis occurring over several days to weeks. The bioactive components in stingray venoms (SRVs) and their molecular targets and mechanisms that mediate these complex responses are not well understood. Given the utility of venom-derived proteins from other venomous species for biomedical and pharmaceutical applications, we set out to characterize the bioactivity of SRV extracts from three local species that belong to the Dasyatoidea ‘whiptail’ superfamily. Multiple cell-based assays were used to quantify and compare the in vitro effects of these SRVs on different cell lines. All three SRVs demonstrated concentration-dependent growth-inhibitory effects on three different human cell lines tested. In contrast, a mouse fibrosarcoma cell line was markedly resistant to all three SRVs, indicating the molecular target(s) for mediating the SRV effects are not expressed on these cells. The multifunctional SRV responses were characterized by an acute disruption of cell adhesion leading to apoptosis. These findings aim to guide future investigations of individual SRV proteins and their molecular targets for potential use in biomedical applications.

BackgroundThe recent growth of eHealth is unprecedented, especially after the COVID-19 pandemic. Within eHealth, wearable technology is increasingly being adopted because it can offer the remote monitoring of chronic and acute conditions in daily life environments. Wearable technology may be used to monitor and track key indicators of physical and psychological stress in daily life settings, providing helpful information for clinicians. One of the key challenges is to present extensive wearable data to clinicians in an easily interpretable manner to make informed decisions. ObjectiveThe purpose of this research was to design a wearable data dashboard, named CarePortal, to present analytic visualizations of wearable data that are meaningful to clinicians. The study was divided into 2 main research objectives: to understand the needs of clinicians regarding wearable data interpretation and visualization and to develop a system architecture for a web application to visualize wearable data and related analytics. MethodsWe used a wearable data set collected from 116 adolescent participants who experienced trauma. For 2 weeks, participants wore a Microsoft Band that logged physiological sensor data such as heart rate (HR). A total of 834 days of HR data were collected. To design the CarePortal dashboard, we used a participatory design approach that interacted directly with clinicians (stakeholders) with backgrounds in clinical psychology and neuropsychology. A total of 8 clinicians were recruited from the Rhode Island Hospital and the University of Massachusetts Memorial Health. The study involved 5 stages of participatory workshops and began with an understanding of the needs of clinicians. A User Experience Questionnaire was used at the end of the study to quantitatively evaluate user experience. Physiological metrics such as daily and hourly maximum, minimum, average, and SD of HR and HR variability, along with HR-based activity levels, were identified. This study investigated various data visualization graphing methods for wearable data, including radar charts, stacked bar plots, scatter plots combined with line plots, simple bar plots, and box plots. ResultsWe created a CarePortal dashboard after understanding the clinicians’ needs. Results from our workshops indicate that overall clinicians preferred aggregate information such as daily HR instead of continuous HR and want to see trends in wearable sensor data over a period (eg, days). In the User Experience Questionnaire, a score of 1.4 was received, which indicated that CarePortal was exciting to use (question 5), and a similar score was received, indicating that CarePortal was the leading edge (question 8). On average, clinicians reported that CarePortal was supportive and can be useful in making informed decisions. ConclusionsWe concluded that the CarePortal dashboard integrated with wearable sensor data visualization techniques would be an acceptable tool for clinicians to use in the future.

Objective: The purpose of this study was to examine system- and patient-level factors associated with the number of healthcare disciplines involved in delivery of patient education among hospitalized older cancer survivors. Methods: We used electronic health record (EHR) data from a single institution documenting patient education among hospitalized older patients (≥65 years) with a history of cancer between 9/1/2018 and 10/1/2019. We used parametric ordinal logistic regression to assess the number of healthcare disciplines involved in documented education activities. Results: The sample (n = 446) was predominantly male, White, and on average 74 years old. Adjusting for patient and system-level variables, men and larger department units had higher odds of receiving education from fewer healthcare disciplines. Patients with a history of breast or prostate cancer and longer lenths of stay had lower odds of receiving patient education from fewer healthcare disciplines. Conclusion: Hospital size, severity of illness, and cancer type are associated with delivery of multidisciplinary education in this sample. Innovation: EHR provides an opportunity to identify patterns in patient education among cancer survivors. Future research should investigate provider perspectives of the findings to inform provider- and system-level strategies to improve patient education.

Summary: Native pollinators are crucial to local ecosystems but are under threat with the introduction of managed pollinators, e.g., honeybees (Apis mellifera). We explored the feasibility of employing the entomological lidar technique in native pollinator abundance studies. This study included individuals of both genders of three common solitary bee species, Osmia californica, Osmia lignaria, and Osmia ribifloris, native to North America. Properties including optical cross-section, degree of linear polarization, and wingbeat power spectra at all three wavelengths have been extracted from the insect signals collected by a compact stand-off sensing system. These properties are then used in the classification analysis. For species with temporal and spatial overlapping, the highest accuracies of our method exceed 96% (O. ribifloris & O. lignaria) and 93% (O. lignaria & O. californica). The benefit of employing the seasonal activity and foraging preference information in enhancing identification accuracy has been emphasized.

Background Higher social support protects people from developing mental disorders. Limited evidence is available on the mechanism through which social support plays this protective role.Objective To investigate the stress-buffering process of social support on depressive symptoms using a novel longitudinal dynamic symptom network approach.Methods A total of 4242 adult participants who completed the first two waves (from May to October 2020) of the International Covid Mental Health Survey were included in the study. Cross-lagged panel network modelling was used to estimate a longitudinal network of self-reported social support, loneliness and depressive symptoms. Standardised regression coefficients from regularised cross-lagged regressions were estimated as edge weights of the network.Findings The results support a unidirectional protective effect of social support on key depressive symptoms, partly mediated through loneliness: A higher number of close confidants and accessible practical help was associated with decreased anhedonia (weight=−0.033) and negative self-appraisal symptoms (weight=−0.038). Support from others was also negatively associated with loneliness, which in turn associated with decreased depressed mood (weight=0.086) and negative self-appraisal (weight=0.077). We identified a greater number of direct relationships from social support to depressive symptoms among men compared with women. Also, the edge weights from social support to depression were generally stronger in the men’s network.Conclusions Reductions in negative self-appraisal might function as a bridge between social support and other depressive symptoms, and, thus, it may have amplified the protective effect of social support. Men appear to benefit more from social support than women.Clinical implications Building community-based support networks to deliver practical support, and loneliness reduction components are critical for depression prevention interventions after stressful experiences.

The underlying theme throughout this series of studies authored by the Multicenter anterior cruciate ligament (ACL) Revision Study consortium has been to determine the modifiable predictors or risk factors of long-term outcomes of revision ACL reconstruction. The observational studies described and summarized in the manuscript are both clinically relevant and of great interest in finding out the long-term consequences of the intervention and its relationship to the original injury. The successful completion of these studies has important implications for both therapy and future clinical trials. The identification of modifiable risk factors will play an important role in secondary prevention, while the identification of nonmodifiable risk factors will aid us in counseling our patients and making surgical decisions. Thus, we expect a profound clinical impact on patients' care. More importantly, this project represents an important step forward in bringing evidence to bear in clinical decision making in orthopedic surgery.

STUDY OBJECTIVES: Sleep problems are common, serving as both a predictor and symptom of posttraumatic stress disorder (PTSD), with these bidirectional relationships well established in the literature. While both sleep phenotypes and PTSD are moderately heritable, there has been a paucity of investigation into potential genetic overlap between sleep and PTSD. Here, we estimate genetic correlations between multiple sleep phenotypes (including insomnia symptoms, sleep duration, daytime sleepiness, and chronotype) and PTSD, using results from the largest genome-wide association study (GWAS) to date of PTSD, as well as publicly available GWAS results for sleep phenotypes within UK Biobank data (23 variations, encompassing four main phenotypes). METHODS: Genetic correlations were estimated utilizing linkage disequilibrium score regression (LDSC), an approach that uses GWAS summary statistics to compute genetic correlations across traits, and Mendelian randomization (MR) analyses were conducted to follow up on significant correlations. RESULTS: Significant, moderate genetic correlations were found between insomnia symptoms (rg range 0.36-0.49), oversleeping (rg range 0.32-0.44), undersleeping (rg range 0.48-0.49), and PTSD. In contrast, there were mixed results for continuous sleep duration and daytime sleepiness phenotypes, and chronotype was not correlated with PTSD. MR analyses did not provide evidence for casual effects of sleep phenotypes on PTSD. CONCLUSION: Sleep phenotypes, particularly insomnia symptoms and extremes of sleep duration, have shared genetic etiology with PTSD, but causal relationships were not identified. This highlights the importance of further investigation into the overlapping influences on these phenotypes as sample sizes increase and new methods to investigate directionality and causality become available.

Childhood maltreatment is highly prevalent and serves as a risk factor for mental and physical disorders. Self-reported childhood maltreatment appears heritable, but the specific genetic influences on this phenotype are largely unknown. The aims of this study were to (1) identify genetic variation associated with self-reported childhood maltreatment, (2) estimate SNP-based heritability (h2snp), (3) assess predictive value of polygenic risk scores (PRS) for childhood maltreatment, and (4) quantify genetic overlap of childhood maltreatment with mental and physical health-related phenotypes, and condition the top hits from our analyses when such overlap is present. Genome-wide association analysis for childhood maltreatment was undertaken, using a discovery sample from the UK Biobank (UKBB) (n = 124,000) and a replication sample from the Psychiatric Genomics Consortium-posttraumatic stress disorder group (PGC-PTSD) (n = 26,290). h2snp for childhood maltreatment and genetic correlations with mental/physical health traits were calculated using linkage disequilibrium score regression. PRS was calculated using PRSice and mtCOJO was used to perform conditional analysis. Two genome-wide significant loci associated with childhood maltreatment (rs142346759, p = 4.35 × 10-8, FOXP1; rs10262462, p = 3.24 × 10-8, FOXP2) were identified in the discovery dataset but were not replicated in PGC-PTSD. h2snp for childhood maltreatment was ~6% and the PRS derived from the UKBB was significantly predictive of childhood maltreatment in PGC-PTSD (r2 = 0.0025; p = 1.8 × 10-15). The most significant genetic correlation of childhood maltreatment was with depressive symptoms (rg = 0.70, p = 4.65 × 10-40), although we show evidence that our top hits may be specific to childhood maltreatment. This is the first large-scale genetic study to identify specific variants associated with self-reported childhood maltreatment. Speculatively, FOXP genes might influence externalizing traits and so be relevant to childhood maltreatment. Alternatively, these variants may be associated with a greater likelihood of reporting maltreatment. A clearer understanding of the genetic relationships of childhood maltreatment, including particular abuse subtypes, with a range of phenotypes, may ultimately be useful in in developing targeted treatment and prevention strategies.

Abstract Backgrounds Individuals with chronic medical conditions are considered highly exposed to COVID-19 pandemic stress, but emerging evidence is demonstrating that resilience is common even among them. We aimed at identifying sustained resilient outcomes and their predictors in chronically ill people during the first year of the pandemic. Methods This international 4-wave 1-year longitudinal online survey included items on socio-demographic characteristics, economic and living situation, lifestyle and habits, pandemic-related issues, and history of mental disorders. Adherence to and approval of imposed restrictions, trust in governments and in scientific community during the pandemic were also investigated. The following tools were administered: the Patient Health Questionnaire, the Generalized Anxiety Disorder scale, the PTSD Checklist DSM-5, the Oslo Social Support Scale, the Padua Inventory, and the Portrait Values Questionnaire. Results One thousand fifty-two individuals reporting a chronic condition out of 8011 total participants from 13 countries were included in the study, and 965 had data available for the final model. The estimated probability of being “sustained-resilient” was 34%. Older male individuals, participants employed before and during the pandemic or with perceived social support were more likely to belong to the sustained-resilience group. Loneliness, a previous mental disorder, high hedonism, fear of COVID-19 contamination, concern for the health of loved ones, and non-approving pandemic restrictions were predictors of not-resilient outcomes in our sample. Conclusions We found similarities and differences from established predictors of resilience and identified some new ones specific to pandemics. Further investigation is warranted and could inform the design of resilience-building interventions in people with chronic diseases.

Abstract Tepary bean (Phaseolus acutifolius A. Gray), indigenous to the arid climates of northern Mexico and the Southwest United States, diverged from common bean (Phaseolus vulgaris L.), approximately 2 million years ago and exhibits a wide range of resistance to biotic stressors. The tepary genome is highly syntenic to the common bean genome providing a foundation for discovery and breeding of agronomic traits between these two crop species. Although a limited number of adaptive traits from tepary bean have been introgressed into common bean, hybridization barriers between these two species required the development of bridging lines to alleviate this barrier. Thus, to fully utilize the extant tepary bean germplasm as both a crop and as a donor of adaptive traits, we developed a diversity panel of 422 cultivated, weedy, and wild tepary bean accessions which were then genotyped and phenotyped to enable population genetic analyses and genome‐wide association studies for their response to a range of biotic stressors. Population structure analyses of the panel revealed eight subpopulations and the differentiation of botanical varieties within P. acutifolius. Genome‐wide association studies revealed loci and candidate genes underlying biotic stress resistance including quantitative trait loci for resistance to weevils, common bacterial blight, Fusarium wilt, and bean common mosaic necrosis virus that can be harnessed not only for tepary bean but also common bean improvement.

Na perspectiva ético-crítica (DUSSEL, 2012), acredita-se que, ao reconhecerem-se como “vítimas” do sistema vigente, as pessoas podem estabelecer formas de se libertar das injustiças que enfrentam. Essa ideia inspira-se na prática de Freire (2019), defensor de uma educação humanizadora, para a qual criou um processo teórico-metodológico denominado Investigação Temática. Este trabalho se propõe engajado com o processo de humanização da comunidade de Vidal Ramos, um município agrícola do interior de Santa Catarina, a fim de transformar as situações de injustiça ali presentes (ainda que muitas não sejam facilmente reconhecidas pela comunidade), a partir de um planejamento didático inspirado na educação ético-crítica e na Investigação Temática. O planejamento foi realizado em encontros no formato de uma oficina, com o grupo Prosa no qual integra uma pessoa com vínculo na comunidade, o qual realizou análise de falas significativas, identificou as contradições, o tema gerador e o contratema, bem como movimento de estudo crítico da situação com a identificação de conhecimentos demandados. Por fim, também se realizou um movimento de planejamento dialógico-problematizador em diferentes áreas curriculares, abordando as contradições discutidas. A partir do desenvolvimento de tais atividades foi possível perceber a factibilidade da perspectiva etico-crítica em um movimento de práxis curricular que parte da escuta da comunidade, da problematização dos limites desumanizadoras identificados nessa escuta e do movimento de identificação dos conhecimentos demandados pela análise crítica dessas situações. Em contrapartida, ficou evidente a exigência de um coletivo diverso e do envolvimento de membros da comunidade local no processo de Investigação Temática Freireana.

IntroductionObservational coding of eating behaviors (e.g., bites, eating rate) captures behavioral characteristics but is limited in its ability to capture dynamic patterns (e.g., temporal changes) across a meal. While the Universal Eating Monitor captures dynamic patterns of eating through cumulative intake curves, it is not commonly used in children due to strict behavioral protocols. Therefore, the objective of this study was to test the ability of computational models to characterize cumulative intake curves from video-coded meals without the use of continuous meal weight measurement.MethodsCumulative intake curves were estimated using Kisslieff’s Quadratic model and Thomas’s logistic ordinary differential equation (LODE) model. To test if cumulative intake curves could be characterized from video-coded meals, three different types of data were simulated: (1) Constant Bite: simplified cumulative intake data; (2) Variable Bite: continuously measured meal weight data; and (3) Bite Measurement Error: video-coded meals that require the use of average bite size rather than measured bite size.ResultsPerformance did not differ by condition, which was assessed by examining model parameter recovery, goodness of fit, and prediction error. Therefore, the additional error incurred by using average bite size as one would with video-coded meals did not impact the ability to accurately estimate cumulative intake curves. While the Quadratic and LODE models were comparable in their ability to characterize cumulative intake curves, the LODE model parameters were more distinct than the Quadradic model. Greater distinctness suggests the LODE model may be more sensitive to individual differences in cumulative intake curves.DiscussionCharacterizing cumulative intake curves from video-coded meals expands our ability to capture dynamic patterns of eating behaviors in populations that are less amenable to strict protocols such as children and individuals with disordered eating. This will improve our ability to identify patterns of eating behavior associated with overconsumption and provide new opportunities for treatment.

Background Four decades of war, political upheaval, economic deprivation and forced displacement have profoundly affected both in-country and refugee Afghan populations. Aims We reviewed literature on mental health and psychosocial well-being, to assess the current evidence and describe mental healthcare systems, including government programmes and community-based interventions. Method In 2022, we conducted a systematic search in Google Scholar, PTSDpubs, PubMed and PsycINFO, and a hand search of grey literature (N = 214 papers). We identified the main factors driving the epidemiology of mental health problems, culturally salient understandings of psychological distress, coping strategies and help-seeking behaviours, and interventions for mental health and psychosocial support. Results Mental health problems and psychological distress show higher risks for women, ethnic minorities, people with disabilities and youth. Issues of suicidality and drug use are emerging problems that are understudied. Afghans use specific vocabulary to convey psychological distress, drawing on culturally relevant concepts of body–mind relationships. Coping strategies are largely embedded in one's faith and family. Over the past two decades, concerted efforts were made to integrate mental health into the nation's healthcare system, train cadres of psychosocial counsellors, and develop community-based psychosocial initiatives with the help of non-governmental organisations. A small but growing body of research is emerging around psychological interventions adapted to Afghan contexts and culture. Conclusions We make four recommendations to promote health equity and sustainable systems of care. Interventions must build cultural relevance, invest in community-based psychosocial support and evidence-based psychological interventions, maintain core mental health services at logical points of access and foster integrated systems of care.

Se realizó un diagnóstico del sistema de agronegocios del camu camu en la provincia de Alto Amazonas- Región Loreto enmarcado desde el ambiente institucional, organizacional y tecnológico, además de analizar las transacciones y nivel de coordinación; complementando con la descripción del entorno interno y externo del SAG. La investigación se realizó en la provincia de Alto Amazonas, departamento de Loreto, aplicando el estudio en los distritos de Jeberos, Lagunas, Santa Cruz y Yurimaguas. Se utilizó el Análisis Estructural Discreto (AED), como metodología para contextualizar de forma sistémica el ambiente institucional (evaluación de los principales hitos e importancia para el sistema), tecnológico (descripción de rendimientos, producción y nivel tecnológico utilizado) y organizacional (identificación y descripción de los principales actores) en donde se desarrolla el SAG del camu camu. Asimismo, se realizó una evaluación del entorno interno y externo SAG de camu camu mediante el Diamante de Porter que describió a los protagonistas y evaluó su posición competitiva. Se concluyó que a nivel organizacional y de coordinación, los actores cuentan con transacciones no alineadas y mal aprovechamiento de ventajas básicas y avanzadas que perjudican el desempeño del SAG camu camu en la región.

Genome-wide association studies (GWASs) have focused primarily on populations of European descent, but it is essential that diverse populations become better represented. Increasing diversity among study participants will advance our understanding of genetic architecture in all populations and ensure that genetic research is broadly applicable. To facilitate and promote research in multi-ancestry and admixed cohorts, we outline key methodological considerations and highlight opportunities, challenges, solutions, and areas in need of development. Despite the perception that analyzing genetic data from diverse populations is difficult, it is scientifically and ethically imperative, and there is an expanding analytical toolbox to do it well.

Lissencephaly is a severe brain malformation in which failure of neuronal migration results in agyria or pachygyria and in which the brain surface appears unusually smooth. It is often associated with microcephaly, profound intellectual disability, epilepsy, and impaired motor abilities. Twenty-two genes are associated with lissencephaly, accounting for approximately 80% of disease. Here we report on 12 individuals with a unique form of lissencephaly; these individuals come from eight unrelated families and have bi-allelic mutations in APC2, encoding adenomatous polyposis coli protein 2. Brain imaging studies demonstrate extensive posterior predominant lissencephaly, similar to PAFAH1B1-associated lissencephaly, as well as co-occurrence of subcortical heterotopia posterior to the caudate nuclei, "ribbon-like" heterotopia in the posterior frontal region, and dysplastic in-folding of the mesial occipital cortex. The established role of APC2 in integrating the actin and microtubule cytoskeletons to mediate cellular morphological changes suggests shared function with other lissencephaly-encoded cytoskeletal proteins such as α-N-catenin (CTNNA2) and platelet-activating factor acetylhydrolase 1b regulatory subunit 1 (PAFAH1B1, also known as LIS1). Our findings identify APC2 as a radiographically distinguishable recessive form of lissencephaly.

BackgroundAlcoholism is a multifactorial disorder influenced by multiple gene loci, each with small effect. Studies suggest shared genetic influences across DSM-IV alcohol dependence symptoms, but shared effects across DSM-5 alcohol use disorder remains unknown. We aimed to test the assumption of genetic homogeneity across the 11 criteria of DSM-5 alcohol use disorder (AUD).MethodsData from 2596 alcohol using individuals of European ancestry from the Study of Addiction: Genetics and Environment were used to examine the genomewide SNP-heritability (h2SNP) and SNP-covariance (rGSNP) between 11 DSM-5 AUD symptoms. Phenotypic relationships between symptoms were examined to confirm an underlying liability of AUD and the SNP-heritability of the observed latent trait and the co-heritabilityamong AUD symptoms was assessed using Genomic-Relatedness-Matrix-Restricted-Maximum-Likelihood. Genetic covariance among symptoms was examined using factor analysis.ResultsPhenotypic relationships confirmed a unidimensional underlying liability to AUD. Factor and parallel analyses of the observed genetic variance/covariance provided evidence of genetic homogeneity. Additive genetic effects on DSM-5 AUD symptoms varied from 0.10 to 0.37 and largely overlapped (rG-SNP across symptoms ranged from 0.49 - 0.92). The additive genetic effect on the DSM-5 AUD factor was 0.36, 0.14 for DSM-5 AUD diagnosis, and was 0.22 for DSM-5 AUD severity.ConclusionsCommon genetic variants influence DSM-5 AUD symptoms. Despite evidence for a common AUD factor, the evidence of only partially overlapping genetic effects across AUD symptoms further substantiates the need to simultaneously model common and symptom-specific genetic effects in molecular genetic studies in order to best characterize the genetic liability.

BackgroundRevision anterior cruciate ligament (ACL) reconstruction has been documented to have worse outcomes than primary ACL reconstruction. The reasons remain varied and not completely understood.MethodsPatients undergoing revision ACL reconstruction were prospectively enrolled. Data collected included baseline demographics, surgical technique and pathological condition, prescribed rehabilitation instructions, and a series of validated patient-reported outcome instruments. Patients were followed for 2 years and asked to complete a set of outcome instruments identical to those completed at baseline. Subsequent surgical procedures on the ipsilateral knee were recorded. Regression analysis was used to control for age, sex, activity level, baseline outcome scores, and the above-mentioned rehabilitation-related variables in order to assess the factors affecting clinical outcomes 2 years after revision ACL reconstruction.ResultsA total of 843 patients met the inclusion criteria and were successfully enrolled, and 82% (695) were followed for 2 years. Two rehabilitation-related factors were found to influence outcome. First, patients who were prescribed an ACL brace for their return to sports had a significantly better Knee injury and Osteoarthritis Outcome Score (KOOS) for sports and recreational activities at 2 years (odds ratio [OR] =1.50, 95% confidence interval [CI] = 1.07 to 2.11; p = 0.019). Second, patients prescribed an ACL brace for the postoperative rehabilitation period were 2.3 times more likely to have subsequent surgery by 2 years (OR = 2.26, 95% CI = 1.11 to 4.60; p = 0.024). The odds of a graft rerupture were not affected by any type of brace wear.ConclusionsRehabilitation-related factors that the physician can control at the time of an ACL reconstruction have the ability to influence clinical outcomes at 2 years. Weight-bearing and motion can be initiated immediately postoperatively. Bracing during the early postoperative period is not helpful. Use of a functional brace early in the postoperative period was associated with an increased risk of a reoperation. Use of a functional brace for a return to sports improved the KOOS on the sports/recreation subscale.Level of evidencePrognostic Level I. See Instructions for Authors for a complete description of levels of evidence.

Subterranean estuaries are connective zones between inland aquifers and the open sea where terrestrial freshwater and circulating seawater mix and undergo major biogeochemical changes. They are biogeochemical reactors that modify groundwater chemistry prior to discharge into the sea. We propose that subterranean estuaries of high-energy beaches are particularly dynamic environments, where the effect of the dynamic boundary conditions propagates tens of meters into the subsurface, leading to strong spatio-temporal variability of geochemical conditions. We hypothesize that they form a unique habitat with an adapted microbial community unlike other typically more stable subsurface environments. So far, however, studies concerning subterranean estuaries of high-energy beaches have been rare and therefore their functioning, and their importance for coastal ecosystems, as well as for carbon, nutrient and trace element cycling, is little understood. We are addressing this knowledge gap within the interdisciplinary research project DynaDeep by studying the combined effect of surface (hydro- and morphodynamics) on subsurface processes (groundwater flow and transport, biogeochemical reactions, microbiology). A unique subterranean estuary observatory was established on the northern beach of the island of Spiekeroog facing the North Sea, serving as an exemplary high-energy research site and model system. It consists of fixed and permanent infrastructure such as a pole with measuring devices, multi-level groundwater wells and an electrode chain. This forms the base for autonomous measurements, regular repeated sampling, interdisciplinary field campaigns and experimental work, all of which are integrated via mathematical modelling to understand and quantify the functioning of the biogeochemical reactor. First results show that the DynaDeep observatory is collecting the intended spatially and temporally resolved morphological, sedimentological and biogeochemical data. Samples and data are further processed ex-situ and combined with experiments and modelling. Ultimately, DynaDeep aims at elucidating the global relevance of these common but overlooked environments.

To examine the association between rehabilitation utilization within 12 months of breast cancer diagnosis and out-of-pocket costs in the second year (12-24mo after diagnosis). Secondary analysis of the 2009-2019 Surveillance, Epidemiology and End Results-Medicare linked database. Individuals who received rehabilitation services were propensity-score matched to individuals who did not receive services. Overall and health care service-specific models were examined using generalized linear models with a gamma distribution. Inpatient and outpatient medical facilities. A total of 35,212 individuals diagnosed with nonmetastatic breast cancer and were continuously enrolled in Medicare Fee-For Service (parts A, B, and D) in the 12 months before and 24 months postdiagnosis. Not applicable. Individual cost responsibility, a proxy for out-of-pocket costs, which was defined as deductibles, coinsurance, and copayments during the second year after diagnosis (12-24mo postdiagnosis). The mean individual cost responsibility was higher in individuals who used rehabilitation than those who did not ($4013 vs $3783), although it was not a clinically meaningful difference (d =0.06). Individuals who received rehabilitative services had significantly higher costs attributed to individual provider care ($1634 vs $1476), institutional outpatient costs ($886 vs $812), and prescription drugs ($959 vs $906), and significantly lower costs attributed to institutional inpatient costs ($455 vs $504), and durable medical equipment ($81 vs $86). Older adults with breast cancer who received rehabilitation services had higher cost responsibility during the second year after diagnosis than those who did not. Future work is needed to examine the relationship between rehabilitation and out-of-pocket costs across longer periods of time and in conjunction with perceived benefit. [ABSTRACT FROM AUTHOR]

Consumer food choices are often focused on protein intake, but the chosen sources are frequently either animal-based protein that has high fat content or plant-based protein that is low in other nutrients. In either case, these protein sources often lack dietary fiber, which is a nutrient of concern in the 2020–2025 Dietary Guide for Americans. Pulse crops, such as dry edible beans (Phaseolus vulgaris L.), are a rich source of dietary protein and contain approximately equal amounts of dietary fiber per 100 kcal edible portion; yet the consumer's attention has not been directed to this important fact. If product labeling were used to draw attention to the similar ratio of dietary protein to dietary fiber in dry bean and other pulses, measures of carbohydrate quality could also be highlighted. Dietary fiber is categorized into three fractions, namely, soluble (SDF), insoluble (IDF), and oligosaccharides (OLIGO), yet nutrient composition databases, as well as food labels, usually report only crude fiber. The objectives of this research were to measure the content of SDF, IDF, and OLIGO in a large genetically diverse panel of bean cultivars and improved germplasm (n = 275) and determine the impact of growing environment on the content of DF. Dietary fiber was evaluated using the American Association of Analytical Chemist 2011.25 method on bean seed grown at two locations. Dry bean cultivars differed for all DF components (P ≤ 0.05). Insoluble dietary fiber constituted the highest portion of total DF (54.0%), followed by SDF (29.1%) and OLIGO (16.8%). Mean total DF and all components did not differ among genotypes grown in two field environments. These results indicate that value could be added to dry bean by cultivar-specific food labeling for protein and components of dietary fiber.