This study examines the influence of board capital on firm performance. Annual reports are used as the main sources for data collection. This study finds that firm performance decreases with gender ...diversity. Next, the interlocking directorate is not associated with firm performance. The findings would be useful to Malaysian policy-makers in deliberating the board’s role as a governance mechanism in strengthening the board structure. The results suggest selecting a director with relevant knowledge and perspective rather than simply meeting the number of board seats.
ObjectiveThere is contrasting evidence on the relationship between socioeconomic status (SES) and age-related macular degeneration (AMD), the most common cause of visual impairment (VI) in developed ...countries. This study examines the relationship between SES, cardiovascular risk factors and self-reported AMD.Methods and analysisOver 500000 people participated in the UK Biobank study from 2006 to 2019, with sociodemographic data and clinical measurements collected using standardised procedures. Visual acuity was measured in 117907 participants with VI defined as LogMAR ≤0.3. We used logistic regression to examine the cross-sectional associations between SES and self-reported AMD.ResultsSelf-reported AMD was available for 133339 participants aged 50 and older. People reporting AMD had higher academic qualifications, lower income, were unable to work due to disability, have higher BMI, diabetes and vascular heart disease after adjusting for age and sex. In a multivariable analysis, higher income was protective of AMD and economic inactivity due to disability increased the odds of AMD (2.02, 95% CI 1.13 to 3.61). Both associations were independent of cardiovascular factors, but was no longer significant after adjusting for VI.ConclusionsThe association between education, employment and household income with AMD was independent of cardiovascular risk factors.
Importance Focal segmental glomerulosclerosis (FSGS) is a common cause of end-stage kidney disease (ESKD) across the lifespan. While 10% to 15% of children and 3% of adults who develop ESKD have ...FSGS, it remains uncertain whether the natural history differs in pediatric vs adult patients, and this uncertainty contributes to the exclusion of children and adolescents in clinical trials. Objective To examine whether there are differences in the kidney health outcomes among children, adolescents, and adults with FSGS. Design, Setting, and Participants This cohort study used pooled and parallel analyses, completed July 5, 2022, from 3 complimentary data sources: (1) Nephrotic Syndrome Rare Disease Clinical Research Network (NEPTUNE); (2) FSGS clinical trial (FSGS-CT); and (3) Kidney Research Network (KRN). NEPTUNE is a multicenter US/Canada cohort study; FSGS-CT is a multicenter US/Canada clinical trial; and KRN is a multicenter US electronic health record–based registry from academic and community nephrology practices. NEPTUNE included 166 patients with incident FSGS enrolled at first kidney biopsy; FSGS-CT included 132 patients with steroid-resistant FSGS randomized to cyclosporine vs dexamethasone with mycophenolate; and KRN included 184 patients with prevalent FSGS. Data were collected from November 2004 to October 2019 and analyzed from October 2020 to July 2022. Exposures Age: children (age <13 years) vs adolescents (13-17 years) vs adults (≥18 years). Covariates of interest included sex, disease duration,APOL1genotype, urine protein–to-creatinine ratio, estimated glomerular filtration rate (eGFR), edema, serum albumin, and immunosuppressive therapy. Main Outcomes and Measures ESKD, composite outcome of ESKD or 40% decline in eGFR, and complete and/or partial remission of proteinuria. Results The study included 127 (26%) children, 102 (21%) adolescents, and 253 (52%) adults, including 215 (45%) female participants and 138 (29%) who identified as Black, 98 (20%) who identified as Hispanic, and 275 (57%) who identified as White. Overall, the median time to ESKD was 11.9 years (IQR, 5.2-19.1 years). There was no difference in ESKD risk among children vs adults (hazard ratio HR, 0.67; 95% CI, 0.43-1.03) or adolescents vs adults (HR, 0.85; 95% CI, 0.52-1.36). The median time to the composite end point was 5.7 years (IQR 1.6-15.2 years), with hazard ratio estimates for children vs adults of 1.12 (95% CI, 0.83-1.52) and adolescents vs adults of 1.06 (95% CI, 0.75-1.50). Conclusions and Relevance In this study, the association of FSGS with kidney survival and functional outcomes was comparable at all ages.
Purpose: This study examines the influence of education diversity in moderating the association between gender diversity and big data analytics investments. Design/methodology/approach: A multimethod ...approach is employed where the data (161 responses) are drawn from two quantitative data sources. The primary data are obtained from the questionnaire survey, and the secondary data are gathered from the annual reports. Multiple linear regression analysis is used as the analytical method. Findings: This study finds that gender diversity is positively and significantly associated with big data analytics investments. Next, the association between gender diversity and big data analytics investments is negatively moderated by education diversity. The association between gender diversity and big data analytics investments is weakened when the education diversity is higher. Originality: This study is one of the first to examine the intervening processes of how gender diversity affects big data analytics investments using education diversity as a moderating variable. This study is novel in its approach to providing empirical evidence and examining the moderating effect of education diversity. Practical implications: This study shows that gender diversity facilitates big data analytics investments. The findings help policymakers encourage the female director’s role in strategic decision-making. The negative moderating effect of education diversity on gender diversity and big data analytics investments association implies that firms may face challenges accessing resources. The findings help firms promote open debates and effective communication in strategic decision-making to leverage education diversity.
Frasier syndrome (FS) is a rare Mendelian form of nephrotic syndrome (NS) caused by variants which disrupt the proper splicing of WT1. This key transcription factor gene is alternatively spliced at ...exon 9 to produce 2 isoforms (“KTS+” and “KTS−”), which are normally expressed in the kidney at a ∼2:1 (KTS+:KTS−) ratio. FS results from variants that reduce this ratio by disrupting the splice donor of the KTS+ isoform. FS is extremely rare, and it is unclear whether any variants beyond the 8 already known could cause FS.
To prospectively identify other splicing-disruptive variants, we leveraged a massively parallel splicing assay. We tested every possible single nucleotide variant (n = 519) in and around WT1 exon 9 for effects upon exon inclusion and KTS+/− ratio.
Splice disruptive variants (SDVs) made up 11% of the tested point variants overall and were tightly concentrated near the canonical acceptor and the KTS+/− alternate donors. Our map successfully identified all 8 known FS or focal segmental glomerulosclerosis (FSGS) variants and 16 additional novel variants which were comparably disruptive to these known pathogenic variants. We also identified 19 variants that, conversely, increased the KTS+/KTS− ratio, of which 2 are observed in unrelated individuals with 46,XX ovotesticular disorder of sex development (46,XX OTDSD).
This splicing effect map can serve as functional evidence to guide the clinical interpretation of newly observed variants in and around WT1 exon 9.
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Childhood-onset nephrotic syndrome has a variable clinical course. Improved predictive markers of long-term outcomes in children with nephrotic syndrome are needed. This study tests the association ...between baseline urinary epidermal growth factor (uEGF) excretion and longitudinal kidney function in children with nephrotic syndrome.
The study evaluated 191 participants younger than 18 years enrolled in the Nephrotic Syndrome Study Network, including 118 with their first clinically indicated kidney biopsy (68 minimal change disease; 50 focal segmental glomerulosclerosis) and 73 with incident nephrotic syndrome without a biopsy. uEGF was measured at baseline for all participants and normalized by the urine creatinine (Cr) concentration. Renal epidermal growth factor (EGF) mRNA was measured in the tubular compartment microdissected from kidney biopsy cores from a subset of patients. Linear mixed models were used to test if baseline uEGF/Cr and EGF mRNA expression were associated with change in estimated glomerular filtration rate (eGFR) over time.
Higher uEGF/Cr at baseline was associated with slower eGFR decline during follow-up (median follow-up = 30 months). Halving of uEGF/Cr was associated with a decrease in eGFR slope of 2.0 ml/min per 1.73 m2 per year (P < 0.001) adjusted for age, race, diagnosis, baseline eGFR and proteinuria, and APOL1 genotype. In the biopsied subgroup, uEGF/Cr was correlated with EGF mRNA expression (r = 0.74; P < 0.001), but uEGF/Cr was retained over mRNA expression as the stronger predictor of eGFR slope after multivariable adjustment (decrease in eGFR slope of 1.7 ml/min per 1.73 m2 per year per log2 decrease in uEGF/Cr; P < 0.001).
uEGF/Cr may be a useful noninvasive biomarker that can assist in predicting the long-term course of kidney function in children with incident nephrotic syndrome.
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Apoptosis and cell survival are two seemingly opposing fate-determining processes that are regulated by distinct and complex signaling pathways. Caspase-8, an apical caspase, plays a pivotal ...regulatory role in initiating apoptosis. c-Src, a prototypical member of the Src family kinases (SFKs), regulates a myriad of cellular processes including cell mitogenesis, proliferation, growth and migration. Although the regulation of caspase-8 by c-Src has been suggested, the reciprocal regulation of these two seemingly opposing signaling molecules, caspase-8 and c-Src, has never been explored. To study this reciprocal regulation, we asked three questions. (1) Can active caspase-8 negatively regulate c-Src activity to allow the propagation of apoptosis? (2) Can c-Src negatively regulate caspase-8 activity to prevent the propagation of apoptosis? (3) Can caspase-8, when its enzymatic activity is inhibited, further promote c-Src activity to allow the propagation of cell survival? To address these questions, we first investigated the effect of active caspase-8 on the activation and activity of c-Src. We discovered that active caspase-8 inhibited c-Src activation and some of its downstream effectors. Next, we investigated whether c-Src could tyrosine phosphorylate caspase-8. We discovered that c-Src could phosphorylate caspase-8 at multiple tyrosine sites. We then examined whether tyrosine phosphorylated caspase-8 prevents apoptosis. We found that phosphorylation of caspase-8 at Y465 prevented its cleavage, and activity towards activating caspase-3 and towards causing cell morphological changes associated with apoptosis. Finally, we studied whether tyrosine phosphorylation of caspase-8 could further promote the activation of c-Src. We showed that phosphorylation of caspase-8 at both Y465 and Y397 resulted in the activation of c-Src and extracellular signal-regulated kinase 1/2 (Erk1/2). In conclusion, this work demonstrated the reciprocal regulation of two opposing signaling molecules, caspase-8 and c-Src. These results also suggest an elegant mechanism for a cell to commit efficiently and rapidly to a fate-determining process, either apoptosis or survival, by further suppression of the opposing signaling pathway.
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