Sleep apnea cardiovascular clinical trials - current status and steps forward: the International Collaboration of Sleep Apnea Cardiovascular Trialists

Sleep apnea is a common chronic disease that is associated with coronary heart disease, stroke, heart failure and mortality, although the ability of sleep apnea treatment to reduce cardiovascular morbidity and mortality has not been demonstrated. In contrast to patients seeking treatment in sleep disorders centers, as many as half of individuals with moderate to severe sleep apnea in the general population do not report excessive sleepiness; however, if treatment of sleep apnea were shown to reduce cardiovascular disease risk, this would provide a strong rationale for treatment of sleep apnea even in the absence of daytime sleepiness. This article summarizes the status of clinical trials evaluating the potential cardiovascular benefits of sleep apnea treatment and discusses the challenges of conducting such trials, and introduces the International Collaboration of Sleep Apnea Cardiovascular Trialists (INCOSACT), a clinical research collaboration formed to foster cardiovascular sleep research.Australian National Health and Medical Research Counci

An integrated general practice and pharmacy-based intervention to promote the use of appropriate preventive medications among individuals at high cardiovascular disease risk: protocol for a cluster randomized controlled trial

Background: Cardiovascular diseases (CVD) are responsible for significant morbidity, premature mortality, and economic burden. Despite established evidence that supports the use of preventive medications among patients at high CVD risk, treatment gaps remain. Building on prior evidence and a theoretical framework, a complex intervention has been designed to address these gaps among high-risk, under-treated patients in the Australian primary care setting. This intervention comprises a general practice quality improvement tool incorporating clinical decision support and audit/feedback capabilities; availability of a range of CVD polypills (fixed-dose combinations of two blood pressure lowering agents, a statin ± aspirin) for prescription when appropriate; and access to a pharmacy-based program to support long-term medication adherence and lifestyle modification. Methods: Following a systematic development process, the intervention will be evaluated in a pragmatic cluster randomized controlled trial including 70 general practices for a median period of 18 months. The 35 general practices in the intervention group will work with a nominated partner pharmacy, whereas those in the control group will provide usual care without access to the intervention tools. The primary outcome is the proportion of patients at high CVD risk who were inadequately treated at baseline who achieve target blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) levels at the study end. The outcomes will be analyzed using data from electronic medical records, utilizing a validated extraction tool. Detailed process and economic evaluations will also be performed. Discussion: The study intends to establish evidence about an intervention that combines technological innovation with team collaboration between patients, pharmacists, and general practitioners (GPs) for CVD prevention. Trial registration: Australian New Zealand Clinical Trials Registry ACTRN1261600023342

A small-angle X-ray scattering study of the effect of chain architecture on the shear-induced crystallization of branched and linear poly(ethylene terephthalate)

The synchrotron-based small-angle X-ray scattering (SAXS) technique was used to investigate the shear-induced crystallization kinetics of branched/unbranched poly(ethylene terephthalate) (PET). Reactive extrusion of bottle-grade PET with the branching and chain-extension agents pyromellitic dianhydride and pentaerythritol results in enhanced rheological properties, such as higher melt strength and higher viscosity. In this study, six samples of PET were investigated: linear PET [intrinsic viscosity (IV) ≈0.76 dm3 g-1]; four branched PETs produced from linear PET by a reactive extrusion technique (IV ≈0.86-1.06 dm3 g-1); and a control PET (IV ≈0.73 dm3 g-1) extruded under the same conditions without reactive agents. SAXS data were recorded for the PET at the melt temperature and time-resolved SAXS data were recorded following the application of a step shear (53 s-1 for 2 s). As the PET IV was increased, the extent of shear-induced orientation increased, whilst the time taken for the polymer to initiate and complete crystallization decreased

Supercritical water gasification of microalgae: The impact of the algal growth water

Investigation into the supercritical water gasification (SCWG) of microalgae has largely used deionized water as the reaction medium. However, real systems would use the algal growth water directly, containing ions that have been known to catalyse SCWG (K+, Na+, OH-, Fe3+, Cl-). Investigation into the effect of the growth water on SCWG was carried out for a range of temperatures (450–550), biomass concentrations (1–3wt%) and catalysts (KOH, Ru/C), using glucose or Chlorella vulgaris as the feedstock was performed. A significant increase in CO2 and reduction in CO content in the gas was observed without a catalyst and with a Ru/C catalyst. An increase in char/tar was also observed without a catalyst. As a result, the impact of the growth water should be considered for the SCWG of microalgae, in laboratory experiments and the selection of algal growth media in industrial applications

Assessment of Iron(III) chloride as a catalyst for the production of hydrogen from the supercritical water gasification of microalgae

Alkali metal salts and supported transition metals have been the dominant catalysts used to maximise hydrogen production from supercritical water gasification (SCWG). Recently, FeCl3 has emerged as an alternative to these that has been found to be more effective in some cases reported in literature. However, to these authors’ knowledge, few studies exist that study this catalyst with none that involve microalgae as the feedstock. Investigation is reported into the effect of FeCl3 on the SCWG of Chlorella vulgaris for a range of temperatures (400–600°C) and biomass concentrations (1–3wt%), with comparisons made to other catalysts (KOH, Ru/C and their combinations). A significant decrease in hydrogen yield, carbon conversion and energy efficiency was observed with the addition of FeCl3, due to a reduced pH which suppressed the water gas shift reaction and catalysed of char forming reactions. This was in contrary to Ru/C and KOH catalysts, where those outcomes increased. Additionally, when FeCl3 was used with Ru/C, the ruthenium was poisoned, nullifying its positive effects. Consequently, FeCl3 is not a suitable catalyst for hydrogen production from microalgae, either alone or in conjunction with a ruthenium catalyst

Recent experiments on a small-angle/wide-angle X-ray scattering beam line at the ESRF

Recent results using a new combined small-angle/wide-angle X-ray scattering (SAXS/WAXS) beam line at the European Synchrotron Radiation Source (ESRF) will be presented. This beam line is specifically designed to be able to handle complicated sample environments required to perform time-resolved experiments mimicking processing conditions used in material science. Besides the attention that has been given to the interfacing of these sample environments to the beam line data acquisition system also the developments in detector technology will be discussed. The influence that a high count rate and low noise WAXS detector can have on the accuracy of experimental results in polymer crystallisation will be shown. It is shown that it is feasible to detect crystalline volume fractions as low as 10-3-10-4 in polymeric systems

To be financed or not : the role of patents for venture capital financing

This paper investigates how patent applications and grants held by new ventures improve their ability to attract venture capital (VC) financing. We argue that investors are faced with considerable uncertainty and therefore rely on patents as signals when trying to assess the prospects of potential portfolio companies. For a sample of VC-seeking German and British biotechnology companies we have identified all patents filed at the European Patent Office (EPO). Applying hazard rate analysis, we find that in the presence of patent applications, VC financing occurs earlier. Our results also show that VCs pay attention to patent quality, financing those ventures faster which later turn out to have high-quality patents. Patent oppositions increase the likelihood of receiving VC, but ultimate grant decisions do not spur VC financing, presumably because they are anticipated. Our empirical results and interviews with VCs suggest that the process of patenting generates signals which help to overcome the liabilities of newness faced by new ventures

Nurse-Led Medicines' Monitoring for Patients with Dementia in Care Homes: A Pragmatic Cohort Stepped Wedge Cluster Randomised Trial

People with dementia are susceptible to adverse drug reactions (ADRs). However, they are not always closely monitored for potential problems relating to their medicines: structured nurse-led ADR Profiles have the potential to address this care gap. We aimed to assess the number and nature of clinical problems identified and addressed and changes in prescribing following introduction of nurse-led medicines' monitoring.Pragmatic cohort stepped-wedge cluster Randomised Controlled Trial (RCT) of structured nurse-led medicines' monitoring versus usual care.Five UK private sector care homes.41 service users, taking at least one antipsychotic, antidepressant or anti-epileptic medicine.Nurses completed the West Wales ADR (WWADR) Profile for Mental Health Medicines with each participant according to trial step.Problems addressed and changes in medicines prescribed.Information was collected from participants' notes before randomisation and after each of five monthly trial steps. The impact of the Profile on problems found, actions taken and reduction in mental health medicines was explored in multivariate analyses, accounting for data collection step and site.Five of 10 sites and 43 of 49 service users approached participated. Profile administration increased the number of problems addressed from a mean of 6.02 [SD 2.92] to 9.86 [4.48], effect size 3.84, 95% CI 2.57-4.11, P <0.001. For example, pain was more likely to be treated (adjusted Odds Ratio [aOR] 3.84, 1.78-8.30), and more patients attended dentists and opticians (aOR 52.76 [11.80-235.90] and 5.12 [1.45-18.03] respectively). Profile use was associated with reduction in mental health medicines (aOR 4.45, 1.15-17.22).The WWADR Profile for Mental Health Medicines can improve the quality and safety of care, and warrants further investigation as a strategy to mitigate the known adverse effects of prescribed medicines.ISRCTN 48133332

Clinical and genetic characterization of individuals with predicted deleterious PHIP variants

Heterozygous deleterious variants in PHIP have been associated with behavioral problems, intellectual disability/developmental delay, obesity/overweight, and dysmorphic features (BIDOD syndrome). We report an additional 10 individuals with pleckstrin homology domain-interacting protein (PHIP)-predicted deleterious variants (four frameshift, three missense, two nonsense, and one splice site; six of which are confirmed de novo). The mutation spectrum is diverse, and there is no clustering of mutations across the protein. The clinical phenotype of these individuals is consistent with previous reports and includes behavioral problems, intellectual disability, developmental delay, hypotonia, and dysmorphic features. The additional individuals we report have a lower frequency of obesity than previous reports and a higher frequency of gastrointestinal problems, social deficits, and behavioral challenges. Characterizing additional individuals with diverse mutations longitudinally will provide better natural history data to assist with medical management and educational and behavioral support

Comparison of ABC Methods with Computerized Estimates of Intracerebral Hemorrhage Volume: The INTERACT2 Study

Background and Purpose: Hematoma volume is a key determinant of outcome in acute intracerebral hemorrhage (ICH). We aimed to compare estimates of ICH volume between simple (ABC/2, length, width, and height) and gold standard planimetric software approaches. Methods: Data are from the second Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2). Multivariable linear regression was used to compare ICH volumes on baseline CT scans using the ABC/2, modified ABC/2 (mABC/2), and MIStar software. Other aspects of ICH morphology examined included location, irregularity, heterogeneity, intraventricular and subarachnoid hemorrhage extension (SAH) of hematoma, and associated white matter lesions and brain atrophy. Results: In 2,084 patients with manual and semiautomated measurements, median (IQR) ICH volumes for each approach were: ABC/2 11.1 (5.11-20.88 mL), mABC/2 7.8 (3.88-14.11 mL), and MIStar 10.7 (5.59-18.66 mL). Median differences between ABC/2 and MIStar, and mABC/2 and MIStar were 0.34 (-1.01 to 2.96) and-2.4 (-4.95 to-0.7416), respectively. Hematoma volumes differed significantly with irregular shape (ABC/2 and MIStar, p < 0.001; mABC/2 and MIStar, p = 0.007) and larger volumes (mABC/2 and MIStar, p < 0.001; ABC/2 and MIStar, p = 0.07). ICH with SAH showed a significant discrepancy between ABC/2 and MIStar (p < 0.001). Conclusions: Overall, ABC/2 performs better than mABC/2 in estimating ICH volume. The largest discrepancies were evidenced against automated software for irregular-shaped and large ICH with SAH, but the clinical significance of this is uncertain