Effects of nebulised iloprost on pulmonary function and gas exchange in severe pulmonary hypertension

SummaryNebulised iloprost is established therapy of severe pulmonary hypertension; however, the effects on the bronchoalveolar compartment have not been investigated so far. We studied the short- and long-term effects of nebulised iloprost on pulmonary function tests and gas exchange in 63 patients with severe pulmonary hypertension (idiopathic n=17, chronic thromboembolism n=15, connective tissue disease n=12, congenital heart disease n=11, respiratory diseases n=8). Patients received iloprost in increasing dose up to 140μg iloprost/24h via an ultrasonic nebuliser.Short-term effects were assessed before and after every nebulisation: peak expiration flow decreased in mean by 1.9% (423±98 to 415±98) and percutaneous oxygen saturation increased in mean by 0.7% (90±6 to 91±5) post-nebulisation. There were no significant differences concerning underlying diagnosis or dose of nebulised iloprost. Within 3 months, 9 patients stopped treatment due to non-compliance with frequent nebulisations (n=3), or severe side effects (n=4); 2 patients with additional obstructive lung disease developed bronchoconstriction.Long-term effects were assessed by pulmonary function tests and gas exchange parameters at baseline and after 3 months treatment. There were no significant differences after 3 months therapy neither in FEV1, FVC, TLC, residual volume nor in diffusions capacity, SO2 at rest and during 6min walking test, also in respect of the underlying diseases. However, there was a significant increase in 6min walking distance (6 MWD) after 3 months (246±113 to 294±115m, P<0.05).In conclusion, treatment with nebulised iloprost leads to functional improvement in severe pulmonary hypertension without systematic adverse short- and long-term effects on pulmonary function test or gas exchange. Patients with additional obstructive lung disease might develop bronchoconstriction. Severe side effects leading to discontinuation of treatment occurred in 9% of patients

Poor survival outcomes in HER2 positive breast cancer patients with low grade, node negative tumours

We present a retrospective analysis on a cohort of low-grade, node-negative patients showing that human epidermal growth factor receptor 2 (HER2) status significantly affects the survival in this otherwise very good prognostic group. Our results provide support for the use of adjuvant trastuzumab in patients who are typically classified as having very good prognosis, not routinely offered standard chemotherapy, and who as such do not fit current UK prescribing guidelines for trastuzumab

Screening for left ventricular hypertrophy in patients with type 2 diabetes mellitus in the community

<p>Abstract</p> <p>Background</p> <p>Left ventricular hypertrophy (LVH) is a strong predictor of cardiovascular disease and is common among patients with type 2 diabetes. However, no systematic screening for LVH is currently recommended for patients with type 2 diabetes. The purpose of this study was to determine whether NT-proBNP was superior to 12-lead electrocardiography (ECG) for detection of LVH in patients with type 2 diabetes.</p> <p>Methods</p> <p>Prospective cross-sectional study comparing diagnostic accuracy of ECG and NT-proBNP for the detection of LVH among patients with type 2 diabetes. Inclusion criteria included having been diagnosed for > 5 years and/or on treatment for type 2 diabetes; patients with Stage 3/4 chronic kidney disease and known cardiovascular disease were excluded. ECG LVH was defined as either the Sokolow-Lyon or Cornell voltage criteria. NT-proBNP level was measured using the Roche Diagnostics Elecsys assay. Left ventricular mass was assessed from echocardiography. Receiver operating characteristic curve analysis was carried out and area under the curve (AUC) was calculated.</p> <p>Results</p> <p>294 patients with type 2 diabetes were recruited, mean age 58 (SD 11) years, BP 134/81 ± 18/11 mmHg, HbA_1c7.3 ± 1.5%. LVH was present in 164 patients (56%). In a logistic regression model age, gender, BMI and a history of hypertension were important determinants of LVH (p < 0.05). Only 5 patients with LVH were detected by either ECG voltage criteria. The AUC for NT-proBNP in detecting LVH was 0.68.</p> <p>Conclusions</p> <p>LVH was highly prevalent in asymptomatic patients with type 2 diabetes. ECG was an inadequate test to identify LVH and while NT-proBNP was superior to ECG it remained unsuitable for detecting LVH. Thus, there remains a need for a screening tool to detect LVH in primary care patients with type 2 diabetes to enhance risk stratification and management.</p

Validation of Phonon Physics in the CDMS Detector Monte Carlo

The SuperCDMS collaboration is a dark matter search effort aimed at detecting the scattering of WIMP dark matter from nuclei in cryogenic germanium targets. The CDMS Detector Monte Carlo (CDMS-DMC) is a simulation tool aimed at achieving a deeper understanding of the performance of the SuperCDMS detectors and aiding the dark matter search analysis. We present results from validation of the phonon physics described in the CDMS-DMC and outline work towards utilizing it in future WIMP search analyses.Comment: 6 Pages, 5 Figures, Proceedings of Low Temperature Detectors 14 Conferenc

Impact of an interatrial shunt device on survival and heart failure hospitalization in patients with preserved ejection fraction

Aims: Impaired left ventricular diastolic function leading to elevated left atrial pressures, particularly during exertion, is a key driver of symptoms and outcomes in heart failure with preserved ejection fraction (HFpEF). Insertion of an interatrial shunt device (IASD) to reduce left atrial pressure in HFpEF has been shown to be associated with short‐term haemodynamic and symptomatic benefit. We aimed to investigate the potential effects of IASD placement on HFpEF survival and heart failure hospitalization (HFH). Methods and results: Heart failure with preserved ejection fraction patients participating in the Reduce Elevated Left Atrial Pressure in Patients with Heart Failure study (Corvia Medical) of an IASD were followed for a median duration of 739 days. The theoretical impact of IASD implantation on HFpEF mortality was investigated by comparing the observed survival of the study cohort with the survival predicted from baseline data using the Meta‐analysis Global Group in Chronic Heart Failure heart failure risk survival score. Baseline and post‐IASD implant parameters associated with HFH were also investigated. Based upon the individual baseline demographic and cardiovascular profile of the study cohort, the Meta‐analysis Global Group in Chronic Heart Failure score‐predicted mortality was 10.2/100 pt years. The observed mortality rate of the IASD‐treated cohort was 3.4/100 pt years, representing a 33% lower rate (P = 0.02). By Kaplan–Meier analysis, the observed survival in IASD patients was greater than predicted (P = 0.014). Baseline parameters were not predictive of future HFH events; however, poorer exercise tolerance and a higher workload‐corrected exercise pulmonary capillary wedge pressure at the 6 months post‐IASD study were associated with HFH. Conclusions: The current study suggests IASD implantation may be associated with a reduction in mortality in HFpEF. Large‐scale ongoing randomized studies are required to confirm the potential benefit of this therapy

Ecological divergence and evolutionary transition of resprouting types in Banksia attenuata

Resprouting is a key functional trait that allows plants to survive diverse disturbances. The fitness benefits associated with resprouting include a rapid return to adult growth, early flowering, and setting seed. The resprouting responses observed following fire are varied, as are the ecological outcomes. Understanding the ecological divergence and evolutionary pathways of different resprouting types and how the environment and genetics interact to drive such morphological evolution represents an important, but under-studied, topic. In the present study, microsatellite markers and microevolutionary approaches were used to better understand: (1) whether genetic differentiation is related to morphological divergence among resprouting types and if so, whether there are any specific genetic variations associated with morphological divergence and (2) the evolutionary pathway of the transitions between two resprouting types in Banksia attenuata (epicormic resprouting from aerial stems or branch; resprouting from a underground lignotuber). The results revealed an association between population genetic differentiation and the morphological divergence of postfire resprouting types in B. attenuata. A microsatellite allele has been shown to be associated with epicormic populations. Approximate Bayesian Computation analysis revealed a likely evolutionary transition from epicormic to lignotuberous resprouting in B. attenuata. It is concluded that the postfire resprouting type in B. attenuata is likely determined by the fire's characteristics. The differentiated expression of postfire resprouting types in different environments is likely a consequence of local genetic adaptation. The capacity to shift the postfire resprouting type to adapt to diverse fire regimes is most likely the key factor explaining why B. attenuata is the most widespread member of the Banksia genus

Access to Dental Care for Children and Young People in Care and Care Leavers: A Global Scoping Review

Aims: This scoping review aimed to explore three research questions: 1. What is the dental care access for children and young people (CYP) in care and care leavers? 2. What factors influence CYP in care and care leavers’ access to dental care? 3. What pathways have been developed to improve access to oral health care for CYP in care and care leavers? Methods: Five databases (Ovid MEDLINE, Ovid Embase, CINAHL, SocINDEX and Dentistry and Oral Sciences Source) and grey literature sources were systematically searched. Articles relating to CYP in care or care leavers aged 0–25 years old, published up to January 2023 were included. Abstracts, posters and publications not in the English language were excluded. The data relating to dental care access were analysed using thematic analysis. Results: The search identified 942 articles, of which 247 were excluded as duplicates. A review of the titles and abstracts yielded 149 studies. Thirty-eight were eligible for inclusion in the review: thirty-three peer-reviewed articles, one PhD thesis and four grey literature sources. All papers were published from very high or medium Human Development Index countries. The studies indicate that despite having higher treatment needs, CYP in care and care leavers experience greater difficulty in accessing dental services than those not care-experienced. Organisational, psycho-social and logistical factors influence their access to dental care. Their experience of dental care may be impacted by adverse childhood events. Pathways to dental care have been developed, but little is known of their impact on access. There are very few studies that include care leavers. The voices of care-experienced CYP are missing from dental access research. Conclusions: care-experienced CYP are disadvantaged in their access to dental care, and there are significant barriers to their treatment needs being met

Improved Color-Temperature Relations and Bolometric Corrections for Cool Stars

We present new grids of colors and bolometric corrections for F-K stars having 4000 K < Teff < 6500 K, 0.0 < log g < 4.5 and -3.0 < [Fe/H] < 0.0. A companion paper extends these calculations into the M giant regime. Colors are tabulated for Johnson U-V and B-V; Cousins V-R and V-I; Johnson-Glass V-K, J-K and H-K; and CIT/CTIO V-K, J-K, H-K and CO. We have developed these color-temperature (CT) relations by convolving synthetic spectra with photometric filter-transmission-profiles. The synthetic spectra have been computed with the SSG spectral synthesis code using MARCS stellar atmosphere models as input. Both of these codes have been improved substantially, especially at low temperatures, through the incorporation of new opacity data. The resulting synthetic colors have been put onto the observational systems by applying color calibrations derived from models and photometry of field stars which have Teffs determined by the infrared-flux method. The color calibrations have zero points and slopes which change most of the original synthetic colors by less than 0.02 mag and 5%, respectively. The adopted Teff scale (Bell & Gustafsson 1989) is confirmed by the extraordinary agreement between the predicted and observed angular diameters of the field stars. We have also derived empirical CT relations from the field-star photometry. Except for the coolest dwarfs (Teff < 5000 K), our calibrated, solar-metallicity model colors are found to match these and other empirical relations quite well. Our calibrated, 4 Gyr, solar-metallicity isochrone also provides a good match to color-magnitude diagrams of M67. We regard this as evidence that our calibrated colors can be applied to many astrophysical problems, including modelling the integrated light of galaxies. (abridged)Comment: To appear in the March 2000 issue of the Astronomical Journal. 72 pages including 16 embedded postscript figures (one page each) and 6 embedded postscript tables (18 pages total

Modelling climate change responses in tropical forests: similar productivity estimates across five models, but different mechanisms and responses

Accurately predicting the response of Amazonia to climate change is important for predicting climate change across the globe. Changes in multiple climatic factors simultaneously result in complex non-linear ecosystem responses, which are difficult to predict using vegetation models. Using leaf- and canopy-scale observations, this study evaluated the capability of five vegetation models (Community Land Model version 3.5 coupled to the Dynamic Global Vegetation model – CLM3.5–DGVM; Ecosystem Demography model version 2 – ED2; the Joint UK Land Environment Simulator version 2.1 – JULES; Simple Biosphere model version 3 – SiB3; and the soil–plant–atmosphere model – SPA) to simulate the responses of leaf- and canopy-scale productivity to changes in temperature and drought in an Amazonian forest. The models did not agree as to whether gross primary productivity (GPP) was more sensitive to changes in temperature or precipitation, but all the models were consistent with the prediction that GPP would be higher if tropical forests were 5 °C cooler than current ambient temperatures. There was greater model–data consistency in the response of net ecosystem exchange (NEE) to changes in temperature than in the response to temperature by net photosynthesis (An), stomatal conductance (gs) and leaf area index (LAI). Modelled canopy-scale fluxes are calculated by scaling leaf-scale fluxes using LAI. At the leaf-scale, the models did not agree on the temperature or magnitude of the optimum points of An, Vcmax or gs, and model variation in these parameters was compensated for by variations in the absolute magnitude of simulated LAI and how it altered with temperature. Across the models, there was, however, consistency in two leaf-scale responses: (1) change in An with temperature was more closely linked to stomatal behaviour than biochemical processes; and (2) intrinsic water use efficiency (IWUE) increased with temperature, especially when combined with drought. These results suggest that even up to fairly extreme temperature increases from ambient levels (+6 °C), simulated photosynthesis becomes increasingly sensitive to gs and remains less sensitive to biochemical changes. To improve the reliability of simulations of the response of Amazonian rainforest to climate change, the mechanistic underpinnings of vegetation models need to be validated at both leaf- and canopy-scales to improve accuracy and consistency in the quantification of processes within and across an ecosystem.This research was enabled by a grant from the Andes–Amazon Initiative of The Gordon and Betty Moore Foundation. L. Rowland gratefully acknowledges financial support from the Natural Environment Research Council (UK) for a NERC PhD studentship, and NERC grant NE/J011002/1; PM also acknowledges support from ARC FT110100457

Evaluation of Lateglacial temperatures in the Southern Alps of New Zealand based on glacier modelling at Irishman Stream, Ben Ohau Range

Climate proxy records from the middle to high latitude Southern Hemisphere indicate that a Lateglacial (15,000-11,500 years ago) climate reversal, approximately coeval with the Antarctic Cold Reversal (ACR), interrupted a warming trend during deglaciation. In New Zealand, some palaeoclimate proxy records indicate a cool episode during the ACR (ca 14,500-12,500 years ago), while others do not express a significant change in climate. Recently published moraine maps and ages present an opportunity to improve the palaeoclimate interpretation through numerical modelling of glaciers. We use a coupled energy-balance and ice-flow model to quantify palaeoclimate from past glacier extent constrained by mapped and dated moraines in the headwaters of Irishman Stream, a high-elevation catchment in the Southern Alps. First, a suite of steady-state model runs is used to identify the temperature and precipitation forcing required to fit the modelled glacier to well-dated Lateglacial moraine crests. Second, time dependent glacier simulations forced by a nearby proxy temperature record derived from chironomids are used to assess the fit with the glacial geomorphic record. Steady-state experiments using an optimal parameter set demonstrate that the conditions under which the 13,000 year old moraine formed were 2.3-3.2 *C colder than present with the range in temperature corresponding to a +/- 20% variance in precipitation relative to the present-day. This reconstructed climate change relative to the present-day corresponds to an equilibrium-line altitude of ca 2000 +/- 40 m above sea level (asl), which is ca 400 m lower than present. Time-dependent simulations of glacier length produce ice advance to within 100 m of the 13,000 year old terminal moraine, indicating that the chironomid-based temperature forcing and moraine record provide consistent information about past climate. Our results, together with other climate proxy reconstructions from pollen records and marine sediment cores, support the notion that temperatures during the ACR in New Zealand were ~2-3 *C cooler than today