Infant RSV immunoprophylaxis changes nasal epithelial DNA methylation at 6 years of age

BackgroundRespiratory syncytial virus (RSV) infection has been associated with childhood wheeze and asthma, and potential mechanisms include persistent epigenetic effects.MethodsIn the randomized, placebo-controlled MAKI trial, 429 preterm infants randomly received RSV immunoprophylaxis with palivizumab or placebo during their first RSV season. Children were followed until age 6 for asthma evaluation. DNA methylation in cells obtained by nasal brushes at age 6 was measured by Illumina MethylationEPIC array.ResultsRSV immunoprophylaxis in infancy had a significant impact on global methylation patterns in nasal cells at age 6. The first principal component (PC) related to the immunoprophylaxis intervention was enriched for the pathway "detection of chemical stimulus involved in sensory perception of smell" and "T cell differentiation." Subsequent analysis of these PCs indicated an effect of RSV immunoprophylaxis on cell type composition of nasal brushed cells. Three CpG sites, cg18040241, cg08243963, and cg19555973 which are annotated to genes GLB1L2, SC5D, and BPIFB1, were differentially methylated at genome-wide significance, but were not associated with asthma. ConclusionThe study provides the first proof of concept that RSV immunoprophylaxis during infancy has long-term effects on nasal epigenetic signatures at age 6, relating to host sensory perception, epidermal growth factor receptor signaling, and adaptive immune responses.</p

Geriatric Screening, Triage Urgency, and 30-Day Mortality in Older Emergency Department Patients

BACKGROUND: Urgency triage in the emergency department (ED) is important for early identification of potentially lethal conditions and extensive resource utilization. However, in older patients, urgency triage systems could be improved by taking geriatric vulnerability into account. We investigated the association of geriatric vulnerability screening in addition to triage urgency levels with 30-day mortality in older ED patients. DESIGN: Secondary analysis of the observational multicenter Acutely Presenting Older Patient (APOP) study. SETTING: EDs within four Dutch hospitals. PARTICIPANTS: Consecutive patients, aged 70 years or older, who were prospectively included. MEASUREMENTS: Patients were triaged using the Manchester Triage System (MTS). In addition, the APOP screener was used as a geriatric screening tool. The primary outcome was 30-day mortality. Comparison was made between mortality within the geriatric high- and low-risk screened patients in every urgency triage category. We calculated the difference in explained variance of mortality by adding the geriatric screener (APOP) to triage urgency (MTS) by calculating Nagelkerke R2. RESULTS: We included 2,608 patients with a median age of 79 (interquartile range = 74-84) years, of whom 521 (20.0%) patients were categorized as high risk accor

Recovery of Meteorological Data for the Observatory of A Guarda, Spain

We herein describe the recovery of a series of data on temperature, humidity, precipitation, evaporation, wind, and local weather conditions from documentary sources obtained from the Jesuit observatory of A Guarda (Galicia, Spain) for the period 1881–1896. The data were digitized and made available in accessible electronic formats. Comparisons were made with present-day meteorological data obtained from two nearby stations. We further believe that the discovery of some new complementary documentary sources made during the present research could be a basis for future data recovery efforts. Among these new results, early ozone data from the period are of outstanding importance to meteorologists

Fostering implementation of health services research findings into practice: a consolidated framework for advancing implementation science

Abstract Background Many interventions found to be effective in health services research studies fail to translate into meaningful patient care outcomes across multiple contexts. Health services researchers recognize the need to evaluate not only summative outcomes but also formative outcomes to assess the extent to which implementation is effective in a specific setting, prolongs sustainability, and promotes dissemination into other settings. Many implementation theories have been published to help promote effective implementation. However, they overlap considerably in the constructs included in individual theories, and a comparison of theories reveals that each is missing important constructs included in other theories. In addition, terminology and definitions are not consistent across theories. We describe the Consolidated Framework For Implementation Research (CFIR) that offers an overarching typology to promote implementation theory development and verification about what works where and why across multiple contexts. Methods We used a snowball sampling approach to identify published theories that were evaluated to identify constructs based on strength of conceptual or empirical support for influence on implementation, consistency in definitions, alignment with our own findings, and potential for measurement. We combined constructs across published theories that had different labels but were redundant or overlapping in definition, and we parsed apart constructs that conflated underlying concepts. Results The CFIR is composed of five major domains: intervention characteristics, outer setting, inner setting, characteristics of the individuals involved, and the process of implementation. Eight constructs were identified related to the intervention (e.g., evidence strength and quality), four constructs were identified related to outer setting (e.g., patient needs and resources), 12 constructs were identified related to inner setting (e.g., culture, leadership engagement), five constructs were identified related to individual characteristics, and eight constructs were identified related to process (e.g., plan, evaluate, and reflect). We present explicit definitions for each construct. Conclusion The CFIR provides a pragmatic structure for approaching complex, interacting, multi-level, and transient states of constructs in the real world by embracing, consolidating, and unifying key constructs from published implementation theories. It can be used to guide formative evaluations and build the implementation knowledge base across multiple studies and settings.http://deepblue.lib.umich.edu/bitstream/2027.42/78272/1/1748-5908-4-50.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/2/1748-5908-4-50-S1.PDFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/3/1748-5908-4-50-S3.PDFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/4/1748-5908-4-50-S4.PDFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/5/1748-5908-4-50.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/6/1748-5908-4-50-S2.PDFPeer Reviewe

Stable isotopic composition of fossil mammal teeth and environmental change in southwestern South Africa during the Pliocene and Pleistocene

The past 5 million years mark a global change from the warmer, more stable climate of the Pliocene to the initiation of glacial-interglacial cycles during the Pleistocene. Marine core sediment records located off the coast of southwestern Africa indicate aridification and intensified upwelling in the Benguela Current over the Pliocene and Pleistocene. However, few terrestrial records document environmental change in southwestern Africa over this time interval. Here we synthesize new and published carbon and oxygen isotope data of the teeth from large mammals (>6 kg) at Langebaanweg (~5 million years ago, Ma), Elandsfontein (1.0 – 0.6 Ma), and Hoedjiespunt (0.35 – 0.20 Ma), to evaluate environmental change in southwestern Africa between the Pliocene and Pleistocene. The majority of browsing and grazing herbivores from these sites yield enamel 13 C values within the range expected for animals with a pure C3 diet, however some taxa have enamel 13C values that suggest the presence of small amounts C4 grasses at times during the Pleistocene. Considering that significant amounts of C4 grasses require a warm growing season, these results indicate that the winter rainfall zone, characteristic of the region today, could have been in place for the past 5 million years. The average 18O value of the herbivore teeth increases ~4.4‰ between Langebaanweg and Elandsfontein for all taxa except suids. This increase may solely be a function of a change in hydrology between the fluvial system at Langebaanweg and the spring-fed environments at Elandsfontein, or a combination of factors that include depositional context, regional circulation and global climate. However, an increase in regional aridity or global cooling between the early Pliocene and mid-Pleistocene cannot explain the entire increase in enamel 18O values. Spring-fed environments like those at Elandsfontein may have 75 provided critical resources for mammalian fauna in the mid-Pleistocene within an increasingly arid southwestern Africa ecosystem

Comparison of prestellar core elongations and large-scale molecular cloud structures in the Lupus 1 region

Turbulence and magnetic fields are expected to be important for regulating molecular cloud formation and evolution. However, their effects on sub-parsec to 100 parsec scales, leading to the formation of starless cores, are not well understood. We investigate the prestellar core structure morphologies obtained from analysis of the Herschel-SPIRE 350 mum maps of the Lupus I cloud. This distribution is first compared on a statistical basis to the large-scale shape of the main filament. We find the distribution of the elongation position angle of the cores to be consistent with a random distribution, which means no specific orientation of the morphology of the cores is observed with respect to the mean orientation of the large-scale filament in Lupus I, nor relative to a large-scale bent filament model. This distribution is also compared to the mean orientation of the large-scale magnetic fields probed at 350 mum with the Balloon-borne Large Aperture Telescope for Polarimetry during its 2010 campaign. Here again we do not find any correlation between the core morphology distribution and the average orientation of the magnetic fields on parsec scales. Our main conclusion is that the local filament dynamics---including secondary filaments that often run orthogonally to the primary filament---and possibly small-scale variations in the local magnetic field direction, could be the dominant factors for explaining the final orientation of each core

Stable isotope ecology of Cape dune mole-rats (Bathyergus suillus) from Elandsfontein, South Africa: implications for C4 vegetation and hominin paleobiology in the Cape Floral Region

The archaeological and paleontological records from the west coast of South Africa have potential to provide insights into ecosystem dynamics in the region during the mid Pleistocene. Although the fossil record suggests an ecosystem quite different than that of the region today, we understand little about the ecological factors that contributed to this disparity. The site of Elandsfontein (EFT) dates to between 1.0 and 0.6 million years ago (Ma), preserves in situ lithic and faunal materials found in direct association with each other, and provides the rare opportunity to examine the relationship between hominin behavioural variability and landscape heterogeneity in a winter rainfall ecosystem. In this study, we examine the stable carbon isotopic composition of a large sample (n = 81) of Cape dune mole-rats (Bathyergus suillus) and contemporaneous large mammals (> 6 kg; n = 194) from EFT. We find that δ13C values of B. suillus are significantly different to those of contemporaneous large mammals from EFT indicating a significant presence of plants utilizing the C4 photosynthetic pathway during the mid-Pleistocene, in contrast to present C3 dominated ecosystems along the west coast of South Africa. Additionally, we find that artifact density at EFT localities is positively correlated with δ13C values in B. suillus enamel suggesting that evidence of more intense hominin occupation may be associated with the presence of more C4 vegetation. Lastly, we hypothesize that this unique distribution of vegetation 1) provided abundant resources for both hominin and non-hominin taxa and 2) may have concentrated hominin and animal behavior in certain places on the ancient landscape

Interdisciplinary Perspectives on Sun Safety and Skin Cancer Risk: achieving consensus

Overexposure to the sun is associated with an increased risk of melanoma and nonmelanoma skin cancer, but indications of improvements in sun protection behavior are poor. Attempts to identify emerging themes in skin cancer control have largely been driven by groups of experts from a single field. In December 2016, 19 experts from various disciplines convened for Interdisciplinary Perspectives on Skin Cancer, a 2-day meeting hosted by the National Academy of Sciences. The group discussed knowledge gaps, perspectives on sun exposure, implications for skin cancer risk and other health outcomes, and new directions. Five themes emerged from the discussion: (1) The definition of risk must be expanded, and categories for skin physiology must be refined to incorporate population diversities. (2) Risky sun exposure often co-occurs with other health-related behaviors. (3) Messages must be nuanced to target at-risk populations. (4) Persons at risk for tanning disorder must be recognized and treated. (5) Sun safety interventions must be scalable. Efficient use of technologies will be required to sharpen messages to specific populations and to integrate them within multilevel interventions. Further interdisciplinary research should address these emerging themes to build effective and sustainable approaches to large-scale behavior change

Measurements of Higgs boson production and couplings in diboson final states with the ATLAS detector at the LHC

Measurements are presented of production properties and couplings of the recently discovered Higgs boson using the decays into boson pairs, H →γ γ, H → Z Z∗ →4l and H →W W∗ →lνlν. The results are based on the complete pp collision data sample recorded by the ATLAS experiment at the CERN Large Hadron Collider at centre-of-mass energies of √s = 7 TeV and √s = 8 TeV, corresponding to an integrated luminosity of about 25 fb−1. Evidence for Higgs boson production through vector-boson fusion is reported. Results of combined fits probing Higgs boson couplings to fermions and bosons, as well as anomalous contributions to loop-induced production and decay modes, are presented. All measurements are consistent with expectations for the Standard Model Higgs boson

Standalone vertex finding in the ATLAS muon spectrometer

A dedicated reconstruction algorithm to find decay vertices in the ATLAS muon spectrometer is presented. The algorithm searches the region just upstream of or inside the muon spectrometer volume for multi-particle vertices that originate from the decay of particles with long decay paths. The performance of the algorithm is evaluated using both a sample of simulated Higgs boson events, in which the Higgs boson decays to long-lived neutral particles that in turn decay to bbar b final states, and pp collision data at √s = 7 TeV collected with the ATLAS detector at the LHC during 2011