Poisoning and envenomation linkage to evaluate outcomes and clinical variation in Australia (PAVLOVA): a longitudinal data-linkage cohort of acute poisonings, envenomations, and adverse drug reactions in New South Wales, Australia, 2011-2020.

INTRODUCTION: Poisoning is a leading cause of morbidity and mortality that is increasing in many countries. Better data are needed to understand epidemiology and outcomes of poisoning. This work describes a new poisoning data linkage cohort in New South Wales, Australia (population approximately 8 million). METHODS: This is a longitudinal health record linkage, 2011-2020, including data from: ambulance call-outs, emergency department presentations, hospital admissions, death registrations, the poisons centre, and four tertiary toxicology units. Individuals with poisoning, venomous animal/plant exposures, or adverse drug reaction events were included. RESULTS: There were 845,217 linkable events relating to 400,642 ambulance, 688,484 emergency department, 682,013 admission, 40,456 toxicology, and 11,879 death records. There were 572,841 people with events; the median age at the time of first event was 57 years, and 51.9% were female. Events leading to patient admission were most commonly adverse drug reactions (n = 511,263), intentional poisonings (n = 68,646), unintentional poisonings (n = 54,840) and animal/plant exposures (n = 11,092). Demographics varied by cause: intentional poisoning (median age 33 years, 64% female); unintentional poisoning/animals/plants (median age 43 years, 45%); and adverse drug reactions (median age 70 years, 54%). Adolescent females had highest rates of intentional poisoning, while unintentional poisoning had a bimodal distribution, highest in children <5 years old and males aged 20 to 50 years. Substance use disorders were documented comorbidities for 44% of intentional poisoning, 29% of unintentional poisoning, and 13% of adverse drug reaction-related admissions; mood disorders were documented for 54%, 17% and 10% of these admissions, respectively. DISCUSSION: Poisonings and hospitalised adverse drug reactions are common in New South Wales, affecting approximately 8% of the population in 10 years. This linkage improves understanding of poisoning risks and outcomes in Australia. CONCLUSIONS: This novel data linkage provides a unique opportunity to study poisoning across multiple settings for an individual over an extended period.

Alzheimer's Disease Linkage to Real-World Evidence (AD-LINE) Study: Linking Claims Data to Phase 3 GRADUATE Study of Gantenerumab.

BACKGROUND: Linking data from clinical trials and real-world claims may improve the robustness of trial data and provide information on the health, economic, and societal impacts of a disease. OBJECTIVE: To report on the feasibility of linking trial data to Medicare claims data in early symptomatic Alzheimer's disease (AD) in the US. DESIGN AND SETTING: Alzheimer's Disease Linkage to Real-World Evidence (AD-LINE) was a noninterventional cohort study that included participants recruited from the GRADUATE program whose trial data were linked to their Medicare claims. PARTICIPANTS: AD-LINE participants were 66 years and older with early symptomatic AD (ie, mild cognitive impairment [MCI] due to AD or mild AD dementia) and were enrolled in the GRADUATE program and a Medicare fee-for-service or Medicare Advantage plan. MEASUREMENTS: The Centers for Medicare and Medicaid Services linked participants' clinical trial identifiers to their Medicare beneficiary identifiers using a deterministic, exact matching process. Demographics and clinical characteristics of the AD-LINE cohort at baseline were collected. Outcomes measured in this study included healthcare resource utilization derived from Medicare claims data. RESULTS: In total, 147 participants across 21 US sites were invited to participate and 111 provided informed consent. Of those, 61 patients had linkable data (ie, Medicare beneficiary identifier), Medicare Parts A/B enrollment, and no health maintenance organization (HMO) enrollment in the year before trial entry. Of the 61 participants whose data were analyzed in this study, 30 had MCI due to AD and 31 had mild AD dementia. Participants in the MCI due to AD group had more healthcare resource utilization on average in the baseline period than those in the mild AD dementia group (29.9 [SD, 20.9] vs 24.5 claims [SD, 12.3]). In an ad hoc analysis, a relatively high concordance (85.3%) was seen between the rates of clinically confirmed AD diagnosis and evidence of AD diagnosis in claims data. CONCLUSION: This linkage process may serve as a proof of concept for researchers interested in linking clinical trial and real-world claims data. The lessons learned from AD-LINE and innovation of data linkage approaches may encourage key stakeholders to link data in the future.

Technically feasible solutions to challenges in preimplantation genetic testing for thalassemia: experiences of multiple centers between 2019 and 2022.

PURPOSE: In clinical practice, the success of preimplantation genetic testing for monogenic diseases (PGT-M) for thalassemia was hindered by the absence of probands, incomplete family members, or failure in detecting embryonic gene mutation sites. This study aimed to address these issues. METHODS: This retrospective study included 342 couples undergoing PGT-M for α- or ß-thalassemia at three reproductive medicine centers from 2019 to 2022. Various methods were used to construct parental haplotypes. A total of 1778 embryos were analyzed and selected for transfer based on chromosomal ploidy and PGT-M results. Follow-up involved amniocentesis results and clinical outcomes. RESULTS: Haplotypes were established using DNA samples from probands or parents, as well as sibling blood samples, single sperm, and affected embryos, achieving an overall success rate was 99.4% (340/342). For α-thalassemia and ß-thalassemia, the concordance between embryo single nucleotide polymorphism (SNP) haplotype analysis results and mutation loci detection results was 93.8% (1011/1078) and 98.2% (538/548), respectively. Multiple annealing and looping-based amplification cycles (MALBAC) showed a higher whole genome amplification success rate than multiple displacement amplification (MDA) (98.8% (1031/1044) vs. 96.2% (703/731), p < 0.001). Amniocentesis confirmed PGT-M outcomes in 100% of cases followed up (99/99). CONCLUSION: This study summarizes feasible solutions to various challenging scenarios encountered in PGT-M for thalassemia, providing valuable insights to enhance success rate of PGT-M in clinical practice.

Genetic association of FTO gene polymorphisms with obesity and its related phenotypes: A case-control study.

Introduction: FTO gene belongs to the non-heme Fe (II) and 2 oxoglutarate-dependent dioxygenase superfamily. Polymorphisms within the first intron of the FTO gene have been examined across various populations, yielding disparate findings.The present study aimed to determine the impact of two intronic polymorphisms FTO 30685T/G (rs17817449) and -23525T/A (rs9939609) on the risk of obesity in Punjab, India. Methods: Genotypic and biochemical analysis were done for 671 unrelated participants (obese=333 and non-obese=338) (age≥18 years). Genotyping of the polymorphisms was done by PCR-RFLP method. However, 50% of the samples were sequenced by Sanger sequencing. Results: Both the FTO variants 30685 (TT vs GG: odds ratio (OR), 2.30; 95% confidence interval (CI), 1.39-3.79) and -23525 (TT vs AA: odds ratio (OR), 2.78; 95% confidence interval (CI), 1.37-5.64) showed substantial risk towards obesity by conferring it 2 times and 3 times, respectively. The analysis by logistic regression showed a significant association for both the variants 30685T/G (rs17817449) and -23525T/A (rs9939609) (OR=2.29; 95%CI: 1.47-3.57) and (OR=5.25; 95% CI: 2.68-10.28) under the recessive genetic model, respectively. The haplotype combination TA (30685; -23525) develops a 4 times risk for obesity (P=0.0001). Among obese, the G allele of 30685T/G and A- allele of -23525T/A showed variance in Body mass index (BMI), waist circumference (WC), waist-to-height ratio(WHtR), systolic blood pressure (SBP), diastolic blood pressure (DBP) and triglyceride(TG). Conclusion: The present investigation indicated that both the FTO 30685T/G (rs17817449) and -23525T/A (rs9939609) polymorphisms have a key impact on an individual's vulnerability to obesity in this population.

Establishing the Vaccine Safety Health Link: A large, linked data resource for the investigation of vaccine safety concerns.

OBJECTIVE: Post-licensure vaccine safety surveillance of adverse events following immunisation is critical to ensure public safety and confidence in vaccines. This paper aims to describe the governance structure and data linkage methodology behind the establishment of the largest linked vaccine safety surveillance data resource in Australia - The Vaccine Safety Health Link (VSHL). METHODS: The Vaccine Safety Health Link contains linked records from the Australian Immunisation Register with records from hospital, perinatal, mortality, and notifiable disease datasets in near real-time. Linkage is done by the Centre for Victorian Data Linkage who receive the datasets in an identifiable format which then undergo standardisation, enrichment, linkage, quality assurance and de-identification, prior to being supplied for analysis. RESULTS: The VSHL data resource allows sensitive and rapid analysis of a broad spectrum of suspected adverse events to ensure the safety of all vaccines administered. It is also used to refute spurious concerns where no associations are found, upholding trust, and maintaining vaccine confidence. CONCLUSIONS: The Vaccine Safety Health Link's surveillance design complements existing vaccine safety surveillance methods. Challenges encountered and lessons learnt using Vaccine Safety Health Link would benefit linkage projects globally. IMPLICATIONS FOR PUBLIC HEALTH: In its first two years, The Vaccine Safety Health Link has been used for 14 vaccine safety investigations. Studies into these conditions would not have otherwise been possible. The Vaccine Safety Health Link also partners with the Global Vaccine Data Network™ for approved collaborative studies with a combined population of over 300 million people.

Genomic changes and stabilization following homoploid hybrid speciation of the Oxford ragwort Senecio squalidus.

Oxford ragwort (Senecio squalidus) is one of only two homoploid hybrid species known to have originated very recently, so it is a unique model for determining genomic changes and stabilization following homoploid hybrid speciation. Here, we provide a chromosome-level genome assembly of S. squalidus with 95% of the assembly contained in the 10 longest scaffolds, corresponding to its haploid chromosome number. We annotated 30,249 protein-coding genes and estimated that ∼62% of the genome consists of repetitive elements. We then characterized genome-wide patterns of linkage disequilibrium, polymorphism, and divergence in S. squalidus and its two parental species, finding that (1) linkage disequilibrium is highly heterogeneous, with a region on chromosome 4 showing increased values across all three species but especially in S. squalidus; (2) regions harboring genetic incompatibilities between the two parental species tend to be large, show reduced recombination, and have lower polymorphism in S. squalidus; (3) the two parental species have an unequal contribution (70:30) to the genome of S. squalidus, with long blocks of parent-specific ancestry supporting a very rapid stabilization of the hybrid lineage after hybrid formation; and (4) genomic regions with major parent ancestry exhibit an overrepresentation of loci with evidence for divergent selection occurring between the two parental species on Mount Etna. Our results show that both genetic incompatibilities and natural selection play a role in determining genome-wide reorganization following hybrid speciation and that patterns associated with homoploid hybrid speciation-typically seen in much older systems-can evolve very quickly following hybridization.

An integrated georeferenced dataset of public investments for soil defence in Italy.

The dataset collects and harmonizes financial data about public works in Italy, focusing on soil defence investments. The data are sourced from three distinct platforms: the Italian Ministry of Economics and Finance's open data platform OpenBDAP, the OpenCoesione website, concerned with interventions framed in cohesion policies financed by additional resources from the European and national budgets, and the ReNDiS database, provided by the Italian Institute for Environmental Protection and Research (ISPRA), that exclusively gathers information about public works in soil defence. The data records belonging to these three sources are linked by a unique project code (CUP), ensuring that there is no duplication of data. The OpenBDAP and OpenCoesione repositories report financial variables classified into various funds. In contrast, the ReNDiS database only provides the total amount of financial resources allocated to each intervention. Consequently, the merged dataset consolidates these financial variables into one, representing the total investment amount. For the first two databases this aggregate is derived by summing the financial flows from the different funds. Geographical referencing has been added to each intervention and each financial observation is associated with an Italian municipality. The database includes information on the region, province, and municipality for each record. Each database entry has also been equipped with the coordinates of the municipality's centroid and with the polygonal shape of the municipality area. Overall, the merged dataset encompasses 28 variables reporting three descriptive variables, one financial variable representing the total amount of financial resources, six geographic variables representing the codes and names of regions, provinces, and municipalities, sixteen variables referring to key dates of the process of public works, two geographical references variables respectively representing the centroids and the shape polygons of the municipality. This comprehensive dataset allows to analyse the spatial distribution of the resources allocated to soil defence investments. It offers insights to policymakers striving to allocate resources more efficiently, thereby fostering sustainable land management practices and ensuring the long-term health of the Italian ecosystems. The dataset can be complemented with additional information related to various concomitant aspects such as those pertaining to the environmental and socio-economic fields. This integration allows for broad analysis of the relationships between soil defence efforts and surrounding environmental and socio-economic contexts.

Causal role of peripheral immune cells in epilepsy: A large-scale genetic correlation study.

BACKGROUND: While an increasing number of researchers have focused on the correlation between the immune system and epilepsy, the precise causal role of immune cells in epilepsy continues to elude scientific understanding. The aim of the study was to examine the causal relationship between peripheral immune phenotypes and epilepsy. METHODS: Mendelian randomization (MR) analysis and linkage disequilibrium score regression (LDSC) were utilized to determine the causal relationship between 731 immune cell traits and various types of epilepsy in this study. RESULTS: LDSC revealed that 80 immunophenotypes showed genetic correlation with epilepsy, including 58 immunophenotypes associated with a single type of epilepsy (72.5 %),14 immunophenotypes associated with two types of epilepsy (17.5 %),7 immunophenotypes with 3 types of epilepsy (8.75 %) and 1 immunophenotype with 5 types of epilepsy (1.25 %). Although none of the types of epilepsy had a statistically significant effect on immunophenotypes, it is noteworthy that the MR revealed the protective effects of five immunophenotypes on epilepsy: CD45RA+CD8br AC (OR:0.86, 95 %CI:0.80-0.93), FSC-A on myeloid DC (OR:0.95, 95 %CI:0.91-0.98）, CM CD8br AC (OR:0.69, 95 %CI:0.59--0.82), CD33 on CD66b++ Myeloid cell (OR:0.88, 95 %CI:0.83-0.93) and CD127 on CD28- CD8br (OR:0.97, 95 %CI:0.95-0.98). Additionally, harmful effects were observed for two immunophenotypes on epilepsy:CD4 Treg %CD4 (OR:1.04, 95 %CI:1.02-1.06) and SSC-A on plasmacytoid DC (OR:1.01, 95 %CI:1.00-1.02). CONCLUSION: Our research has demonstrated the causal connections between immune cells and epilepsy, potentially providing valuable insights for future clinical studies.

No bidirectional association between serum 25-hydroxyvitamin D and erectile dysfunction: Mendelian randomization and genetic association studies.

Background: The causal relationship between the level of serum 25-hydroxyvitamin D [25(OH)D] and the risk of erectile dysfunction (ED) is still unclear. Aim: We tried to determine the causal relationship between the level of serum 25(OH)D and ED risk. Methods: In this study, we used genome-wide association study data from the UK Biobank to analyse the relationship between serum 25(OH)D (as the exposure) and ED (as the outcome). Linkage disequilibrium score regression (LDSC) was used to assess the genetic correlation between 2 traits. The CAUSE (Causal Analysis using Summary Effect estimates) method and Mendelian randomization (MR) were employed to evaluate the bidirectional causal relationship. The MRlap method was utilized to assess the impact of sample overlap on the results. To assess potential heterogeneity and horizontal pleiotropy, we utilized methods such as MR-Egger, MR-PRESSO (Mendelian Randomization Pleiotropy Residual Sum and Outlier), weighted median, and others. Outcomes: The primary outcome was defined as self or physician-reported ED, or using oral ED medication, or a history of surgery related to ED. Results: The LDSC analysis did not reveal a significant genetic correlation between serum 25(OH)D and ED (rg = 0.2787, P = .3536). Additionally, the CAUSE (P value testing that the causal model is a better fit >.05) and MR analyses (odds ratio, 0.8951; 95% confidence interval, 0.7480-1.0710; P = .2260) did not support a causal relationship between 25(OH)D and ED, and our study did not detect any heterogeneity and pleiotropy. Clinical implications: This study provides evidence on whether vitamin D needs to be ingested to prevent or treat ED. Strengths and limitations: We used LDSC and MR to avoid bias. However, the population in this study was limited to European ancestry. Conclusion: No causal relationship was found between 25(OH)D and ED.

Linkability measures to assess the data characteristics for record linkage.

OBJECTIVES: Accurate record linkage (RL) enables consolidation and de-duplication of data from disparate datasets, resulting in more comprehensive and complete patient data. However, conducting RL with low quality or unfit data can waste institutional resources on poor linkage results. We aim to evaluate data linkability to enhance the effectiveness of record linkage. MATERIALS AND METHODS: We describe a systematic approach using data fitness ("linkability") measures, defined as metrics that characterize the availability, discriminatory power, and distribution of potential variables for RL. We used the isolation forest algorithm to detect abnormal linkability values from 188 sites in Indiana and Colorado, and manually reviewed the data to understand the cause of anomalies. RESULT: We calculated 10 linkability metrics for 11 potential linkage variables (LVs) across 188 sites for a total of 20 680 linkability metrics. Potential LVs such as first name, last name, date of birth, and sex have low missing data rates, while Social Security Number vary widely in completeness among all sites. We investigated anomalous linkability values to identify the cause of many records having identical values in certain LVs, issues with placeholder values disguising data missingness, and orphan records. DISCUSSION: The fitness of a variable for RL is determined by its availability and its discriminatory power to uniquely identify individuals. These results highlight the need for awareness of placeholder values, which inform the selection of variables and methods to optimize RL performance. CONCLUSION: Evaluating linkability measures using the isolation forest algorithm to highlight anomalous findings can help identify fitness-for-use issues that must be addressed before initiating the RL process to ensure high-quality linkage outcomes.

A theoretical framework for linking hospitals longitudinally: demonstrated using German Hospital Quality Reports 2016-2020.

BACKGROUND: In longitudinal health services research, hospital identification using an ID code, often supplemented with several additional variables, lacks clarity regarding representativeness and variable influence. This study presents an operational method for hospital identity delimitation and a novel longitudinal identification approach, demonstrated using a case study. METHODS: The conceptualisation considers hospitals as evolving entities, identifying "similar enough" pairs across two time points using an automated similarity matrix. This method comprises key variable selection, similarity scoring, and tolerance threshold definition, tailored to data source characteristics and clinical relevance. This linking method is tested by applying the identification of minimum caseload requirements-related German hospitals, utilizing German Hospital Quality Reports (GHQR) 2016-2020. RESULTS: The method achieved a success rate (min: 97.9% - max: 100%, mean: 99.9%) surpassing traditional hospital ID-code linkage (min: 91.5% - max: 98.8%, mean: 96.6%), with a remarkable 99% reduction in manual work through automation. CONCLUSIONS: This method, rooted in a comprehensive understanding of hospital identities, offers an operational, automated, and customisable process serving diverse clinical topics. This approach has the advantage of simultaneously considering multiple variables and systematically observing temporal changes in hospitals. It also enhances the precision and efficiency of longitudinal hospital identification in health services research.

Using latent variable modelling to identify etiological heterogeneity in preterm delivery.

AIMS: To identify a subgroup of mothers at high risk of preterm delivery, defined by empirical classes of multimorbidity and recurrence across three consecutive births. METHODS: The data were extracted from the perinatal data collection (PDC) of all inpatient live births (n = 435 912) occurring in the Australian state of Queensland between January 2009 and December 2015. Within this data, a total of 7714 primiparous mothers delivered three consecutive singleton live births (total births = 23 142), and comprise the sample for all analyses. RESULTS: The LCA indicated a four-class solution fit the data best at each time point, including (i) a 'normative' or healthy class with little morbidity (including >80% of the sample at each birth); (ii) a preterm, high morbidity class (<2% of the sample); (ii) a delivery morbidity class (4-8% of the sample); and (iii) preterm, low morbidity class (5-6% of the sample). Each group exhibited unique and consistent associations with maternal and pregnancy-related factors across births. After accounting for these factors, the high morbidity class and preterm, low morbidity class strongly predicted these same classes across consecutive births, and from birth 1 to birth 3 (second-order transition). CONCLUSIONS: A small but highly morbid class of neonatal deliveries emerged, exhibiting strong continuity across consecutive births (odds ratios >10), independent of a range of maternal and pregnancy-related factors. This group of women, if subject to further investigation, could provide valuable insight into the aetiology of prematurity and associated morbidity, perhaps providing information to improve birth outcomes among all women.

Effect of a Male-Targeted Digital Decision Support Application Aimed at Increasing Linkage to HIV Care Among Men: Findings from the HITS Cluster Randomized Clinical Trial in Rural South Africa.

Linkage to HIV care remains suboptimal among men. We investigated the effectiveness of a male-targeted HIV-specific decision support app, Empowering People through Informed Choices for HIV (EPIC-HIV), on increasing linkage to HIV care among men in rural South Africa. Home-Based Intervention to Test and Start (HITS) was a multi-component cluster-randomized controlled trial conducted among 45 communities in uMkhanyakude, KwaZulu-Natal. The development of EPIC-HIV was guided by self-determination theory and human-computer interaction design to increase intrinsic motivation to seek HIV testing and care among men. EPIC-HIV was offered in two stages: EPIC-HIV 1 at the time of home-based HIV counseling and testing (HBHCT), and EPIC-HIV 2 at 1 month after a positive HIV diagnosis if not linked to care. Sixteen communities were randomly assigned to the arms to receive EPIC-HIV, and 29 communities to the arms without EPIC-HIV. Among all eligible men, we compared linkage to care (initiation or resumption of antiretroviral therapy after > 3 months of care interruption) at local clinics within 1 year of a home visit, ascertained from individual clinical records. Intention-to-treat analysis was performed using modified Poisson regression with adjustment for receiving another intervention (i.e., financial incentives) and clustering at the community level. We also conducted a satisfaction survey for EPIC-HIV 2. A total of 13,894 men were eligible (i.e., aged ≥ 15 years and resident in the 45 communities). The mean age was 34.6 (±16.8) years, and 65% were married or in an informal union. Overall, 20.7% received HBHCT, resulting in 122 HIV-positive and 6 discordant tests. Among these, 54 men linked to care within 1 year after HBHCT. Additionally, of the 13,765 eligible participants who did not receive HBHCT or received HIV-negative results, 301 men linked to care within 1 year. Overall, only 13 men received EPIC-HIV 2. The proportion of linkage to care did not differ between the arms randomized to EPIC-HIV and those without EPIC-HIV (adjusted risk ratio = 1.05; 95% CI:0.86-1.29). All 13 men who used EPIC-HIV 2 reported the app was acceptable, user-friendly, and useful for getting information on HIV testing and treatment. The reach was low, although the acceptability and usability of the app were very high among those who engaged with it. Enhanced digital support applications could form part of interventions to increase knowledge of HIV treatment among men. Clinical Trial Number: ClinicalTrials.gov # NCT03757104.

ON BLOCKWISE AND REFERENCE PANEL-BASED ESTIMATORS FOR GENETIC DATA PREDICTION IN HIGH DIMENSIONS.

Genetic prediction holds immense promise for translating genetic discoveries into medical advances. As the high-dimensional covariance matrix (or the linkage disequilibrium (LD) pattern) of genetic variants often presents a block-diagonal structure, numerous methods account for the dependence among variants in predetermined local LD blocks. Moreover, due to privacy considerations and data protection concerns, genetic variant dependence in each LD block is typically estimated from external reference panels rather than the original training data set. This paper presents a unified analysis of blockwise and reference panel-based estimators in a high-dimensional prediction framework without sparsity restrictions. We find that, surprisingly, even when the covariance matrix has a block-diagonal structure with well-defined boundaries, blockwise estimation methods adjusting for local dependence can be substantially less accurate than methods controlling for the whole covariance matrix. Further, estimation methods built on the original training data set and external reference panels are likely to have varying performance in high dimensions, which may reflect the cost of having only access to summary level data from the training data set. This analysis is based on novel results in random matrix theory for block-diagonal covariance matrix. We numerically evaluate our results using extensive simulations and real data analysis in the UK Biobank.

Genotype selection identified elite lines through quantitative trait loci mapping of agronomically important traits in wheat.

Wheat is one of the most important staple foods in the world. Genetic characterization of wheat agronomically important traits is crucial for yield improvement through molecular breeding. In this study, a recombinant inbred line (RIL) population was developed by crossing a local adapted high yield variety Jimai 22 (JM22) with an external variety Cunmai no.1 (CM1). A high-density genetic map containing 7,359 single nucleotide polymorphism (SNP) markers was constructed. Quantitative trait loci (QTL) mapping identified 61 QTL for eight yield-related traits under six environments (years). Among them, 17 QTL affecting spike number per plant, grain number per spike and thousand grain weight showed high predictability for theoretical yield per plant (TYP), of which, 12 QTL alleles positively contributed to TYP. Nine promising candidate genes for seven of the 12 QTL were identified including three known wheat genes and six rice orthologs. Four elite lines with TYP increased by 5.6%-15.2% were identified through genotype selection which carried 7-9 favorable alleles from JM22 and 2-3 favorable alleles from CM1 of the 12 QTL. Moreover, the linked SNPs of the 12 QTL were converted to high-throughput kompetitive allele-specific PCR (KASP) markers and validated in the population. The mapped QTL, identified promising candidate genes, developed elite lines and KASP markers are highly valuable in future genotype selection to improve wheat yield. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01496-3.

Dealing With Assumptions and Sampling Bias in the Estimation of Effective Population Size: A Case Study in an Amphibian Population.

Accurately estimating effective population size (N e) is essential for understanding evolutionary processes and guiding conservation efforts. This study investigates N e estimation methods in spatially structured populations using a population of moor frog (Rana arvalis) as a case study. We assessed the behaviour of N e estimates derived from the linkage disequilibrium (LD) method as we changed the spatial configuration of samples. Moor frog eggs were sampled from 25 breeding patches (i.e., separate vernal ponds, ditches or parts of larger fens) within a single population, revealing an isolation-by-distance pattern and a local spatial genetic structure. Varying buffer sizes around each patch were used to examine the impact of sampling window size on the estimation of effective number of breeders (N b). Our results indicate a downward bias in LD N b estimates with increasing buffer size, suggesting an underestimation of N b. The observed bias is attributed to LD resulting from including genetically divergent individuals (mixture-LD) confounding LD due to drift. This emphasises the significance of considering even subtle spatial genetic patterns. The implications of these findings are discussed, emphasising the need to account for spatial genetic structure to accurately assess population viability and inform conservation efforts. This study contributes to our understanding of the challenges associated with N e estimation in spatially structured populations and underscores the importance of refining methodologies to address population-specific spatial dynamics for effective conservation planning and management.

Trajectories in mammographic breast screening participation in middle-age overweight and obese women: A retrospective cohort study using linked data.

OBJECTIVES: Despite the established benefits and availability of mammographic breast screening, participation rates remain suboptimal. Women with higher BMIs may not screen regularly, despite being at increased risk of postmenopausal breast cancer and worse outcomes. This study investigated the association between prospective changes in BMI and longitudinal adherence to mammographic screening among women with overweight or obesity. METHODS: Retrospective cohort study of women (N = 2822) participating in the Australian Longitudinal Study on Women's Health with an average follow-up of 20 years, with screening participation enumerated via BreastScreen NSW, Australia clinical records over the period 1996-2016. Association between BMI and subsequent adherence to screening was investigated in a series of marginal structural models, incorporating a time variant/invariant socio-demographic, clinical, and health behaviour confounders. Models were also stratified by a proxy measure of socio-economic status (education). RESULTS: Participants with overweight/obesity were less adherent to mammography screening, compared to healthy/underweight participants (OR=1.29, 95 % CI=1.07, 1.55). The association between overweight/obesity and non-adherence was higher among those who ever had private health insurance (OR=1.30, 95 % CI=1.05, 1.61) compared to those who never had private health insurance and among those with lower educational background (OR=1.38, 95 % CI=1.08, 1.75) compared to those with higher educational background. CONCLUSIONS: Long-term impacts on screening participation exist among women with higher BMI, who are less likely to participate in routinely organised breast screening. Women with a higher BMI should be a focus of efforts to improve breast screening participation, particularly given their increased risk of breast cancer and association of higher BMI with worse breast cancer outcomes among older women.

Local adaptation can cause both peaks and troughs in nucleotide diversity within populations.

The amount of standing variation present within populations is a fundamental quantity of interest in population genetics, commonly represented by calculating the average number of differences between pairs of nucleotide sequences (nucleotide diversity, π). It is well understood that both background and positive selection can cause reductions in nucleotide diversity, but less clear how local adaptation affects it. Depending on the assumptions and parameters, some theoretical studies have emphasized how local adaptation can reduce nucleotide diversity, while others have shown that it can increase it. Here, we explore how local adaptation shapes genome-wide patterns in within-population nucleotide diversity, extending previous work to study the effects of polygenic adaptation, genotypic redundancy, and population structure. We show that local adaptation produces two very different patterns depending on the relative strengths of migration and selection, either markedly decreasing or increasing within-population diversity at linked sites at equilibrium. At low migration, regions of depleted diversity can extend large distances from the causal locus, with substantially more diversity eroded than expected with background selection. With higher migration, peaks occur over much smaller genomic distances but with much larger magnitude changes in diversity. Across spatially extended environmental gradients, both patterns can be found within a single species, with increases in diversity at the center of the range and decreases towards the periphery. Our results demonstrate that there is no universal diagnostic signature of local adaptation based on within-population nucleotide diversity, so it will not be broadly useful for explaining increased FST. However, given that neither background nor positive selection inflate diversity, when peaks are found they suggest local adaptation may be acting on a causal allele in the region.

System interoperability and data linkage in the era of health information management: A bibliometric analysis.

Background: Across the world, health data generation is growing exponentially. The continuous rise of new and diversified technology to obtain and handle health data places health information management and governance under pressure. Lack of data linkage and interoperability between systems undermines best efforts to optimise integrated health information technology solutions. Objective: This research aimed to provide a bibliometric overview of the role of interoperability and linkage in health data management and governance. Method: Data were acquired by entering selected search queries into Google Scholar, PubMed, and Web of Science databases and bibliometric data obtained were then imported to Endnote and checked for duplicates. The refined data were exported to Excel, where several levels of filtration were applied to obtain the final sample. These sample data were analysed using Microsoft Excel (Microsoft Corporation, Washington, USA), WORDSTAT (Provalis Research, Montreal, Canada) and VOSviewer software (Leiden University, Leiden, Netherlands). Results: The literature sample was retrieved from 3799 unique results and consisted of 63 articles, present in 45 different publications, both evaluated by two specific in-house global impact rankings. Through VOSviewer, three main clusters were identified: (i) e-health information stakeholder needs; (ii) e-health information quality assessment; and (iii) e-health information technological governance trends. A residual correlation between interoperability and linkage studies in the sample was also found. Conclusion: Assessing stakeholders' needs is crucial for establishing an efficient and effective health information system. Further and diversified research is needed to assess the integrated placement of interoperability and linkage in health information management and governance. Implications: This research has provided valuable managerial and theoretical contributions to optimise system interoperability and data linkage within health information research and information technology solutions.

Genetic liability to higher frailty index may increase the risk of ophthalmic disease.

PURPOSE: Frailty and age-related eye diseases are common in older people; however, whether there is a causal link remains unknown. We aimed to explore the causal associations between the frailty index (FI) and ophthalmic traits and identify modifiable mediators. METHODS: Linkage disequilibrium score regression and two-sample Mendelian randomization were applied to identify genetic correlations and causal associations between FI and ophthalmic traits. Summary data for FI was obtained from a genome-wide association study that included 175,226 individuals of European ancestry. Summary-level statistics for ophthalmic traits were obtained from relative GWASs. Summary-level data for cardiovascular risk factors, inflammatory biomarkers, and the central nervous system were used to identify the possible mediators. RESULTS: FI had a significant genetic correlation with 10 ophthalmic traits. Per SD increment of FI, the odds ratio was 1.329 (95% CI, 1.123, 1.573; P = 9.5 × 10-4) for cataracts, 1.825 (95% CI, 1.115, 2.986; P = 0.016) for keratitis, 1.798 (95% CI, 1.039, 3.11; P = 0.036) for disorders of vitreous body and 1.478 (95% CI, 1.005, 2.173; P = 0.046) for disorders of sclera, cornea, iris and ciliary body. The MR effect estimates of FI on ophthalmic traits were attenuated after adjusting for mental disorders, type 2 diabetes, triglyceride, and interleukin-8 (IL-8) levels. CONCLUSION: This study reports a genetic correlation and causal association between FI and ophthalmic traits, in which mental disorders, type 2 diabetes, triglycerides, and IL-8 may play a mediating role. These findings highlight a possible method to reduce the risk of FI-related ophthalmic diseases.