The Grizzly, September 18, 1987

Union to Be Bumped to Wismer • Tremper Tackles New College Art Facilities • Constitution Celebrates 200th • Monthly Film Series Started • REM: Documental Proof • Letters: Parking a Problem; Light the Lounge! • Bet They Didn\u27t Get U.C. • Ec / BA Invests • Reaching for STARs • Notes: Oct. 11 Will be a Super Sunday; Myrin Hosts Art Exhibit; Annual Fall Book Sale to Begin • Despite Hopes, Bears Lose 21-0 • Men Harriers Ace First Tryst • Runner O\u27Donohue Athlete of the Week for Record Fourth Time • Fourth Down for the NFL • Hockey Ties Place in Season Openers • Forum to Present Peace • Ursinus in Kutztown? • New Look for Myrin • Jazz Kicks off Forum Fine Arts Serieshttps://digitalcommons.ursinus.edu/grizzlynews/1192/thumbnail.jp

Differential associations of cystatin C versus creatinine‐based kidney function with risks of cardiovascular event and mortality among South Asian individuals in the UK Biobank

Background: South Asian individuals have increased cardiovascular disease and mortality risks. Reliance on creatinine‐ rather than cystatin C–based estimated glomerular filtration rate (eGFRcys) may underestimate the cardiovascular disease risk associated with chronic kidney disease. Methods and Results: Among 7738 South Asian UK BioBank participants without prevalent heart failure (HF) or atherosclerotic cardiovascular disease, we investigated associations of 4 eGFRcys and creatinine‐based estimated glomerular filtration rate categories (<45, 45–59, 60–89, and ≥90 mL/min per 1.73 m2) with risks of all‐cause mortality, incident HF, and incident atherosclerotic cardiovascular disease. The mean age was 53±8 years; 4085 (53%) were women. Compared with creatinine, cystatin C identified triple the number of participants with estimated glomerular filtration <45 (n=35 versus n=113) and 6 times the number with estimated glomerular filtration 45 to 59 (n=80 versus n=481). After multivariable adjustment, the eGFRcys 45 to 59 category was associated with higher risks of mortality (hazard ratio [HR], 2.38 [95% CI, 1.55–3.65]) and incident HF (sub‐HR [sHR], 1.87 [95% CI, 1.09–3.22]) versus the eGFRcys ≥90 category; the creatinine‐based estimated glomerular filtration rate 45 to 59 category had no significant associations with outcomes. Of the 7623 participants with creatinine‐based estimated glomerular filtration rate ≥60, 498 (6.5%) were reclassified into eGFRcys <60 categories. Participants who were reclassified as having eGFRcys <45 had higher risks of mortality (HR, 4.88 [95% CI, 2.56–9.31]), incident HF (sHR, 4.96 [95% CI, 2.21–11.16]), and incident atherosclerotic cardiovascular disease (sHR, 2.29 [95% CI, 1.14–4.61]) versus those with eGFRcys ≥90; those reclassified as having eGFRcys 45 to 59 had double the mortality risk (HR, 2.25 [95% CI, 1.45–3.51]). Conclusions: Among South Asian individuals, cystatin C identified a high‐risk chronic kidney disease population that was not detected by creatinine and enhanced estimated glomerular filtration rate–based risk stratification for mortality, incident HF, and incident atherosclerotic cardiovascular disease

Assessment of Cystatin C level for risk stratification in adults with chronic kidney disease

Importance: Kidney function is usually estimated from serum creatinine level, whereas an alternative glomerular filtration marker (cystatin C level) associates more closely with future risk of cardiovascular disease (CVD) and mortality. Objectives: To evaluate whether testing concordance between estimated glomerular filtration rates based on cystatin C (eGFRcys) and creatinine (eGFRcr) levels would improve risk stratification for future outcomes and whether estimations differ by age. Design, Setting, and Participants: A prospective population-based cohort study (UK Biobank), with participants recruited between 2006-2010 with median follow-up of 11.5 (IQR, 10.8-12.2) years; data were collected until August 31, 2020. Participants had eGFRcr greater than or equal to 45 mL/min/1.73 m2, albuminuria (albumin <30 mg/g), and no preexisting CVD or kidney failure. Exposures: Chronic kidney disease status was categorized by concordance between eGFRcr and eGFRcys across the threshold for hronic kidney disease (CKD) diagnosis (60 mL/min/1.73 m2). Main Outcomes and Measures: Ten-year probabilities of CVD, mortality, and kidney failure were assessed according to CKD status. Multivariable-adjusted Cox proportional hazards models tested associations between CVD and mortality. Area under the receiving operating curve tested discrimination of eGFRcr and eGFRcys for CVD and mortality. The Net Reclassification Index assessed the usefulness of eGFRcr and eGFRcys for CVD risk stratification. Analyses were stratified by older (age 65-73 years) and younger (age <65 years) age. Results: There were 428 402 participants: median age was 57 (IQR, 50-63) years and 237 173 (55.4%) were women. Among 76 629 older participants, there were 9335 deaths and 5205 CVD events. Among 351 773 younger participants, there were 14 776 deaths and 9328 CVD events. The 10-year probability of kidney failure was less than 0.1%. Regardless of the eGFRcr, the 10-year probabilities of CVD and mortality were low when eGFRcys was greater than or equal to 60 mL/min/1.73 m2; conversely, with eGFRcys less than 60 mL/min/1.73 m2, 10-year risks were nearly doubled in older adults and more than doubled in younger adults. Use of eGFRcys better discriminated CVD and mortality risk than eGFRcr. Across a 7.5% 10-year risk threshold for CVD, eGFRcys improved case Net Reclassification Index by 0.7% (95% CI, 0.6%-0.8%) in older people and 0.7% (95% CI, 0.7%-0.8%) in younger people; eGFRcr did not add to CVD risk estimation. Conclusions and Relevance: The findings of this study suggest that eGFRcr 45 to 59 mL/min/1.73 m2 includes a proportion of individuals at low risk and fails to capture a substantial proportion of individuals at high-risk for CVD and mortality. The eGFRcys appears to be more sensitive and specific for CVD and mortality risks in mild CKD

Cystatin C- and creatinine-based estimated GFR differences: prevalence and predictors in the UK Biobank

Rationale & objective: Large differences between estimated glomerular filtration rate (eGFR) based on cystatin C (eGFRcys) and creatinine (eGFRcr) occur commonly. A comprehensive evaluation of factors that contribute to these differences is needed to guide the interpretation of discrepant eGFR values. Study design: Cohort study. Setting & participants: 468,969 participants in the UK Biobank. Exposures: Candidate sociodemographic, lifestyle factors, comorbidities, medication usage, and physical and laboratory predictors. Outcomes: eGFRdiff, defined as eGFRcys minus eGFRcr, categorized into 3 levels: lower eGFRcys (eGFRdiff, less than -15 mL/min/1.73 m2), concordant eGFRcys and eGFRcr (eGFRdiff, -15 to < 15 mL/min/1.73 m2), and lower eGFRcr (eGFRdiff, ≥15 mL/min/1.73 m2). Analytical approach: Multinomial logistic regression models were constructed to identify predictors of lower eGFRcys or lower eGFRcr. We developed 2 prediction models comprising 375,175 participants: (1) a clinical model using clinically available variables and (2) an enriched model additionally including lifestyle variables. The models were internally validated in an additional 93,794 participants. Results: Mean ± standard deviation of eGFRcys was 88 ± 16 mL/min/1.73 m2, and eGFRcr was 95 ± 13 mL/min/1.73 m2; 25% and 5% of participants were in the lower eGFRcys and lower eGFRcr groups, respectively. In the multivariable enriched model, strong predictors of lower eGFRcys were older age, male sex, South Asian ethnicity, current smoker (vs never smoker), history of thyroid dysfunction, chronic inflammatory disease, steroid use, higher waist circumference and body fat, and urinary albumin-creatinine ratio >300 mg/g. Odds ratio estimates for these predictors were largely inverse of those in the lower eGFRcr group. The model's area under the curve was 0.75 in the validation set, with good calibration (1.00). Limitations: Limited generalizability. Conclusions: This study highlights the multitude of demographic, lifestyle, and health characteristics that are associated with large eGFRdiff. The clinical model may identify individuals who are likely to have discrepant eGFR values and thus should be prioritized for cystatin C testing

Human SNP links differential outcomes in inflammatory and infectious disease to a FOXO3-regulated pathway

The clinical course and eventual outcome, or prognosis, of complex diseases varies enormously between affected individuals. This variability critically determines the impact a disease has on a patient’s life but is very poorly understood. Here, we exploit existing genome-wide association study data to gain insight into the role of genetics in prognosis. We identify a noncoding polymorphism in FOXO3A (rs12212067: T > G) at which the minor (G) allele, despite not being associated with disease susceptibility, is associated with a milder course of Crohn’s disease and rheumatoid arthritis and with increased risk of severe malaria. Minor allele carriage is shown to limit inflammatory responses in monocytes via a FOXO3-driven pathway, which through TGFβ1 reduces production of proinflammatory cytokines, including TNFα, and increases production of anti-inflammatory cytokines, including IL-10. Thus, we uncover a shared genetic contribution to prognosis in distinct diseases that operates via a FOXO3-driven pathway modulating inflammatory responses. PAPERCLIP

Violence against children during the COVID-19 pandemic.

The coronavirus disease 2019 (COVID-19) pandemic has affected children's risk of violence in their homes, communities and online, and has compromised the ability of child protection systems to promptly detect and respond to cases of violence. However, the need to strengthen violence prevention and response services has received insufficient attention in national and global pandemic response and mitigation strategies. In this paper, we summarize the growing body of evidence on the links between the pandemic and violence against children. Drawing on the World Health Organization's INSPIRE framework to end violence against children, we illustrate how the pandemic is affecting prevention and response efforts. For each of the seven INSPIRE strategies we identify how responses to the pandemic have changed children's risk of violence. We offer ideas for how governments, policy-makers, and international and civil society organizations can address violence in the context of a protracted COVID-19 crisis. We conclude by highlighting how the current pandemic offers opportunities to improve existing child protection systems to address violence against children. We suggest enhanced multisectoral coordination across the health, education, law enforcement, housing, child and social protection sectors. Actions need to prioritize the primary prevention of violence and promote the central role of children and adolescents in decision-making and programme design processes. Finally, we stress the continued need for better data and evidence to inform violence prevention and response strategies that can be effective during and beyond the COVID-19 pandemic

Chapter 29: Restoration Priorities and Benefits within Landscapes and Catchments and Across the Amazon Basin

Restoration can be applied in many different Amazonian contexts but will be most effective at leveraging environmental and social benefits when it is prioritized across the Amazon Basin and within landscapes and catchments. Here we outline the considerations that are most relevant for planning and scaling restoration

Chapter 28: Restoration Options for the Amazon

This chapter examines site-specific opportunities and approaches for restoring terrestrial and aquatic systems, focusing on local actions and their immediate benefits. Landscape, catchment, and biome-wide considerations are addressed in Chapter 29. Conservation approaches are addressed in Chapter 2

Chapter 27: Conservation measures to counter the main threats to Amazonian biodiversity

Present-day human activities are reducing and altering Amazonian biodiversity and disrupting the functioning of terrestrial and aquatic ecosystems (Chapter 19 & 20). This chapter outlines some of the approaches required to address the main threats to the Amazon’s biodiversity and ecosystems, i.e.,deforestation, damming of rivers, mining, hunting, illegal trade, drug production and trafficking, illegal logging, overfishing, and infrastructure expansion. The role of restoration is addressed in Chapters 28 and 29