A Pilot Study Comparing the Efficacy of Lactate Dehydrogenase Levels Versus Circulating Cell-Free microRNAs in Monitoring Responses to Checkpoint Inhibitor Immunotherapy in Metastatic Melanoma Patients.

Serum lactate dehydrogenase (LDH) is a standard prognostic biomarker for stage IV melanoma patients. Often, LDH levels do not provide real-time information about the metastatic melanoma patients\u27 disease status and treatment response. Therefore, there is a need to find reliable blood biomarkers for improved monitoring of metastatic melanoma patients who are undergoing checkpoint inhibitor immunotherapy (CII). The objective in this prospective pilot study was to discover circulating cell-free microRNA (cfmiR) signatures in the plasma that could assess melanoma patients\u27 responses during CII. The cfmiRs were evaluated by the next-generation sequencing (NGS) HTG EdgeSeq microRNA (miR) Whole Transcriptome Assay (WTA; 2083 miRs) in 158 plasma samples obtained before and during the course of CII from 47 AJCC stage III/IV melanoma patients\u27 and 73 normal donors\u27 plasma samples. Initially, cfmiR profiles for pre- and post-treatment plasma samples of stage IV non-responder melanoma patients were compared to normal donors\u27 plasma samples. Using machine learning, we identified a 9 cfmiR signature that was associated with stage IV melanoma patients being non-responsive to CII. These cfmiRs were compared in pre- and post-treatment plasma samples from stage IV melanoma patients that showed good responses. Circulating miR-4649-3p, miR-615-3p, and miR-1234-3p demonstrated potential prognostic utility in assessing CII responses. Compared to LDH levels during CII, circulating miR-615-3p levels were consistently more efficient in detecting melanoma patients undergoing CII who developed progressive disease. By combining stage III/IV patients, 92 and 17 differentially expressed cfmiRs were identified in pre-treatment plasma samples from responder and non-responder patients, respectively. In conclusion, this pilot study demonstrated cfmiRs that identified treatment responses and could allow for real-time monitoring of patients receiving CII

Optical BVI Imaging and HI Synthesis Observations of the Dwarf Irregular Galaxy ESO 364-G 029

As part of an effort to enlarge the number of well-studied Magellanic-type galaxies, we obtained broadband optical imaging and neutral hydrogen radio synthesis observations of the dwarf irregular galaxy ESO 364-G 029. The optical morphology characteristically shows a bar-like main body with a one-sided spiral arm, an approximately exponential light distribution, and offset photometric and kinematic centers. The HI distribution is mildly asymmetric and, although slightly offset from the photometric center, roughly follows the optical brightness distribution, extending to over 1.2 Holmberg radii (where mu_B = 26.5 mag/arcsec^2). In particular, the highest HI column densities closely follow the bar, one-arm spiral, and a third optical extension. The rotation is solid-body in the inner parts but flattens outside of the optical extent. The total HI flux F_HI = 23.1 pm 1.2 Jy km/s, yielding a total HI mass M_HI= (6.4 pm 1.7) x 10^8 Msun (for a distance D = 10.8 pm 1.4 Mpc) and a total HI mass-to-blue-luminosity ratio M_HI/L_B = (0.96 pm 0.14) Msun / Lsun,B (distance independent). The HI data suggest a very complex small-scale HI structure, with evidence of large shells and/or holes, but deeper observations are required for a detailed study. Follow-up observations are also desirable for a proper comparison with the Large Magellanic Cloud, where despite an optical morphology very similar to ESO 364-G 029 the HI bears little resemblance to the optical.Comment: 10 pages, 11 figures, accepted by A&

Physical activity through sustainable transport approaches (PASTA): protocol for a multi-centre, longitudinal study

BACKGROUND: Physical inactivity is one of the leading risk factors for non-communicable diseases, yet many are not sufficiently active. The Physical Activity through Sustainable Transport Approaches (PASTA) study aims to better understand active mobility (walking and cycling for transport solely or in combination with public transport) as an innovative approach to integrate physical activity into individuals' everyday lives. The PASTA study will collect data of multiple cities in a longitudinal cohort design to study correlates of active mobility, its effect on overall physical activity, crash risk and exposure to traffic-related air pollution. METHODS/DESIGN: A set of online questionnaires incorporating gold standard approaches from the physical activity and transport fields have been developed, piloted and are now being deployed in a longitudinal study in seven European cities (Antwerp, Barcelona, London, Oerebro, Rome, Vienna, Zurich). In total, 14000 adults are being recruited (2000 in each city). A first questionnaire collects baseline information; follow-up questionnaires sent every 13 days collect prospective data on travel behaviour, levels of physical activity and traffic safety incidents. Self-reported data will be validated with objective data in subsamples using conventional and novel methods. Accelerometers, GPS and tracking apps record routes and activity. Air pollution and physical activity are measured to study their combined effects on health biomarkers. Exposure-adjusted crash risks will be calculated for active modes, and crash location audits are performed to study the role of the built environment. Ethics committees in all seven cities have given independent approval for the study. DISCUSSION: The PASTA study collects a wealth of subjective and objective data on active mobility and physical activity. This will allow the investigation of numerous correlates of active mobility and physical activity using a data set that advances previous efforts in its richness, geographical coverage and comprehensiveness. Results will inform new health impact assessment models and support efforts to promote and facilitate active mobility in cities

Integrated Assessment of Circulating Cell-Free MicroRNA Signatures in Plasma of Patients with Melanoma Brain Metastasis.

Primary cutaneous melanoma frequently metastasizes to distant organs including the brain. Identification of cell-free microRNAs (cfmiRs) found in the blood can be used as potential body fluid biomarkers for detecting and monitoring patients with melanoma brain metastasis (MBM). In this pilot study, we initially aimed to identify cfmiRs in the blood of MBM patients. Normal donors plasma (healthy, n = 48) and pre-operative MBM patients\u27 plasma samples (n = 36) were compared for differences in \u3e2000 microRNAs (miRs) using a next generation sequencing (NGS) probe-based assay. A 74 cfmiR signature was identified in an initial cohort of MBM plasma samples and then verified in a second cohort of MBM plasma samples (n = 24). Of these, only 58 cfmiRs were also detected in MBM tissues (n = 24). CfmiR signatures were also found in patients who have lung and breast cancer brain metastasis (n = 13) and glioblastomas (n = 36) compared to MBM plasma samples. The 74 cfmiR signature and the latter cfmiR signatures were then compared. We found a 6 cfmiR signature that was commonly upregulated in MBM plasma samples in all of the comparisons, and a 29 cfmiR signature that distinguishes MBM patients from normal donors\u27 samples. In addition, we assessed for cfmiRs in plasma (n = 20) and urine (n = 14) samples collected from metastatic melanoma patients receiving checkpoint inhibitor immunotherapy (CII). Pre- and post-treatment samples showed consistent changes in cfmiRs. Analysis of pre- and post-treatment plasma samples showed 8 differentially expressed (DE) cfmiRs that overlapped with the 35 cfmiR signature found in MBM patients. In paired pre-treatment plasma and urine samples receiving CII 8 cfmiRs overlapped. This study identified specific cfmiRs in MBM plasma samples that may potentially allow for assessment of melanoma patients developing MBM. The cfmiR signatures identified in both blood and urine may have potential utility to assess CII responses after further validation

The health impacts of waste-to-energy emissions: A systematic review of the literature

Waste-to-energy (WtE) processes, or the combustion of refuse-derived fuel (RDF) for energygeneration, has the potential to reduce landfill volume while providing a renewable energy source.We aimed to systematically review and summarise current evidence on the potential health effects(benefits and risks) of exposure to WtE/RDF-related combustion emissions.We searched PubMed and Google Scholar using terms related to health and WtE/RDFcombustion emissions, following PRISMA guidelines. Two authors independently screened titles,abstracts and then full-texts of original, peer-reviewed research articles published until 20th March2020, plus their relevant references. Overall quality of included epidemiological studies were ratedusing an amended Navigation framework.We found 19 articles from 269 search results that met our inclusion criteria, including twoepidemiological studies, five environmental monitoring studies, seven health impact or riskassessments (HIA/HRA), and five life-cycle assessments. We found a dearth of health studiesrelated to the impacts of exposure to WtE emissions. The limited evidence suggests thatwell-designed and operated WtE facilities using sorted feedstock (RDF) are critical to reducepotential adverse health (cancer and non-cancer) impacts, due to lower hazardouscombustion-related emissions, compared to landfill or unsorted incineration. Poorly fed WtEfacilities may emit concentrated toxins with serious potential health risks, such as dioxins/furansand heavy metals; these toxins may remain problematic in bottom ash as a combustion by-product.Most modelling studies estimate that electricity (per unit) generated from WtE generally emits lesshealth-relevant air pollutants (also less greenhouse gases) than from combustion of fossil fuels (e.g.coal). Some modelled estimates vary due to model sensitivity for type of waste processed, modelinputs used, and facility operational conditions.We conclude that rigorous assessment (e.g. HRA including sensitivity analyses) of WtEfacility/technological characteristics and refuse type used is necessary when planning/proposing facilities to protect human health as the technology is adopted worldwide

Health impact assessment of active transportation: A systematic review

Objective Walking and cycling for transportation (i.e. active transportation, AT), provide substantial health benefits from increased physical activity (PA). However, risks of injury from exposure to motorized traffic and their emissions (i.e. air pollution) exist. The objective was to systematically review studies conducting health impact assessment (HIA) of a mode shift to AT on grounds of associated health benefits and risks. Methods Systematic database searches of MEDLINE, Web of Science and Transportation Research International Documentation were performed by two independent researchers, augmented by bibliographic review, internet searches and expert consultation to identify peer-reviewed studies from inception to December 2014. Results Thirty studies were included, originating predominantly from Europe, but also the United States, Australia and New Zealand. They compromised of mostly HIA approaches of comparative risk assessment and cost–benefit analysis. Estimated health benefit–risk or benefit–cost ratios of a mode shift to AT ranged between − 2 and 360 (median = 9). Effects of increased PA contributed the most to estimated health benefits, which strongly outweighed detrimental effects of traffic incidents and air pollution exposure on health. Conclusion Despite different HIA methodologies being applied with distinctive assumptions on key parameters, AT can provide substantial net health benefits, irrespective of geographical context

Transport mode choice and body mass index: Cross-sectional and longitudinal evidence from a European-wide study.

BACKGROUND: In the fight against rising overweight and obesity levels, and unhealthy urban environments, the renaissance of active mobility (cycling and walking as a transport mode) is encouraging. Transport mode has been shown to be associated to body mass index (BMI), yet there is limited longitudinal evidence demonstrating causality. We aimed to associate transport mode and BMI cross-sectionally, but also prospectively in the first ever European-wide longitudinal study on transport and health. METHODS: Data were from the PASTA project that recruited adults in seven European cities (Antwerp, Barcelona, London, Oerebro, Rome, Vienna, Zurich) to complete a series of questionnaires on travel behavior, physical activity levels, and BMI. To assess the association between transport mode and BMI as well as change in BMI we performed crude and adjusted linear mixed-effects modeling for cross-sectional (n = 7380) and longitudinal (n = 2316) data, respectively. RESULTS: Cross-sectionally, BMI was 0.027 kg/m2 (95%CI 0.015 to 0.040) higher per additional day of car use per month. Inversely, BMI was -0.010 kg/m2 (95%CI -0.020 to -0.0002) lower per additional day of cycling per month. Changes in BMI were smaller in the longitudinal within-person assessment, however still statistically significant. BMI decreased in occasional (less than once per week) and non-cyclists who increased cycling (-0.303 kg/m2, 95%CI -0.530 to -0.077), while frequent (at least once per week) cyclists who stopped cycling increased their BMI (0.417 kg/m2, 95%CI 0.033 to 0.802). CONCLUSIONS: Our analyses showed that people lower their BMI when starting or increasing cycling, demonstrating the health benefits of active mobility

Stringency of COVID-19 containment response policies and air quality changes: a global analysis across 1851 cities

The COVID-19 containment response policies (CRPs) had a major impact on air quality (AQ). These CRPs have been time-varying and location-specific. So far, despite having numerous studies on the effect of COVID-19 lockdown on AQ, a knowledge gap remains on the association between stringency of CRPs and AQ changes across the world, regions, nations, and cities. Here, we show that globally across 1851 cities (each more than 300000 people) in 149 countries, after controlling for the impacts of relevant covariates (e.g., meteorology), Sentinel-5P satellite-observed nitrogen dioxide (NO2) levels decreased by 4.9% (95% CI: 2.2, 7.6%) during lockdowns following stringent CRPs compared to pre-CRPs. The NO2 levels did not change significantly during moderate CRPs and even increased during mild CRPs by 2.3% (95% CI: 0.7, 4.0%), which was 6.8% (95% CI: 2.0, 12.0%) across Europe and Central Asia, possibly due to population avoidance of public transportation in favor of private transportation. Among 1768 cities implementing stringent CRPs, we observed the most NO2 reduction in more populated and polluted cities. Our results demonstrate that AQ improved when and where stringent COVID-19 CRPs were implemented, changed less under moderate CRPs, and even deteriorated under mild CRPs. These changes were location-, region-, and CRP-specific

Engaging Undergraduates in Science Research: Not Just About Faculty Willingness.

Despite the many benefits of involving undergraduates in research and the growing number of undergraduate research programs, few scholars have investigated the factors that affect faculty members' decisions to involve undergraduates in their research projects. We investigated the individual factors and institutional contexts that predict faculty members' likelihood of engaging undergraduates in their research project(s). Using data from the Higher Education Research Institute's 2007-2008 Faculty Survey, we employ hierarchical generalized linear modeling to analyze data from 4,832 science, technology, engineering, and mathematics (STEM) faculty across 194 institutions to examine how organizational citizenship behavior theory and social exchange theory relate to mentoring students in research. Key findings show that faculty who work in the life sciences and those who receive government funding for their research are more likely to involve undergraduates in their research project(s). In addition, faculty at liberal arts or historically Black colleges are significantly more likely to involve undergraduate students in research. Implications for advancing undergraduate research opportunities are discussed