SIGGMA: A Survey of Ionized Gas in the Galaxy, Made with the Arecibo Telescope

A Survey of Ionized Gas in the Galaxy, made with the Arecibo telescope (SIGGMA) uses the Arecibo L-band Feed Array (ALFA) to fully sample the Galactic plane (30 < l < 75 and -2 < b < 2; 175 < l < 207 and -2 < b < 1) observable with the telescope in radio recombination lines (RRLs). Processed data sets are being produced in the form of data cubes of 2 degree (along l) x 4 degree (along b) x 151 (number of channels), archived and made public. The 151 channels cover a velocity range of 600 km/s and the velocity resolution of the survey changes from 4.2 km/s to 5.1 km/s from the lowest frequency channel to the highest frequency channel, respectively.RRL maps with 3.4 arcmin resolution and line flux density sensitivity of 0.5 mJy will enable us to identify new HII regions, measure their electron temperatures, study the physics of photodissociation regions (PDRs) with carbon RRLs, and investigate the origin of the extended low density medium (ELDM). Twelve Hn{\alpha} lines fall within the 300 MHz bandpass of ALFA; they are resampled to a common velocity resolution to improve the signal-to-noise ratio (SN) by a factor of 3 or more and preserve the line width. SIGGMA will produce the most sensitive fully sampled RRL survey to date. Here we discuss the observing and data reduction techniques in detail. A test observation toward the HII region complex S255/S257 has detected Hn{\alpha} and Cn{\alpha} lines with SN>10

There is a low rate of major adverse cardiovascular events in chest pain patients with a moderate risk heart score referred from urgent care for expedited outpatient cardiology evaluation: a multi-center study

Background The HEART score is an effective method of risk stratifying emergency department (ED) patients with chest pain. The rate of major adverse cardiovascular events (MACE) in patients with moderate HEART score referred from an urgent care (UC) for an expedited outpatient cardiology evaluation for 11 months was described in 133 patients in a previous study. This is a follow-up study with 18 months of data and 206 patients.Aim. The primary outcome was to examine the rate of MACE when patients with moderate HEART score were referred for an expedited outpatient cardiology follow-up after evaluation in urgent care. The secondary outcome was to determine if there is a decrease in rate of ED transfer after this protocol was introduced.Methods. A cross-sectional study was conducted by a multispecialty group in Las Vegas, Nevada, which included 206 patients with a HEART score of 4 to 6 (i.e.: moderate risk) who presented to one of five UC centers with chest pain or an anginal equivalent. A streamlined evaluation protocol to assess each HEART score component was adopted by all UC providers to facilitate an expedited outpatient cardiology follow-up, as an alternative to referral to the emergency department. Data was collected from February 14, 2019 through August 13, 2020. The population was followed for 6 weeks with a primary endpoint of MACE determined by electronic medical record review and direct phone contact with patients. Outcomes were confirmed in 98% of patients. Chest pain transfer data was compared between 12 months prior to implementing HEART protocol and 18 months of data analysis while using the new protocol.Results. Over the course of 18 months, 206 patients with a moderate risk HEART score were referred to outpatient cardiology in an expedited manner. The average age was 65 with 53% female and 47% male patients. 150 patients (73% of the 206) were seen within 3 days, 114 (55%) underwent stress testing, 6 (3%) had coronary computed tomography angiogram, and 6 (3%) received an invasive coronary angiogram. Five patients were found to have MACE: one patient who had a non-ST-elevation myocardial infarction and subsequent coronary stent, two patients were found to have obstructive disease after coronary angiography with subsequent coronary artery bypass graft, one patient had an abnormal stress test and subsequent coronary stent, and one patient had critical mitral stenosis, multi-vessel coronary artery disease and underwent coronary artery bypass graft with mitral valve replacement with complications of renal failure and COVID-19 and expired. The emergency department referral rate declined by 21%.Conclusion. Patients with a moderate risk HEART score referred from UC for an expedited outpatient cardiology evaluation had a low rate of MACE and no deaths due to delay of care. There was also a significant decrease in the rate of ED referrals.Background. The HEART score is an effective method of risk stratifying emergency department (ED) patients with chest pain. The rate of major adverse cardiovascular events (MACE) in patients with moderate HEART score referred from an urgent care (UC) for an expedited outpatient cardiology evaluation for 11 months was described in 133 patients in a previous study. This is a follow-up study with 18 months of data and 206 patients.Aim. The primary outcome was to examine the rate of MACE when patients with moderate HEART score were referred for an expedited outpatient cardiology follow-up after evaluation in urgent care. The secondary outcome was to determine if there is a decrease in rate of ED transfer after this protocol was introduced.Methods. A cross-sectional study was conducted by a multispecialty group in Las Vegas, Nevada, which included 206 patients with a HEART score of 4 to 6 (i.e.: moderate risk) who presented to one of five UC centers with chest pain or an anginal equivalent. A streamlined evaluation protocol to assess each HEART score component was adopted by all UC providers to facilitate an expedited outpatient cardiology follow-up, as an alternative to referral to the emergency department. Data was collected from February 14, 2019 through August 13, 2020. The population was followed for 6 weeks with a primary endpoint of MACE determined by electronic medical record review and direct phone contact with patients. Outcomes were confirmed in 98% of patients. Chest pain transfer data was compared between 12 months prior to implementing HEART protocol and 18 months of data analysis while using the new protocol.Results. Over the course of 18 months, 206 patients with a moderate risk HEART score were referred to outpatient cardiology in an expedited manner. The average age was 65 with 53% female and 47% male patients. 150 patients (73% of the 206) were seen within 3 days, 114 (55%) underwent stress testing, 6 (3%) had coronary computed tomography angiogram, and 6 (3%) received an invasive coronary angiogram. Five patients were found to have MACE: one patient who had a non-ST-elevation myocardial infarction and subsequent coronary stent, two patients were found to have obstructive disease after coronary angiography with subsequent coronary artery bypass graft, one patient had an abnormal stress test and subsequent coronary stent, and one patient had critical mitral stenosis, multi-vessel coronary artery disease and underwent coronary artery bypass graft with mitral valve replacement with complications of renal failure and COVID-19 and expired. The emergency department referral rate declined by 21%.Conclusion. Patients with a moderate risk HEART score referred from UC for an expedited outpatient cardiology evaluation had a low rate of MACE and no deaths due to delay of care. There was also a significant decrease in the rate of ED referrals

Exposure to ambient particulate matter is associated with accelerated functional decline in idiopathic pulmonary fibrosis

BACKGROUND: Idiopathic pulmonary fibrosis (IPF), a progressive disease with an unknown pathogenesis, may be due in part to an abnormal response to injurious stimuli by alveolar epithelial cells. Air pollution and particulate inhalation of matter evoke a wide variety of pulmonary and systemic inflammatory diseases. We therefore hypothesized that increased average ambient particulate matter (PM) concentrations would be associated with an accelerated rate of decline in FVC in IPF. METHODS: We identified a cohort of subjects seen at a single university referral center from 2007 to 2013. Average concentrations of particulate matter < 10 and < 2.5 μg/m3 (PM10 and PM2.5, respectively) were assigned to each patient based on geocoded residential addresses. A linear multivariable mixed-effects model determined the association between the rate of decline in FVC and average PM concentration, controlling for baseline FVC at first measurement and other covariates. RESULTS: One hundred thirty-five subjects were included in the final analysis after exclusion of subjects missing repeated spirometry measurements and those for whom exposure data were not available. There was a significant association between PM10 levels and the rate of decline in FVC during the study period, with each μg/m3 increase in PM10 corresponding with an additional 46 cc/y decline in FVC (P = .008). CONCLUSIONS: Ambient air pollution, as measured by average PM10 concentration, is associated with an increase in the rate of decline of FVC in IPF, suggesting a potential mechanistic role for air pollution in the progression of disease

Glastir Monitoring & Evaluation Programme. Second year annual report

What is the purpose of Glastir Monitoring and Evaluation Programme? Glastir is the main scheme by which the Welsh Government pays for environmental goods and services whilst the Glastir Monitoring and Evaluation Programme (GMEP) evaluates the scheme’s success. Commissioning of the monitoring programme in parallel with the launch of the Glastir scheme provides fast feedback and means payments can be modified to increase effectiveness. The Glastir scheme is jointly funded by the Welsh Government (through the Rural Development Plan) and the EU. GMEP will also support a wide range of other national and international reporting requirements. What is the GMEP approach? GMEP collects evidence for the 6 intended outcomes from the Glastir scheme which are focussed on climate change, water and soil quality, biodiversity, landscape, access and historic environment, woodland creation and management. Activities include; a national rolling monitoring programme of 1km squares; new analysis of long term data from other schemes combining with GMEP data where possible; modelling to estimate future outcomes so that adjustments can be made to maximise impact of payments; surveys to assess wider socio-economic benefits; and development of novel technologies to increase detection and efficiency of future assessments. How has GMEP progressed in this 2nd year? 90 GMEP squares were surveyed in Year 2 to add to the 60 completed in Year 1 resulting in 50% of the 300 GMEP survey squares now being completed. Squares will be revisited on a 4 year cycle providing evidence of change in response to Glastir and other pressures such as changing economics of the farm business, climate change and air pollution. This first survey cycle collects the baseline against which future changes will be assessed. This is important as GMEP work this year has demonstrated land coming into the scheme is different in some respects to land outside the scheme. Therefore, future analysis to detect impact of Glastir will be made both against the national backdrop from land outside the scheme and this baseline data from land in scheme. A wide range of analyses of longterm data has been completed for all Glastir Outcomes with the exception of landscape quality and historic features condition for which limited data is available. This has involved combining data with 2013/14 GMEP data when methods allow. Overall analysis of long term data indicates one of stability but with little evidence of improvement with the exception of headwater quality, greenhouse gas emissions and woodland area for which there has been improvement over the last 20 years. Some headline statistics include: 51% of historic features in excellent or sound condition; two thirds of public rights of way fully open and accessible; improvement in hedgerow management with 85% surveyed cut in the last 3 years but < 1% recently planted; 91% of streams had some level of modification but 60% retained good ecological quality; no change topsoil carbon content over last 25 years. What is innovative? GMEP has developed various new metrics to allow for more streamlined reporting in the future. For example a new Priority Bird species Index for Wales which combines data from 35 species indicates at least half have stable or increasing populations. The new GMEP Visual Quality Landscape Index has been tested involving over 2600 respondents. Results have demonstrated its value as an objective and repeatable method for quantifying change in visual landscape quality. A new unified peat map for Wales has been developed which has been passed to Glastir Contract Managers to improve targeting of payments when negotiating Glastir contracts. An estimate of peat soil contribution to current greenhouse gas emissions due to human modification has been calculated. Models have allowed quantification of land area helping to mitigate rainfall runoff. We are using new molecular tools to explore the effects of Glastir on soil organisms and satellite technologies to quantify e.g. small woody features and landcover change. Finally we are using a community approach to develop a consensus on how to define and report change in High Nature Value Farmland which will be reported in the Year 3 GMEP report

Suppression of MAPK11 or HIPK3 reduces mutant Huntingtin levels in Huntington's disease models.

Most neurodegenerative disorders are associated with accumulation of disease-relevant proteins. Among them, Huntington disease (HD) is of particular interest because of its monogenetic nature. HD is mainly caused by cytotoxicity of the defective protein encoded by the mutant Huntingtin gene (HTT). Thus, lowering mutant HTT protein (mHTT) levels would be a promising treatment strategy for HD. Here we report two kinases HIPK3 and MAPK11 as positive modulators of mHTT levels both in cells and in vivo. Both kinases regulate mHTT via their kinase activities, suggesting that inhibiting these kinases may have therapeutic values. Interestingly, their effects on HTT levels are mHTT-dependent, providing a feedback mechanism in which mHTT enhances its own level thus contributing to mHTT accumulation and disease progression. Importantly, knockout of MAPK11 significantly rescues disease-relevant behavioral phenotypes in a knockin HD mouse model. Collectively, our data reveal new therapeutic entry points for HD and target-discovery approaches for similar diseases

Recovery of Phenanthrene-Degrading Bacteria after Simulated in Situ Persulfate Oxidation in Contaminated Soil

A continuous-flow column study was conducted to investigate the long-term effects of persulfate oxidation on the abundance and activity of the indigenous microbial community and phenanthrene-degrading bacteria in contaminated soil from a former manufactured gas plant (MGP) site. Approximately six pore volumes of a 20 g/L persulfate solution were introduced into the column, followed by simulated groundwater for 500 d. Soil samples were collected from the surface of the soil bed and along the column length immediately before and after persulfate injection and up to 500 d following injection. Exposure to persulfate led to a two- to three-log reduction in total bacterial 16S rRNA genes, severe inhibition of 14C-acetate mineralization (as a measure of general microbial activity), and a decrease in community diversity. However, relatively rapid recovery of both bacterial gene abundance and activity was observed within 30 d after persulfate exposure. Mineralization of 14C-phenanthrene was also inhibited but did not recover until 100 d post-oxidation. Known phenanthrene-degrading bacterial groups decreased to below detection limits throughout the column, with recovery times from 100 d to 500 d after persulfate injection. These findings suggest that coupling biological processes with persulfate oxidation is possible, although recovery of specific contaminant degraders may occur much later than the general microbial community recovers. Furthermore, the use of total bacterial quantity or non-specific measures of activity as a surrogate for the recovery of contaminant degraders may be inappropriate for evaluating the compatibility of chemical treatment with subsequent bioremediation

Cluster randomized trial of the impact of an obesity prevention intervention on child care center nutrition and physical activity environment over two years

Objective: The prevalence of obesity among preschool-aged children in the United States remains unacceptably high. Here we examine the impact of Healthy Caregivers-Healthy Children (HC2) Phase 2, a child care center (CCC)-based obesity prevention intervention on changes in the CCC nutrition and physical activity environment over two school years. Design: This was a cluster randomized trial with 12 CCC receiving the HC2 intervention arm and 12 in the control arm. The primary outcome was change in the Environment and Policy Assessment and Observation (EPAO) tool over two school years (Fall-2015, Spring-2016 and Spring-2017). Changes in EPAO physical activity and nutrition score were analyzed via a (1) random effects mixed models and (2) mixed models to determine the effect of HC2 versus control. Setting: The study was conducted in 24 CCCs serving low-income, ethnically diverse families in Miami-Dade County. Participants: Intervention CCCs received (1) teachers/parents/children curriculum; (2) snack, beverage, physical activity, and screen time policies; and (3) menu modifications. Results: Two-year EPAO nutrition score changes in intervention CCCs were almost twice that of control CCCs. The EPAO physical activity environment scores only slightly improved in intervention CCCs versus control CCCs. Intervention CCCs showed higher combined EPAO physical activity and nutrition scores compared to control CCCs over the 2-year study period (β=0.09, P=0.05). Conclusions: Obesity prevention programs can have a positive impact on the CCC nutrition environment and can promote healthy weight in early childhood. CCCs may need consistent support to improve the physical activity environment to ensure the policies remain intact

Histone deacetylases suppress cgg repeat-induced neurodegeneration via transcriptional silencing in models of Fragile X Tremor Ataxia Syndrome

Fragile X Tremor Ataxia Syndrome (FXTAS) is a common inherited neurodegenerative disorder caused by expansion of a CGG trinucleotide repeat in the 59UTR of the fragile X syndrome (FXS) gene, FMR1. The expanded CGG repeat is thought to induce toxicity as RNA, and in FXTAS patients mRNA levels for FMR1 are markedly increased. Despite the critical role of FMR1 mRNA in disease pathogenesis, the basis for the increase in FMR1 mRNA expression is unknown. Here we show that overexpressing any of three histone deacetylases (HDACs 3, 6, or 11) suppresses CGG repeat-induced neurodegeneration in a Drosophila model of FXTAS. This suppression results from selective transcriptional repression of the CGG repeat-containing transgene. These findings led us to evaluate the acetylation state of histones at the human FMR1 locus. In patient-derived lymphoblasts and fibroblasts, we determined by chromatin immunoprecipitation that there is increased acetylation of histones at the FMR1 locus in pre-mutation carriers compared to control or FXS derived cell lines. These epigenetic changes correlate with elevated FMR1 mRNA expression in pre-mutation cell lines. Consistent with this finding, histone acetyltransferase (HAT) inhibitors repress FMR1 mRNA expression to control levels in pre-mutation carrier cell lines and extend lifespan in CGG repeat-expressing Drosophila. These findings support a disease model whereby the CGG repeat expansion in FXTAS promotes chromatin remodeling in cis, which in turn increases expression of the toxic FMR1 mRNA. Moreover, these results provide proof of principle that HAT inhibitors or HDAC activators might be used to selectively repress transcription at the FMR1 locus.open293

ICH S1 prospective evaluation study and weight of evidence assessments: commentary from industry representatives

Industry representatives on the ICH S1B(R1) Expert Working Group (EWG) worked closely with colleagues from the Drug Regulatory Authorities to develop an addendum to the ICH S1B guideline on carcinogenicity studies that allows for a weight-of-evidence (WoE) carcinogenicity assessment in some cases, rather than conducting a 2-year rat carcinogenicity study. A subgroup of the EWG composed of regulators have published in this issue a detailed analysis of the Prospective Evaluation Study (PES) conducted under the auspices of the ICH S1B(R1) EWG. Based on the experience gained through the Prospective Evaluation Study (PES) process, industry members of the EWG have prepared the following commentary to aid sponsors in assessing the standard WoE factors, considering how novel investigative approaches may be used to support a WoE assessment, and preparing appropriate documentation of the WoE assessment for presentation to regulatory authorities. The commentary also reviews some of the implementation challenges sponsors must consider in developing a carcinogenicity assessment strategy. Finally, case examples drawn from previously marketed products are provided as a supplement to this commentary to provide additional examples of how WoE criteria may be applied. The information and opinions expressed in this commentary are aimed at increasing the quality of WoE assessments to ensure the successful implementation of this approach