Matrix Estimation for Individual Fairness

In recent years, multiple notions of algorithmic fairness have arisen. One such notion is individual fairness (IF), which requires that individuals who are similar receive similar treatment. In parallel, matrix estimation (ME) has emerged as a natural paradigm for handling noisy data with missing values. In this work, we connect the two concepts. We show that pre-processing data using ME can improve an algorithm's IF without sacrificing performance. Specifically, we show that using a popular ME method known as singular value thresholding (SVT) to pre-process the data provides a strong IF guarantee under appropriate conditions. We then show that, under analogous conditions, SVT pre-processing also yields estimates that are consistent and approximately minimax optimal. As such, the ME pre-processing step does not, under the stated conditions, increase the prediction error of the base algorithm, i.e., does not impose a fairness-performance trade-off. We verify these results on synthetic and real data.Comment: 23 pages, 3 figures, ICML 202

Protein microarray: sensitive and effective immunodetection for drug residues

<p>Abstract</p> <p>Background</p> <p>Veterinary drugs such as clenbuterol (CL) and sulfamethazine (SM₂) are low molecular weight (<1000 Da) compounds, or haptens, that are difficult to develop immunoassays due to their low immunogenicity. In this study, we conjugated the drugs to ovalbumin to increase their immunogenicity for antiserum production in rabbits and developed a protein microarray immunoassay for detection of clenbuterol and sulfamethazine. The sensitivity of this approach was then compared to traditional ELISA technique.</p> <p>Results</p> <p>The artificial antigens were spotted on microarray slides. Standard concentrations of the compounds were added to compete with the spotted antigens for binding to the antisera to determine the IC₅₀. Our microarray assay showed the IC₅₀were 39.6 ng/ml for CL and 48.8 ng/ml for SM₂, while the traditional competitive indirect-ELISA (ci-ELISA) showed the IC₅₀were 190.7 ng/ml for CL and 156.7 ng/ml for SM₂. We further validated the two methods with CL fortified chicken muscle tissues, and the protein microarray assay showed 90% recovery while the ci-ELISA had 76% recovery rate. When tested with CL-fed chicken muscle tissues, the protein microarray assay had higher sensitivity (0.9 ng/g) than the ci-ELISA (0.1 ng/g) for detection of CL residues.</p> <p>Conclusions</p> <p>The protein microarrays showed 4.5 and 3.5 times lower IC₅₀than the ci-ELISA detection for CL and SM₂, respectively, suggesting that immunodetection of small molecules with protein microarray is a better approach than the traditional ELISA technique.</p

Main and interacting effects of physical activity and sedentary time on older adults' BMI: The moderating roles of socio-demographic and environmental attributes

Objectives Our first aim was to examine the main and interacting effects of accelerometer-based sedentary time (ST) and moderate-to-vigorous physical activity (MVPA) with BMI and the likelihood of being overweight/obese in Hong Kong and Ghent (Belgium) older adults. Second, we examined whether these main associations and interactions between MVPA and ST were moderated by socio-demographics (gender, education) and objective neighbourhood attributes supposed to be associated with healthy food intake (food outlet density, neighbourhood-level SES). Finally, we determined whether the associations and interactions were generalisable across study sites. Methods Data from the ALECS (Hong Kong) and BEPAS Seniors studies (Ghent), two comparable observational studies, were used. Older adults (n = 829, 65+) provided self-reported socio-demographic information and objective MVPA and ST data using Actigraph accelerometers. Annual household income data and GIS software were used to assess neighbourhood-level SES and food outlet density. Generalised additive mixed models were conducted in R. Results ST was linearly and positively related to both weight outcomes in the overall sample, while MVPA was not. The overall-sample analyses including the two-way interaction between MVPA and ST showed no interactions between these behaviours on weight outcomes. Three site-specific findings were identified, showing distinct associations in Hong Kong compared to Ghent. Study site moderated the interaction between ST and MVPA on both weight outcomes, the interaction between education and ST on both weight outcomes and the interaction between the number of food outlets and ST on being overweight/obese. Conclusions The country-specific effects confirm the cultural dependency and complexity of the associations between PA, ST and weight outcomes. Future longitudinal international studies including older adults from multiple regions assessing PA, ST, weight outcomes and dietary intake should be encouraged. Such studies are needed to refine the recommendations regarding ST and PA in older adults in light of preventing overweight and obesity

How the perceived neighbourhood environment influences active living in older dwellers of an Asian ultra-dense metropolis

The way older adults perceive their neighbourhood environment may determine their levels of physical activity. We examined the associations of perceived neighbourhood environmental attributes with accelerometry-assessed and self-reported physical activity and sedentary time in Hong Kong Chinese older adults. In doing so, we estimated the inter-relationships among perceived environmental attributes, the mediating role of physical activity in the environment-sedentary time nexus and the moderating role of sex. We used data from the Active Lifestyle and the Environment in Chinese Seniors (ALECS) project collected on older adults (N = 909; ≥65 years) living in neighbourhoods varying in walkability and socio-economic status (71 % response rate). Self-reported physical activity and perceived neighbourhood attributes were assessed with validated questionnaires. Accelerometer-based physical activity and sedentary time were collected in 402 participants. Older adults who perceived their neighbourhood to be walkable, safe, aesthetically pleasing and equipped with public sitting facilities engaged in more physical activity and less sedentary time. Curvilinear relations of perceived residential density and activity-friendly urban design features indicated that extreme levels of density may not be optimal for older adults to adopt an active lifestyle because they do not provide sufficient space for sitting facilities and greenery and do not result in better perceptions of neighbourhood walkability when compared to areas with moderate-to-high levels of density. Creative solutions for the incorporation of greenery and public places for sitting in megacities are needed

Plant-RRBS, a bisulfite and next-generation sequencing-based methylome profiling method enriching for coverage of cytosine positions

Background: Cytosine methylation in plant genomes is important for the regulation of gene transcription and transposon activity. Genome-wide methylomes are studied upon mutation of the DNA methyltransferases, adaptation to environmental stresses or during development. However, from basic biology to breeding programs, there is a need to monitor multiple samples to determine transgenerational methylation inheritance or differential cytosine methylation. Methylome data obtained by sodium hydrogen sulfite (bisulfite)-conversion and next-generation sequencing (NGS) provide genome- wide information on cytosine methylation. However, a profiling method that detects cytosine methylation state dispersed over the genome would allow high-throughput analysis of multiple plant samples with distinct epigenetic signatures. We use specific restriction endonucleases to enrich for cytosine coverage in a bisulfite and NGS-based profiling method, which was compared to whole-genome bisulfite sequencing of the same plant material. Methods: We established an effective methylome profiling method in plants, termed plant-reduced representation bisulfite sequencing (plant-RRBS), using optimized double restriction endonuclease digestion, fragment end repair, adapter ligation, followed by bisulfite conversion, PCR amplification and NGS. We report a performant laboratory protocol and a straightforward bioinformatics data analysis pipeline for plant-RRBS, applicable for any reference-sequenced plant species. Results: As a proof of concept, methylome profiling was performed using an Oryza sativa ssp. indica pure breeding line and a derived epigenetically altered line (epiline). Plant-RRBS detects methylation levels at tens of millions of cytosine positions deduced from bisulfite conversion in multiple samples. To evaluate the method, the coverage of cytosine positions, the intra-line similarity and the differential cytosine methylation levels between the pure breeding line and the epiline were determined. Plant-RRBS reproducibly covers commonly up to one fourth of the cytosine positions in the rice genome when using MspI-DpnII within a group of five biological replicates of a line. The method predominantly detects cytosine methylation in putative promoter regions and not-annotated regions in rice. Conclusions: Plant-RRBS offers high-throughput and broad, genome- dispersed methylation detection by effective read number generation obtained from reproducibly covered genome fractions using optimized endonuclease combinations, facilitating comparative analyses of multi-sample studies for cytosine methylation and transgenerational stability in experimental material and plant breeding populations

Mortality, outcomes, costs, and use of medicines following a first heart failure hospitalization: EVOLUTION HF

Background: There are few contemporary data on outcomes, costs, and treatment following a hospitalization for heart failure (hHF) in epidemiologically representative cohorts. Objectives: The study sought to describe rehospitalizations, hospitalization costs, use of guideline-directed medical therapy (GDMT) (renin-angiotensin system inhibitors, sacubitril/valsartan, beta-blockers, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter-2 inhibitors), and mortality after hHF. Methods: EVOLUTION HF (Utilization of Dapagliflozin and Other Guideline Directed Medical Therapies in Heart Failure Patients: A Multinational Observational Study Based on Secondary Data) is an observational, longitudinal cohort study using data from electronic health records or claims data sources in Japan, Sweden, the United Kingdom, and the United States. Adults with a first hHF discharge between 2018 and 2022 were included. One-year event rates per 100 patient-years (ERs) for death and rehospitalizations (with a primary diagnosis of heart failure (HF), chronic kidney disease [CKD], myocardial infarction, stroke, or peripheral artery disease) were calculated. Hospital health care costs were cumulatively summarized. Cumulative GDMT use was assessed using Kaplan-Meier estimates. Results: Of 263,525 patients, 28% died within the first year post-hHF (ER: 28.4 [95% CI: 27.0-29.9]). Rehospitalizations were mainly driven by HF (ER: 13.6 [95% CI: 9.8-17.4]) and CKD (ER: 4.5 [95% CI: 3.6-5.3]), whereas the ERs for myocardial infarction, stroke, and peripheral artery disease were lower. Health care costs were predominantly driven by HF and CKD. Between 2020 and 2022, use of renin-angiotensin system inhibitors, sacubitril/valsartan, beta-blockers, and mineralocorticoid receptor antagonists changed little, whereas uptake of sodium-glucose cotransporter-2 inhibitors increased 2- to 7-fold. Conclusions: Incident post-hHF rehospitalization risks and costs were high, and GDMT use changed little in the year following discharge, highlighting the need to consider earlier and greater implementation of GDMT to manage risks and reduce costs

Neighbourhood environment, physical activity, quality of life and depressive symptoms in Hong Kong older adults: a protocol for an observational study

INTRODUCTION: The neighbourhood environment can assist the adoption and maintenance of an active lifestyle and affect the physical and mental well-being of older adults. The psychosocial and behavioural mechanisms through which the environment may affect physical and mental well-being are currently poorly understood. AIM: This observational study aims to examine associations between the physical and social neighbourhood environments, physical activity, quality of life and depressive symptoms in Chinese Hong Kong older adults. METHODS AND ANALYSES: An observational study of the associations of measures of the physical and social neighbourhood environment, and psychosocial factors, with physical activity, quality of life and depressive symptoms in 900 Hong Kong older adults aged 65+ years is being conducted in 2012-2016. The study involves two assessments taken 6 months apart. Neighbourhood walkability and access to destinations are objectively measured using Geographic Information Systems and environmental audits. Demographics, socioeconomic status, walking for different purposes, perceived neighbourhood and home environments, psychosocial factors, health status, social networks, depressive symptoms and quality of life are being assessed using validated interviewer-administered self-report measures and medical records. Physical functionality is being assessed using the Short Physical Performance Battery. Physical activity and sedentary behaviours are also being objectively measured in approximately 45% of participants using accelerometers over a week. Physical activity, sedentary behaviours, quality of life and depressive symptoms are being assessed twice (6 months apart) to examine seasonality effects on behaviours and their associations with quality of life and depressive symptoms. ETHICS AND DISSEMINATION: The study received ethical approval from the University of Hong Kong Human Research Ethics Committee for Non-Clinical Faculties (EA270211) and the Department of Health (Hong Kong SAR). Data are stored in a password-protected secure database for 10 years, accessible only to the named researchers. Findings will be submitted for publication in peer-reviewed journals

THOR is a targetable epigenetic biomarker with clinical implications in breast cancer

Breast cancer (BC) is the most frequently diagnosed cancer and a leading cause of death among women worldwide. Early BC is potentially curable, but the mortality rates still observed among BC patients demon‑ strate the urgent need of novel and more efective diagnostic and therapeutic options. Limitless self-renewal is a hallmark of cancer, governed by telomere maintenance. In around 95% of BC cases, this process is achieved by telom‑ erase reactivation through upregulation of the human telomerase reverse transcriptase (hTERT). The hypermethylation of a specifc region within the hTERT promoter, termed TERT hypermethylated oncological region (THOR) has been associated with increased hTERT expression in cancer. However, its biological role and clinical potential in BC have never been studied to the best of our knowledge. Therefore, we aimed to investigate the role of THOR as a biomarker and explore the functional impact of THOR methylation status in hTERT upregulation in BC.info:eu-repo/semantics/publishedVersio

Novel Genetic Variants for Cartilage Thickness and Hip Osteoarthritis

Osteoarthritis is one of the most frequent and disabling diseases of the elderly. Only few genetic variants have been identified for osteoarthritis, which is partly due to large phenotype heterogeneity. To reduce heterogeneity, we here examined cartilage thickness, one of the structural components of joint health. We conducted a genome-wide association study of minimal joint space width (mJSW), a proxy for cartilage thickness, in a discovery set of 13,013 participants from five different cohorts and replication in 8,227 individuals from seven independent cohorts. We identified five genome-wide significant (GWS, P≤5·0×10−8) SNPs annotated to four distinct loci. In addition, we found two additional loci that were significantly replicated, but results of combined meta-analysis fell just below the genome wide significance threshold. The four novel associated genetic loci were located in/near TGFA (rs2862851), PIK3R1 (rs10471753), SLBP/FGFR3 (rs2236995), and TREH/DDX6 (rs496547), while the other two (DOT1L and SUPT3H/RUNX2) were previously identified. A systematic prioritization for underlying causal genes was performed using diverse lines of evidence. Exome sequencing data (n = 2,050 individuals) indicated that there were no rare exonic variants that could explain the identified associations. In addition, TGFA, FGFR3 and PIK3R1 were differentially expressed in OA cartilage lesions versus non-lesioned cartilage in the same individuals. In conclusion, we identified four novel loci (TGFA, PIK3R1, FGFR3 and TREH) and confirmed two loci known to be associated with cartilage thickness.The identified associations were not caused by rare exonic variants. This is the first report linking TGFA to human OA, which may serve as a new target for future therapies