Sendaway capillary NT-proBNP in pulmonary hypertension

\ua9 Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. BACKGROUND: N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a biomarker of cardiac ventricular wall stress that is incorporated into pulmonary hypertension (PH) risk stratification models. Sendaway sampling may enable patients to perform NT-proBNP tests remotely. This UK-wide study aimed to assess the agreement of sendaway NT-proBNP with standard venous NT-proBNP and to assess the effect of delayed processing. METHODS: Reference venous NT-proBNP was collected from PH patients. Samples for capillary and venous sendaway tests were collected contemporaneously, mailed to a reference laboratory and processed at 3 and 7 days using a Roche Cobas e411 device. Differences in paired measurements were analysed with Passing-Bablok regression, percentage difference plots and the % difference in risk strata. RESULTS: 113 patients were included in the study. 13% of day 3 capillary samples were insufficient. Day 3 capillary samples were not equivalent to reference samples (Passing Bablok analysis slope of 0.91 (95% CI 0.88 to 0.93) and intercept of 6.0 (95% CI 0.2 to 15.9)). The relative median difference was -7% and there were acceptable limits of agreement. Day 3 capillary NT-proBNP accurately risk stratified patients in 93.5% of cases. By comparison, day 3 venous results accurately risk stratified patients in 90.1% of cases and were equivalent by Passing-Bablok regression. Delayed sampling of sendaway tests led to an unacceptable level of agreement and systematically underestimated NT-proBNP. CONCLUSIONS: Sendaway NT-proBNP sampling may provide an objective measure of right ventricular strain for virtual PH clinics. Results must be interpreted with caution in cases of delayed sampling

Predicting the Impact of Climate Change on Threatened Species in UK Waters

Global climate change is affecting the distribution of marine species and is thought to represent a threat to biodiversity. Previous studies project expansion of species range for some species and local extinction elsewhere under climate change. Such range shifts raise concern for species whose long-term persistence is already threatened by other human disturbances such as fishing. However, few studies have attempted to assess the effects of future climate change on threatened vertebrate marine species using a multi-model approach. There has also been a recent surge of interest in climate change impacts on protected areas. This study applies three species distribution models and two sets of climate model projections to explore the potential impacts of climate change on marine species by 2050. A set of species in the North Sea, including seven threatened and ten major commercial species were used as a case study. Changes in habitat suitability in selected candidate protected areas around the UK under future climatic scenarios were assessed for these species. Moreover, change in the degree of overlap between commercial and threatened species ranges was calculated as a proxy of the potential threat posed by overfishing through bycatch. The ensemble projections suggest northward shifts in species at an average rate of 27 km per decade, resulting in small average changes in range overlap between threatened and commercially exploited species. Furthermore, the adverse consequences of climate change on the habitat suitability of protected areas were projected to be small. Although the models show large variation in the predicted consequences of climate change, the multi-model approach helps identify the potential risk of increased exposure to human stressors of critically endangered species such as common skate (Dipturus batis) and angelshark (Squatina squatina)

Not just a matter of size:a hospital-level risk factor analysis of MRSA bacteraemia in Scotland

Background: Worldwide, there is a wealth of literature examining patient-level risk 6 factors for methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia. At the hospital-level it is generally accepted that MRSA bacteraemia is more common in larger hospitals. In Scotland, size does not fully explain all the observed variation among hospitals. The aim of this study was to identify risk factors for the presence and rate of MRSA bacteraemia cases in Scottish mainland hospitals. Specific hypotheses regarding hospital size, type and connectivity were examined. Methods: Data from 198 mainland Scottish hospitals (defined as having at least one inpatient per year) were analysed for financial year 2007-08 using logistic regression (Model 1: presence/absence of MRSA bacteraemia) and Poisson regression (Model 2: rate of MRSA bacteraemia). The significance of risk factors representing various measures of hospital size, type and connectivity were investigated. Results: In Scotland, size was not the only significant risk factor identified for the presence and rate of MRSA bacteraemia. The probability of a hospital having at least one case of MRSA bacteraemia increased with hospital size only if the hospital exceeded a certain level of connectivity. Higher levels of MRSA bacteraemia were associated with the large, highly connected teaching hospitals with high ratios of patients to domestic staff. Conclusions: A hospital’s level of connectedness within a network may be a better measure of a hospital’s risk of MRSA bacteraemia than size. This result could be used to identify high risk hospitals which would benefit from intensified infection control measures

HARPS3 for a roboticized Isaac Newton telescope

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.We present a description of a new instrument development, HARPS3, planned to be installed on an upgraded and roboticized Isaac Newton Telescope by end-2018. HARPS3 will be a high resolution (R = 115,000) echelle spectrograph with a wavelength range from 380-690 nm. It is being built as part of the Terra Hunting Experiment - a future 10 year radial velocity measurement programme to discover Earth-like exoplanets. The instrument design is based on the successful HARPS spectrograph on the 3.6m ESO telescope and HARPS-N on the TNG telescope. The main changes to the design in HARPS3 will be: a customised fibre adapter at the Cassegrain focus providing a stabilised beam feed and on-sky fibre diameter ~ 1.4 arcsec, the implementation of a new continuous flow cryostat to keep the CCD temperature very stable, detailed characterisation of the HARPS3 CCD to map the effective pixel positions and thus provide an improved accuracy wavelength solution, an optimised integrated polarimeter and the instrument integrated into a robotic operation. The robotic operation will optimise our programme which requires our target stars to be measured on a nightly basis. We present an overview of the entire project, including a description of our anticipated robotic operation.R.H. acknowledges the Science and Technologies Facilities Council (STFC) for his PhD studentship award (2015).J.I.G.H. acknowledges financial support from the Spanish Ministry of Economy and Competitiveness (MINECO) under the 2013 Ram´on y Cajal program MINECO RYC-2013-14875.J.I.G.H., R.R., and S.S.T. also acknowledge the Spanish ministry project MINECO AYA2014-56359-P.NP and ES are grateful to Knut and Alice Wallenberg Foundation for a generous support of the Swedish contribution to the THE project.AD acknowledges the support from Russian Foundation for Basic Research as part of research grant 15-52-12371

Circumstellar disks and planets. Science cases for next-generation optical/infrared long-baseline interferometers

We present a review of the interplay between the evolution of circumstellar disks and the formation of planets, both from the perspective of theoretical models and dedicated observations. Based on this, we identify and discuss fundamental questions concerning the formation and evolution of circumstellar disks and planets which can be addressed in the near future with optical and infrared long-baseline interferometers. Furthermore, the importance of complementary observations with long-baseline (sub)millimeter interferometers and high-sensitivity infrared observatories is outlined.Comment: 83 pages; Accepted for publication in "Astronomy and Astrophysics Review"; The final publication is available at http://www.springerlink.co

A diagnostic algorithm combining clinical and molecular data distinguishes Kawasaki disease from other febrile illnesses

<p>Abstract</p> <p>Background</p> <p>Kawasaki disease is an acute vasculitis of infants and young children that is recognized through a constellation of clinical signs that can mimic other benign conditions of childhood. The etiology remains unknown and there is no specific laboratory-based test to identify patients with Kawasaki disease. Treatment to prevent the complication of coronary artery aneurysms is most effective if administered early in the course of the illness. We sought to develop a diagnostic algorithm to help clinicians distinguish Kawasaki disease patients from febrile controls to allow timely initiation of treatment.</p> <p>Methods</p> <p>Urine peptidome profiling and whole blood cell type-specific gene expression analyses were integrated with clinical multivariate analysis to improve differentiation of Kawasaki disease subjects from febrile controls.</p> <p>Results</p> <p>Comparative analyses of multidimensional protein identification using 23 pooled Kawasaki disease and 23 pooled febrile control urine peptide samples revealed 139 candidate markers, of which 13 were confirmed (area under the receiver operating characteristic curve (ROC AUC 0.919)) in an independent cohort of 30 Kawasaki disease and 30 febrile control urine peptidomes. Cell type-specific analysis of microarrays (csSAM) on 26 Kawasaki disease and 13 febrile control whole blood samples revealed a 32-lymphocyte-specific-gene panel (ROC AUC 0.969). The integration of the urine/blood based biomarker panels and a multivariate analysis of 7 clinical parameters (ROC AUC 0.803) effectively stratified 441 Kawasaki disease and 342 febrile control subjects to diagnose Kawasaki disease.</p> <p>Conclusions</p> <p>A hybrid approach using a multi-step diagnostic algorithm integrating both clinical and molecular findings was successful in differentiating children with acute Kawasaki disease from febrile controls.</p

A chemical survey of exoplanets with ARIEL

Thousands of exoplanets have now been discovered with a huge range of masses, sizes and orbits: from rocky Earth-like planets to large gas giants grazing the surface of their host star. However, the essential nature of these exoplanets remains largely mysterious: there is no known, discernible pattern linking the presence, size, or orbital parameters of a planet to the nature of its parent star. We have little idea whether the chemistry of a planet is linked to its formation environment, or whether the type of host star drives the physics and chemistry of the planet’s birth, and evolution. ARIEL was conceived to observe a large number (~1000) of transiting planets for statistical understanding, including gas giants, Neptunes, super-Earths and Earth-size planets around a range of host star types using transit spectroscopy in the 1.25–7.8 μm spectral range and multiple narrow-band photometry in the optical. ARIEL will focus on warm and hot planets to take advantage of their well-mixed atmospheres which should show minimal condensation and sequestration of high-Z materials compared to their colder Solar System siblings. Said warm and hot atmospheres are expected to be more representative of the planetary bulk composition. Observations of these warm/hot exoplanets, and in particular of their elemental composition (especially C, O, N, S, Si), will allow the understanding of the early stages of planetary and atmospheric formation during the nebular phase and the following few million years. ARIEL will thus provide a representative picture of the chemical nature of the exoplanets and relate this directly to the type and chemical environment of the host star. ARIEL is designed as a dedicated survey mission for combined-light spectroscopy, capable of observing a large and well-defined planet sample within its 4-year mission lifetime. Transit, eclipse and phase-curve spectroscopy methods, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allow us to measure atmospheric signals from the planet at levels of 10–100 part per million (ppm) relative to the star and, given the bright nature of targets, also allows more sophisticated techniques, such as eclipse mapping, to give a deeper insight into the nature of the atmosphere. These types of observations require a stable payload and satellite platform with broad, instantaneous wavelength coverage to detect many molecular species, probe the thermal structure, identify clouds and monitor the stellar activity. The wavelength range proposed covers all the expected major atmospheric gases from e.g. H2O, CO2, CH4 NH3, HCN, H2S through to the more exotic metallic compounds, such as TiO, VO, and condensed species. Simulations of ARIEL performance in conducting exoplanet surveys have been performed – using conservative estimates of mission performance and a full model of all significant noise sources in the measurement – using a list of potential ARIEL targets that incorporates the latest available exoplanet statistics. The conclusion at the end of the Phase A study, is that ARIEL – in line with the stated mission objectives – will be able to observe about 1000 exoplanets depending on the details of the adopted survey strategy, thus confirming the feasibility of the main science objectives.Peer reviewedFinal Published versio

A comprehensive study on the role of the Yersinia pestis virulence markers in an animal model of pneumonic plague

We determined the role of Yersinia pestis virulence markers in an animal model of pneumonic plague. Eleven strains of Y. pestis were characterized using PCR assays to detect the presence of known virulence genes both encoded by the three plasmids as well as chromosomal markers. The virulence of all Y. pestis strains was compared in a mouse model for pneumonic plague. The presence of all known virulence genes correlated completely with virulence in the Balb/c mouse model. Strains which lacked HmsF initially exhibited visible signs of disease whereas all other strains (except wild-type strains) did not exhibit any disease signs. Forty-eight hours post-infection, mice which had received HmsF– strains regained body mass and were able to control infection; those infected with strains possessing a full complement of virulence genes suffered from fatal disease. The bacterial loads observed in the lung and other tissues reflected the observed clinical signs as did the cytokine changes measured in these animals. We can conclude that all known virulence genes are required for the establishment of pneumonic plague in mammalian animal models, the role of HmsF being of particular importance in disease progression

Effects of Blood Collection Conditions on Ovarian Cancer Serum Markers

Evaluating diagnostic and early detection biomarkers requires comparing serum protein concentrations among biosamples ascertained from subjects with and without cancer. Efforts are generally made to standardize blood processing and storage conditions for cases and controls, but blood sample collection conditions cannot be completely controlled. For example, blood samples from cases are often obtained from persons aware of their diagnoses, and collected after fasting or in surgery, whereas blood samples from some controls may be obtained in different conditions, such as a clinic visit. By measuring the effects of differences in collection conditions on three different markers, we investigated the potential of these effects to bias validation studies.We analyzed serum concentrations of three previously studied putative ovarian cancer serum biomarkers-CA 125, Prolactin and MIF-in healthy women, women with ovarian cancer undergoing gynecologic surgery, women undergoing surgery for benign ovary pathology, and women undergoing surgery with pathologically normal ovaries. For women undergoing surgery, a blood sample was collected either in the clinic 1 to 39 days prior to surgery, or on the day of surgery after anesthesia was administered but prior to the surgical procedure, or both. We found that one marker, prolactin, was dramatically affected by collection conditions, while CA 125 and MIF were unaffected. Prolactin levels were not different between case and control groups after accounting for the conditions of sample collection, suggesting that sample ascertainment could explain some or all of the previously reported results about its potential as a biomarker for ovarian cancer.Biomarker validation studies should use standardized collection conditions, use multiple control groups, and/or collect samples from cases prior to influence of diagnosis whenever feasible to detect and correct for potential biases associated with sample collection