Prevalence and Distribution of Unexpected Actionable Germline Pathogenic Variants Identified on Broad-Based Multigene Panel Testing Among Patients With Cancer.

Purpose: In patients with a variety of malignancies undergoing multigene panel testing (MGPT), we examined the frequency of a pathogenic/likely pathogenic variant (PV) that would not have been predicted on the basis of the patient's personal and family history of cancer.

Methods: This is a retrospective review of patients with cancer ascertained from a single academic cancer center who underwent broad-based MGPT of ≥20 cancer predisposition genes not selected on the basis of personal or family cancer history from 2015 to 2021. Low-penetrance variants and recessive inheritance genes were excluded.

The Wise Mind Balances the Abstract and the Concrete.

We explored how individuals' mental representations of complex and uncertain situations impact their ability to reason wisely. To this end, we introduce situated methods to capture abstract and concrete mental representations and the switching between them when reflecting on social challenges. Using these methods, we evaluated the alignment of abstractness and concreteness with four integral facets of wisdom: intellectual humility, open-mindedness, perspective-taking, and compromise-seeking.

Clinicopathological characteristics and eligibility for adjuvant olaparib of germline BRCA1/2 mutation carriers with HER2-negative early breast cancer.

Following the survival benefit demonstrated in the OlympiA trial, one year of adjuvant olaparib is now recommended for all patients with germline BRCA1/2 pathogenic/likely pathogenic variants (PV) and high-risk, HER2-negative early breast cancer after chemotherapy. However, optimal identification of high-risk patients who may derive benefit from this genomically-directed therapy is debated. In this study, we sought to characterize the real-world proportion of gBRCA1/2 PV carriers eligible for adjuvant olaparib according to the OlympiA criteria, and to compare clinicopathologic characteristics and outcomes between eligible and ineligible patients.

Advancing Precision Oncology in Hereditary Paraganglioma-Pheochromocytoma Syndromes: Integrated Interpretation and Data Sharing of the Germline and Tumor Genomes.

Standard methods of variant assessment in hereditary cancer susceptibility genes are limited by the lack of availability of key supporting evidence. In cancer, information derived from tumors can serve as a useful source in delineating the tumor behavior and the role of germline variants in tumor progression. We have previously demonstrated the value of integrating tumor and germline findings to comprehensively assess germline variants in hereditary cancer syndromes.

Development and evaluation of INTGRATE: a platform for comprehensive assessment of the role of germline variants informed by tumor signature profile in Lynch syndrome.

The presence of variants of uncertain significance (VUS) in DNA mismatch repair (MMR) genes leads to uncertainty in the clinical management of patients being evaluated for Lynch syndrome (LS). Currently, there is no platform to systematically use tumor-derived evidence alongside germline data for the assessment of VUS in relation to LS. We developed INTGRATE (INTegrated INTerpretation of GeRmline And Tumor gEnomes) to leverage information from the tumor genome to inform the potential role of constitutional VUS in MMR genes.

Commingling Effects of Anterior Load and Walking Surface on Dynamic Gait Stability in Young Adults.

Treadmill walking has been used as a surrogate for overground walking to examine how load carriage affects gait. The validity of using treadmill walking to investigate load carriage's effects on stability has not been established. Thirty young adults were randomized into 3 front-loaded groups (group 1: 0%, 2: 10%, or 3: 20% of bodyweight).

Preliminary race-ethnicity-based analyses of fall risk among people with multiple sclerosis.

Background: Mounting evidence suggests differences in the disease characteristics of multiple sclerosis (MS) across ethnic and racial groups. Although it is widely recognized that falls are a significant concern for people with MS (PwMS), no study has explored if the fall risk is related to race/ethnicity in PwMS. The primary purpose of this pilot study was to examine whether the risk of falls is different between age-matched White, Black, and Latinx PwMS.

What factors contribute to e-scooter crashes: A first look using a naturalistic riding approach.

Introduction: Shared dockless electric scooters (e-scooters) are a popular shared mobility service providing an accessible last-mile transportation option in urban and campus environments. However, city and campus stakeholders may hesitate to introduce these scooters due to safety concerns. While prior e-scooter safety studies have collected injury data from hospitals or riding data under controlled or naturalistic conditions, these datasets are limited and did not identify risk factors associated with e-scooter riding safety.

Effects of vibration training on quality of life in older adults: a preliminary systematic review and meta-analysis.

Purpose: Older adults experience reduced quality of life (QOL). Vibration training has been applied in older adults. However, it remains inconclusive whether vibration training improves QOL in this population.

The 2019 Conference on Health and Active Transportation: Research Needs and Opportunities.

Active transportation (AT) is widely viewed as an important target for increasing participation in aerobic physical activity and improving health, while simultaneously addressing pollution and climate change through reductions in motor vehicular emissions. In recent years, progress in increasing AT has stalled in some countries and, furthermore, the coronavirus (COVID-19) pandemic has created new AT opportunities while also exposing the barriers and health inequities related to AT for some populations. This paper describes the results of the December 2019 Conference on Health and Active Transportation (CHAT) which brought together leaders from the transportation and health disciplines.

Measuring Nature Contact: A Narrative Review.

While many studies suggest evidence for the health benefits of nature, there is currently no standardized method to measure time spent in nature or nature contact, nor agreement on how best to define nature contact in research. The purpose of this review is to summarize how nature contact has been measured in recent health research and provide insight into current metrics of exposure to nature at individual and population scales. The most common methods include surrounding greenness, questionnaires, and global positioning systems (GPS) tracking.

Unresolved Gamma-Ray Sky through its Angular Power Spectrum.

The gamma-ray sky has been observed with unprecedented accuracy in the last decade by the Fermi -large area telescope (LAT), allowing us to resolve and understand the high-energy Universe. The nature of the remaining unresolved emission [unresolved gamma-ray background (UGRB)] below the LAT source detection threshold can be uncovered by characterizing the amplitude and angular scale of the UGRB fluctuation field. This Letter presents a measurement of the UGRB autocorrelation angular power spectrum based on eight years of Fermi-LAT Pass 8 data products.

Investigating the Nature of Late-Time High-Energy GRB Emission Through Joint Observations.

We use joint observations by the X-ray Telescope (XRT) and the Large Area Telescope (LAT) of gamma-ray burst (GRB) afterglows to investigate the nature of the long-lived high-energy emission observed by LAT. Joint broadband spectral modeling of XRT and LAT data reveal that LAT non-detections of bright X-ray afterglows are consistent with a cooling break in the inferred electron synchrotron spectrum below the LAT and/or XRT energy ranges. Such a break is sufficient to suppress the high-energy emission so as to be below the LAT detection threshold.

Correlates of the Built Environment and Active Travel: Evidence from 20 US Metropolitan Areas.

Background: Walking and bicycling are health-promoting and environmentally friendly alternatives to the automobile. Previous studies that explore correlates of active travel and the built environment are for a single metropolitan statistical area (MSA) and results often vary among MSAs.

Objectives: Our goal was to model the relationship between the built environment and active travel for 20 MSAs spanning the continental United States.

Einstein@Home discovers a radio-quiet gamma-ray millisecond pulsar.

Millisecond pulsars (MSPs) are old neutron stars that spin hundreds of times per second and appear to pulsate as their emission beams cross our line of sight. To date, radio pulsations have been detected from all rotation-powered MSPs. In an attempt to discover radio-quiet gamma-ray MSPs, we used the aggregated power from the computers of tens of thousands of volunteers participating in the Einstein@Home distributed computing project to search for pulsations from unidentified gamma-ray sources in Fermi Large Area Telescope data.

Policies to Promote Active Travel: Evidence from Reviews of the Literature.

Purpose Of Review: While many levels of government recognize that walking and cycling (active travel) are critical to healthy cities, a continued challenge is to identify and prioritize strategies that will increase walking and cycling for transportation. We review evidence on policies that can increase active travel.

Recent Findings: The reviews included here conclude that policies related to active travel may operate at various levels of the socio-ecological framework, including society, cities, routes or individuals.

Evaluating performance over time: Is improving better than being consistently good?

In many decision contexts, people evaluate others based on intertemporal performance records and commonly face a choice between two distinct profiles: performance that is consistently high versus performance that improves over time to that high level. We proposed that these two profiles could be appealing for different reasons, and thus evaluators' preferences will differ across decision contexts. In three studies, participants were presented with candidates (e.

Trends in Walking and Cycling Safety: Recent Evidence From High-Income Countries, With a Focus on the United States and Germany.

Objectives: To examine changes in pedestrian and cyclist fatalities per capita (1990-2014) and per kilometer (2000-2010) in selected high-income countries, and in fatalities and serious injuries per kilometer by age in the United States and Germany (2001-2009).

Methods: We used Organisation for Economic Cooperation and Development data to estimate 5-year annual averages of per-capita fatalities relative to the 1990-1994 average. To control for exposure, we divided fatalities and serious injuries by kilometers of walking or cycling per year for countries with comparable data from national household travel surveys.

Search for Spectral Irregularities due to Photon-Axionlike-Particle Oscillations with the Fermi Large Area Telescope.

We report on the search for spectral irregularities induced by oscillations between photons and axionlike-particles (ALPs) in the γ-ray spectrum of NGC 1275, the central galaxy of the Perseus cluster. Using 6 years of Fermi Large Area Telescope data, we find no evidence for ALPs and exclude couplings above 5×10^{-12}  GeV^{-1} for ALP masses 0.5≲m_{a}≲5  neV at 95% confidence.

Resolving the Extragalactic γ-Ray Background above 50 GeV with the Fermi Large Area Telescope.

The Fermi Large Area Telescope (LAT) Collaboration has recently released a catalog of 360 sources detected above 50 GeV (2FHL). This catalog was obtained using 80 months of data re-processed with Pass 8, the newest event-level analysis, which significantly improves the acceptance and angular resolution of the instrument. Most of the 2FHL sources at high Galactic latitude are blazars.

Measurement of the high-energy gamma-ray emission from the Moon with the Fermi Large Area Telescope.

We have measured the gamma-ray emission spectrum of the Moon using the data collected by the Large Area Telescope onboard the Fermi satellite during its first seven years of operation, in the energy range from 30 MeV up to a few GeV. We have also studied the time evolution of the flux, finding a correlation with the solar activity. We have developed a full Monte Carlo simulation describing the interactions of cosmic rays with the lunar surface.

Searching for Dark Matter Annihilation from Milky Way Dwarf Spheroidal Galaxies with Six Years of Fermi Large Area Telescope Data.

The dwarf spheroidal satellite galaxies (dSphs) of the Milky Way are some of the most dark matter (DM) dominated objects known. We report on γ-ray observations of Milky Way dSphs based on six years of Fermi Large Area Telescope data processed with the new Pass8 event-level analysis. None of the dSphs are significantly detected in γ rays, and we present upper limits on the DM annihilation cross section from a combined analysis of 15 dSphs.