Exposure to Polyfluoroalkyl Chemicals and Cholesterol, Body Weight, and Insulin Resistance in the General U.S. Population

BACKGROUND. Polyfluoroalkyl chemicals (PFCs) are used commonly in commercial applications and are detected in humans and the environment worldwide. Concern has been raised that they may disrupt lipid and weight regulation. OBJECTIVES. We investigated the relationship between PFC serum concentrations and lipid and weight outcomes in a large publicly available data set. METHODS. We analyzed data from the 2003-2004 National Health and Nutrition Examination Survey (NHANES) for participants 12-80 years of age. Using linear regression to control for covariates, we studied the association between serum concentrations of perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorooctane sulfonic acid (PFOS), and perfluorohexane sulfonic acid (PFHxS) and measures of cholesterol, body size, and insulin resistance. RESULTS. We observed a positive association between concentrations of PFOS, PFOA, and PFNA and total and non-high-density cholesterol. We found the opposite for PFHxS. Those in the highest quartile of PFOS exposure had total cholesterol levels 13.4 mg/dL [95% confidence interval (CI), 3.8-23.0] higher than those in the lowest quartile. For PFOA, PFNA, and PFHxS, effect estimates were 9.8 (95% CI, -0.2 to 19.7), 13.9 (95% CI, 1.9-25.9), and -7.0 (95% CI, -13.2 to -0.8), respectively. A similar pattern emerged when exposures were modeled continuously. We saw little evidence of a consistent association with body size or insulin resistance. CONCLUSIONS. This exploratory cross-sectional study is consistent with other epidemiologic studies in finding a positive association between PFOS and PFOA and cholesterol, despite much lower exposures in NHANES. Results for PFNA and PFHxS are novel, emphasizing the need to study PFCs other than PFOS and PFOA.National Institute of Environmental Health Sciences (R21ES013724, T32ES014562

Early Antiretroviral Therapy at High CD4 Counts Does Not Improve Arterial Elasticity: A Substudy of the Strategic Timing of AntiRetroviral Treatment (START) Trial

BACKGROUND: Both human immunodeficiency virus (HIV) infection and antiretroviral therapy (ART) may increase cardiovascular disease (CVD) risk. Vascular function assessments can be used to study CVD pathogenesis. We compared the effect of immediate versus deferred ART initiation at CD4 counts >500 cells/mm(3) on small arterial elasticity (SAE) and large artery elasticity (LAE). METHODS: Radial artery blood pressure waveforms were recorded noninvasively. Small arterial elasticity and LAE were derived from analysis of the diastolic pulse waveform. Randomized treatment groups were compared with linear models at each visit and longitudinal mixed models. RESULTS: Study visits involved 332 participants in 8 countries: mean (standard deviation [SD]) age 35 (10), 70% male, 66% nonwhite, 30% smokers, and median CD4 count 625 cells/mm(3) and 10-year Framingham risk score for CVD 1.7%. Mean (SD) SAE and LAE values at baseline were 7.3 (2.9) mL/mmHg × 100 and 16.6 (4.1) mL/mmHg × 10, respectively. Median time on ART was 47 and 12 months in the immediate and deferred ART groups, respectively. The treatment groups did not demonstrate significant within-person changes in SAE or LAE during the follow-up period, and there was no difference in mean change from baseline between treatment groups. The lack of significant differences persisted after adjustment, when restricted to early or late changes, after censoring participants in deferred group who started ART, and among subgroups defined by CVD and HIV risk factors. CONCLUSIONS: Among a diverse global population of HIV-positive persons with high CD4 counts, these randomized data suggest that ART treatment does not have a substantial influence on vascular function among younger HIV-positive individuals with preserved immunity

Ethical considerations in prehospital ambulance based research : qualitative interview study of expert informants

Abstract: Background: Prehospital ambulance based research has unique ethical considerations due to urgency, time limitations and the locations involved. We sought to explore these issues through interviews with experts in this research field. Methods: We undertook semi-structured interviews with expert informants, primarily based in the UK, seeking their views and experiences of ethics in ambulance based clinical research. Participants were questioned regarding their experiences of ambulance based research, their opinions on current regulations and guidelines, and views about their general ethical considerations. Participants were chosen because they were actively involved in, or in their expert capacity (e.g. law) expressed an interest in, ambulance based research. Results: Fourteen participants were interviewed including principal investigators, researchers, ethicists and medical lawyers. Five major themes were identified: Capacity, Consent, Clinical Considerations, Consultation and Regulation. Questions regarding consent and capacity were foremost in the discussions as all participants highlighted these as areas for concern. The challenges and use of multiple consent models reflected the complexity of research in this environment. The clinical theme referred to the role of paramedics in research and how research involving ambulance services is increasingly informing improvements to patient care and outcomes and reducing the burden on hospital services. Most felt that, although current regulations were fit for purpose, more specific guidance on implementing these in the ambulance setting would be beneficial. This related closely to the theme of consultation, which examined the key role of ethics committees and other regulatory bodies, as well as public engagement. Conclusions: By interviewing experts in research or ethics in this setting we were able to identify key concerns and highlight areas for future development such as improved guidance

Splenic size after division of the short gastric vessels in Nissen fundoplication in children

Item does not contain fulltextPURPOSE: Nissen fundoplication is an effective treatment for gastro-esophageal reflux disease (GERD). Mobilization of the gastric fundus during fundoplication requires division of short gastric vessels of the spleen, which may cause splenic ischemia. The aim of this study was to determine if Nissen fundoplication results in hypotrophy of the spleen. METHODS: We performed pre-operative and post-operative ultrasound measurements of the spleen in children undergoing Nissen fundoplication. During operation, the surgeon estimated the compromised blood flow by assessment of the percentage of discoloration of the spleen. RESULTS: Twenty-four consecutive children were analyzed. Discoloration of the upper pole of the spleen was observed in 11 patients (48%) of a median estimated splenic surface of 20% (range 5-50%). The median ratio for pre-operative and post-operative length, width, and area of the spleen was 0.97, 1.03, and 0.96, respectively. The percentage of the estimated perfusion defect during surgery was not correlated with the ratios. In three patients, the area ratio was smaller than 0.8 (0.67-0.75), meaning that the area decreased with at least 20% after surgery. In none of these patients a discoloration was observed. CONCLUSION: Discoloration of the spleen after Nissen fundoplication is not associated with post-operative splenic atrophy.1 maart 201

ParaVR: A Virtual Reality Training Simulator for Paramedic Skills maintenance

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Paramedic Practice, copyright © MA Healthcare, after peer review and technical editing by the publisher. To access the final edited and published work see https://www.paramedicpractice.com/features/article/paravr-a-virtual-reality-training-simulator-for-paramedic-skills-maintenance.Background, Virtual Reality (VR) technology is emerging as a powerful educational tool which is used in medical training and has potential benefits for paramedic practice education. Aim The aim of this paper is to report development of ParaVR, which utilises VR to address skills maintenance for paramedics. Methods Computer scientists at the University of Chester and the Welsh Ambulance Services NHS Trust (WAST) developed ParaVR in four stages: 1. Identifying requirements and specifications 2. Alpha version development, 3. Beta version development 4. Management: Development of software, further funding and commercialisation. Results Needle Cricothyrotomy and Needle Thoracostomy emerged as candidates for the prototype ParaVR. The Oculus Rift head mounted display (HMD) combined with Novint Falcon haptic device was used, and a virtual environment crafted using 3D modelling software, ported (a computing term meaning transfer (software) from one system or machine to another) onto Oculus Go and Google cardboard VR platform. Conclusion VR is an emerging educational tool with the potential to enhance paramedic skills development and maintenance. The ParaVR program is the first step in our development, testing, and scaling up of this technology

Opioid but not nonopioid stress-induced analgesia is enhanced following prenatal exposure to ethanol

Two neurochemically distinct forms of stress-induced analgesia were examined in adult rats following prenatal ethanol exposure. Rats were exposed to ethanol during the last 2 weeks of gestation through a liquid diet presented to the dams. Analgesia testing was conducted when the offspring were 150–210 days of age. Two forms of footshock stress were administered; one that resulted in a naloxone-sensitive (opioid-mediated) analgesia and one that resulted in a naloxone-insensitive (nonopioid) form of analgesia. Rats prenatally exposed to ethanol demonstrated significantly enhanced opioid-mediated analgesia, but unaltered nonpoioid analgesia compared to controls. These results confirm previous findings that prenatal exposure to ethanol leads to long-term alterations in responding to some, but not all forms of stress. The possibility that prenatal exposure to ethanol leads to perturbations in the endogenous opioid systems is discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46435/1/213_2004_Article_BF00427329.pd

In vivo STED microscopy visualizes morphological changes of large PSD95 assemblies over several hours in the mouse visual cortex

Abstract The post-synaptic density (PSD) is an electron dense region consisting of ~1000 proteins, found at the postsynaptic membrane of excitatory synapses, which varies in size depending upon synaptic strength. PSD95 is an abundant scaffolding protein in the PSD and assembles a family of supercomplexes comprised of neurotransmitter receptors, ion channels, as well as signalling and structural proteins. We use superresolution STED (STimulated Emission Depletion) nanoscopy to determine the size and shape of PSD95 in the anaesthetised mouse visual cortex. Adult knock-in mice expressing eGFP fused to the endogenous PSD95 protein were imaged at time points from 1 min to 6 h. Superresolved large assemblies of PSD95 show different sub-structures; most large assemblies were ring-like, some horse-shoe or figure-8 shaped, and shapes were continuous or made up of nanoclusters. The sub-structure appeared stable during the shorter (minute) time points, but after 1 h, more than 50% of the large assemblies showed a change in sub-structure. Overall, these data showed a sub-morphology of large PSD95 assemblies which undergo changes within the 6 hours of observation in the anaesthetised mouse

Seismic and geochemical evidence for large-scale mantle upwelling beneath the eastern Atlantic and western and central Europe

Seismic tomography and the isotope geochemistry of Cenozoic volcanic rocks suggest the existence of a large, sheet-like region of upwelling in the upper mantle which extends from the eastern Atlantic Ocean to central Europe and the western Mediterranean. A belt of extension and rifting in the latter two areas appears to lie above the intersection of the centre of the upwelling region with the base of the lithosphere. Lead, strontium and neodymium isotope data for all three regions converge on a restricted composition, inferred to be that of the upwelling mantle

Search for Kaluza-Klein Graviton Emission in ppˉp\bar{p} Collisions at s=1.8\sqrt{s}=1.8 TeV using the Missing Energy Signature

We report on a search for direct Kaluza-Klein graviton production in a data sample of 84 ${pb}^{-1}$ of \ppb collisions at $\sqrt{s}$ = 1.8 TeV, recorded by the Collider Detector at Fermilab. We investigate the final state of large missing transverse energy and one or two high energy jets. We compare the data with the predictions from a $3+1+n$-dimensional Kaluza-Klein scenario in which gravity becomes strong at the TeV scale. At 95% confidence level (C.L.) for $n$=2, 4, and 6 we exclude an effective Planck scale below 1.0, 0.77, and 0.71 TeV, respectively.Comment: Submitted to PRL, 7 pages 4 figures/Revision includes 5 figure

Measurement of the average time-integrated mixing probability of b-flavored hadrons produced at the Tevatron

We have measured the number of like-sign (LS) and opposite-sign (OS) lepton pairs arising from double semileptonic decays of $b$ and $\bar{b}$-hadrons, pair-produced at the Fermilab Tevatron collider. The data samples were collected with the Collider Detector at Fermilab (CDF) during the 1992-1995 collider run by triggering on the existence of $\mu \mu$ and $e \mu$ candidates in an event. The observed ratio of LS to OS dileptons leads to a measurement of the average time-integrated mixing probability of all produced $b$-flavored hadrons which decay weakly, $\bar{\chi} = 0.152 \pm 0.007$ (stat.) $\pm 0.011$ (syst.), that is significantly larger than the world average $\bar{\chi} = 0.118 \pm 0.005$.Comment: 47 pages, 10 figures, 15 tables Submitted to Phys. Rev.