Postural Changes in Blood Pressure Associated with Interactions between Candidate Genes for Chronic Respiratory Diseases and Exposure to Particulate Matter

BACKGROUND. Fine particulate matter [aerodynamic diameter ≤ 2.5 μm (PM2.5)] has been associated with autonomic dysregulation. OBJECTIVE. We hypothesized that PM2.5 influences postural changes in systolic blood pressure (ΔSBP) and in diastolic blood pressure (ΔDBP) and that this effect is modified by genes thought to be related to chronic lung disease. METHODS. We measured blood pressure in participants every 3-5 years. ΔSBP and ΔDBP were calculated as sitting minus standing SBP and DBP. We averaged PM2.5 over 48 hr before study visits and analyzed 202 single nucleotide polymorphisms (SNPs) in 25 genes. To address multiple comparisons, data were stratified into a split sample. In the discovery cohort, the effects of SNP x PM2.5 interactions on ΔSBP and ΔDBP were analyzed using mixed models with subject-specific random intercepts. We defined positive outcomes as p < 0.1 for the interaction; we analyzed only these SNPs in the replicate cohort and confirmed them if p < 0.025 with the same sign. Confirmed associations were analyzed within the full cohort in models adjusted for anthropometric and lifestyle factors. RESULTS. Nine hundred forty-five participants were included in our analysis. One interaction with rs9568232 in PHD finger protein 11 (PHF11) was associated with greater ΔDBP. Interactions with rs1144393 in matrix metalloprotease 1 (MMP1) and rs16930692, rs7955200, and rs10771283 in inositol 1,4,5-triphosphate receptor, type 2 (ITPR2) were associated with significantly greater ΔSBP. Because SNPs associated with ΔSBP in our analysis are in genes along the renin-angiotensin pathway, we then examined medications affecting that pathway and observed significant interactions for angiotensin receptor blockers but not angiotensin-converting enzyme inhibitors with PM2.5. CONCLUSIONS. PM2.5 influences blood pressure and autonomic function. This effect is modified by genes and drugs that also act along this pathway.National Institute of Environmental Health Sciences (T32 ES07069, ES0002, ES015172-01, ES014663, P01 ES09825); United States Environmental Protection Agency (R827353, R832416); National Institutes of Health/National Institute of Aging (AG027014); United States Department of Veterans Affairs; Massachusetts Veterans Epidemiology Research and Information Cente

H.E.S.S. Observations of Sgr A*

The Galactic Centre has been studied with the High Energy Stereoscopic System (H.E.S.S.) for over 10 years, showing a bright, complex gamma-ray morphology. Other than a strong point-like very-high-energy gamma-ray source coincident with the supermassive black hole Sgr A*, previous analyses also revealed a diffuse ridge of gamma-ray emission, indicative of a powerful cosmic-ray accelerator in this region. It has been widely studied in the multiwavelength, exhibiting flares from radio to X-ray, but in the VHE regime it has always been stable. A gas cloud called G2 was found travelling straight to the Galactic Centre in 2011. Accretion rate was expected to increase which might possibly lead to flares in different wavebands. The addition of a fifth telescope with 600 m2 mirror area to the centre of the H.E.S.S. array has increased the energy range accessible, allowing observations to take place down to 100 GeV and potentially below. The sensitivity is also increased which means it has better ability to detect VHE flares from the Galactic Centre. In this work, long-term study of Sgr A* with H.E.S.S. I and data involving H.E.S.S. II around pericentre passage time of G2 is presented. Varibility tests are also applied to check for transient events. The overall spectrum and spectra for individual years have been stable over the years. The results of variability tests also revealed stability in the flux

Scaling relations of X-ray Luminous Clusters in the Hyper Suprime-Cam Subaru Strategic Program Field

We present the XMM-Newton X-ray analysis of 19 X-ray luminous galaxy clusters of low-to-mid redshift ($< 0.4$) selected from the MCXC cluster catalogue in the Hyper Supri%survey as the first work in our series paper. We derive the hydrostatic equilibrium mass and study scaling relations using i) the whole sample, ii) only relaxed clusters and iii) only disturbed clusters. When considering the whole sample, the $Y_{\rm X}$-$M_{\rm tot}$ and $M_{\rm gas}$-$M_{\rm tot}$ relations agree with self-similarity. In terms of morphology, relaxed clusters show a flatter relation in $L_{\rm X,ce}$-$M_{\rm tot}$, $L_{\rm X,bol}$-$M_{\rm tot}$, $L_{\rm X,ce}$-$T$, $L_{\rm bol,ce}$-$T$, $M_{\rm gas}$-$M_{\rm tot}$ and $Y_{\rm X}$-$M_{\rm tot}$. The $L_{\rm bol,ce}$-$M_{\rm tot}$, $L_{\rm X,ce}$-$M_{\rm tot}$ $L_{\rm bol,ce}$-$T$ and $L_{\rm X,ce}$-$T$ relations show a slope $\sim$3$\sigma$ steeper. The residuals in the $M_{\rm gas}$-$M_{\rm tot}$ and $T$-$M_{\rm tot}$ relations and the intrinsic covariance between $M_{\rm gas}$ and $T$ show hints of positive correlation, casting doubt on whether the $Y_{\rm X}$ parameter is a truly low scatter mass proxy. The $M_{\rm gas}$-$M_{\rm tot}$ and $T$-$M_{\rm tot}$ plots color-coded with the offset of the $L_{\rm X,ce}$-$M_{\rm tot}$ relation show these two relations to be brightness dependent but not the $L_{\rm X,ce}$-$T$ relation, suggesting relations involving $M_{\rm tot}$ are biased due to sample selection based on luminosity. Following the work which studied an optical sample and combining our result with literature studies, we find the $M_{\rm tot}$ derived not using mass proxies deviate from $L_{\rm X}$ $\propto$ $M_{\rm gas}^{2}M_{\rm tot}^{-1}$ and $M_{\rm tot}$ based on hydrostatic equilibrium are more massive than what is expected by their relation using caustic masses. This indicates mass bias plays an important role in scaling relations.Comment: Accepted for publication in MNRAS, 16 pages, 19 figure

Developmental Exposure to PCBs, MeHg, or Both: Long-Term Effects on Auditory Function

Background: Developmental exposure to polychlorinated biphenyls (PCBs) or methylmercury (MeHg) can result in a variety of neurotoxic effects, including long-term auditory deficits. However, little is known about the effects of combined exposure to PCBs and MeHg on auditory function. Objective: We developmentally exposed rats to PCBs and/or MeHg and assessed auditory function in adulthood to determine the effects of exposure to these contaminants individually and in combination. Methods: We exposed female Long-Evans rats to 1 or 3 mg/kg PCB in corn oil, 1.5 or 4.5 ppm MeHg in drinking water, or combined exposure to 1 mg/ kg PCB + 1.5 ppm MeHg or 3 mg/kg PCB + 4.5 ppm MeHg. Controls received corn oil vehicle and unadulterated water. Dosing began 28 days before breeding and continued until weaning at postnatal day (PND) 21. Auditory function of the offspring was assessed at approximately PND 200 by measuring distortion product otoacoustic emissions (DPOAEs) and auditory brainstem responses (ABRs). Results: Groups exposed to PCBs alone had attenuated DPOAEs amplitudes, elevated DPOAE thresholds, and elevated ABR thresholds compared with controls. Groups exposed to MeHg alone did not differ from controls. Unexpectedly, the effects of PCB exposure appeared to be attenuated by coexposure to MeHg. Conclusions: Developmental exposure to PCBs can result in permanent hearing deficits, and the change in DPOAE amplitudes and threshold suggest a cochlear site of action. Coexposure to MeHg appeared to attenuate the PCB-related deficits, but the mechanism for this unexpected interaction remains to be determined

Postural Changes in Blood Pressure Associated with Interactions between Candidate Genes for Chronic Respiratory Diseases and Exposure to Particulate Matter

Background: Fine particulate matter [aerodynamic diameter ≤ 2.5 μm (PM2.5)] has been associated with autonomic dysregulation.Objective We hypothesized that PM2.5 influences postural changes in systolic blood pressure (ΔSBP) and in diastolic blood pressure (ΔDBP) and that this effect is modified by genes thought to be related to chronic lung disease. Methods: We measured blood pressure in participants every 3–5 years. ΔSBP and ΔDBP were calculated as sitting minus standing SBP and DBP. We averaged PM2.5 over 48 hr before study visits and analyzed 202 single nucleotide polymorphisms (SNPs) in 25 genes. To address multiple comparisons, data were stratified into a split sample. In the discovery cohort, the effects of SNP × PM2.5 interactions on ΔSBP and ΔDBP were analyzed using mixed models with subject-specific random intercepts. We defined positive outcomes as p < 0.1 for the interaction; we analyzed only these SNPs in the replicate cohort and confirmed them if p < 0.025 with the same sign. Confirmed associations were analyzed within the full cohort in models adjusted for anthropometric and lifestyle factors. Results: Nine hundred forty-five participants were included in our analysis. One interaction with rs9568232 in PHD finger protein 11 (PHF11) was associated with greater ΔDBP. Interactions with rs1144393 in matrix metalloprotease 1 (MMP1) and rs16930692, rs7955200, and rs10771283 in inositol 1,4,5-triphosphate receptor, type 2 (ITPR2) were associated with significantly greater ΔSBP. Because SNPs associated with ΔSBP in our analysis are in genes along the renin–angiotensin pathway, we then examined medications affecting that pathway and observed significant interactions for angiotensin receptor blockers but not angiotensin-converting enzyme inhibitors with PM2.5. Conclusions: PM2.5 influences blood pressure and autonomic function. This effect is modified by genes and drugs that also act along this pathway

The Influence of the Metal Mass Fraction Z, Age, and Mixing-length Parameter on the RGB Bump Magnitude for the M4 Cluster

We identify the location of the RGB bump of M4 (NGC 6121) using the available photometric data, and measure VRGBB (similar to 13.57 +/- 0.04 mag). According to the observed [Fe/H], we compute theoretical isochrones with the scaled-solar composition in the MESA model and alpha-enhanced composition in the BaSTI model, respectively. Using a color-magnitude diagram, we compare these isochrones with the observed data to obtain the magnitude difference delta V-bump between the predicted and the observed bump magnitude. Based on the best fit of the MESA model with [Fe/H] = -1.05, [alpha/Fe] =0, alpha(MLT) = 2.0, and t = 13.3 Gyr, the bump magnitude difference delta V-bump is about 0.46 mag. Based on the best fit of the BaSTI model with alpha(MLT) = 2.2 similar to 2.4, [Fe/H] = -1.05, [alpha/Fe] = 0.4, and t = 12.5 Gyr, the bump magnitude difference delta V-bump is about 0.2 mag. To try and explain the bump magnitude differences, the metal mass fraction Z is enhanced as 0.0037, 0.00591, 0.0076, and 0.0085. Accordingly, delta V-RGBB vertical bar(t=12.0,alpha MLT =2.2, [alpha/Fe] = 0,Z=0.0076), delta V-RGBB vertical bar(t=12.0,alpha MLT) (=2.2, [alpha/Fe]=0, Z=0.0085), and delta V-RGBB vertical bar(t=11.0,alpha MLT=2.4,[alpha/Fe]=0,Z=0.0085) by the MESA model are 0, -0.01, and 0 mag, respectively. Increasing the assumed metallicity can decrease the discrepancy between the predicted and observed bump magnitudes. However, a metallicity increase large enough to resolve the offset, roughly similar to 0.60 dex for the MESA models, is ruled out by the spectroscopic data

Audit of short term outcomes of surgical and medical second trimester termination of pregnancy

<p>Abstract</p> <p>Background</p> <p>As comparisons of modern medical and surgical second trimester termination of pregnancy (TOP) are limited, and the optimum method of termination is still debated, an audit of second trimester TOP was undertaken, with the objective of comparing the outcomes of modern medical and surgical methods.</p> <p>Methods</p> <p>All cases of medical and surgical TOP between the gestations of 13 and 20 weeks from 1st January 2007 to 30th June 2008, among women residing in the local health board district, a tertiary teaching hospital in an urban setting, were identified by a search of ICD-10 procedure codes (surgical terminations) and from a ward database (medical terminations). Retrospective review of case notes was undertaken. A total of 184 cases, 51 medical and 133 surgical TOP, were identified. Frequency data were compared using Chi-squared or Fischer's Exact tests as appropriate and continuous data are presented as mean and standard deviation if normally distributed or median and interquartile range if non-parametric.</p> <p>Results</p> <p>Eighty-one percent of surgical terminations occurred between 13 to 16 weeks gestation, while 74% of medical terminations were performed between 17 to 20 weeks gestation. The earlier surgical TOP occurred in younger women and were more often indicated for maternal mental health. Sixteen percent of medical TOP required surgical delivery of the placenta. Evacuation of retained products was required more often after medical TOP (10%) than after surgical TOP (1%). Other serious complications were rare.</p> <p>Conclusion</p> <p>Both medical and surgical TOP are safe and effective for second trimester termination. Medical TOP tend to be performed at later gestations and are associated with a greater likelihood of manual removal of the placenta and delayed return to theatre for retained products. This case series does not address long term complications.</p

Communicating with the dead:lipids, lipid mediators and extracellular vesicle

Apoptosis is a key event in the control of inflammation. However, for this to be successful, dying cells must efficiently and effectively communicate their presence to phagocytes to ensure timely removal of dying cells. Here we consider apoptotic cell-derived extracellular vesicles (ACdEV) and the role of contained lipids and lipid mediators in ensuring effective control of inflammation. We discuss key outstanding issues in the study of cell death and cell communication, and introduce the concept of the ‘active extracellular vesicle’ as a metabolically-active and potentially changing intercellular communicator

Impact of COVID-19 pandemic on surgical neuro-oncology multi-disciplinary team decision making: a national survey (COVID-CNSMDT Study).

OBJECTIVES: Pressures on healthcare systems due to COVID-19 has impacted patients without COVID-19 with surgery disproportionally affected. This study aims to understand the impact on the initial management of patients with brain tumours by measuring changes to normal multidisciplinary team (MDT) decision making. DESIGN: A prospective survey performed in UK neurosurgical units performed from 23 March 2020 until 24 April 2020. SETTING: Regional neurosurgical units outside London (as the pandemic was more advanced at time of study). PARTICIPANTS: Representatives from all units were invited to collect data on new patients discussed at their MDT meetings during the study period. Each unit decided if management decision for each patient had changed due to COVID-19. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome measures included number of patients where the decision to undergo surgery changed compared with standard management usually offered by that MDT. Secondary outcome measures included changes in surgical extent, numbers referred to MDT, number of patients denied surgery not receiving any treatment and reasons for any variation across the UK. RESULTS: 18 units (75%) provided information from 80 MDT meetings that discussed 1221 patients. 10.7% of patients had their management changed-the majority (68%) did not undergo surgery and more than half of this group not undergoing surgery had no active treatment. There was marked variation across the UK (0%-28% change in management). Units that did not change management could maintain capacity with dedicated oncology lists. Low volume units were less affected. CONCLUSION: COVID-19 has had an impact on patients requiring surgery for malignant brain tumours, with patients receiving different treatments-most commonly not receiving surgery or any treatment at all. The variations show dedicated cancer operating lists may mitigate these pressures. STUDY REGISTRATION: This study was registered with the Royal College of Surgeons of England's COVID-19 Research Group (https://www.rcseng.ac.uk/coronavirus/rcs-covid-research-group/)

Subchronic toxicity of Baltic herring oil and its fractions in the rat II: Clinical observations and toxicological parameters

This study aimed to increase the knowledge about the toxicity of fish-derived organohalogen pollutants in mammals. The strategy chosen was to separate organohalogen pollutants derived from Baltic herring (Clupea harengus) fillet, in order to obtain fractions with differing proportions of identified and unidentified halogenated pollutants, and to perform a subchronic toxicity study in rats, essentially according to the OECD guidelines, at three dose levels. Nordic Sea Iodda (Mallotus villosus) oil, with low levels of persistent organohalogen pollutants, was used as an additional control diet. The toxicological examination showed that exposure to Baltic herring oil and its fractions at dose levels corresponding to a human intake in the range of 1.6 to 34.4 kg Baltic herring per week resulted in minimal effects. The spectrum of effects was similar to that, which is observed after low-level exposure to pollutants such as chlorinated dibenzo-p-dioxins and dibenzofurans (CDD/F) and chlorinated biphenyls, despite the fact that these contaminants contribute to a minor part of the extractable organically bound chlorine (EOC1). The study confirmed previous findings that induction of hepatic ethoxyresorufin deethylase (EROD) activity takes place at daily intake levels 0.15 ng fish-derived CDD/F-TEQs/kg body weight. The study also demonstrated that hepatic vitamin A reduction takes place at somewhat higher daily exposure levels, i.e. 0.16-0.30 ng fish-derived CDD/F-TEQs/kg body weight. Halogenated fatty acids, the major component of EOC1, could not be linked to any of the measured effects. From a risk management point of view, the study provides important new information of effect levels for Ah-receptor mediated responses following low level exposure to organohalogen compounds from a matrix relevant for human exposure