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ABSTRACT: Background: As healthcare moves from a one-size-fits-all approach towards precision care, individual risk prediction is an important step in disease prevention and early detection. Biobank-linked healthcare systems can generate knowledge about genomic risk and test the impact of implementing that knowledge in care. Risk-stratified prostate cancer screening is one clinical application that might benefit from such an approach. Methods: We developed a clinical translation pipeline for genomics-informed prostate cancer screening in a national healthcare system. We used data from 585,418 male participants of the Veterans Affairs (VA) Million Veteran Program (MVP), among whom 101,920 self-identify as Black/African-American, to develop and validate the Prostate CAncer integrated Risk Evaluation (P-CARE) model, a prostate cancer risk prediction model based on a polygenic score, family history, and genetic principal components. The model was externally validated in data from 18,457 PRACTICAL Consortium participants. A novel blended genome-exome (BGE) platform was used to develop a clinical laboratory assay for both the P-CARE model and rare variants in prostate cancer-associated genes, including additional validation in 74,331 samples from the All of Us Research Program. Results: In overall and ancestry-stratified analyses, the polygenic score of 601 variants was associated with any, metastatic, and fatal prostate cancer in MVP and PRACTICAL. Values of the P-CARE model at ≥80th percentile in the multiancestry cohort overall were associated with hazard ratios (HR) of 2.75 (95% CI 2.66-2.84), 2.78 (95% CI 2.54-2.99), and 2.59 (95% CI 2.22-2.97) for any, metastatic, and fatal prostate cancer in MVP, respectively, compared to the median. When high– and low-risk groups were defined as P-CARE HR>1.5 and HR

COVID presented an opportunity to revolutionize the traditional format of Medical Grand Rounds (MGR). In this Commentary, we explore the educational ramifications of shifting MGR virtually with a focus on COVID-related content and its long-term sustainability. This transformation offers an inclusive interdisciplinary approach to sustain learner interest and improve education.

ABSTRACT: This article describes the regulatory and evidence requirements necessary for the authorization of antimethanogenic feed additives (AMFA) aimed at mitigating enteric methane (CH4) emissions from ruminants. It outlines the legislation and legal procedures in Australia, Canada, the European Union, New Zealand, South Korea, the United Kingdom, and the United States as illustrative examples, offering insights for applicants seeking authorization. Additionals objectives are to highlight consequential similarities and differences in regulations and evidence requirements and offer recommendations for scientists and applicants. The pivotal role that scientific evidence plays in the evaluation and approval processes is emphasized, along with the need for applicants and researchers to understand and adhere to the specific regulations of each jurisdiction. Feed additives are regulated to ensure their safety for animals, humans, and the environment, and to verify their effectiveness for the intended use of enteric CH4 mitigation. Regulations cover various aspects, including ingredient safety, manufacturing practices, product labeling, and the establishment of permissible limits for certain substances to ensure their safe use in animal feed. Compliance with these regulations is mandatory, and they are enforced by regulatory agencies within each jurisdiction, aiming to protect animal health, promote food safety, and prevent misleading claims and unsafe practices. The assessment processes involve evaluating scientific evidence submitted by applicants, along with evaluations of quality control procedures, and record-keeping practices. The major difference in regulations is that each jurisdiction developed unique criteria to legally classify AMFA, making it challenging to satisfy all legal classifications with a single set of criteria for scientific evidence. However, numerous similarities and a universal reliance on the concept of intended use indicate consistency across all jurisdictions on the need for robust evidence for efficacy, safety, and product quality and documentation even if the type, size, duration, and location of the studies they require differ. Recommendations are made for both scientists and applicants, emphasizing the importance of designing, conducting, and reporting scientific evaluations transparently, using validated standards and methods, and communicating with regulatory bodies to ensure compliance with regulations and evidence requirements.

Abstract Background The Gas6/TAM (Tyro3, Axl, and Mer) receptor system has been implicated in demyelination and delayed remyelination in experimental animal models, but data in humans are scarce. We aimed to investigate the role of Gas6/TAM in neurodegenerative processes in multiple sclerosis (MS). Methods From a prospective 5-year follow-up study, soluble Gas6/TAM biomarkers were analyzed in cerebrospinal fluid (CSF) by enzyme-linked immunosorbent assay (ELISA) at baseline in patients with relapsing–remitting MS (RRMS) (n = 40), progressive MS (PMS) (n = 20), and healthy controls (HC) (n = 25). Brain volumes, including myelin content (MyC) and white matter (WM) were measured by synthetic magnetic resonance imaging at baseline, 12 months, and 60-month follow-up. Associations with brain volume changes were investigated in multivariable linear regression models. Gas6/TAM concentrations were also determined at 12 months follow-up in RRMS to assess treatment response. Results Baseline concentrations of Tyro3, Axl, and Gas6 were significantly higher in PMS vs. RRMS and HC. Mer was higher in PMS vs. HC. Tyro3 and Gas6 were associated with reduced WM (β = 25.5, 95% confidence interval [CI] [6.11–44.96, p = 0.012; β = 11.4, 95% CI [0.42–22.4], p = 0.042, respectively) and MyC (β = 7.95, 95%CI [1.84–14.07], p = 0.012; β = 4.4, 95%CI [1.04–7.75], p = 0.012 respectively) at 60 months. Patients with evidence of remyelination at last follow-up had lower baseline soluble Tyro3 (p = 0.033) and Gas6 (p = 0.014). Except Mer, Gas6/TAM concentrations did not change with treatment in RRMS. Discussion Our data indicate a potential role for the Gas6/TAM receptor system in neurodegenerative processes influencing demyelination and ineffective remyelination.

Abstract COVID presented an opportunity to revolutionize the traditional format of Medical Grand Rounds (MGR). In this Commentary, we explore the educational ramifications of shifting MGR virtually with a focus on COVID-related content and its long-term sustainability. This transformation offers an inclusive interdisciplinary approach to sustain learner interest and improve education.

Abstract Post-COVID syndrome is affecting many organ systems and arises as a major public health problem with millions of cases worldwide. The primary aim of this study is the analysis of health problems, activity limitations and participation restrictions (ALPR) of participants with post-COVID symptoms and the investigation of correlations between these elements to derive statements about the rehabilitation need, also depending on sex. A retrospective cohort study was performed to collect longitudinal data from January 2022 to January 2023 using the Covid-19 Rehabilitation Needs Questionnaire (RehabNeQ). Patients completed the questionnaire at the Department of Rehabilitation- and Sports Medicine at Hannover Medical School. The 1st assessment included 307 study participants, of whom 54 showed up for the 2nd, 7 for the 3rd and one for the 4th assessment. Study participants with post-COVID symptoms also experience ALPR. The results show no significant difference in symptom intensity in women and men, but in intensity of ALPR. We found many correlations of varying degrees between various factors with ALPR. We found frequent correlations between fatigue and several ALPR. While these correlations apply to both sexes, we also found different correlations in women and men, indicating the different rehabilitation need of women and men.

Abstract Background Bacterial pathogens such as Staphylococcus aureus colonize body surfaces of part of the human population, which represents a critical risk factor for skin disorders and invasive infections. However, such pathogens do not belong to the human core microbiomes. Beneficial commensal bacteria can often prevent the invasion and persistence of such pathogens by using molecular strategies that are only superficially understood. We recently reported that the commensal bacterium Staphylococcus lugdunensis produces the novel antibiotic lugdunin, which eradicates S. aureus from the nasal microbiomes of hospitalized patients. However, it has remained unclear if S. lugdunensis may affect S. aureus carriage in the general population and which external factors might promote S. lugdunensis carriage to enhance its S. aureus-eliminating capacity. Results We could cultivate S. lugdunensis from the noses of 6.3% of healthy human volunteers. In addition, S. lugdunensis DNA could be identified in metagenomes of many culture-negative nasal samples indicating that cultivation success depends on a specific bacterial threshold density. Healthy S. lugdunensis carriers had a 5.2-fold lower propensity to be colonized by S. aureus indicating that lugdunin can eliminate S. aureus also in healthy humans. S. lugdunensis-positive microbiomes were dominated by either Staphylococcus epidermidis, Corynebacterium species, or Dolosigranulum pigrum. These and further bacterial commensals, whose abundance was positively associated with S. lugdunensis, promoted S. lugdunensis growth in co-culture. Such mutualistic interactions depended on the production of iron-scavenging siderophores by supportive commensals and on the capacity of S. lugdunensis to import siderophores. Video Abstract Conclusions These findings underscore the importance of microbiome homeostasis for eliminating pathogen colonization. Elucidating mechanisms that drive microbiome interactions will become crucial for microbiome-precision editing approaches.

Caring for children with developmental delays or disabilities places significant stress on caregivers, which is often exacerbated in low-resource settings. The World Health Organization developed a caregiver skills training for families of children with developmental delays or disabilities, which includes a three-session caregiver well-being module based on Acceptance and Commitment Therapy, that aims to help caregivers build psychological flexibility (i.e. the ability to focus on the present moment, make space for difficult thoughts and emotions and commit to value-driven actions that enrich their lives). We investigated whether this brief caregiver well-being programme was feasible, acceptable and contributed to positive outcomes for caregivers in a rural South African town. We adapted the intervention to the local context using a participatory approach. The 'Well-Beans for Caregivers' adaptation of the World Health Organization Caregiver Skills Training Caregiver Wellbeing module was then delivered by trained facilitators to a group of 10 caregivers in three weekly, 2-h sessions. Most caregivers were single and unemployed. Feedback from the facilitators, caregivers and trainee observers was obtained before, during and after the programme. Results suggested that this brief programme shows promise as a feasible and acceptable intervention, which may lead to improved caregiver well-being and mental health in communities in South Africa. [This article was written with the WHO CST Team.]

46, XX Male Syndrome is a rare genetic condition in which an individual has a male phenotype despite having a 46, XX karyotype. This is most often due to a translocation of the SRY gene from the short arm of the Y-chromosome onto the X chromosomes during paternal meiosis. Due to the absence of the long arm of the Y-chromosome, there is a de facto deletion of AZF regions a-c, and this results in infertility. We present a case of a 35-year-old male who was diagnosed with 46,XX (SRY+) Male Syndrome upon work-up for infertility and hypogonadism.

Background and purpose: Growing evidence suggests that spatial dose variations across the rectal surface influence toxicity risk after radiotherapy. Existing methodologies employ a fixed, arbitrary physical extent for rectal dose mapping, limiting their analysis. We developed a method to standardise rectum contours, unfold them into 2D cylindrical surface maps, and identify subregions where higher doses increase rectal toxicities. Materials and methods: Data of 1,048 patients with prostate cancer from the REQUITE study were used. Deep learning based automatic segmentations were generated to ensure consistency. Rectum length was standardised using linear transformations superior and inferior to the prostate. The automatic contours were validated against the manual contours through contour variation assessment with cylindrical mapping. Voxel-based analysis of the dose surface maps for the manual and automatic contours against individual rectal toxicities was performed using Student’s t permutation test and Cox Proportional Hazards Model (CPHM). Significance was defined by permutation testing. Results: Our method enabled the analysis of 1,048 patients using automatic segmentation. Student’s t-test showed significance (p

Montessori education is the oldest and most widely implemented alternative education in the world and includes a full system of lessons and hands-on materials for children from birth to 18 years, presented individually, and embedded in a philosophical framework regarding children's development and its optimal conditions. The objectives of this review were to examine the effectiveness of Montessori education in improving academic and nonacademic outcomes compared to traditional education, and to determine the degree to which grade level, Montessori setting (public Montessori vs. private Montessori), random assignment, treatment duration, and length of follow-up measurements moderate the magnitude of Montessori effects. Relevant studies were searched in 19 academic databases, in a variety of sources known to publish gray literature, in Montessori-related journals, and in the references of studies retrieved through these searches. This review found that Montessori education had a significant positive impact on academic and nonacademic outcomes. Studies with random assignment, elementary school age level, and private Montessori schools had larger effects.

The year 2024 marks significant anniversaries in the field of Swiss disability policies, reflecting a complex trajectory where notable advances in inclusion and non-discrimination coexist with path-dependency and competing political priorities. This special issue sheds light on the conflicting agendas of the promotion of human rights, inclusion and equality for people with disabilities and their actual implementation, which is confronted by cost-containment measures that restrict access to disability benefits and hinder progressive reforms in disability services. The ambition of this special issue is to highlight the fundamental contradictions between the potentials and limits of disability policy transformation. This editorial introduces how these paradoxes of disability policies operate both internationally and in the Swiss context while providing an overview of the insightful papers included in this special issue.

This study investigates the environmental and food security implications of livestock abortions and calf mortality in Tanzanian dairy systems and Kenyan beef systems by utilizing data from previously published studies. The environmental impact of livestock abortion is assessed in Tanzanian dairy systems, examining indigenous and exotic breeds of cattle and goats in Northern Tanzania. Calf mortality’s impact is evaluated in Kenyan beef systems, involving local cattle breeds in western Kenya. Greenhouse gas (GHG) emission intensity (EI) is estimated for both countries. The GHG emissions in Tanzania consider enteric fermentation, manure management, and feed production in different cattle and goat groups, as well as total milk production. In Kenya, enteric methane (CH4) EI related to calf mortality is assessed by estimating lifetime enteric CH4 emissions and total carcass production from dams and their offspring. The EI is compared between the observed scenario (16% calf mortality) and alternative scenarios (8, 4, and 0% calf mortality). A life cycle assessment using the Global Livestock Environmental Assessment Model-interactive (GLEAM-i) examines GHG sources and potential tradeoffs. Estimates are made for milk and carcass losses due to abortions and calf mortality, scaled to represent the entire country. Abortion increases milk EI by 4–18% in Tanzania, while Kenya’s EI ranges from 25.9 to 27.6 kg CO2 eq per kg carcass weight. Animal protein loss due to abortions is equivalent to the potential annual animal protein requirements of approximately 649 thousand people in Tanzania, while a 16% calf mortality rate in Kenya is equivalent to per capita consumption of 4.5 million people. The findings highlight the significant impact of abortions and calf mortality on GHG emissions and animal protein availability, emphasizing the potential for reduced emissions and improved food security through mitigation efforts. The contribution of emissions from enteric fermentation and manure management is significant across both countries, underscoring the importance of a systems perspective in evaluating the environmental impact of livestock production. This study provides insights into the environmental and food security implications of livestock abortions and calf mortality in Tanzania and Kenya, emphasizing the need for targeted interventions in sustainable livestock production.

Background and purpose: Image-based data mining (IBDM) requires spatial normalisation to reference anatomy, which is challenging in breast radiotherapy due to variations in the treatment position, breast shape and volume. We aim to optimise spatial normalisation for breast IBDM. Materials and methods: Data from 996 patients treated with radiotherapy for early-stage breast cancer, recruited in the REQUITE study, were included. Patients were treated supine (n = 811), with either bilateral or ipsilateral arm(s) raised (551/260, respectively) or in prone position (n = 185). Four deformable image registration (DIR) configurations for extrathoracic spatial normalisation were tested. We selected the best-performing DIR configuration and further investigated two pathways: i) registering prone/supine cohorts independently and ii) registering all patients to a supine reference. The impact of arm positioning in the supine cohort was quantified. DIR accuracy was estimated using Normalised Cross Correlation (NCC), Dice Similarity Coefficient (DSC), mean Distance to Agreement (MDA), 95 % Hausdorff Distance (95 %HD), and inter-patient landmark registration uncertainty (ILRU). Results: DIR using B-spline and normalised mutual information (NMI) performed the best across all evaluation metrics. Supine-supine registrations yielded highest accuracy (0.98 ± 0.01, 0.91 ± 0.04, 0.23 ± 0.19 cm, 1.17 ± 1.18 cm, 0.51 ± 0.26 cm for NCC, DSC, MDA, 95 %HD, and ILRU), followed by prone-prone and supine-prone registrations. Arm positioning had no significant impact on registration performance. For the best DIR strategy, uncertainty of 0.44 and 0.81 cm in the breast and shoulder regions was found. Conclusions: B-spline algorithm using NMI and registered supine and prone cohorts independently provides the most optimal spatial normalisation strategy for breast IBDM.

BackgroundThe quality of care of the 6.5 million Americans living with dementia has been suboptimal, leading to worse outcomes and higher costs. Few health systems have formal systems in place to guide the care of these patients. To help improve the care of persons living with dementia, we developed and preliminarily evaluated the effectiveness of electronic health record (EHR)-generated recommendations for patients with dementia.MethodsThis quality improvement study was conducted from October 2020 through June 2022 at a single academic healthcare system and included patients identified as having dementia on their problem list and their physicians. Ten (seven outpatient and three inpatient) algorithms based on clinical logic and evidence were embedded in an EHR system to generate specific recommendations based on combinations of utilization, diagnosis, and medications. The number of each type of recommendation generated, and orders for each type of recommendation were recorded, as well as physician's perceptions of this approach.ResultsThree thousand six hundred and nine recommendations on 763 patients were triggered by the algorithms in the outpatient setting, and 185 referrals were placed. The most common recommendations were for ongoing care through the UCLA Alzheimer's and Dementia Care program, Palliative Care, the Extensivist Clinic, Urogynecology, and Clinical Pharmacy. The most commonly acted upon by providers were recommendations for referral to Pharmacists and the UCLA Alzheimer's and Dementia Care program. The most common reason for not responding to specific recommendations was that these were not perceived as relevant to the patient. Compared to general medicine physicians, geriatricians felt more comfortable managing dementia care without a referral to a service (23% (95% CI 15%-34%) versus 3% (95% CI 0%-17%), p = 0.012) and less commonly felt the recommendation was appropriate (1% (95% CI 0%-7%) versus 13% (95% CI 4%-30%), p = 0.02).ConclusionsEHR-generated algorithms can help guide patients with dementia to appropriate clinical services.

Although prematurity is the single largest cause of death in children under 5 years of age, the current definition of prematurity, based on gestational age, lacks the precision needed for guiding care decisions. Here, we propose a longitudinal risk assessment for adverse neonatal outcomes in newborns based on a deep learning model that uses electronic health records (EHRs) to predict a wide range of outcomes over a period starting shortly before conception and ending months after birth. By linking the EHRs of the Lucile Packard Children's Hospital and the Stanford Healthcare Adult Hospital, we developed a cohort of 22,104 mother-newborn dyads delivered between 2014 and 2018. Maternal and newborn EHRs were extracted and used to train a multi-input multitask deep learning model, featuring a long short-term memory neural network, to predict 24 different neonatal outcomes. An additional cohort of 10,250 mother-newborn dyads delivered at the same Stanford Hospitals from 2019 to September 2020 was used to validate the model. Areas under the receiver operating characteristic curve at delivery exceeded 0.9 for 10 of the 24 neonatal outcomes considered and were between 0.8 and 0.9 for 7 additional outcomes. Moreover, comprehensive association analysis identified multiple known associations between various maternal and neonatal features and specific neonatal outcomes. This study used linked EHRs from more than 30,000 mother-newborn dyads and would serve as a resource for the investigation and prediction of neonatal outcomes. An interactive website is available for independent investigators to leverage this unique dataset: https://maternal-child-health-associations.shinyapps.io/shiny_app/.

PurposeThe purpose of this study was to evaluate the agreement between paraspinal muscle composition measurements obtained from fat-water images using % fat-signal fraction (%FSF) in comparison to those obtained from T2-weighted magnetic resonance images (MRI) using a thresholding method.MethodsA sample of 35 subjects (19 females, 16 males; 40.26 ± 11.3 years old) was selected from a cohort of patients with chronic low back pain (LBP). Axial T2-weighted and IDEAL (Lava-Flex, 2 echo sequence) fat and water MR images were obtained using a 3.0 Tesla GE scanner. Multifidus, erector spinae, and psoas major muscle composition measurements were acquired bilaterally at L4-L5 and L5-S1 using both imaging sequences and related measurement methods. All measurements were obtained by the same rater, with a minimum of 7 days between each method. Intra-class correlation coefficients (ICCs) were calculated to assess intra-rater reliability. Pearson Correlation and Bland-Altman 95% limits of agreement were used to assess the agreement between both measurement methods.ResultsThe intra-rater reliability was excellent for all measurements with ICCs varying between 0.851 and 0.997. Strong positive correlations indicating a strong relationship between composition measurements were obtained from fat-water and T2-weighted images for bilateral multifidus and erector spinae muscles at both spinal levels and the right psoas major muscle at L4-L5, with correlation coefficient r ranging between 0.67 and 0.92. Bland-Altman plots for bilateral multifidus and erector spinae muscles at both levels revealed excellent agreement between the two methods, however, systematic differences between both methods were evident for psoas major fat measurements.ConclusionOur findings suggest that utilizing fat-water and T2-weighted MR images are comparable for quantifying multifidus and erector spinae muscle composition but not of the psoas major. While this suggests that both methods could be used interchangeably for the multifidus and erector spinae, further evaluation is required to expand and confirm our findings to other spinal levels.

Children and adolescents often reject healthcare interven-tions due to various experiences, expectations, cognitive abilities and understanding of medical treatment. They may respond aggressively to different approaches from healthcare staff. The likelihood of an aggressive response is particularly high when a child or adolescent is in poor physical condition, frightened, under the influence of psychopathological experiences or psychoactive substances. Managing such situations poses a complex challenge for healthcare professionals, requiring an individualized and holistic approach. The goal of healthcare is to establish a safe environment. This ensures that the child or adolescent remains uninjured and it prevents worsening of the current mental state for which they were admitted. Safety is ensured through a series of concurrent nursing interventions. The facilities at the Unit for Intensive Child and Adolescent Psychiatry are therefore technically adapted. During treatment, staff employ de-escalation techniques to create a therapeutic environment, allowing children and adolescents to express distress in a safe manner. Predictive factor scales for the occurrence of auto or heteroaggressive behavior are also used. Following the doctor's instructions, medications are administered in cases of escalating aggressive behavior, and/or in extreme cases, a specific protective measure is implemented in accordance with legal standards and nursing protocols.

Otroci in mladostniki zaradi različnih izkušenj, pričakovanj, kognitivnih sposobnosti in razumevanja zdravstvene obravnave, le to pogosto odklanjajo in se na različne pristope zdravstvenega osebja lahko odzovejo agresivno. Kadar je otrok ali mladostnik v slabem telesnem stanju, prestrašen, pod vpli-vom psihopatološkega doživljanja ali različnih psihoaktivnih snovi, je verjetnost za agresiven odziv večja. Obravnava zato zaposlenim predstavlja kompleksen izziv, ki zahteva individualen in celosten pristop. Najpomembnejši cilj zdravstvene nege je vzpostavitev varnega okolja. Ta pripomore, da otrok ali mladostnik ostane nepoškodovan, oziroma da se prepreči poslabšanje trenutnega psihičnega stanja, zaradi katerega je bil sprejet na enoto. Varnost se zagotavlja z vrsto sočasno potekajočih intervencij zdravstvene nege. Na Enoti za intenzivno otroško in adolescentno psihiatrijo so v ta namen prostori tehnično prilagojeni. Med obravnavo zaposleni uporabljajo deeskalacijske tehnike, s katerimi ustvarjajo terapevtsko okolje, ki omogoča otrokom in mladostnikom izraziti stisko na varen način. V pomoč so tudi lestvice za ugotavljanje napovednih dejavnikov za pojav avto ali heteroagresivnega vedenja. Po navodilu zdravnika se ob stopnjevanju agresivnega vedenja aplicira zdravilo in/ali v skrajnem primeru uvede posebni varovalni ukrep. Ta je definiran v Zakonu o duševnem zdravju in se izvede v skladu s Standardom zdravstvene nege in Nacionalnim protokolom Zbornice zdravstvene in babiške nege Slovenije.

BackgroundProstate cancer risk stratification using single-nucleotide polymorphisms (SNPs) demonstrates considerable promise in men of European, Asian, and African genetic ancestries, but there is still need for increased accuracy. We evaluated whether including additional SNPs in a prostate cancer polygenic hazard score (PHS) would improve associations with clinically significant prostate cancer in multi-ancestry datasets.MethodsIn total, 299 SNPs previously associated with prostate cancer were evaluated for inclusion in a new PHS, using a LASSO-regularized Cox proportional hazards model in a training dataset of 72,181 men from the PRACTICAL Consortium. The PHS model was evaluated in four testing datasets: African ancestry, Asian ancestry, and two of European Ancestry-the Cohort of Swedish Men (COSM) and the ProtecT study. Hazard ratios (HRs) were estimated to compare men with high versus low PHS for association with clinically significant, with any, and with fatal prostate cancer. The impact of genetic risk stratification on the positive predictive value (PPV) of PSA testing for clinically significant prostate cancer was also measured.ResultsThe final model (PHS290) had 290 SNPs with non-zero coefficients. Comparing, for example, the highest and lowest quintiles of PHS290, the hazard ratios (HRs) for clinically significant prostate cancer were 13.73 [95% CI: 12.43-15.16] in ProtecT, 7.07 [6.58-7.60] in African ancestry, 10.31 [9.58-11.11] in Asian ancestry, and 11.18 [10.34-12.09] in COSM. Similar results were seen for association with any and fatal prostate cancer. Without PHS stratification, the PPV of PSA testing for clinically significant prostate cancer in ProtecT was 0.12 (0.11-0.14). For the top 20% and top 5% of PHS290, the PPV of PSA testing was 0.19 (0.15-0.22) and 0.26 (0.19-0.33), respectively.ConclusionsWe demonstrate better genetic risk stratification for clinically significant prostate cancer than prior versions of PHS in multi-ancestry datasets. This is promising for implementing precision-medicine approaches to prostate cancer screening decisions in diverse populations.