The Ursinus Weekly, October 28, 1963

69 women pledge sororities at bid signing Saturday • Class of 1966 to sell slaves at Bazaar • Annual Founders Day November 3; Five honorary degrees to be awarded • Navy debate team bows UC 31-29 • Young Democrats begin activities • Halloween reading night October 30 • Indians warpath at Jr. turnabout • Pre-med society hears Dr. French • Biggest bargain of the year: 1964 Ruby sales begin • $8500 scholarships available for Univ. of Hawaii • Editorial: Which way out?; Action, please • Letters to the editor • Conservatism reconsidered: Spencer\u27s article decried • Human understanding theme of presentation • Fundamental need unfilled • Penna. seeks librarians • Groups schedule career conf. • Federal service exam November 23 • Greek gleanings • Kaffee klatsch: Foreign students reception • Bears topple Swarthmore on fine team effort, 14-6 • Player of the week • Soccer team bows twice • Hockey team still undefeatedhttps://digitalcommons.ursinus.edu/weekly/1255/thumbnail.jp

Perceived physical fatigability predicts all-cause mortality in older adults

BACKGROUND: Perceived physical fatigability is highly prevalent in older adults and associated with mobility decline and other health consequences. We examined the prognostic value of perceived physical fatigability as an independent predictor of risk of death among older adults. METHODS: Participants (N = 2 906), mean age 73.5 [SD, 10.4] years, 54.2% women, 99.7% white enrolled in the Long Life Family Study, were assessed at Visit 2 (2014-2017) with 2.7 [SD, 1.0] years follow-up. The Pittsburgh Fatigability Scale (PFS), a 10-item, self-administered validated questionnaire (score range 0-50, higher = greater fatigability) measured perceived physical fatigability at Visit 2. Deaths post-Visit 2 through December 31, 2019 were identified by family members notifying field centers, reporting during another family member\u27s annual phone follow-up, an obituary, or Civil Registration System (Denmark). We censored all other participants at their last contact. Cox proportional hazard models predicted mortality by fatigability severity, adjusted for family relatedness and other covariates. RESULTS: Age-adjusted PFS Physical scores were higher for those who died (19.1 [SE, 0.8]) compared with alive (12.2, [SE, 0.4]) overall, as well as across age strata (p \u3c .001), except for those 60-69 years (p = .79). Participants with the most severe fatigability (PFS Physical scores ≥ 25) were over twice as likely to die (hazard ratio, 2.33 [95% CI, 1.65-3.28]) compared with those who had less severe fatigability (PFS Physical scores \u3c 25) after adjustment. CONCLUSIONS: Our work underscores the utility of the PFS as a novel patient-reported prognostic indicator of phenotypic aging that captures both overt and underlying disease burden that predicts death

Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or  ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention

Travel burden and clinical presentation of retinoblastoma: analysis of 1024 patients from 43 African countries and 518 patients from 40 European countries

BACKGROUND: The travel distance from home to a treatment centre, which may impact the stage at diagnosis, has not been investigated for retinoblastoma, the most common childhood eye cancer. We aimed to investigate the travel burden and its impact on clinical presentation in a large sample of patients with retinoblastoma from Africa and Europe. METHODS: A cross-sectional analysis including 518 treatment-naïve patients with retinoblastoma residing in 40 European countries and 1024 treatment-naïve patients with retinoblastoma residing in 43 African countries. RESULTS: Capture rate was 42.2% of expected patients from Africa and 108.8% from Europe. African patients were older (95% CI -12.4 to -5.4, p<0.001), had fewer cases of familial retinoblastoma (95% CI 2.0 to 5.3, p<0.001) and presented with more advanced disease (95% CI 6.0 to 9.8, p<0.001); 43.4% and 15.4% of Africans had extraocular retinoblastoma and distant metastasis at the time of diagnosis, respectively, compared to 2.9% and 1.0% of the Europeans. To reach a retinoblastoma centre, European patients travelled 421.8 km compared to Africans who travelled 185.7 km (p<0.001). On regression analysis, lower-national income level, African residence and older age (p<0.001), but not travel distance (p=0.19), were risk factors for advanced disease. CONCLUSIONS: Fewer than half the expected number of patients with retinoblastoma presented to African referral centres in 2017, suggesting poor awareness or other barriers to access. Despite the relatively shorter distance travelled by African patients, they presented with later-stage disease. Health education about retinoblastoma is needed for carers and health workers in Africa in order to increase capture rate and promote early referral

The global retinoblastoma outcome study : a prospective, cluster-based analysis of 4064 patients from 149 countries

DATA SHARING : The study data will become available online once all analyses are complete.BACKGROUND : Retinoblastoma is the most common intraocular cancer worldwide. There is some evidence to suggest that major differences exist in treatment outcomes for children with retinoblastoma from different regions, but these differences have not been assessed on a global scale. We aimed to report 3-year outcomes for children with retinoblastoma globally and to investigate factors associated with survival. METHODS : We did a prospective cluster-based analysis of treatment-naive patients with retinoblastoma who were diagnosed between Jan 1, 2017, and Dec 31, 2017, then treated and followed up for 3 years. Patients were recruited from 260 specialised treatment centres worldwide. Data were obtained from participating centres on primary and additional treatments, duration of follow-up, metastasis, eye globe salvage, and survival outcome. We analysed time to death and time to enucleation with Cox regression models. FINDINGS : The cohort included 4064 children from 149 countries. The median age at diagnosis was 23·2 months (IQR 11·0–36·5). Extraocular tumour spread (cT4 of the cTNMH classification) at diagnosis was reported in five (0·8%) of 636 children from high-income countries, 55 (5·4%) of 1027 children from upper-middle-income countries, 342 (19·7%) of 1738 children from lower-middle-income countries, and 196 (42·9%) of 457 children from low-income countries. Enucleation surgery was available for all children and intravenous chemotherapy was available for 4014 (98·8%) of 4064 children. The 3-year survival rate was 99·5% (95% CI 98·8–100·0) for children from high-income countries, 91·2% (89·5–93·0) for children from upper-middle-income countries, 80·3% (78·3–82·3) for children from lower-middle-income countries, and 57·3% (52·1-63·0) for children from low-income countries. On analysis, independent factors for worse survival were residence in low-income countries compared to high-income countries (hazard ratio 16·67; 95% CI 4·76–50·00), cT4 advanced tumour compared to cT1 (8·98; 4·44–18·18), and older age at diagnosis in children up to 3 years (1·38 per year; 1·23–1·56). For children aged 3–7 years, the mortality risk decreased slightly (p=0·0104 for the change in slope). INTERPRETATION : This study, estimated to include approximately half of all new retinoblastoma cases worldwide in 2017, shows profound inequity in survival of children depending on the national income level of their country of residence. In high-income countries, death from retinoblastoma is rare, whereas in low-income countries estimated 3-year survival is just over 50%. Although essential treatments are available in nearly all countries, early diagnosis and treatment in low-income countries are key to improving survival outcomes.The Queen Elizabeth Diamond Jubilee Trust and the Wellcome Trust.https://www.thelancet.com/journals/langlo/homeam2023Paediatrics and Child Healt

Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways

Impact of Prediabetes and Type-2 Diabetes on Outcomes in Patients with COVID-19

Introduction. The true impact of prediabetes and type-2 diabetes in patients with COVID-19 remains unknown, with studies thus far providing conflicting evidence. Methods. This is a single-center retrospective observational study involving 843 hospitalized patients with SARS-CoV-2 infection. Primary outcomes, mortality, and mechanical ventilation use were compared among the three groups: control, prediabetes, and type-2 diabetes. Binomial regression analysis was used to determine predictors of mortality and mechanical ventilation requirement. Results. Age was a significant predictor of mortality. On stratifying our patients based on their age, older patients aged 55 years and above had no difference in mortality or mechanical ventilation requirement among the three groups of control, prediabetes, and type-2 diabetes. However, among the younger population aged less than 55 years, patients with type-2 diabetes had significantly higher mortality as compared with patients in control and prediabetes groups (27% vs 12.5% vs 9%, p 0.025). Additionally, newly diagnosed type-2 diabetes patients demonstrated lower mortality rate in comparison to previously known type-2 diabetes patients (18% vs 40%, p 0.005). Outcomes in the prediabetes group were similar to that in the control group. Admission hyperglycemia was associated with higher mortality regardless of diabetes status. Conclusion. In older patients aged 55 years and above, status of type-2 diabetes does not influence their mortality. However, in younger patients aged less than 55 years, the presence of type-2 diabetes is an important driver of mortality. Newly diagnosed type-2 diabetes, in comparison with previously diagnosed type-2 diabetes, may have better survival. Presence of prediabetes did not affect outcomes in patients with COVID-19 infection

Higher Fatigue Prospectively Increases the Risk of Falls in Older Men

Background and objectivesFatigue is a common complaint and shares many risk factors with falls, yet the independent contribution of fatigue on fall risk is unclear. This study's primary aim was to assess the association between fatigue and prospective fall risk in 5642 men aged 64-100 enrolled in the Osteoporotic Fractures in Men Study (MrOS). The secondary aim was to examine the association between fatigue and recurrent fall risk.Research design and methodsFatigue was measured at baseline using the Medical Outcomes Study (short form) single-item question "During the past four weeks, how much of the time did you feel energetic?" Responses were then classified: higher fatigue = "none," "a little," or "some" of the time and lower fatigue = "a good bit," "most," or "all" of the time. We assessed falls using triannual questionnaires. Fall risk was examined prospectively over 3 years; recurrent falling was defined as at least 2 falls within the first year. Generalized estimating equations and multinomial logistic regression modeled prospective and recurrent fall risk as a function of baseline fatigue status, adjusted for demographics, medications, physical activity, and gait speed.ResultsMen with higher (26%) versus lower baseline fatigue were older (75.1 ± 6.2 vs 73.2 ± 5.7 years), 24% less active, and had worse physical function (gait speed = 1.09 ± 0.24 vs 1.24 ± 0.21 m/s), all p &lt; .0001. Within 1 year, 25.4% (n = 1409) had fallen at least once, of which 47.4% (n = 668) were recurrent fallers. Men with higher versus lower fatigue had 25% increased fall risk (relative risk = 1.25, 95% CI: 1.14-1.36) over 3 years follow-up, but had 50% increased odds of recurrent falling (odds ratio = 1.50, 95% CI: 1.22-1.85) within the first year.Discussion and implicationsFatigue is an important risk factor of falling independent of established risk factors. Reductions in fatigue (ie, increased energy) may lessen the burden of falls in older men and provide a novel avenue for fall risk intervention