New allowed mSUGRA parameter space from variations of the trilinear scalar coupling A0

In minimal Supergravity (mSUGRA) models the lightest supersymmetric particle (assumed to be the lightest neutralino) provides an excellent cold dark matter (CDM) candidate. The supersymmetric parameter space is significantly reduced, if the limits on the CDM relic density, obtained from WMAP data, are used. Assuming a vanishing trilinear scalar coupling A0 and fixed values of tan(beta), these limits result in narrow lines of allowed regions in the m0-m1/2 plane, the so called WMAP strips. In this analysis the trilinear coupling A0 has been varied within +/-4 TeV. A fixed non vanishing A0 value leads to a shift of the WMAP strips in the m0-m1/2 plane.Comment: Typos corrected, Fig.1. updated, references adde

Dosimetric Analysis of Proximal Bronchial Tree Subsegments to Assess The Risk of Severe Toxicity After Stereotactic Body Radiation Therapy of Ultra-central Lung Tumors

Background and purpose Stereotactic body radiotherapy (SBRT) of ultra-central lung tumors (UCLT) is associated with an increased risk of severe toxicity. The aim of this study was to perform a detailed dosimetric analysis of the proximal bronchial tree (PBT) anatomical sub-segments to evaluate the safety of risk-adapted SBRT and to evaluate potential differences in radiation tolerance between PBT sub-segments. Material and methods Fifty-seven patients treated with SBRT for UCLT between 2014 and 2021 were included. UCLT were defined as tumor abutting or overlapping with the trachea, PBT, or esophagus. This study analyzed overall survival, local control, progression-free survival, and grade ≥3 toxicity events. Bayesian inference was used to build a dose-response model with upper limits for toxicity. Results Twenty-seven (47.4%) of the irradiated lesions were primary or locoregionally recurrent NSCLC and 30 (52.6%) oligometastases. All patients were treated with risk-adapted SBRT of median 45.0 Gy (range: 30.0-60.0 Gy) in 8 or 10 fractions. Grade ≥3 radiation pneumonitis was observed in two patients (3.5%), while no bronchial stenosis, hemorrhage or fistula were observed. The dose-response model predicted a grade ≥3 toxicity (stenosis, hemorrhage or fistula) limited to 4.9% (0 - 11.4%) when delivering EQD2$\_$3 = 100 Gy to any location of the PBT (D0.2cc). Detailed dosimetric analysis of PBT substructures showed no variation in the dose-response model between the anatomical PBT sub-segments. Conclusion Risk-adapted SBRT regimens delivered in 8 or 10 fractions for ultra-central lung tumors resulted in high rates of local tumor control with low toxicity rates, without differences in radiation tolerance between the anatomical PBT sub-segments

External Validation of Three Prognostic Scores for Brain Metastasis Velocity in Patients Treated with Intracranial Stereotactic Radiotherapy

BACKGROUND AND INTRODUCTION Brain metastasis velocity (BMV) has been proposed as a prognostic factor for overall survival (OS) in patients with brain metastases (BMs). In this study, we conducted an external validation and comparative assessment of the performance of all three BMV scores. MATERIALS AND METHODS Patients treated with intracranial stereotactic radiotherapy (SRT) for BM at a single center between 2014 and 2018 were identified. Where possible, all three BMV scores were calculated. Log-rank tests and linear, logistic and Cox regression analysis were used for validation and predictor identification of OS. RESULTS For 333 of 384 brain metastasis patients, at least one BMV score could be calculated. In a sub-group of 187 patients, "classic" BMV was validated as categorical (p<0.0001) and continuous variable (HR 1.02; 95% CI 1.02-1.03; p<0.0001). In a sub-group of 284 patients, "initial" BMV was validated as categorical variable (high-risk vs. low-risk; p<0.01), but not as continuous variable (HR 1.02; 95% CI 0.99-1.04; p=0.224). "Volume-based" BMV could not be validated in a sub-group of 104 patients. On multivariable Cox regression analysis, iBMV (HR 1.85; 95% CI 1.01-3.38; p<0.05) and cBMV (HR 2.32; 95% CI 1.15 4.68; p<0.05) were predictors for OS for intermediate-risk patients after first SRT and first DBFs, respectively. cBMV proved to be the dominant predictor for OS for high-risk patients (HR 2.99; 95% CI 1.30-6.91; p<0.05). CONCLUSION This study externally validated cBMV and iBMV as prognostic scores for OS in patients treated with SRT for BMs whereas validation of vBMV was not achieved

Cross-cutting principles for planetary health education

Since the 2015 launch of the Rockefeller Foundation Lancet Commission on planetary health,1 an enormous groundswell of interest in planetary health education has emerged across many disciplines, institutions, and geographical regions. Advancing these global efforts in planetary health education will equip the next generation of scholars to address crucial questions in this emerging field and support the development of a community of practice. To provide a foundation for the growing interest and efforts in this field, the Planetary Health Alliance has facilitated the first attempt to create a set of principles for planetary health education that intersect education at all levels, across all scales, and in all regions of the world—ie, a set of cross-cutting principles

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

An new method to determine the arrival direction of individual air showers with a single Air Cherenkov Telescope

We present a new method to reconstruct the arrival direction of individual air showers. The method is based in part on the arrival direction reconstruction method of Lessard et al. [1] from the Whipple collaboration, but yields a significant 30 % improvement in the obtained angular resolution. The method was successfully tested on Monte Carlo Simulations and real data of Mkn 421, Mkn 501 and 1ES1959 from the HEGRA Cherenkov Telescope CT1. Based on the same data an angular resolution of 0.1 ◦ could be derived. 1