Geographical distance and reduced access to palliative radiotherapy: Systematic Review and Meta-Analysis

Background. Palliative radiotherapy (PRT) is an effective way of reducing symptoms caused by advanced incurable cancer. Several studies have investigated factors that contribute to inequalities in access to PRT; distance to a radiotherapy centre has been identified as one potential barrier.Aim. To assess whether there is an association between distance to a radiotherapy centre and utilisation rates of PRT in adults with cancer.Methods. A systematic review and meta-analysis protocol was registered in the PROSPERO database (CRD42020190772). MEDLINE, EMBASE, CINAHL and APA-PsycINFO were searched for relevant papers up to 28 February 2021.Results. Twenty-one studies were included. Twelve studies focused on whether patients with incurable cancer received PRT, as part of their treatment package. Pooled results reported that living ≥50 km vs <50 km from the radiotherapy centre was associated with a reduced likelihood of receiving PRT (OR 0.84 (95%CI 0.80, 0.88)). Nine focused on distance from the radiotherapy centre and compared single-fraction (SF) versus multiple-fraction PRT, indicating that patients living further away were more likely to receive SF. Pooled results comparing ≥50 km versus <50 km showed increased odds of receiving SF for those living ≥50 km (OR 1.48 (95%CI 1.26,1.75)).Conclusion. Patients living further away from radiotherapy centres were less likely to receive PRT and those who received PRT were more likely to receive SF PRT, providing some evidence of inequalities in access to PRT treatment based on proximity to centres providing radiotherapy. Further research is needed to understand whether these inequalities are influenced by clinical referral patterns or by patients unwilling or unable to travel longer distances

Survival of patients with small cell lung cancer undergoing lung resection in England, 1998–2009

Introduction: Chemotherapy or chemoradiotherapy is the recommended treatment for small cell lung cancer (SCLC), except in stage I disease where clinical guidelines state there may be a role for surgery based on favourable outcomes in case series. Evidence supporting adjuvant chemotherapy in resected SCLC is limited but this is widely offered. Methods: Data on 359 873 patients who were diagnosed with a first primary lung cancer in England between 1998 and 2009 were grouped according to histology (SCLC or non-SCLC (NSCLC)) and whether they underwent a surgical resection. We explored their survival using Kaplan-Meier analysis and Cox regression, adjusting for age, sex, comorbidity and socioeconomic status. Results: The survival of 465 patients with resected SCLC was lower than patients with resected NSCLC (5-year survival 31% and 45%, respectively), but much higher than patients of either group who were not resected (3%). The difference between resected SCLC and NSCLC diminished with time after surgery. Survival was superior for the subgroup of 198 'elective' SCLC cases where the diagnosis was most likely known before resection than for the subgroup of 267 'incidental' cases where the SCLC diagnosis was likely to have been made after resection. Conclusions: These data serve as a natural experiment testing the survival after surgical management of SCLC according to NSCLC principles. Patients with SCLC treated surgically for early stage disease may have survival outcomes that approach those of NSCLC, supporting the emerging clinical practice of offering surgical resection to selected patients with SCLC

1 Personality Polygenes, Positive Affect, and Life Satisfaction

Approximately half of the variation in wellbeing measures overlaps with variation in personality traits. Studies of non-human primate pedigrees and human twins suggest that this is due to common genetic influences. We tested whether personality polygenic scores for the NEO Five-Factor Inventory (NEO-FFI) domains and for item response theory (IRT) derived extraversion and neuroticism scores predict variance in wellbeing measures. Polygenic scores were based on published genome-wide association (GWA) results in over 17,000 individuals for the NEO-FFI and in over 63,000 for the IRT extraversion and neuroticism traits. The NEO-FFI polygenic scores were used to predict life satisfaction in 7 cohorts, positive affect in 12 cohorts, and general wellbeing in 1 cohort (maximal N = 46,508). Meta-analysis of these results showed no significant association between NEO-FFI personality polygenic scores and the wellbeing measures. IRT extraversion and neuroticism polygenic scores were used to predict life satisfaction and positive affect in almost 37,000 individuals from UK Biobank. Significant positive associations (effect sizesPeer reviewe

Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention

Although physical activity and sedentary behavior are moderately heritable, little is known about the mechanisms that influence these traits. Combining data for up to 703,901 individuals from 51 studies in a multi-ancestry meta-analysis of genome-wide association studies yields 99 loci that associate with self-reported moderate-to-vigorous intensity physical activity during leisure time (MVPA), leisure screen time (LST) and/or sedentary behavior at work. Loci associated with LST are enriched for genes whose expression in skeletal muscle is altered by resistance training. A missense variant in ACTN3 makes the alpha-actinin-3 filaments more flexible, resulting in lower maximal force in isolated type IIA muscle fibers, and possibly protection from exercise-induced muscle damage. Finally, Mendelian randomization analyses show that beneficial effects of lower LST and higher MVPA on several risk factors and diseases are mediated or confounded by body mass index (BMI). Our results provide insights into physical activity mechanisms and its role in disease prevention. Multi-ancestry meta-analyses of genome-wide association studies for self-reported physical activity during leisure time, leisure screen time, sedentary commuting and sedentary behavior at work identify 99 loci associated with at least one of these traits

Effects of Wolves on Elk and Cattle Behaviors: Implications for Livestock Production and Wolf Conservation

BACKGROUND: In many areas, livestock are grazed within wolf (Canis lupus) range. Predation and harassment of livestock by wolves creates conflict and is a significant challenge for wolf conservation. Wild prey, such as elk (Cervus elaphus), perform anti-predator behaviors. Artificial selection of cattle (Bos taurus) might have resulted in attenuation or absence of anti-predator responses, or in erratic and inconsistent responses. Regardless, such responses might have implications on stress and fitness. METHODOLOGY/PRINCIPAL FINDINGS: We compared elk and cattle anti-predator responses to wolves in southwest Alberta, Canada within home ranges and livestock pastures, respectively. We deployed satellite- and GPS-telemetry collars on wolves, elk, and cattle (n = 16, 10 and 78, respectively) and measured seven prey response variables during periods of wolf presence and absence (speed, path sinuosity, time spent head-up, distance to neighboring animals, terrain ruggedness, slope and distance to forest). During independent periods of wolf presence (n = 72), individual elk increased path sinuosity (Z = -2.720, P = 0.007) and used more rugged terrain (Z = -2.856, P = 0.004) and steeper slopes (Z = -3.065, P = 0.002). For cattle, individual as well as group behavioral analyses were feasible and these indicated increased path sinuosity (Z = -2.720, P = 0.007) and decreased distance to neighbors (Z = -2.551, P = 0.011). In addition, cattle groups showed a number of behavioral changes concomitant to wolf visits, with variable direction in changes. CONCLUSIONS/SIGNIFICANCE: Our results suggest both elk and cattle modify their behavior in relation to wolf presence, with potential energetic costs. Our study does not allow evaluating the efficacy of anti-predator behaviors, but indicates that artificial selection did not result in their absence in cattle. The costs of wolf predation on livestock are often compensated considering just the market value of the animal killed. However, society might consider refunding some additional costs (e.g., weight loss and reduced reproduction) that might be associated with the changes in cattle behaviors that we documented

Exome-Derived Adiponectin-Associated Variants Implicate Obesity and Lipid Biology

Circulating levels of adiponectin, an adipocyte-secreted protein associated with cardiovascular and metabolic risk, are highly heritable. To gain insights into the biology that regulates adiponectin levels, we performed an exome array meta-analysis of 265,780 genetic variants in 67,739 individuals of European, Hispanic, African American, and East Asian ancestry. We identified 20 loci associated with adiponectin, including 11 that had been reported previously (p .60) spanning as much as 900 kb. To identify potential genes and mechanisms through which the previously unreported association signals act to affect adiponectin levels, we assessed cross-trait associations, expression quantitative trait loci in subcutaneous adipose, and biological pathways of nearby genes. Eight of the nine loci were also associated (p <1 x 10(-4)) with at least one obesity or lipid trait. Candidate genes include PRKAR2A, PTH1R, and HDAC9, which have been suggested to play roles in adipocyte differentiation or bone marrow adipose tissue. Taken together, these findings provide further insights into the processes that influence circulating adiponectin levels.Peer reviewe