Long-Term Changes of Source Apportioned Particle Number Concentrations in a metropolitan Area of the Northeastern United States

The northeastern United States has experienced significant emissions reductions in the last two decades leading to a decrease in PM2.5, major gaseous pollutants (SO2, CO, NOx) and ultrafine particles (UFPs) concentrations. Emissions controls were implemented for coal-fired power plants, and new heavy-duty diesel trucks were equipped with particle traps and NOx control systems, and ultralow sulfur content is mandatory for both road and non-road diesel as well as residual oil for space heating. At the same time, economic changes also influenced the trends in air pollutants. Investigating the influence of these changes on ultrafine particle sources is fundamental to determine the success of the mitigation strategies and to plan future actions. Particle size distributions have been measured in Rochester, NY since January 2002. The particle sources were investigated with positive matrix factorization (PMF) of the size distributions (11–470 nm) and measured criteria pollutants during five periods (2002–2003, 2004–2007, 2008–2010, 2011–2013, and 2014–2016) and three seasons (winter, summer, and transition). Monthly, weekly, and hourly source contributions patterns were evaluated

The Association between Respiratory Infection and Air Pollution in the Setting of Air Quality Policy and Economic Change

Rationale: Fine particulate air pollution (≤2.5µm; PM2.5) has been associated with an increased risk of respiratory disease, but assessments of specific respiratory infections in adults are lacking. Objective: To estimate the rate of respiratory infection healthcare encounters in adults associated with acute increases in PM2.5 concentrations. Methods: Using case-crossover methods, we studied 498,118 adult New York State residents with a primary diagnosis of influenza, bacterial pneumonia, or culture negative pneumonia upon hospitalization or emergency department (ED) visit (2005-2016). We estimated the rate of healthcare encounters associated with increases in PM2.5 in the previous 1-7 days and explored differences Before (2005 to 2007), During (2008-2013), and After (2014-2016) implementation of air quality policies and economic changes. Results: Interquartile range increases in PM2.5 over the previous 7 days were associated with increased excess rates of culture negative pneumonia hospitalizations (2.5%; 95% CI 1.7%, 3.2%) and ED visits (2.5%; 95% CI 1.4%, 3.6%), and increased excess rates of influenza ED visits (3.9%; 95% CI 2.1%, 5.6%). Bacterial pneumonia hospitalizations but not ED visits were associated with increases in PM2.5 and though imprecise, were of a similar magnitude to culture negative pneumonia (Lag day 6 ER 2.3%; 95% CI: 0.3, 4.3). Increased relative rates of influenza ED visits and culture negative pneumonia hospitalizations were generally larger in the After period (p< 0.025 for both outcomes), compared to the During period, despite reductions in overall PM2.5 concentrations. Conclusion: Increased rates of culture negative pneumonia and influenza were associated with increased PM2.5 concentrations during the previous week, which persisted despite reductions in PM2.5 from air quality policies and economic changes. Though unexplained, this temporal variation may reflect altered toxicity of different PM2.5 mixtures or increased pathogen virulence

Changes in the Acute Response of Respiratory Diseases to PM2.5 in New York State from 2005 to 2016

Prior studies reported that exposure to increased concentrations of fine particulate matter (PM2.5) were associated with increased rates of hospitalization and emergency department (ED) visits for asthma and chronic obstructive pulmonary disease (COPD). In this study, rates were examined from 2005 to 2016 using a case-crossover design to ascertain if there have been changes in the rates per unit mass exposure given substantial reductions in PM2.5 concentration and changes in its composition. PM2.5 concentrations were reduced through a combination of policies designed to improve air quality and economic drivers, including the 2008 economic recession and shifts in the relative costs of coal and natural gas. The study period was split into three periods reflecting that much of the emissions changes occurred between 2008 and 2013. Thus, the three periods were defined as: BEFORE (2005 to 2007), DURING (2008–2013), and AFTER (2014–2016). In general, the number of hospitalizations and ED visits declined with the decreased concentration of PM2.5. However, the rate of COPD hospitalizations and asthma ED visits associated with each interquartile range increase in ambient PM2.5 concentration was larger in the AFTER period than the DURING and BEFORE periods. For example, each 6.8 μg/m3 increase in PM2.5 on the same day was associated with 0.4% (0.0%, 0.8%), 0.3% (−0.2%, 0.7%), and 2.7% (1.9%, 3.5) increases in the rate of asthma emergency department visits in the BEFORE, DURING, and AFTER periods, respectively, suggesting the same mass concentration of PM2.5 was more toxic in the AFTER period

Virtual screening for inhibitors of the human TSLP:TSLPR interaction

The pro-inflammatory cytokine thymic stromal lymphopoietin (TSLP) plays a pivotal role in the pathophysiology of various allergy disorders that are mediated by type 2 helper T cell (Th2) responses, such as asthma and atopic dermatitis. TSLP forms a ternary complex with the TSLP receptor (TSLPR) and the interleukin-7-receptor subunit alpha (IL-7Ra), thereby activating a signaling cascade that culminates in the release of pro-inflammatory mediators. In this study, we conducted an in silico characterization of the TSLP: TSLPR complex to investigate the drugability of this complex. Two commercially available fragment libraries were screened computationally for possible inhibitors and a selection of fragments was subsequently tested in vitro. The screening setup consisted of two orthogonal assays measuring TSLP binding to TSLPR: a BLI-based assay and a biochemical assay based on a TSLP: alkaline phosphatase fusion protein. Four fragments pertaining to diverse chemical classes were identified to reduce TSLP: TSLPR complex formation to less than 75% in millimolar concentrations. We have used unbiased molecular dynamics simulations to develop a Markov state model that characterized the binding pathway of the most interesting compound. This work provides a proof-ofprinciple for use of fragments in the inhibition of TSLP: TSLPR complexation

External beam irradiation of myocardial carcinoid metastases: a case report

The heart is an exceedingly rare site of metastatic involvement in carcinoid tumors. Only nineteen cases have been described in the literature over the past 30 years. We report here on a patient who presented with progressive carcinoid syndrome despite surgical resection of her liver metastases. She was found to have cardiac metastases on inidium-111-pentetreotide scintigraphy and subsequently underwent external beam radiation to the heart resulting in symptomatic palliation of her syndrome and objective radiographic response. To our knowledge, this is the first reported case of metastatic cardiac carcinoid treated with external beam irradiation

Molecular crowding defines a common origin for the Warburg effect in proliferating cells and the lactate threshold in muscle physiology

Aerobic glycolysis is a seemingly wasteful mode of ATP production that is seen both in rapidly proliferating mammalian cells and highly active contracting muscles, but whether there is a common origin for its presence in these widely different systems is unknown. To study this issue, here we develop a model of human central metabolism that incorporates a solvent capacity constraint of metabolic enzymes and mitochondria, accounting for their occupied volume densities, while assuming glucose and/or fatty acid utilization. The model demonstrates that activation of aerobic glycolysis is favored above a threshold metabolic rate in both rapidly proliferating cells and heavily contracting muscles, because it provides higher ATP yield per volume density than mitochondrial oxidative phosphorylation. In the case of muscle physiology, the model also predicts that before the lactate switch, fatty acid oxidation increases, reaches a maximum, and then decreases to zero with concomitant increase in glucose utilization, in agreement with the empirical evidence. These results are further corroborated by a larger scale model, including biosynthesis of major cell biomass components. The larger scale model also predicts that in proliferating cells the lactate switch is accompanied by activation of glutaminolysis, another distinctive feature of the Warburg effect. In conclusion, intracellular molecular crowding is a fundamental constraint for cell metabolism in both rapidly proliferating- and non-proliferating cells with high metabolic demand. Addition of this constraint to metabolic flux balance models can explain several observations of mammalian cell metabolism under steady state conditions

A Dust Trap in the Young Multiple System HD 34700

This is the author accepted manuscript. The final version is available from the American Astronomical Society via the DOI in this recordMillimeter observations of disks around young stars reveal substructures indicative of gas pressure traps that may aid grain growth and planet formation. We present Submillimeter Array observations of HD 34700- two Herbig Ae stars in a close binary system (Aa/Ab, ∼0.25 AU), surrounded by a disk presenting a large cavity and spiral arms seen in scattered light, and two distant, lower mass companions. These observations include 1.3 mm continuum emission and the 12CO 2-1 line at ∼ 0. 005 (178 AU) resolution. They resolve a prominent azimuthal asymmetry in the continuum, and Keplerian rotation of a circumbinary disk in the 12CO line. The asymmetry is located at a radius of 155+11 −7 AU, consistent with the edge of the scattered light cavity, being resolved in both radius (72+14 −15 AU) and azimuth (FWHM = 64◦+8 −7 ). The strong asymmetry in millimeter continuum emission could be evidence for a dust trap, together with the more symmetric morphology of 12CO emission and small grains. We hypothesize an unseen circumbinary companion, responsible for the cavity in scattered light and creating a vortex at the cavity edge that manifests in dust trapping. The disk mass has limitations imposed by the detection of 12CO and non-detection of 13CO. We discuss its consequences for the potential past gravitational instability of this system, likely accounting for the rapid formation of a circumbinary companion. We also report the discovery of resolved continuum emission associated with HD 34700B (projected separation ∼ 1850AU), which we explain through a circumstellar disk.National Science Foundation (NSF

Clostridium septicum sepsis and colorectal cancer - a reminder

<p>Abstract</p> <p>Background</p> <p>Spontaneous clostridium septicum infections are rare and are associated with a high mortality. Association of clostridium infection with colorectal malignancies have been previously reported and most cases are described in tumours of the ascending colon. We report our experience of clostridium septicum infection in the presence of tumour perforation in a series of two patients as a reminder of its association with sepsis in the presence of colorectal malignancy.</p> <p>Case Presentation</p> <p>We isolated clostridium septicum infection in a series of two patients admitted as emergencies. One patient was found to have a perforated caecal tumour intraoperatively whilst the other had a perforated rectal tumour. The clinical outcome and management of each case are reported and underlying reasons for variations in outcome are discussed.</p> <p>Conclusion</p> <p>Although uncomman, the possibility of clostridium septicum sepsis should be borne in mind in patients who present with underlying malignancy and have sepsis. The cumulative effect of sepsis and malignant perforation is associated with a high morbidity and mortality. Awareness and early diagnosis of clostridium septicum may improve the prognosis of what is usually regarded as a fatal infection.</p

Selection at a single locus leads to widespread expansion of toxoplasma gondii lineages that are virulent in mice

The determinants of virulence are rarely defined for eukaryotic parasites such as T. gondii, a widespread parasite of mammals that also infects humans, sometimes with serious consequences. Recent laboratory studies have established that variation in a single secreted protein, a serine/threonine kinase known as ROPO18, controls whether or not mice survive infection. Here, we establish the extent and nature of variation in ROP18among a collection of parasite strains from geographically diverse regions. Compared to other genes, ROP18 showed extremely high levels of diversification and changes in expression level, which correlated with severity of infection in mice. Comparison with an out-group demonstrated that changes in the upstream region that regulates expression of ROP18 led to an historical increase in the expression and exposed the protein to diversifying selective pressure. Surprisingly, only three atypically distinct protein variants exist despite marked genetic divergence elsewhere in the genome. These three forms of ROP18 are likely adaptations for different niches in nature, and they confer markedly different virulence to mice. The widespread distribution of a single mouse-virulent allele among geographically and genetically disparate parasites may have consequences for transmission and disease in other hosts, including humans