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BACKGROUND: Incorporating genomic data into risk prediction has become an increasingly popular approach for rapid identification of individuals most at risk for complex disorders such as PTSD. Our goal was to develop and validate Methylation Risk Scores (MRS) using machine learning to distinguish individuals who have PTSD from those who do not. METHODS: Elastic Net was used to develop three risk score models using a discovery dataset (n = 1226; 314 cases, 912 controls) comprised of 5 diverse cohorts with available blood-derived DNA methylation (DNAm) measured on the Illumina Epic BeadChip. The first risk score, exposure and methylation risk score (eMRS) used cumulative and childhood trauma exposure and DNAm variables; the second, methylation-only risk score (MoRS) was based solely on DNAm data; the third, methylation-only risk scores with adjusted exposure variables (MoRSAE) utilized DNAm data adjusted for the two exposure variables. The potential of these risk scores to predict future PTSD based on pre-deployment data was also assessed. External validation of risk scores was conducted in four independent cohorts. RESULTS: The eMRS model showed the highest accuracy (92%), precision (91%), recall (87%), and f1-score (89%) in classifying PTSD using 3730 features. While still highly accurate, the MoRS (accuracy = 89%) using 3728 features and MoRSAE (accuracy = 84%) using 4150 features showed a decline in classification power. eMRS significantly predicted PTSD in one of the four independent cohorts, the BEAR cohort (beta = 0.6839, p=0.006), but not in the remaining three cohorts. Pre-deployment risk scores from all models (eMRS, beta = 1.92; MoRS, beta = 1.99 and MoRSAE, beta = 1.77) displayed a significant (p

Abstract Climate change is currently one of humanity’s greatest threats. To help scholars understand the psychology of climate change, we conducted an online quasi-experimental survey on 59,508 participants from 63 countries (collected between July 2022 and July 2023). In a between-subjects design, we tested 11 interventions designed to promote climate change mitigation across four outcomes: climate change belief, support for climate policies, willingness to share information on social media, and performance on an effortful pro-environmental behavioural task. Participants also reported their demographic information (e.g., age, gender) and several other independent variables (e.g., political orientation, perceptions about the scientific consensus). In the no-intervention control group, we also measured important additional variables, such as environmentalist identity and trust in climate science. We report the collaboration procedure, study design, raw and cleaned data, all survey materials, relevant analysis scripts, and data visualisations. This dataset can be used to further the understanding of psychological, demographic, and national-level factors related to individual-level climate action and how these differ across countries.

The common bean (Phaseolus vulgaris L.) is a globally cultivated leguminous crop. Fusarium wilt (FW), caused by Fusarium oxysporum f. sp. phaseoli (Fop), is a significant disease leading to substantial yield loss in common beans. Disease-resistant cultivars are recommended to counteract this. The objective of this investigation was to identify single nucleotide polymorphism (SNP) markers associated with FW resistance and to pinpoint potential resistant common bean accessions within a core collection, utilizing a panel of 157 accessions through the Genome-wide association study (GWAS) approach with TASSEL 5 and GAPIT 3. Phenotypes for Fop race 1 and race 4 were matched with genotypic data from 4740 SNPs of BARCBean6K_3 Infinium Bea Chips. After ranking the 157-accession panel and revealing 21 Fusarium wilt-resistant accessions, the GWAS pinpointed 16 SNPs on chromosomes Pv04, Pv05, Pv07, Pv8, and Pv09 linked to Fop race 1 resistance, 23 SNPs on chromosomes Pv03, Pv04, Pv05, Pv07, Pv09, Pv10, and Pv11 associated with Fop race 4 resistance, and 7 SNPs on chromosomes Pv04 and Pv09 correlated with both Fop race 1 and race 4 resistances. Furthermore, within a 30 kb flanking region of these associated SNPs, a total of 17 candidate genes were identified. Some of these genes were annotated as classical disease resistance protein/enzymes, including NB-ARC domain proteins, Leucine-rich repeat protein kinase family proteins, zinc finger family proteins, P-loopcontaining nucleoside triphosphate hydrolase superfamily, etc. Genomic prediction (GP) accuracy for Fop race resistances ranged from 0.26 to 0.55. This study advanced common bean genetic enhancement through marker-assisted selection (MAS) and genomic selection (GS) strategies, paving the way for improved Fop resistance.

Abstract This paper describes an approach for developing strategic cycle network planning tools. Based on our experience developing and deploying the Cycle Route Uptake and Scenario Estimation (CRUSE) Tool for Ireland, we outline the underlying methods, including disaggregation of origin–destination data with the open source ‘odjitter’ software, incorporation of additional trip purposes, routing, scenario generation, and development of an intuitive user interface that is tested and used by practitioners. Commissioned by the national infrastructure agency Transport Infrastructure Ireland, CRUSE provides estimates of current and potential future cycling levels under ‘snapshot’ scenarios to inform investment decisions. The publicly available results at https://cruse.bike/ enable planners, engineers, and other stakeholders to make more evidence-based decisions. CRUSE goes beyond previous work by: modeling networks at high spatial resolution; simulating multiple trip purposes (social, shopping, personal utility, recreational, and cycle touring), supplementing official origin–destination datasets on travel for work and education; and providing estimates of ‘quietness’ (a proxy for cyclist comfort and route preference) at the route segment level. Three network types—‘Fastest’, ‘Balanced’, and ‘Quietest’—help plan both arterial and residential cycle networks. Workshops with stakeholders were used to inform the development of the tool. Feedback shows that the tool has a wide range of uses and is already being used in practice to inform urban, inter-urban, and rural cycle network designs. The approach is flexible and open source, allowing the underlying ideas and code to be adapted, supporting more evidence-based and effective cycling policies and interventions internationally.

There is a growing movement in Canada towards youth homelessness prevention. One such response, called shelter diversion aims to move young people into safe and supportive housing as quickly as possible. The objective of this project is to assess how, and in what ways, shelter diversion operates and whether this intervention permanently or temporarily diverts youth from homelessness. Our project is grounded in principles of community-based participatory research including community/university partnerships and an advisory committee of lived-experience experts. Our team is utilizing mixed methods to capture the outcomes of diversion programs. Data collection began in September 2022 and ended in May 2024. Quantitative and qualitative data analysis is underway. Preliminary results show differences in how diversion is defined and implemented across organizations. There are also differences in staffing models and program budgets. The findings from this study will contribute to a recommendation for a national definition and adaptable program model for shelter diversion, easily accessible to support the expansion of diversion programs into youth-serving organizations across Canada. This study is the first in Canada to examine the effectiveness of shelter diversion as an early intervention strategy to prevent youth homelessness on a national scale.

Abstract Background Incorporating genomic data into risk prediction has become an increasingly popular approach for rapid identification of individuals most at risk for complex disorders such as PTSD. Our goal was to develop and validate Methylation Risk Scores (MRS) using machine learning to distinguish individuals who have PTSD from those who do not. Methods Elastic Net was used to develop three risk score models using a discovery dataset (n = 1226; 314 cases, 912 controls) comprised of 5 diverse cohorts with available blood-derived DNA methylation (DNAm) measured on the Illumina Epic BeadChip. The first risk score, exposure and methylation risk score (eMRS) used cumulative and childhood trauma exposure and DNAm variables; the second, methylation-only risk score (MoRS) was based solely on DNAm data; the third, methylation-only risk scores with adjusted exposure variables (MoRSAE) utilized DNAm data adjusted for the two exposure variables. The potential of these risk scores to predict future PTSD based on pre-deployment data was also assessed. External validation of risk scores was conducted in four independent cohorts. Results The eMRS model showed the highest accuracy (92%), precision (91%), recall (87%), and f1-score (89%) in classifying PTSD using 3730 features. While still highly accurate, the MoRS (accuracy = 89%) using 3728 features and MoRSAE (accuracy = 84%) using 4150 features showed a decline in classification power. eMRS significantly predicted PTSD in one of the four independent cohorts, the BEAR cohort (beta = 0.6839, p=0.006), but not in the remaining three cohorts. Pre-deployment risk scores from all models (eMRS, beta = 1.92; MoRS, beta = 1.99 and MoRSAE, beta = 1.77) displayed a significant (p

Abstract Background Despite continuing advancements in treatments for opioid use disorder (OUD), continued high rates of relapse indicate the need for more effective approaches, including novel pharmacological interventions. Glucagon-like peptide 1 receptor agonists (GLP-1RA) provide a promising avenue as a non-opioid medication for the treatment of OUD. Whereas GLP-1RAs have shown promise as a treatment for alcohol and nicotine use disorders, to date, no controlled clinical trials have been conducted to determine if a GLP-1RA can reduce craving in individuals with OUD. The purpose of the current protocol was to evaluate the potential for a GLP-1RA, liraglutide, to safely and effectively reduce craving in an OUD population in residential treatment. Method This preliminary study was a randomized, double-blinded, placebo-controlled clinical trial designed to test the safety and efficacy of the GLP-1RA, liraglutide, in 40 participants in residential treatment for OUD. Along with taking a range of safety measures, efficacy for cue-induced craving was evaluated prior to (Day 1) and following (Day 19) treatment using a Visual Analogue Scale (VAS) in response to a cue reactivity task during functional near-infrared spectroscopy (fNIRS) and for craving. Efficacy of treatment for ambient craving was assessed using Ecological Momentary Assessment (EMA) prior to (Study Day 1), across (Study Days 2–19), and following (Study Days 20–21) residential treatment. Discussion This manuscript describes a protocol to collect clinical data on the safety and efficacy of a GLP-1RA, liraglutide, during residential treatment of persons with OUD, laying the groundwork for further evaluation in a larger, outpatient OUD population. Improved understanding of innovative, non-opioid based treatments for OUD will have the potential to inform community-based interventions and health policy, assist physicians and health care professionals in the treatment of persons with OUD, and to support individuals with OUD in their effort to live a healthy life. Trial registration: ClinicalTrials.gov: NCT04199728. Registered 16 December 2019, https://clinicaltrials.gov/study/NCT04199728?term=NCT04199728 . Protocol Version 10 May 2023

Abstract Importance Large-scale estimates of bronchopulmonary dysplasia (BPD) are warranted for adequate prevention and treatment. However, systematic approaches to ascertain rates of BPD are lacking. Objective To conduct a systematic review and meta-analysis to assess the prevalence of BPD in very low birth weight (≤ 1,500 g) or very low gestational age (

Abstract Background Despite wide scale assessments, it remains unclear how large-scale severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination affected the wastewater concentration of the virus or the overall disease burden as measured by hospitalization rates. Methods We used weekly SARS-CoV-2 wastewater concentration with a stratified random sampling of seroprevalence, and linked vaccination and hospitalization data, from April 2021–August 2021 in Jefferson County, Kentucky (USA). Our susceptible ( $$S$$ S ), vaccinated ( $$V$$ V ), variant-specific infected ( $${I}_{1}$$ I 1 and $${I}_{2}$$ I 2 ), recovered ( $$R$$ R ), and seropositive ( $$T$$ T ) model ( $${SV}{I}_{2}{RT}$$ S V I 2 R T ) tracked prevalence longitudinally. This was related to wastewater concentration. Results Here we show the 64% county vaccination rate translate into about a 61% decrease in SARS-CoV-2 incidence. The estimated effect of SARS-CoV-2 Delta variant emergence is a 24-fold increase of infection counts, which correspond to an over 9-fold increase in wastewater concentration. Hospitalization burden and wastewater concentration have the strongest correlation (r = 0.95) at 1 week lag. Conclusions Our study underscores the importance of continuing environmental surveillance post-vaccine and provides a proof-of-concept for environmental epidemiology monitoring of infectious disease for future pandemic preparedness.

This pilot randomized controlled trial protocol aims to (1) assess the impact on the wellbeing of Syrian refugee young adults (18–24 years) of being a community mental health worker (CMHW) implementing WHO's evidence-based psychosocial intervention - Problem Management Plus (PM+) - with adults in their community, and (2) identify the mechanisms associated with the outcomes of enhanced wellbeing and coping, and reduced stress among these CMHWs. Over 108 million people have been forcibly displaced as of the end of 2022. Mental health consequences of these displacements are significant, yet human resources for health are not sufficient to meet the needs. A large proportion of refugee populations are youth and young adults (YA). Evidence indicates their engagement in supporting their communities leads to their own enhanced wellbeing and that of their community. This trial trains Syrian refugees to serve their communities as CMHW (n=19) or tutors (n=19) and compare wellbeing, stress and coping outcomes between these two groups and a control group (n = 40). We will also assess 7 mechanisms as potential pathways for the interventions to influence outcomes. Surveys will assess outcomes and mechanisms, hair samples will measure stress cortisol. The primary analysis will use a Bayesian Hierarchical Model approach to model the trajectories of the mechanisms and primary study endpoints over time for individuals in each of the arms. Our results will elucidate critical mechanisms in which engagement of young adults to support their community enhances their own wellbeing. Trial registration: National Institutes of Mental Health, NCT05265611, Registered prospectively in 2021. Lebanon clinical trials registry #: LBCTR2023015206, Registered in 2023.

OBJECTIVE: Although family-based treatment (FBT) is considered a first-line treatment for adolescent anorexia nervosa (AN), it is underutilized in community settings and is unavailable to many families for a multitude of practical reasons (e.g., costs of treatment, transportation constraints). Adapting FBT interventions for delivery in home-based and community-based settings may reduce pragmatic barriers to treatment uptake and engagement. METHODS: This pilot effectiveness-implementation trial will assess outcomes, implementation, and mechanisms of FBT adapted for the home setting (FBT-HB), delivered in the context of community-based behavioral health agencies. Adolescents with AN-spectrum disorders (n = 50) and their caregivers will be randomly assigned to either FBT-HB or home-based treatment as usual (TAU; integrated family therapy approach). Caregivers and adolescents will provide data on weight, eating, and putative treatment mechanisms, including caregiver self-efficacy and adolescent eating-related and weight-related distress. Implementation constructs of feasibility, acceptability, and appropriateness will be measured among providers and participating families. HYPOTHESES: We expect that FBT-HB will be feasible, acceptable, and appropriate, and will outperform TAU in terms of improvements in adolescent weight and eating-related psychopathology. We further expect that caregiver self-efficacy and adolescent eating-related and weight-related distress, but not general distress, will show greater improvements in FBT-HB relative to TAU and will be associated with better adolescent weight and eating outcomes in FBT-HB. POTENTIAL IMPLICATIONS: The proposed study has clear potential to advance scientific and clinical understanding of the real-world effectiveness of FBT for AN, including whether adapting it for the home setting improves its accessibility and effects on treatment outcome.

A educação digital tem se feito presente de forma cada vez mais diversa e consistente, desde o ensino formal até a produção de conteúdos educacionais em redes sociais. Nessas práticas, ganham destaque materiais de ensino-aprendizagem, dentre os quais destacamos os recursos educacionais digitais – ou recursos educacionais abertos (REAs). Por outro lado, a discussão acerca dos gêneros do discurso tem ganhado cada vez mais relevância e experimentado novos desdobramentos. Assim, considerando a importância que os REAs têm contemporaneamente na educação e a sua complexidade textual e discursiva, este trabalho tem como objetivo geral discutir a sua caracterização no quadro dos gêneros do discurso, mais especificamente sua constituição como gênero ou como hipergênero. Para isso, são mobilizados conceitos teóricos acerca do campo da educação e tecnologia, a exemplo de Castro Filho et al (2008), Santos (2013) Santana, Rossini e Pretto (2012), e dos estudos do texto e do discurso, como Marcuschi (2008), Távora (2008), Bonini (2011) e Bakhtin (2011). Os exemplares usados para análise são REAs produzidos no âmbito do Projeto EPTrilhas, desenvolvido pela Universidade Federal de Santa Catarina em parceria com a Secretaria de Educação Profissional e Tecnológica (SETEC) do Ministério da Educação. Essa análise evidenciou, pelas características do gênero, mídia e suporte, que os REAs multimodais em suporte virtual possuem características que os identificam como hipergêneros.

BackgroundLytic or malpositioned tunnels may require bone grafting during revision anterior cruciate ligament reconstruction (rACLR) surgery. Patient characteristics and effects of grafting on outcomes after rACLR are not well described.PurposeTo describe preoperative characteristics, intraoperative findings, and 2-year outcomes for patients with rACLR undergoing bone grafting procedures compared with patients with rACLR without grafting.Study designCohort study; Level of evidence, 3.MethodsA total of 1234 patients who underwent rACLR were prospectively enrolled between 2006 and 2011. Baseline revision and 2-year characteristics, surgical technique, pathology, treatment, and patient-reported outcome instruments (International Knee Documentation Committee [IKDC], Knee injury and Osteoarthritis Outcome Score [KOOS], Western Ontario and McMaster Universities Osteoarthritis Index, and Marx Activity Rating Scale [Marx]) were collected, as well as subsequent surgery information, if applicable. The chi-square and analysis of variance tests were used to compare group characteristics.ResultsA total of 159 patients (13%) underwent tunnel grafting-64 (5%) patients underwent 1-stage and 95 (8%) underwent 2-stage grafting. Grafting was isolated to the femur in 31 (2.5%) patients, the tibia in 40 (3%) patients, and combined in 88 patients (7%). Baseline KOOS Quality of Life (QoL) and Marx activity scores were significantly lower in the 2-stage group compared with the no bone grafting group (P≤ .001). Patients who required 2-stage grafting had more previous ACLRs (P < .001) and were less likely to have received a bone-patellar tendon-bone or a soft tissue autograft at primary ACLR procedure (P≤ .021) compared with the no bone grafting group. For current rACLR, patients undergoing either 1-stage or 2-stage bone grafting were more likely to receive a bone-patellar tendon-bone allograft (P≤ .008) and less likely to receive a soft tissue autograft (P≤ .003) compared with the no bone grafting group. At 2-year follow-up of 1052 (85%) patients, we found inferior outcomes in the 2-stage bone grafting group (IKDC score = 68; KOOS QoL score = 44; KOOS Sport/Recreation score = 65; and Marx activity score = 3) compared with the no bone grafting group (IKDC score = 77; KOOS QoL score = 63; KOOS Sport/Recreation score = 75; and Marx activity score = 7) (P≤ .01). The 1-stage bone graft group did not significantly differ compared with the no bone grafting group.ConclusionTunnel bone grafting was performed in 13% of our rACLR cohort, with 8% undergoing 2-stage surgery. Patients treated with 2-stage grafting had inferior baseline and 2-year patient-reported outcomes and activity levels compared with patients not undergoing bone grafting. Patients treated with 1-stage grafting had similar baseline and 2-year patient-reported outcomes and activity levels compared with patients not undergoing bone grafting.

A Meta-analysis of selected studies on the effectiveness of gamification method for children. Multiple gamification methods are used to motivate students to improve their learning outcomes. Yet, this method is still very rarely used in learning for children aged 6-10 years. This systematic review and meta-analysis aim to objectively determine the effectiveness of gamification method in increasing knowledge, skills and attitudes of children aged 6-10 years.The data were obtained from the ERIC, Emerald and Elsevier databases published between 2014-2018 using the keywords of "gamification on education", "gamification methods", and "children". In the chosen systematical analysis, 6 studies were then reviewed using a meta-analysis. The effect summary showed a value of 1.01 with confident interval of 0.98-1.05, which indicates that gamification method is statistically effective in improving students' knowledge, skills, and children's attitudes. The Z test with a value of 0.68 and a significance level of 5% also showed a significant effect of this method calculated by random-effect models.

IntroductionVolunteering in the community is thought to provide unique benefits to people who experience limited engagement in society. In the global South, volunteer programs are often framed as empowering women and benefiting the poor, without empirical evidence or systematic investigation of what this means from a local perspective. For this reason, it is critical to represent stakeholder knowledge, understand how change happens systemically, and reduce cultural bias in scientific inquiry and public policy. As such, efforts to respect diverse narratives and problem-solving approaches are key to science diplomacy – they help us understand cultural relevance, program efficacy, and for whom a program is considered transformative.Methods and resultsThis study shows how Syrian refugee and Jordanian women, living in resource-poor families, articulated (i) concepts of empowerment and life satisfaction and (ii) the benefits of engaging in community-based volunteering programs. Through engaging in a participatory methodology known as Fuzzy Cognitive Mapping, women generated visual representations of these constructs and cause-and-effect reasoning. They identified several dimensions of empowerment (e.g., cultural, financial, and psychological empowerment) and several meanings of life satisfaction (e.g. adaptation, acceptance, and contentment). They also mapped connections between variables, identifying those that might catalyze change. We were specifically interested in evaluating understandings of We Love Reading, a program that trains volunteers to become changemakers in their local community. In simulations, we modelled how employment, education, money, and volunteering would drive system change, with notable results on cultural empowerment.DiscussionThrough visual maps and scenarios of change, the study demonstrates a participatory approach to localizing knowledge and evaluating programs. This is key to improving scientific enquiry and public policy.

The 2019 London Extinction Rebellion was the first attempt by environmental protesters to create prolonged large-scale disruption in a Western capital city. The effects on public opinion were difficult to predict because protests seen as extreme can reduce support, but protests seen as justified can increase support. We studied longitudinal opinion changes in a nationally representative sample (n = 832) before, during, and after the rebellion, in conjunction with experimental analysis of the causal effects of media reports (n = 1441). The rebellion was longitudinally associated with national increases in environmental concern, and activist media increased dissatisfaction with current government action. Reports from different media sources caused activism intentions and support to move in different directions, contributing to longitudinally increased polarisation in attitudes to activism. The rebellion had minimal effects on belief in whether ordinary people can produce relevant change (based on collective efficacy and support for a Citizens’ Assembly). The rebellion thus apparently succeeded in strengthening general environmental attitudes without polarising them, and probably somewhat grew the pool of engaged activists, but did not lead to major growth in collective mobilisation or improved environmental policy.

Abstract Background and Aim C‐reactive protein (CRP)‐to‐albumin ratio (CAR) is a novel score with prognostic value in inflammatory conditions. This study assessed the performance of CAR as an objective marker of disease activity and prediction of subtherapeutic infliximab trough levels in patients with inflammatory bowel disease (IBD). Methods A retrospective study was conducted on three different patient cohorts with IBD: patients who had (i) fecal calprotectin (FC) measurements; (ii) Mayo Endoscopic Scores; and (iii) infliximab trough levels available. The relative performances of CAR, albumin, and CRP were compared in predicting disease activity (based on FC or Mayo Endoscopic Score) and infliximab trough levels. Results In both the FC (n = 289) and endoscopy (n = 65) cohorts, albumin and CAR correlated with objective disease activity. CAR (area under the curve [AUC] 0.70) was only marginally better at detecting active disease, measured by FC, compared to CRP (AUC 0.68). A CAR >0.15 was able to detect Mayo 3 disease (AUC 0.83, sensitivity 81%, specificity 89%). Albumin (r = 0.38) and CAR (r = −0.42) correlated with infliximab trough levels (n = 204). The optimal CAR for detecting subtherapeutic infliximab trough levels was >0.08 (AUC 0.70, sensitivity 66%, specificity 64%). Both albumin and CAR were independent predictors of subtherapeutic infliximab trough levels but correlated poorly with infliximab trough levels longitudinally in the same patient. Conclusion CAR was only a modest discriminator of subtherapeutic infliximab levels and offers little more than CRP in detecting active disease. CAR has potential to detect severe Mayo 3 disease and could be calculated in patients admitted with suspected acute severe ulcerative colitis.

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

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.