Response to pulmonary arterial hypertension drug therapies in patients with pulmonary arterial hypertension and cardiovascular risk factors.

The age at diagnosis of pulmonary arterial hypertension (PAH) and the prevalence of cardiovascular (CV) risk factors are increasing. We sought to determine whether the response to drug therapy was influenced by CV risk factors in PAH patients. We studied consecutive incident PAH patients (n = 146) between January 1, 2008, and July 15, 2011. Patients were divided into two groups: the PAH-No CV group included patients with no CV risk factors (obesity, systemic hypertension, type 2 diabetes mellitus, permanent atrial fibrillation, mitral and/or aortic valve disease, and coronary artery disease), and the PAH-CV group included patients with at least one. The response to PAH treatment was analyzed in all the patients who received PAH drug therapy. The PAH-No CV group included 43 patients, and the PAH-CV group included 69 patients. Patients in the PAH-No CV group were younger than those in the PAH-CV group (P < 0.0001). In the PAH-No CV group, 16 patients (37%) improved on treatment and 27 (63%) did not improve, compared with 11 (16%) and 58 (84%) in the PAH-CV group, respectively (P = 0.027 after adjustment for age). There was no difference in survival at 30 months (P = 0.218). In conclusion, in addition to older age, CV risk factors may predict a reduced response to PAH drug therapy in patients with PAH

The effect of magnesium on the local structure and initial dissolution rate of simplified UK Magnox waste glasses

A series of simplified glasses were prepared to mimic the United Kingdom’'s Magnox radioactive waste glasses and determine the separate effect of the presence of Mg on the glass structure and the initial dissolution rate. These glasses had an alkaline earth (Ca/Mg) content of 6.5 mol% and relative ratios of Si, B and Na similar to 25 wt% waste loaded Magnox waste glass simulant. Each simplified glass had similar macroscopic properties, differing only in Ca/Mg ratio. 25Mg magic angle spinning nuclear magnetic resonance (MASNMR) spectra of the simplified Mg endmember (MgEM) glass (with no Ca) and the full-component simulant glass were similar, consistent with the similar Mg local environments in both glasses. 11B MASNMR spectra of the series of simplified glasses showed a systematic increase in the amount of three-coordinated boron ([3]B) with increasing amounts of Mg. A clear change in the charge balancing of four-coordinated boron ([4]B) by Mg compared with Ca is observed. However, 11B NMR measurements of the leached material showed that the additional [3]B was not preferentially leached from the Mg containing samples. Despite the structural changes in the glass induced by Ca/Mg substitution, initial dissolution rates (r0) remained invariant, within error, with Ca/Mg ratio. This indicates that the poorer aqueous durability of Mg-containing Magnox waste glass measured experimentally in long-term leaching experiments, compared with SON68 glass containing Ca, is not caused by a primary structural effect in the glass.R. Guo acknowledges the EPSRC and the University of Cambridge for an International Doctoral Scholarship. A portion of this work was funded by Radioactive Waste Management Limited (C.T. Brigden, S.W. Swanton and I. Farnan). The UK 850 MHz solid-state NMR Facility used in this research was funded by EPSRC and BBSRC (contract reference PR140003), as well as the University of Warwick including via part funding through Birmingham Science City Advanced Materials Projects 1 and 2 supported by Advantage West Midlands (AWM) and the European Regional Development Fund (ERDF). Collaborative assistance from the 850 MHz Facility Manager (Dinu Iuga, University of Warwick) is acknowledged

The patient experience of pulmonary hypertension : a large cross-sectional study of UK patients

Background Pulmonary Hypertension Association UK (PHA-UK) is the only charity in the UK especially for people affected by pulmonary hypertension (PH). To better understand the impact of PH on patients and carers beyond clinical symptoms, the PHA-UK carried out a cross-sectional survey on the effect of PH on daily living, along with a follow-up survey assessing the financial impact of PH. Methods This is a descriptive cross-sectional survey of adult patients with PH in the UK. A quantitative survey of four key topics (time to diagnosis, quality of life [QoL], financial impact and specialist treatment), was made available to PHA-UK members and patients on PH therapy, with a follow-up financial impact survey sent to those responders who agreed to be contacted further. Data collection was carried out in January and February 2017 for the main survey, and November and December 2017 for the financial impact survey. Results The main survey was completed by 567 individuals, and the financial follow-up survey by 171. Mean age of responders was 69 ± 17 years with 70% female. 60% of respondents said PH had a major impact on their QoL, with 45% reporting that treatment and management improves their QoL ‘a lot’. The time between first experiencing symptoms and diagnosis was ≥1 year for 48% of patients, with 40% seeing 4+ doctors before diagnosis. 63% of patients reported financial worries. Patients in part-time and full-time work reported the greatest financial burden, with a 13 and 33% fall in monthly income respectively. Patients had positive experiences of treatment in specialist centres, with 62% rating their care ‘excellent’, and 92% saying they preferred travelling to a specialist centre rather than seeing a local non-specialist. Conclusions This study reports the largest UK survey exploring issues affecting patients with PH. The study shows that despite the availability of new therapies, patients are still experiencing delays prior to diagnosis, and experiencing both emotional and financial impacts from the disease. By identifying the areas patients find most important in their treatment, this research can inform future care policies and long-term management to support patients living with PH and their families

Stromal and Tumor Glioma-Derived Cells with Similar Characteristics have Differences in α-Smooth Muscle Actin Expression and Localization

Gliomas are solid brain tumors composed of tumor cells and recruited heterogenic stromal components. The study of the interactions between the perivascular niche and its surrounding cells is of great value in unraveling mechanisms of drug resistance in malignant gliomas. In this study, we isolated the stromal diploid cell population from oligodendroglioma and a mixed population of tumor aneuploid and stromal diploid cells from astrocytoma specimens. The stromal cells expressed neural stem/progenitor and mesenchymal markers showing the same discordant phenotype that is typical for glioma cells. Moreover, some of the stromal cells expressed CD133. For the first time, we demonstrated that this type of stromal cells had the typical myofibroblastic phenotype as the α-SMA+ cells formed α-SMA fibers and exhibited the specific function to deposit extracellular matrix (ECM) proteins at least in vitro. Immunofluorescent analysis showed diffuse or focal α-SMA staining in the cytoplasm of the astrocytoma-derived, A172, T98G, and U251MG glioma cells. We could suggest that α-SMA may be one of the main molecules, bearing protective functions. Possible mechanisms and consequences of α-SMA disruptions in gliomas are discussed

Northern Hemisphere Urban Heat Stress and Associated Labor Hour Hazard from ERA5 Reanalysis

Increasing surface air temperature is a fundamental characteristic of a warming world. Rising temperatures have potential impacts on human health through heat stress. One heat stress metric is the wet-bulb globe temperature, which takes into consideration the effects of radiation, humidity, and wind speed. It also has broad health and environmental implications. This study presents wet-bulb globe temperatures calculated from the fifth-generation European Centre for Medium-Range Weather Forecasts atmospheric reanalysis and combines it with health guidelines to assess heat stress variability and the potential for reduction in labor hours over the past decade on both the continental and urban scale. Compared to 2010–2014, there was a general increase in heat stress during the period from 2015 to 2019 throughout the northern hemisphere, with the largest warming found in tropical regions, especially in the northern part of the Indian Peninsula. On the urban scale, our results suggest that heat stress might have led to a reduction in labor hours by up to ~20% in some Asian cities subject to work–rest regulations. Extremes in heat stress can be explained by changes in radiation and circulation. The resultant threat is highest in developing countries in tropical areas where workers often have limited legal protection and healthcare. The effect of heat stress exposure is therefore a collective challenge with environmental, economic, and social implications.publishedVersio

The effect of magnesium on the local structure and initial dissolution rate of simplified UK Magnox waste glasses

A series of simplified glasses were prepared to mimic the United Kingdom's Magnox radioactive waste glasses and determine the separate effect of the presence of Mg on the glass structure and the initial dissolution rate. These glasses had an alkaline earth (Ca/Mg) content of 6.5 mol% and relative ratios of Si, B and Na similar to 25 wt% waste loaded Magnox waste glass simulant. Each simplified glass had similar macroscopic properties, differing only in Ca/Mg ratio. 25Mg magic angle spinning nuclear magnetic resonance (MAS NMR) spectra of the simplified Mg endmember (MgEM) glass (with no Ca) and the full-component simulant glass were similar, consistent with the similar Mg local environments in both glasses. 11B MAS NMR spectra of the series of simplified glasses showed a systematic increase in the amount of three-coordinated boron ([3]B) with increasing amounts of Mg. A clear change in the charge balancing of four-coordinated boron ([4]B) by Mg compared with Ca is observed. However, 11B NMR measurements of the leached material showed that the additional [3]B was not preferentially leached from the Mg containing samples. Despite the structural changes in the glass induced by Ca/Mg substitution, initial dissolution rates (r0) remained invariant, within error, with Ca/Mg ratio. This indicates that the poorer aqueous durability of Mg-containing Magnox waste glass measured experimentally in long-term leaching experiments, compared with SON68 glass containing Ca, is not caused by a primary structural effect in the glass

GAMMA-RAY SPECTROMETRY OF HOT PLASMAS

Gamma-ray spectrometry provides diagnostics of fast ion behavior in plasmas of large tokamaks. Information acquiring with the gamma-ray diagnostics gives possibility to identify and distinguish simultaneously presence of fast alpha-particles and other ions He), to obtain its relative densities and also to perform tomographic radial profile reconstruction of the gammaemission sources

Association of NPAC score with survival after acute myocardial infarction

BACKGROUND AND AIMS: Risk stratification in acute myocardial infarction (AMI) is important for guiding clinical management. Current risk scores are mostly derived from clinical trials with stringent patient selection. We aimed to establish and evaluate a composite scoring system to improve short-term mortality classification after index episodes of AMI, independent of electrocardiography (ECG) pattern, in a large real-world cohort. METHODS: Using electronic health records, patients admitted to our regional teaching hospital (derivation cohort, n = 1747) and an independent tertiary care center (validation cohort, n = 1276), with index acute myocardial infarction between January 2013 and December 2017, as confirmed by principal diagnosis and laboratory findings, were identified retrospectively. RESULTS: Univariate logistic regression was used as the primary model to identify potential contributors to mortality. Stepwise forward likelihood ratio logistic regression revealed that neutrophil-to-lymphocyte ratio, peripheral vascular disease, age, and serum creatinine (NPAC) were significant for 90-day mortality (Hosmer- Lemeshow test, p = 0.21). Each component of the NPAC score was weighted by beta-coefficients in multivariate analysis. The C-statistic of the NPAC score was 0.75, which was higher than the conventional Charlson's score (C-statistic = 0.63). Judicious application of a deep learning model to our dataset improved the accuracy of classification with a C-statistic of 0.81. CONCLUSIONS: The NPAC score comprises four items from routine laboratory parameters to basic clinical information and can facilitate early identification of cases at risk of short-term mortality following index myocardial infarction. Deep learning model can serve as a gatekeeper to facilitate clinical decision-making