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S2 Open Access 2014
2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines

Anne C Goldberg, D. Levy, Donald M. Lloyd-Jones et al.

(Circulation. 2014;129[suppl 2]:S1-S45) © 2013 The Expert Panel Members. The Journal of the American College of Cardiology is published on behalf of the American College of Cardiology Foundation by Elsevier Inc.; Circulation is published on behalf of the American Heart Association, Inc., by Wolters Kluwer. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial-NoDervis License, which permits use, distribution, and reproduction in any medium, provided that the Contribution is properly cited, the use is non-commercial, and no modifications or adaptations are made.

2211 sitasi en
arXiv Open Access 2026
What Papers Don't Tell You: Recovering Tacit Knowledge for Automated Paper Reproduction

Lehui Li, Ruining Wang, Haochen Song et al.

Automated paper reproduction -- generating executable code from academic papers -- is bottlenecked not by information retrieval but by the tacit knowledge that papers inevitably leave implicit. We formalize this challenge as the progressive recovery of three types of tacit knowledge -- relational, somatic, and collective -- and propose \method, a graph-based agent framework with a dedicated mechanism for each: node-level relation-aware aggregation recovers relational knowledge by analyzing implementation-unit-level reuse and adaptation relationships between the target paper and its citation neighbors; execution-feedback refinement recovers somatic knowledge through iterative debugging driven by runtime signals; and graph-level knowledge induction distills collective knowledge from clusters of papers sharing similar implementations. On an extended ReproduceBench spanning 3 domains, 10 tasks, and 40 recent papers, \method{} achieves an average performance gap of 10.04\% against official implementations, improving over the strongest baseline by 24.68\%. The code will be publicly released upon acceptance; the repository link will be provided in the final version.

en cs.AI
arXiv Open Access 2026
"Girl, I'm so Serious": CARE, a Capability Framework for Reproductive Equity in Human-AI Interaction

Alice Zhong, Phoebe Chen, Anika Sharma et al.

Sexual and reproductive health (SRH) remains shaped by structural barriers that leave many without judgment-free information. AI chatbots offer anonymous alternatives, but access alone does not ensure equity when socioeconomic determinants shape whose capabilities these tools expand or constrain. Conventional methods for evaluating human-AI interaction were not designed to capture whether technologies holistically support reproductive autonomy. We introduce CARE, Capability Approach for Reproductive Equity, developing capabilities, functionings, and conversion factors into a Normative Design Lens and an Evaluation Lens for AI in SRH contexts. Evaluating SRH-specific non-LLM chatbots, general-use LLMs, and search engine features along credibility and reasoning, we identify two epistemic harms: source opacity and response rigidity. We conclude with design and evaluation recommendations, participatory auditing strategies, and policy implications for high-stakes domains where AI intersects with inequity.

arXiv Open Access 2026
Activation Outliers in Transformer Quantization: Reproduction, Statistical Analysis, and Deployment Tradeoffs

Pranav Kumar Kaliaperumal

Post-training quantization (PTQ) of transformers is known to suffer from severe accuracy degradation due to structured activation outliers, as originally analyzed by Bondarenko et al. (EMNLP 2021) in work associated with Qualcomm AI Research. This paper provides a reproducible empirical reproduction and systems-level extension of that phenomenon in BERT-base fine-tuned on QNLI. When global W8A8 quantization is applied, validation accuracy drops sharply from 89.66% (FP32) to 54.33%, a decrease of 35.33 points. Statistical analysis of FP32 activations shows strongly heavy-tailed behavior that intensifies with model depth: kurtosis reaches 271 in the final layers and approximately 55% of activation energy is concentrated in the top 1% of channels. We evaluate several mitigation strategies. Mixed precision PTQ restores accuracy close to the FP32 baseline (89.42%). Per-embedding-group (PEG) quantization shows strong sensitivity to grouping structure, improving accuracy from 66.12% with three groups to 86.18% with four groups. In contrast, percentile-based calibration, even at thresholds between 99.0 and 99.99, fails to recover accuracy (about 50.54%), indicating that large activation channels encode structured signal rather than rare noise. Deployment profiling on an RTX 3050 GPU shows minimal differences in latency and memory usage across methods (median latency about 58-59 ms; VRAM usage about 484-486 MB), highlighting the importance of hardware-aware evaluation. Overall, the results show that PTQ failure in transformers is primarily driven by structured channel dominance amplified through residual connections. Effective mitigation therefore requires channel-aware precision allocation rather than scalar clipping alone.

en cs.LG, cs.AI
arXiv Open Access 2025
Enhancing Automated Paper Reproduction via Prompt-Free Collaborative Agents

Zijie Lin, Qilin Cai, Liang Shen et al.

Automated paper reproduction has emerged as a promising approach to accelerate scientific research, employing multi-step workflow frameworks to systematically convert academic papers into executable code. However, existing frameworks often lack mechanisms to verify and refine the outputs at each generation step, or rely heavily on manually designed prompts for self-refinement, which limits their adaptability and scalability. To address these limitations, we propose a prompt-free collaborative agent framework that automatically enhances the quality of paper-to-code generation. Our approach employs two collaborative agents: a verification agent that examines whether the outputs at each step satisfy the requirements specified in the corresponding system prompt, and a refinement agent that revises the outputs based on the identified issues. Unlike previous methods that require human experts to craft specific refinement prompts for each step, our framework achieves automatic verification and improvement by leveraging only the original system prompts. We integrate our collaborative agents into the Paper2Code framework and conduct comprehensive experiments on PaperBench Code-Dev and Paper2CodeBench datasets. Experimental results demonstrate that our approach significantly improves the accuracy and completeness of reproduced code, achieving performance gains of approximately 15\% and 13\%, respectively, compared to the baseline without our agents. Furthermore, comparative experiments against Self-Refine validate the robustness and consistency of our prompt-free approach across different datasets.

en cs.AI
arXiv Open Access 2025
A Semi-Lagrangian scheme on embedded manifolds using generalized local polynomial reproductions

Thomas Hangelbroek, Christian Rieger, Grady B. Wright

We analyze rates of uniform convergence for a class of high-order semi-Lagrangian schemes for first-order, time-dependent partial differential equations on embedded submanifolds of $\mathbb{R}^d$ (including advection equations on surfaces) by extending the error analysis of Falcone and Ferretti. A central requirement in our analysis is a remapping operator that achieves both high approximation orders and strong stability, a combination that is challenging to obtain and of independent interest. For this task, we propose a novel mesh-free remapping operator based on $\ell_1$ minimizing generalized polynomial reproduction, which uses only point values and requires no additional geometric information from the manifold (such as access to tangent spaces or curvature). Our framework also rigorously addresses the numerical solution of ordinary differential equations on manifolds via projection methods. We include numerical experiments that support the theoretical results and also suggest some new directions for future research.

en math.NA
arXiv Open Access 2025
Learning Individual Reproductive Behavior from Aggregate Fertility Rates via Neural Posterior Estimation

Daniel Ciganda, Ignacio Campón, Iñaki Permanyer et al.

Age-specific fertility rates (ASFRs) provide the most extensive record of reproductive change, but their aggregate nature obscures the individual-level behavioral mechanisms that drive fertility trends. To bridge this micro-macro divide, we introduce a likelihood-free Bayesian framework that couples a demographically interpretable, individual-level simulation model of the reproductive process with Sequential Neural Posterior Estimation (SNPE). We show that this framework successfully recovers core behavioral parameters governing contemporary fertility, including preferences for family size, reproductive timing, and contraceptive failure, using only ASFRs. The framework's effectiveness is validated on cohorts from four countries with diverse fertility regimes. Most compellingly, the model, estimated solely on aggregate data, successfully predicts out-of-sample distributions of individual-level outcomes, including age at first sex, desired family size, and birth intervals. Because our framework yields complete synthetic life histories, it significantly reduces the data requirements for building microsimulation models and enables behaviorally explicit demographic forecasts.

en stat.AP, cs.LG
arXiv Open Access 2025
Agentic Bug Reproduction for Effective Automated Program Repair at Google

Runxiang Cheng, Michele Tufano, Jürgen Cito et al.

Bug reports often lack sufficient detail for developers to reproduce and fix the underlying defects. Bug Reproduction Tests (BRTs), tests that fail when the bug is present and pass when it has been resolved, are crucial for debugging, but they are rarely included in bug reports, both in open-source and in industrial settings. Thus, automatically generating BRTs from bug reports has the potential to accelerate the debugging process and lower time to repair. This paper investigates automated BRT generation within an industry setting, specifically at Google, focusing on the challenges of a large-scale, proprietary codebase and considering real-world industry bugs extracted from Google's internal issue tracker. We adapt and evaluate a state-of-the-art BRT generation technique, LIBRO, and present our agent-based approach, BRT Agent, which makes use of a fine-tuned Large Language Model (LLM) for code editing. Our BRT Agent significantly outperforms LIBRO, achieving a 28% plausible BRT generation rate, compared to 10% by LIBRO, on 80 human-reported bugs from Google's internal issue tracker. We further investigate the practical value of generated BRTs by integrating them with an Automated Program Repair (APR) system at Google. Our results show that providing BRTs to the APR system results in 30% more bugs with plausible fixes. Additionally, we introduce Ensemble Pass Rate (EPR), a metric which leverages the generated BRTs to select the most promising fixes from all fixes generated by APR system. Our evaluation on EPR for Top-K and threshold-based fix selections demonstrates promising results and trade-offs. For example, EPR correctly selects a plausible fix from a pool of 20 candidates in 70% of cases, based on its top-1 ranking.

en cs.SE, cs.AI
DOAJ Open Access 2025
Insights into natural neocentromere evolution from a cattle T2T X chromosome

Paulene S. Pineda, Callum MacPhillamy, Yan Ren et al.

Abstract The cattle genome is crucial for understanding ruminant biology, but it remains incomplete. Here we present a telomere-to-telomere haplotype-resolved X chromosome and four autosomes of cattle in a near-complete assembly that is 431 Mb (16%) longer than the current reference genome. Using this assembly (UOA_Wagyu_1) we identify 738 new protein-coding genes and support the characterization of centromeric repeats, identification of transposable elements, and enabled the detection of 2397 more structural variants from 20 Wagyu animals than using ARS-UCD2.0. We find that the cattle X centromere is a natural neocentromere with highly identical inverted repeats, no bovine satellite repeats, low CENP-A signal, low methylation, and low CpG content, in contrast to the autosomal centromeres that are comprised of typical bovine satellite repeats and epigenetic features. Our results suggest it likely formed from transposable element expansion and CpG deamination, suggesting dynamic evolution. We find eighteen X-pseudoautosomal region genes have conserved testes expression between cattle and apes. We also find all cattle X neocentromere protein-coding genes are expressed in testes, which suggests they potentially play a role in reproduction.

DOAJ Open Access 2025
Effectiveness and cost-effectiveness of community perinatal mental health services on access, experience, recovery/relapse and obstetric and neonate outcomes: the ESMI-II mixed-methods study

Heather O’Mahen, Louise Howard, Helen Sharp et al.

Background Perinatal mental health disorders affect one in five mothers during pregnancy or within 2 years post childbirth. These disorders can lead to poor pregnancy and childbirth outcomes and maternal deaths. Additionally, they negatively affect a child’s cognitive, social and emotional development. Stigma and a lack of specialised services have limited access to mental health care. National Health Service England invested £365M in community perinatal mental health teams, but their impact on women and infants’ outcomes are not known. Objectives Develop a taxonomy of community perinatal mental health teams (work package 1). Compare and validate two assessments of quality of mother–infant interaction for use by community perinatal mental health teams (work package 2). Evaluate the effectiveness and cost-effectiveness of community perinatal mental health teams (work packages 3 and 4). Design Mixed-methods study. Setting Community perinatal mental health teams in England. Participants Women who were pregnant or within 2 years postnatal. Methods and outcome measures Work package 1: Typology of community perinatal mental health teams in England. Work package 2: Reliability and validity of two observational assessments of parent–infant interaction. Work package 3: Realist evaluation interviews with women, partners/close others, and staff to determine effective community perinatal mental health team components. Work package 4: Analysis of linked data: Association of community perinatal mental health teams with access to secondary care mental health services. Risk of acute relapse and improved obstetric and neonate outcomes for women with pre-existing severe disorders in areas with community perinatal mental health teams compared to generic services. Economic analysis of cost of community perinatal mental health teams. Results Objective 1: Community perinatal mental health team typologies revealed in 2020, 84% had basic staffing levels and 63% had more multi-professionals. Objective 2: The ‘Parent Infant Interaction Observation Scale’ and ‘National Institute of Child Health and Human Development’ assessments of mother–infant interaction were reliable and valid; the National Institute of Child Health and Human Development is more suitable for community perinatal mental health teams. Objective 3: Work package 3: Interviews with 139 women, 55 partners/close others and 80 health workers highlighted the importance of specialist perinatal knowledge, responding in a warm and non-judgemental way, working closely with other healthcare providers, optimising medication, supporting mothers to reduce conflict and improve social support, helping mother–infant bonding, and teaching emotional management. Work package 4: Analysis of linked health data revealed higher risks for obstetric and neonate problems in women with severe mental health disorders, particularly recent or very serious episodes. Work package 4: Areas with community perinatal mental health teams saw increased mental health access among perinatal women and reduced need for acute care, albeit at a higher cost and with greater neonatal risks. Limitations High levels of missing data on diagnosis and mental health outcomes in existing health and service data. Lack of data on child outcomes. Evaluation occurred during community perinatal mental health team changes and the coronavirus disease discovered in 2019 pandemic limiting a full assessment of the impact of community perinatal mental health teams on maternal and child outcomes. Conclusions Community perinatal mental health teams can support perinatal women with complex, moderate/severe mental health disorders, but further attention to women’s physical needs is essential. The use of observational assessments of parent–infant relationships will enhance the evaluation of community perinatal mental health teams’ impact on infant outcomes. Future work Research should focus on prospective studies that gather mental health and child outcomes from community perinatal mental health teams and primary care mental health, to assess broader impacts of perinatal-specific treatment across care pathways. Study registration This study is registered on Research Registry as researchregistry5463. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: 17/49/38) and is published in full in Health and Social Care Delivery Research; Vol. 13, No. 38. See the NIHR Funding and Awards website for further award information. Plain language summary We evaluated how well community perinatal mental health teams were working. The study had four work packages. Work package 1 created community perinatal mental health team categories in England. In 2020, 84% had basic staffing, and 63% had more multi-professionals involved in mother and baby care. Work package 2 evaluated two assessments of mother–baby interaction. ‘Parent Infant Interaction Observation Scale’ was better at predicting how babies would be developmentally at age 2, though is best used for babies 2–8 months old. ‘National Institute of Child Health and Human Development-3’ could be better for community perinatal mental health teams, because it can be used for babies 3–24 months old, is simpler to use and takes less staff training time. Work package 3 used interviews to look at what aspects of community perinatal mental health team care helped women. We interviewed 139 women, 55 family members and 80 health workers in 10 community perinatal mental health teams throughout England. Good community perinatal mental health teams were comprehensive and had staff who were relational, approachable and non-judgemental. They understood what new mothers needed. Mothers and babies were greatly helped by: community perinatal mental health teams working closely with other health providers perinatal-specific medication advice helping mothers connect with other mothers supporting mothers to reduce conflict and get more support helping mother–infant bonding teaching mums how to manage their emotions. Work package 4 evaluated National Health Service maternity and mental health data. We found women with serious mental health problems had a higher chance of having childbirth and newborn difficulties. The risk was greatest for women with very recent or serious mental health problems. In areas with community perinatal mental health teams, more perinatal women accessed earlier help with their mental health, with fewer women having highest levels of care. Areas with community perinatal mental health teams cost more money and newborns had greater health risks. Community perinatal mental health teams are good at helping perinatal women with mental health problems, but further work is needed to understand how to help their newborn baby’s health. Scientific summary Background Perinatal mental health (PMH) disorders (mental disorders occurring in pregnancy or 2 years after childbirth) are widely prevalent, affecting one in five mothers. Women with PMH have distressing symptoms and poor functioning that can affect their relationships with their families and infant. There is growing evidence that PMH disorders are associated with pregnancy complications, poor childbirth outcomes, maternal deaths in the first postnatal year and long-term negative effects on child cognitive, social and emotional development. Stigma, lack of specialist services and trained staff, and lack of clinically feasible assessments, particularly for the parent–infant relationship, have meant access to mental health care has been poor. In the ‘Five Year Forward’ and ‘Long Term Plans’, NHS England invested over £365M to improve access to community perinatal mental health teams (CPMHTs), but the effectiveness of these services on women and children’s health and well-being is not known. Objectives Develop a taxonomy of variations characterising CPMHTs [work package (WP) 1]. Compare and validate two observational assessments of quality of mother–infant interaction for use by CPMHTs (WP2). Evaluate the effectiveness and cost-effectiveness of CPMHTs (WPs 3 and 4). WP3: Which CPMHT components promote access to treatment and which components work, for whom, in what circumstances, how and why to reduce PMH problems? WP4: In women with pre-existing severe disorders are CPMHTs (compared with generic services) associated with: higher levels of access to secondary care mental health services (generic and CPMHTs)? lower risk of relapse? improved birth outcomes? greater cost-effectiveness? Methods (2020–3) Work package 1/RQ1 To characterise service variations [research questions (RQ1)], we created a taxonomy classifying CPMHT elements. Using published data, expert and patient consensus, we created a programme theory on optimal service provision. A programme theory explains how, when and why a programme is expected to work. We used service-level data gathered from CPMHT annual reports to NHS England (2020), NHS Benchmarking (2015–8), Royal College of Psychiatry Perinatal Quality Network, and National Maternity and Perinatal Audit (2017 and 2019) to develop the taxonomy relative to the programme theory. Work package 2/RQ2 We assessed the reliability and predictive validity of two observational assessments of the parent–infant relationship. Observational assessments of the parent–infant relationship are considered superior to self-report, but there is a lack of consensus on which assessments have the best predictive validity to later child outcomes. We used video archive material from a prospective, longitudinal Medical Research Council-funded study from pregnancy to school age (The Wirral Child Health and Development Study) to evaluate the Parent–Infant Interaction Observation Scale (PIIOS; for use with infants 2–8 months) and the National Institute for Child Health and Human Development (NICHD; for use with infants) system. Using 250 mother–infant interactions recorded at 6–8 months of age, 2 research assistants coded 3-, 5- and 7-minute clips from the 7-minute recorded observation available using each system. Inter-rater reliability and intrarater reliability were assessed. Predictive validity was determined in relation to (1) attachment security from the Strange-Situation Paradigm and (2) child internalising (emotional) and externalising (behavioural) problem scores from the Brief Infant Toddler Socio-Emotional Assessment (age 1 and 2) and Pre-school Child Behaviour Checklist at school entry. We tested whether we could identify a briefer reliable and valid form of either assessment for use in routine clinical practice. Work package 3/RQ3 We carried out a realist evaluation assessing components of CPMHTs that promoted treatment access and perceived outcomes (RQ3). Using WP1 typology and programme theory, we selected 10 CPMHTs for variations on service components and configurations (e.g. level of mother–infant/psychological interventions, integration with other services). We employed a purposive sampling approach (with maximum variation in characteristics), to identify and interview at least 10 women, their (consenting) partners or close other (CO), and up to 10 staff from each service to help us refine and test aspects of our programme theory, which identified how programme activities were associated with outcomes. Women were eligible if they were near the end of their care with the CPMHT or had finished care within the past 2 years. Interviews, up to 60 minutes in duration, assessed domains from our programme theory (e.g. experiences/acceptability of care, service components they believed made a difference to their care and outcomes and how this made an impact on their mental health and functioning with their family, including their infant). Where individuals had ‘less successful’ outcomes, we asked them for their opinions on what might have helped. We asked partners/CO related questions about impact of care received and how/if the CPMHT involved the CO. We asked staff how teams operate, which service components improve mother and baby outcomes, and which populations CPMHTs work best for. We also gathered service-level data on monthly referral numbers, referral source, ethnicity of women on the service and staffing breakdown. A realist logic of analysis was used. Work package 4/RQ4 We used linked NHS routinely collected data from the Maternity Services Data Set, the Mental Health Services Data Set and the Hospital Episode Statistics between 2016 and 2019. Using an initial data set from 2016, we firstly examined associations between women who had a history of severe and complex mental health problems and obstetric and neonatal outcomes. We investigated whether there was a relationship between severity, as indicated by an acute hospitalisation, and recency of the mental health problem and these outcomes. For RQ4, we used data between 2016 and 2019 and we compared areas with a CPMHT to those without on women’s access to secondary mental health care, acute post partum relapse (defined as admission to either inpatient or crisis team care), duration of admissions and associated costs. We also examined obstetric and neonatal outcomes (including birthweight, prematurity and infant death and stillbirth) for perinatal women with a history of severe and complex mental health problems in areas with CPMHTs compared to those without. Results Work package 1/RQ1 In 2020, there were 55 CPMHTs. This represented coverage across 94.8% of mental health trusts in the country. Using staff configurations that captured variations in service provision relative to the programme theory, we created a hierarchical taxonomy consisting of a basic, foundational classification of services based on presence of a psychiatrist, nurse and psychologist (84% of CPMHTs), and a secondary, comprehensive level with greater service differentiation in line with key domains in the long-term plan (63% of CPMHTs). These included the basic classification as well as occupational therapists and nursery nurses. Work package 2/RQ2 We found evidence for the reliability and predictive validity of the total-score PIIOS and a three-item form of the NICHD (NICHD-3; parental sensitivity, intrusiveness and positive regard/warmth), and the total-score PIIOS. No shorter form of PIIOS was identified with sufficient predictive validity. Filming for a 5-minute period achieved optimal reliability and predictive (discriminative) validity to age 2 mental health outcomes for both NICHD-3 and PIIOS total score, although PIIOS had broader predictive validity to age 2 internalising and externalising mental health outcomes. Neither observational tool predicted longer-term mental health outcomes at school entry, consistent with the high number of intervening events in this time period. Work package 3/RQ3 Across 10 different CPMHTs, we interviewed 139 women, 55 partners/CO and 80 health and social care practitioners to determine effective CPMHT components. As predicted, comprehensive CPMHTs resulted in improvements in the experiences and mental health outcomes of women and infants, with some women stating CPMHTs were a ‘transformative’ experience. These improvements were grounded in the collaborative, integrative care provided between comprehensive CPMHTs and other health providers. Integration across care pathways was greatest with maternity, mother and baby hospitals, obstetrics, and crisis teams and was lowest with general practitioners and adult mental health. Perinatal women with mental health disorders strongly preferred treatment from health professionals with specialist PMH knowledge as they felt these individuals were best placed to understand their complex family-related needs. Women described style of treatment delivery as critical to their perceived outcomes, including compassionate, open, non-judgemental care. These factors were associated with their perceptions that they got the ‘right’ treatments and their descriptions of their level of treatment engagement. The value of adaptable treatment catering to changing schedules and locations (home, clinic, remote, etc.) was emphasised. A holistic approach, typically combining pharmacological and relational treatments, yielded positive perceived results. Women appreciated the CPMHTs’ expertise optimising their medication by providing comprehensive, up-to-date information on the risks and benefits of medications during the perinatal period. This was especially important for women with severe mental illness (SMI). Women described how CPMHTs reduced isolation and stigma by improving social connectedness among parents, enhanced social support and reduced family conflicts, facilitated better bonding between mothers and their infants, and equipped women with emotional management skills while supporting their engagement in meaningful activities. Expansion of CPMHTs to meet the long-term plan was ongoing during the evaluation, with varying provision across different teams. While SMI care pathways were robust in most teams, disparities in referral pathways and interventions for other mental health problems were apparent. For example, some CPMHTs lacked psychological support, with negative effects on women with post-traumatic stress disorder, obsessive–compulsive disorder, anxiety and depression. Treatments that directly intervened with the parent–infant or couple’s relationship were not yet widely available. This especially affected women who had experienced acute or complex trauma, and those who described experiencing problems bonding with their baby and/or heightened conflict in their relationships. Numbers of ethnically diverse women seen in CPMHTs were lower than expected based on local prevalence estimates. Work package 4/RQ4 We found that depending on definition, between 7% and 9% of women had histories of secondary mental healthcare contact, indicating presence of a severe and complex mental health disorder. We found a significant increased risk for negative obstetric and neonatal outcomes in women who had a history of severe and complex mental health disorders, as indicated by previous contact with secondary mental health care. These risks were greatest for women with the most severe mental health problems, as indicated by a history of hospitalisation, and those who had contact in the last year with secondary mental health care. When comparing mental health treatment access and related costs in areas with and without CPMHTs (RQ4), we found greater access to higher overall use of community mental health treatment and lower risk of acute relapse (lower rates of hospitalisation or crisis resolution teams). When examining acute care components separately, there were more acute hospitalisations and longer durations of stay and less use of crisis resolution teams in areas with CPMHTs compared to those without. These differences resulted in overall higher costs in areas with CPMHTs [mean £651, standard deviation (SD) 4634] compared to areas without (mean £414, SD 4196) which were statistically significant [fully adjusted mean difference £111, 95% confidence interval (CI) £29 to £192, p = 0.008]. There were higher risks of neonatal death and stillbirth and the birth of a baby small for gestational age in areas with CPMHTs versus those without, but lower risks of premature births. Conclusion Between 7% and 9% of women had a history of serious and complex PMH problems and they were at increased risks for negative obstetric and neonatal outcomes. The availability of CPMHTs, relative to areas without CPMHTs, increased overall use of specialist mental healthcare services and reduced postnatal risk of acute relapse. This was associated with overall higher costs in areas with CPMHTs. Our results also suggest the risks of stillbirth/neonatal death and babies born small for gestational age may increase with a CPMHT. There was considerable variation in CPMHT configurations. Those with comprehensive provision provided greater access to a wider range of evidence-based care across mental health problems but many still lacked parent–infant and family treatment offers. CPMHTs were often not serving expected numbers from diverse communities. Feasible parent–infant assessments are available and may help to highlight need and ensure parent–infant dyads get appropriate care. We found both the PIIOS and NICHD-3 were valid and reliable assessments of the parent–infant relationship, but the NICHD-3 may have greater clinical utility due to its brevity to train (2 days vs. 3 days) and code (~15 minutes vs. 20–30 minutes), its predictive validity to attachment security and externalising problems, and application from 3 to 24 months of age. Implications for health care WP2 showed that the PIIOS mother–infant assessment had broader predictive validity to child outcomes at age 2 but should only be used with infants between 2 and 8 months. The NICHD-3 had good predictive validity, is shorter to train and code and can be used with a broader age range between 3 and 24 months, so may be more appropriate for CPMHTs. WP3 demonstrated CPMHT staff need perinatal specific training and supervision to ensure they have the perinatal specialist skills women want and benefit from. WP3 found staff’s ‘soft skills’, being warm, non-judgemental, reliable and offering outreach, made a key difference to women’s engagement and outcomes. Despite their importance, ‘soft skills’ often go unmeasured and undervalued in mental health services. A culture shift is needed to prioritise, support and value ‘soft skills’. This should include training, job planning to include time for these skills, measurement, performance management and assessing staff attitudes. In WP3, women and COs benefitted when family was included in treatment (with woman’s permission). Our results highlighted reducing conflict and improving support, approaches aligned with recommendations from NHS England’s guide on good practices for partners and family members. WP4 showed CPMHTs are effective at improving access to needed and effective treatments, but pregnancy/neonate outcomes are an area of concern. Further research into the causes of this relationships is urgently needed, but several steps may help to promote positive outcomes. First, CPMHTs should encourage collaboration between mental health services and maternity/neonate services to ensure equitable attention to both health and mental health concerns. Second, treatment burden may affect women/birthing people (bp) ability to attend both health and mental health appointments. Colocated services and joint clinic sessions could reduce treatment burden. Lastly, training mental health practitioners on the physical health needs of women could support improved potential for timely communication with maternity for health concerns. Research recommendations We need to know the biological, social and healthcare determinants of increased neonate risk in areas with CPMHTs. Routine mental health data have very high levels of missing data on diagnosis and mental health outcomes. CPMHTs have also had limited time to fully embed themselves into practice, making it difficult to retrospectively assess their impact on women and their babies. Prospective studies that recruit women from case identification and follow them through the perinatal period and with longer-term follow-up assessing mental health, service use, health and linked child outcomes are needed to reliably assess the effectiveness and cost-effectiveness of CPMHTs. Research should focus on the development, evaluation and implementation of interventions tailored for underserved and diverse perinatal populations. WP4 data were based solely on secondary care data. A broader approach, using primary care data sets, data on talking therapies and aspects of different characteristics of CPMHTs could include women with a wider range of problems and severity and provide a better understanding of treatment components that work across the care pathway. Future research needs to evaluate the NICHD and PIIOS measures’ sensitivity to change following parent–infant intervention. Study registration This study is registered on Research Registry as researchregistry5463. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: 17/49/38) and is published in full in Health and Social Care Delivery Research; Vol. 13, No. 38. See the NIHR Funding and Awards website for further award information.

Medicine (General), Public aspects of medicine
DOAJ Open Access 2025
Advancing Understanding of Anorectal Malformations Through Microfocus Computed Tomography Imaging of Resected Material

Daniël Docter, Bernadette S. de Bakker, Jaco Hagoort et al.

Background and Aims: Patients born with anorectal malformations (ARMs) might experience constipation and fecal incontinence. During ARM surgery (anterior and posterior sagittal anorectoplasty procedure), the distal part of the bowel (fistula) is usually resected. Microfocus computed tomography (micro-CT) imaging, capable of imaging samples in ultra-high 3-dimensional resolution, can be used to learn from this resected material. Through this technique, we aim to investigate whether or not structures, such as the internal anal sphincter (IAS), are present within this fistula. Methods: Pediatric patients undergoing surgical reconstruction for ARM were eligible for inclusion. Resected fistulas were fixed using 4% paraformaldehyde and stained with 3.75% B-Lugol for 48 hours to improve soft tissue contrast. Scans were performed on a Phoenix Nanotom micro-CT with a voxel size between 4–6 μm. Samples were destained for subsequent histopathological examination. Outcomes were presence of structures like the IAS, epithelial transition zone and ganglia. ARM fistulas were compared with a fetal anal canal sample derived from the Dutch Fetal Biobank. Results: Eleven ARM fistulas were analyzed. All samples showed evidence of normal development of the rectal wall. Columnar epithelium and stratified squamous epithelium were observed. Muscle fibers were present, arranged in circular pattern that expanded toward the distal end, becoming the intrinsic sphincter (IAS). Ganglia were present with normal appearance. Conclusion: We present micro-CT imaging to research resected material to provide new insights in microscale anatomy. The fistula, currently resected during surgical reconstruction for ARM, contains vital structures like the IAS, normal epithelial transition zone and normal ganglion cells. Although clinical functionality should be studied in the future, our results indicate that the fistula has a normal anal canal morphology and should be spared during ARM reconstruction if possible.

Diseases of the digestive system. Gastroenterology
DOAJ Open Access 2025
Biocontrol Potential of Entomopathogenic Fungi Against Plant-Parasitic Nematodes: A <i>Caenorhabditis elegans</i>-Based Screening and Mechanistic Study

Cheng Cheng, Renjun Zhang, Yanzhen Wang et al.

Plant-parasitic nematodes and insect pests critically threaten agricultural productivity, but chemical pesticides face limitations due to resistance and environmental concerns, necessitating eco-friendly biopesticides targeting both pests and nematodes. Here, we developed a high-throughput screening platform using <i>Caenorhabditis elegans</i> to identify entomopathogenic fungi exhibiting nematocidal activity against <i>Meloidogyne incognita</i>. Among 32 tested strains, nine <i>Metarhizium</i> spp. and one <i>Beauveria</i> strain demonstrated dual efficacy against <i>C. elegans</i> and <i>M. incognita</i>. <i>Metarhizium anisopliae</i> CQMa421 showed the highest virulence, suppressing nematode reproduction by 42.7% and inducing >80% mortality. Pot experiments revealed a 50% reduction in the root galling index and 50.3% fewer root galls in <i>Solanum lycopersicum</i>. The CQMa421 filtrate caused irreversible locomotor deficits and reduced egg hatching rates by 28%. Concurrently, intestinal damage, elevated oxidative stress and autophagy were observed in <i>C. elegans</i>. This was accompanied by a transcriptome-wide modulation of genes involved in detoxification and immune defense pathways. These findings demonstrate the efficacy of our <i>C. elegans</i>-based screening method for identifying fungi with nematocidal potential. CQMa421’s virulence against <i>M. incognita</i> suggests its promise for pest management, while molecular insights highlight pathways that may contribute to the future design of future nematicides. This study advances fungal biocontrol agents and offers a sustainable strategy for agriculture.

Biology (General)
DOAJ Open Access 2025
Evidence of nearshore in-lake spawning Walleye in the central basin of Lake Erie

Carey T. Knight, Ann Marie Gorman, Graham F. Montague

Walleye Sander vitreus are economically and ecologically vital to Lake Erie and have multiple spawning stocks that contribute to the lakewide population. These unique Walleye stocks typically spawn in discrete spawning aggregations in riverine and shallow, open-lake reef habitats during springtime in the western, eastern, and central basins. Yet, most spawning research has been conducted in the western and eastern basins. Therefore, the goal of our study was to document evidence of Walleye utilizing a central basin nearshore reef for reproduction. We used gill nets from 20 March to 15 May 2012, on Hardy Point Reef (HPR; near Fairport Harbor, Ohio) to collect spawning Walleye. Larval light traps and egg mats were deployed to capture fertilized eggs and newly hatched larvae. We captured 281 actively spawning Walleye using overnight-set gill nets from HPR. Five fertilized Walleye eggs and two larval Walleye were captured from HPR. Our study provided evidence that successful Walleye spawning occurred at HPR in the central basin of Lake Erie. Further research should identify potential additional Walleye spawning locations in the central basin and quantify these contributions to the Lake Erie population to help facilitate lake wide management and preservation of spawning stocks.

Environmental sciences, Ecology
arXiv Open Access 2024
Imitate, Explore, and Self-Improve: A Reproduction Report on Slow-thinking Reasoning Systems

Yingqian Min, Zhipeng Chen, Jinhao Jiang et al.

Recently, slow-thinking reasoning systems, such as o1, have demonstrated remarkable capabilities in solving complex reasoning tasks. These systems typically engage in an extended thinking process before responding to a query, allowing them to generate more thorough, accurate, and well-reasoned solutions. These systems are primarily developed and maintained by industry, with their core techniques not publicly disclosed. In response, an increasing number of studies from the research community aim to explore the technical foundations underlying these powerful reasoning systems. Building on these prior efforts, this paper presents a reproduction report on implementing o1-like reasoning systems. We introduce an ``imitate, explore, and self-improve'' framework, denoted as \textbf{STILL-2}, as our primary technical approach to train the reasoning model. In the initial phase, we use distilled long-form thought data to fine-tune the reasoning model, enabling it to invoke a slow-thinking mode. The model is then encouraged to explore challenging problems by generating multiple rollouts, which can result in increasingly more high-quality trajectories that lead to correct answers. Furthermore, the model undergoes self-improvement by iteratively refining its training dataset. To verify the effectiveness of this approach, we conduct extensive experiments on three challenging benchmarks. The experimental results demonstrate that our approach achieves competitive performance compared to industry-level reasoning systems on these benchmarks.

en cs.AI, cs.CL
arXiv Open Access 2024
Risk Estimate under a Time-Varying Autoregressive Model for Data-Driven Reproduction Number Estimation

Barbara Pascal, Samuel Vaiter

COVID-19 pandemic has brought to the fore epidemiological models which, though describing a wealth of behaviors, have previously received little attention in signal processing literature. In this work, a generalized time-varying autoregressive model is considered, encompassing, but not reducing to, a state-of-the-art model of viral epidemics propagation. The time-varying parameter of this model is estimated via the minimization of a penalized likelihood estimator. A major challenge is that the estimation accuracy strongly depends on hyperparameters fine-tuning. Without available ground truth, hyperparameters are selected by minimizing specifically designed data-driven oracles, used as proxy for the estimation error. Focusing on the time-varying autoregressive Poisson model, Stein's Unbiased Risk Estimate formalism is generalized to construct asymptotically unbiased risk estimators based on the derivation of an original autoregressive counterpart of Stein's lemma. The accuracy of these oracles and of the resulting estimates are assessed through intensive Monte Carlo simulations on synthetic data. Then, elaborating on recent epidemiological models, a novel weekly scaled Poisson model is proposed, better accounting for intrinsic variability of the contaminations while being robust to reporting errors. Finally, the data-driven procedure is particularized to the estimation of COVID-19 reproduction number from weekly infection counts demonstrating its ability to tackle real-world applications.

en stat.ME, eess.SP

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