Exposure to ambient air toxicants and the risk of amyotrophic lateral sclerosis (ALS): A matched case control study.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder with few risk factors identified and no known cure. Gene-environment interaction is hypothesized especially for sporadic ALS cases (90-95%) which are of unknown etiology. We aimed to investigate risk factors for ALS including exposure to ambient air toxics. METHODS: This population-based case-control study included 267 ALS cases (from the United States [U.S.] Centers for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry National ALS Registry and Biorepository) and 267 age, sex, and county-matched controls identified via a commercial database. Exposure assessment for 34 ambient air toxicants was performed by assigning census tract-level U.S. Environmental Protection Agency (EPA) 2011 National Air Toxics Assessment (NATA) data to participants' residential ZIP codes. Conditional logistic regression was used to compute adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for individual compounds, chemical classes, and overall exposure. Sensitivity analyses using both conditional logistic regression and Bayesian grouped weighted quartile sum (GWQS) models were performed to assess the integrity of findings. RESULTS: Using the 2011 NATA, the highest exposure quartile (Q4) compared to the lowest (Q1) of vinyl chloride (aOR = 6.00, 95% CI: 1.87-19.25), 2,4-dinitrotoluene (aOR = 5.45, 95% CI: 1.53-19.36), cyanide (aOR = 4.34, 95% CI: 1.52-12.43), cadmium (aOR = 3.30, 95% CI: 1.11-9.77), and carbon disulfide (aOR = 2.98, 95% CI: 1.00-8.91) was associated with increased odds of ALS. Residential air selenium showed an inverse association with ALS (second quartile [Q2] vs. Q1: aOR = 0.38, 95% CI: 0.18-0.79). Additionally, residential exposure to organic/chlorinated solvents (Q4 vs Q1: aOR = 2.62, 95% CI: 1.003-6.85) was associated with ALS. CONCLUSIONS: Our findings using the 2011 NATA linked by census tract to residential area provide evidence of increased ALS risk in cases compared to controls for 2,4-dinitrotoluene, vinyl chloride, cyanide, and the organic/chlorinated solvents class. This underscores the importance of ongoing surveillance of potential exposures for at-risk populations.

Modulating T-cell activation with antisense oligonucleotides targeting lymphocyte cytosolic protein 2.

Dysregulated T-cell activation is a hallmark of several autoimmune diseases such as rheumatoid arthritis (RA) and multiple sclerosis (MS). The lymphocyte cytosolic protein 2 (LCP2), also known as SLP-76, is essential for the development and activation of T cells. Despite the critical role of LCP2 in T-cell activation and the need for developing drugs that modify T-cell activation, no LCP2 inhibitors have been developed. This can be explained by the "undruggable" nature of LCP2, lacking a structure permissive to standard small molecule inhibitor modalities. Here, we explored an alternative drug modality, developing antisense oligonucleotides (ASOs) targeting LCP2 mRNAs, and evaluated its activity in modulating T-cell activation. We identified a set of 3' UTR targeting LCP2 ASOs, which knocked down LCP2 in a human T-cell line and primary human T cells and found that these suppressed T-cell receptor mediated activation. We also found that the ASOs suppressed FcεR1-mediated mast cell activation, in line with the role of LCP2 in mast cells. Taken together, our data provide examples of how immunomodulatory ASOs that interfere with undruggable targets can be developed and propose that such drug modalities can be used to treat autoimmune diseases.

Post hoc closure of large bore vascular access using the MANTA closure device.

Successful closure of large bore vascular access (≥12 Fr) is facilitated by the MANTA vascular closure device; however, it requires a critical first step of measuring "skin to arterial wall" depth of the access site using the depth locator before dilating the vessel above 8 Fr. It may be challenging at times to acquire the deployment depth at the onset of the procedure due to case urgency, delayed closure, or when large bore access is obtained at a different institution. We discuss a novel technique of measuring the deployment depth and successful delayed closure of large bore arterial access using the MANTA closure device.

CoreValve bioprosthesis dysfunction treated with a Sapien 3 valve-in-valve transcatheter aortic valve replacement and BASILICA technique.

Structural deterioration of transcatheter heart valve (THV) has been previously described. With the expansion of transcatheter aortic valve replacement (TAVR) indications toward treating lower risk patients with longer life expectancy, there will be increased necessity of managing the patients with THV dysfunction including those at risk for coronary obstruction or sinus sequestration. Coronary access also remains a challenge in such cases with THV dysfunction undergoing valve-in-transcatheter heart valve (ViTHV) TAVR. A unique and first reported case of THV deterioration treated with Sapien 3 ViTHV-TAVR inside a 31 mm CoreValve bioprosthesis along with left coronary leaflet laceration using the BASILICA technique has been presented.

Proteinase 3 Autoreactivity in Anti-Neutrophil Cytoplasmic Antibody-associated vasculitis-Immunological versus clinical features.

ANCA-associated vasculitis (AAV) is a group of chronic inflammatory diseases of small- and medium-sized vessels, which are broadly subdivided based on organ manifestations and disease-specific autoantibodies. The so called anti-neutrophil cytoplasmic antibodies (ANCA) mostly target one of the enzymes, proteinase 3 (PR3) or myeloperoxidase (MPO). Accumulating genetic data demonstrates that these two autoantibodies discriminate two distinct disease entities, more so than the clinical subdivision which is mainly criteria-based. Treatment of AAV includes heavy immunosuppression and is guided by which organs that are involved. Generally, patients with PR3-ANCA display higher risk for disease relapse than patients with MPO-ANCA. In this review, we will focus on the autoimmune features of PR3+ AAV and our current understanding of its triggers and the potential translation into clinical practice.

Retino-choroidal changes in patients with acute pancreatitis: A prospective analysis of a novel biomarker.

BACKGROUND: There is paucity of data on ocular changes in acute Pancreatitis (AP). Moreover, subclinical alterations in retina & choroid have not been studied in AP. OBJECTIVE: To prospectively study retino-choroidal changes in AP. METHODS: Sixty patients (mean age 39.07 years; 41 males) with AP were followed up till recovery/death. Baseline slit-lamp examination, choroidal thickness (CT), retinal thickness (RT), choroidal vascularity index (CVI), retinal capillary density index (CDI) and arteriovenous ratio (AVR) were recorded. The patients were divided into two groups - mild (Group A; 5 patients) and moderately severe/severe (Group B; 55 patients) as per revised Atlanta classification. RESULTS: Fundus examination showed mild optic disc edema with retinal hemorrhages in 6 (10%) patients in group B as compared to none in group A (p = 1.00). None of the patients had Purtscher retinopathy. Mean CT (317 ± 56.29 µm) was increased as compared to normal subjects (278.90 ± 57.84 µm, p = 0.003). The mean CVI (0.62 ± 0.04) was decreased as compared to normal (0.66 ± 0.01, p < 0.0001) as was the mean AVR (0.67 ± 0.03 vs. 0.7 ± 0.02, p < 0.0001). However, the mean RT of subjects with AP (239.68 ± 33.76 µm) was not significantly different compared to the normal subjects 253.17 ± 33.67 µm (p=NS). The mean CDI of superficial and deep plexus were comparable between normal and patients with AP. CT, RT, CVI, AVR and CDI were comparable between group A and group B as well as survivors and non-survivors. CONCLUSIONS: Clinically significant ocular changes are seen infrequently in AP. However, subclinical changes in CT, CVI and AVR are observed in patients with AP compared to normal individuals.

Maternal Obesity, Birth Size, and Risk of Childhood Cancer Development.

Infants and children are particularly vulnerable to in utero and early-life exposures. Thus, a mother's exposures before and during pregnancy could have important consequences for her child's health, including cancer development. We examined whether birth certificate-derived maternal anthropometric characteristics were associated with increased risk of subsequent childhood cancer development, accounting for established maternal and infant risk factors. Pennsylvania birth and cancer registry files were linked by the state Department of Health, yielding a virtual cohort of births and childhood cancers from 2003 through 2016. The analysis included 1,827,875 infants (13,785,309 person-years at risk), with 2,352 children diagnosed with any cancer and 747 with leukemia before age 14 years. Children born to mothers with a body mass index (weight (kg)/height (m)2) of ≥40 had a 57% (95% confidence interval: 12, 120) higher leukemia risk. Newborn size of ≥30% higher than expected was associated with 2.2-fold and 1.8-fold hazard ratios for total childhood cancer and leukemia, respectively, relative to those with expected size. Being <30% below expected size also increased the overall cancer risk (P for curvilinearity < 0.0001). Newborn size did not mediate the association between maternal obesity and childhood cancer. The results suggest a significant role of early-life exposure to maternal obesity- and fetal growth-related factors in childhood cancer development.

Relationship between left ventricular dyssynchrony and scar burden in the genesis of ventricular tachyarrhythmia.

BACKGROUND: Left ventricular (LV) ejection fraction (EF) has poor predictive value for ventricular tachyarrhythmia (VT). Other parameters such as LV dyssynchrony (LVD), and LV scar burden have also been individually associated with VT, but the interplay of these factors in the genesis of VT has not been explored. This retrospective study sought to evaluate the relationship between LVD and imaging characteristics of the myocardial substrate in predicting VT. METHODS: We identified 183 patients (150 men; mean age: 64 ± 14 years and mean LVEF: 23% ± 7%), who received an implantable cardioverter defibrillator (ICD) for primary prevention and who underwent a gated single-photon emission computed tomography (GSPECT) myocardial perfusion scan prior to ICD implantation. LVD was determined by phase analysis of the GSPECT images. Occurrence of VTs was established through routine ICD interrogations and review of electronic medical records. RESULTS: LVD was present in 136 (74%) patients. VT occurred in 48 (26%) patients. Ninety-eight percent of patient who experienced VT had LVD. Patients without LVD had a significantly better survival free of both sustained and non-sustained VT (HR, 95% CI 4.90, 2.12-11.20; P < 0.0001). The combination of LVD and myocardial scar occupying > 6% of LV myocardium accounted for 83% of all VT events. CONCLUSIONS: LVD assessment by GSPECT is strongly associated with incident VT in patients with low LVEF. The combination of LVD and scar burden predicted the majority of VT events.

Systemic inflammatory markers associated with cardiovascular disease and acute and chronic exposure to fine particulate matter air pollution (PM2.5) among US NHANES adults with metabolic syndrome.

BACKGROUND: There has been no investigation to date of adults with metabolic syndrome examining the association of short and long-term exposure to fine particulate matter (PM2.5) air pollution with cardiovascular-disease related inflammatory marker (WBC and CRP) levels in a nationally representative sample. The goal of this study is to assess the susceptibility of adults with metabolic syndrome to PM2.5 exposure as suggested by increased cardiovascular-disease related inflammatory marker levels. METHODS: A cross sectional analysis of adult National Health and Nutrition Examination Survey (NHANES) participants (2000-2008) was carried out with linkage of CDC WONDER meteorological data and downscaler modeled USEPA air pollution data for census tracts in the continental United States. Participants were non-pregnant NHANES adults (2000-2008) with complete data for evaluating presence of metabolic syndrome and laboratory data on WBC and CRP. Exposures studied included short (lags 0-3 days and their averages), long-term (30 and 60 day moving and annual averages) PM2.5 exposure levels at the census tract level in the continental United States. The main outcomes included CRP and WBC levels the day of NHANES study visit analyzed using multiple linear regression, adjusting for age, gender, race, education, smoking status, history of any cardiovascular disease, maximum apparent temperature and ozone level, for participants with and without metabolic syndrome. RESULTS: A total of 7134 NHANES participants (35% with metabolic syndrome) met the inclusion criteria. After adjusting for confounders, we observed a significant effect of PM2.5 acutely at lag day 0 on CRP level; a 10µg/m3 rise in lag day 0 PM2.5 level was associated with a 10.1% increase (95% CI: 2.2-18.6%) in CRP levels for participants with metabolic syndrome. For those without metabolic syndrome, the change in CRP was -1.3% (95% CI -8.8%, 6.8%). There were no significant associations for WBC count. In this first national study of the effect of PM2.5 air pollution on levels of cardiovascular-disease related inflammatory markers in adults with metabolic syndrome, CRP levels were found to be significantly increased in those with this condition with increased fine particulate matter levels at lag day 0. With one third of US adults with metabolic syndrome, the health impact of PM2.5 in this sensitive population may be significant.

Electrocardiographic Impact of Myocardial Diffuse Fibrosis and Scar: MESA (Multi-Ethnic Study of Atherosclerosis).

Purpose To examine the associations of myocardial diffuse fibrosis and scar with surface electrocardiographic (ECG) parameters in individuals free of prior coronary heart disease in four different ethnicities. Materials and Methods This prospective cross-sectional study was approved by the institutional review boards, and all participants gave informed consent. A total of 1669 participants in the Multi-Ethnic Study of Atherosclerosis, or MESA, who were free of prior myocardial infarction underwent both ECG and cardiac magnetic resonance imaging. In individuals without a late gadolinium enhancement-defined myocardial scar (n = 1131), T1 mapping was used to assess left ventricular (LV) interstitial diffuse fibrosis. The associations of LV diffuse fibrosis or myocardial scar with ECG parameters (QRS voltage, QRS duration, and corrected QT interval [QTc]) were evaluated by using multivariable regression analyses adjusted for demographic data, risk factors for scar, LV end-diastolic volume, and LV mass. Results The mean age of the 1669 participants was 67.4 years ± 8.7 (standard deviation); 49.8% were women. Lower postcontrast T1 time at 12 minutes was significantly associated with lower QRS Sokolow-Lyon voltage (ß = 15.1 µV/10 msec, P = .004), lower QRS Cornell voltage (ß = 9.2 µV/10 msec, P = .031), and shorter QRS duration (ß = 0.16 msec/10 msec, P = .049). Greater extracellular volume (ECV) fraction was also significantly associated with lower QRS Sokolow-Lyon voltage (ß = -35.2 µV/1% ECV increase, P < .001) and Cornell voltage (ß = -23.7 µV/1% ECV increase, P < .001), independent of LV structural indexes. In contrast, the presence of LV scar (n = 106) was associated with longer QTc (ß = 4.3 msec, P = .031). Conclusion In older adults without prior coronary heart disease, underlying greater LV diffuse fibrosis is associated with lower QRS voltage and shorter QRS duration at surface ECG, whereas clinically unrecognized myocardial scar is associated with a longer QT interval. © RSNA, 2016 Online supplemental material is available for this article.

Association between central sleep apnea and left ventricular structure: the Multi-Ethnic Study of Atherosclerosis.

We assessed whether the presence of central sleep apnea is associated with adverse left ventricular structural changes. We analysed 1412 participants from the Multi-Ethnic Study of Atherosclerosis who underwent both overnight polysomnography and cardiac magnetic resonance imaging. Subjects had been recruited 10 years earlier when free of cardiovascular disease. Our main exposure is the presence of central sleep apnea as defined by central apnea-hypopnea index = 5 or the presence of Cheyne-Stokes breathing. Outcome variables were left ventricular mass/height, left ventricular ejection fraction, and left ventricular mass/volume ratio. Multivariate linear regression models adjusted for age, gender, race, waist circumference, tobacco use, hypertension, and the obstructive apnea-hypopnea index were fit for the outcomes. Of the 1412 participants, 27 (2%) individuals had central sleep apnea. After adjusting for covariates, the presence of central sleep apnea was significantly associated with elevated left ventricular mass/volume ratio (ß = 0.11 ± 0.04 g mL-1 , P = 0.0071), an adverse cardiac finding signifying concentric remodelling.

Clinical significance of presence and extent of extrapancreatic necrosis in acute pancreatitis.

BACKGROUND AND AIM: Extrapancreatic necrosis (EPN) alone represents a subgroup of pancreatitis with better outcome than patients with pancreatic parenchymal necrosis (PN). However, data on clinical significance of EPN is limited, and significance of the extent of EPN is not known. METHODS: Two hundred thirteen patients (136 [63.8%] males; mean age: 39.8 ± 13.2 years) with acute pancreatitis were prospectively enrolled and followed up till recovery or death. Contrast-enhanced computed tomography of each patient was retrospectively evaluated for presence of PN and EPN, pleural effusion and ascites. EPN was termed extensive if it extended to paracolic gutters or pelvis. RESULTS: Twenty-one (9.9%) patients had interstitial pancreatitis, seven (3.3%) patients had PN alone, 48 (22.5%) patients had EPN alone, and 137 (64.3%) patients had combined PN and EPN. Patients with EPN alone had significantly higher frequency of organ failure than patients with interstitial pancreatitis. Compared with patients with EPN alone, the patients with combined necrosis had significantly higher frequency of pleural effusion (88.2% vs. 75%), ascites (41% vs. 20.8%), and need for intervention (32.6% vs. 14.6%). Patients with extensive EPN (n = 57) had significantly higher frequency of pleural effusion, ascites, and multi-organ failure than those with limited EPN. CONCLUSION: EPN alone should be considered as a separate category of acute pancreatitis as it has less severe course than PN but has more severe course than interstitial pancreatitis. Patients with extensive EPN in spite of having increased frequency of ascites, pleural effusion, and multi-organ failure had similar outcome as compared to patients with limited EPN.

Fine particulate matter and the risk of autism spectrum disorder.

The causes of autism spectrum disorder (ASD) are not well known. Recent investigations have suggested that air pollution, including PM2.5, may play a role in the onset of this condition. The objective of the present work was to investigate the association between prenatal and early childhood exposure to fine particulate matter (PM2.5) and risk for childhood ASD. A population-based case-control study was conducted in children born between January 1, 2005 and December 31, 2009 in six counties in Southwestern Pennsylvania. ASD cases were recruited from specialty autism clinics, local pediatric practices, and school-based special needs services. ASD cases were children who scored 15 or above on the Social Communication Questionnaire (SCQ) and had written documentation of an ASD diagnosis. Controls were children without ASD recruited from a random sample of births from the Pennsylvania state birth registry and frequency matched to cases on birth year, gender, and race. A total of 217 cases and 226 controls were interviewed. A land use regression (LUR) model was used to create person- and time-specific PM2.5 estimates for individual (pre-pregnancy, trimesters one through three, pregnancy, years one and two of life) and cumulative (starting from pre-pregnancy) key developmental time periods. Logistic regression was used to investigate the association between estimated exposure to PM2.5 during key developmental time periods and risk of ASD, adjusting for mother's age, education, race, and smoking. Adjusted odds ratios (AOR) were elevated for specific pregnancy and postnatal intervals (pre-pregnancy, pregnancy, and year one), and postnatal year two was significant, (AOR=1.45, 95% CI=1.01-2.08). We also examined the effect of cumulative pregnancy periods; noting that starting with pre-pregnancy through pregnancy, the adjusted odds ratios are in the 1.46-1.51 range and significant for pre-pregnancy through year 2 (OR=1.51, 95% CI=1.01-2.26). Our data indicate that both prenatal and postnatal exposures to PM2.5 are associated with increased risk of ASD. Future research should include multiple pollutant models and the elucidation of the biological mechanism for PM2.5 and ASD.

Air toxics and the risk of autism spectrum disorder: the results of a population based case-control study in southwestern Pennsylvania.

BACKGROUND: Autism spectrum disorders (ASD) constitute a major public health problem affecting one in 68 children. There is little understanding of the causes of ASD despite its serious social impact. Air pollution contains many toxicants known to have adverse effects on the fetus. We conducted a population based case-control study in southwestern Pennsylvania to estimate the association between ASD and 2005 US EPA modeled NATA (National Air Toxics Assessment) levels for 30 neurotoxicants. METHODS: A total of 217 ASD cases born between 2005 and 2009 were recruited from local ASD diagnostic and treatment centers. There were two different control groups: 1) interviewed controls (N = 224) frequency matched by child's year of birth, sex and race with complete residential histories from prior to pregnancy through the child's second birthday, and 2) 5,007 controls generated from a random sample of birth certificates (BC controls) using residence at birth. We used logistic regression analysis comparing higher to first quartile of exposure to estimate odds ratios (ORs) and 95% confidence intervals (CI), adjusting for mother's age, education, race, smoking status, child's year of birth and sex. RESULTS: Comparing fourth to first quartile exposures for all births, the adjusted OR for styrene was 2.04 (95% CI = 1.17-3.58, p = 0.013) for the interviewed case-control analysis and 1.61 (95% CI = 1.08-2.40, p = 0.018) for the BC analysis. In the BC comparison, chromium also exhibited an elevated OR of 1.60 (95% CI = 1.08-2.38, p = 0.020), which was similarly elevated in the interviewed analysis (OR = 1.52, 95% CI = 0.87-2.66). There were borderline significant ORs for the BC comparison for methylene chloride (OR = 1.41, 95% CI = 0.96-2.07, p = 0.082) and PAHs (OR = 1.44, 95% CI = 0.98-2.11, p = 0.064). CONCLUSIONS: Living in areas with higher levels of styrene and chromium during pregnancy was associated with increased risk of ASD, with borderline effects for PAHs and methylene chloride. These results are consistent with other studies. It is unclear, however, whether these chemicals are risk factors themselves or if they reflect the effect of a mixture of pollutants. Future work should include improved spatiotemporal estimates of exposure to air toxics, taking into account the dynamic movement of individuals during daily life.

Otitis media with effusion: experiences of children with cleft palate and their parents.

OBJECTIVE: To explore the views of children with cleft palate and their parents about daily life with otitis media with effusion and associated hearing loss. DESIGN: A qualitative study. Semistructured interviews were used to collect data from parents. Participatory techniques, including activities on a tablet computer, were used to collect data from children. Framework analysis was applied to interview transcripts. SETTING: Two English cleft units. PARTICIPANTS: A purposive sample of parents of 37 children aged 0 to 11 years with experience of otitis media with effusion. Their children also took part if aged 6 to 11 years (n = 22). RESULTS: Themes related to the following: (1) emotions (frustration, anger, sadness, happiness, anxiety), (2) educational experiences (struggling at school, having to sit at the front of the class, requiring extra support, missing lessons for appointments or due to ear infections), (3) social interactions (isolation, communication, reliance on siblings, participation in activities). CONCLUSIONS: A number of areas of interviewees' everyday life were affected by the presence of otitis media with effusion. Parents may need to be forewarned about the possible ongoing nature of this condition and its impact on a child's social and emotional experiences. Children may also benefit from age-appropriate information about otitis media with effusion and its treatment, including information on hearing tests, to help reduce any anxiety.

Case-control study of environmental toxins and risk of amyotrophic lateral sclerosis involving the national ALS registry.

Objective: Neurotoxic chemicals are suggested in the etiology of amyotrophic lateral sclerosis (ALS). We examined the association of environmental and occupational risk factors including persistent organochlorine pesticides (OCPs) and ALS risk among cases from the Centers for Disease Control and Prevention National ALS Registry and age, sex, and county-matched controls. Methods: Participants completed a risk factor survey and provided a blood sample for OCP measurement. ALS cases were confirmed through the Registry. Conditional logistic regression assessed associations between ALS and risk factors including OCP levels. Results: 243 matched case-control pairs (61.7% male, mean [SD] age = 62.9 [10.1]) were included. Fifteen of the 29 OCPs examined had sufficient detectable levels for analysis. Modest correlations of self-reported years of exposure to residential pesticide mixtures and OCP serum levels were found (p<.001). Moreover, occupational exposure to lead including soldering and welding with lead/metal dust and use of lead paint/gasoline were significantly related to ALS risk (OR = 1.77, 95% CI: 1.11-2.83). Avocational gardening was a significant risk factor for ALS (OR = 1.57, 95% CI: 1.04-2.37). ALS risk increased for each 10 ng/g of α-Endosulfan (OR = 1.42, 95% CI: 1.14-1.77) and oxychlordane (OR = 1.24, 95% CI: 1.01-1.53). Heptachlor (detectable vs. nondetectable) was also associated with ALS risk (OR = 3.57, 95% CI: 1.50-8.52). Conclusion: This national case-control study revealed both survey and serum levels of OCPs as risk factors for ALS. Despite the United States banning many OCPs in the 1970s and 1980s, their use abroad and long half-lives continue to exert possible neurotoxic health effects.

Assessment of effluent contaminants from three facilities discharging Marcellus Shale wastewater to surface waters in Pennsylvania.

Unconventional natural gas development in Pennsylvania has created a new wastewater stream. In an effort to stop the discharge of Marcellus Shale unconventional natural gas development wastewaters into surface waters, on May 19, 2011 the Pennsylvania Department of Environmental Protection (PADEP) requested drilling companies stop disposing their wastewater through wastewater treatment plants (WWTPs). This research includes a chemical analysis of effluents discharged from three WWTPs before and after the aforementioned request. The WWTPs sampled included two municipal, publicly owned treatment works and a commercially operated industrial wastewater treatment plant. Analyte concentrations were quanitified and then compared to water quality criteria, including U.S. Environmental Protection Agency MCLs and "human health criteria." Certain analytes including barium, strontium, bromides, chlorides, total dissolved solids, and benzene were measured in the effluent at concentrations above criteria. Analyte concentrations measured in effluent samples before and after the PADEP's request were compared for each facility. Analyte concentrations in the effluents decreased in the majority of samples after the PADEP's request (p < .05). This research provides preliminary evidence that these and similar WWTPs may not be able to provide sufficient treatment for this wastewater stream, and more thorough monitoring is recommended.

Assessment and longitudinal analysis of health impacts and stressors perceived to result from unconventional shale gas development in the Marcellus Shale region.

INTRODUCTION: Concerns for health and social impacts have arisen as a result of Marcellus Shale unconventional natural gas development. Our goal was to document the self-reported health impacts and mental and physical health stressors perceived to result from Marcellus Shale development. METHODS: Two sets of interviews were conducted with a convenience sample of community members living proximal to Marcellus Shale development, session 1 March-September 2010 (n = 33) and session 2 January-April 2012 (n = 20). Symptoms of health impacts and sources of psychological stress were coded. Symptom and stressor counts were quantified for each interview. The counts for each participant were compared longitudinally. RESULTS: Participants attributed 59 unique health impacts and 13 stressors to Marcellus Shale development. Stress was the most frequently-reported symptom. Over time, perceived health impacts increased (P = 0·042), while stressors remained constant (P = 0·855). DISCUSSION: Exposure-based epidemiological studies are needed to address identified health impacts and those that may develop as unconventional natural gas extraction continues. Many of the stressors can be addressed immediately.

Echocardiographic and Clinical Outcomes in Symptomatic Patients With Less Than Severe Aortic Stenosis After Supra-Annular Self-Expanding Transcatheter Aortic Valve Replacement.

Optimal timing for aortic valve replacement in symptomatic patients with less than severe aortic stenosis (AS) is not well defined. There is limited information on the benefit of valve replacement in these patients. Symptomatic patients with less than severe AS, defined as a mean aortic gradient ≥20 and <40 mm Hg, peak aortic velocity >3 and <4 m/s, and aortic valve area >1.0 and <1.5 cm2, enrolled in the Society for Thoracic Surgery/American College of Cardiology Transcatheter Valve Therapy Registry and who underwent attempted supra-annular, self-expanding transcatheter aortic valve replacement (TAVR) were reviewed. Site-reported valve hemodynamics, clinical events, and quality of life metrics were analyzed at 30 days and 1 year after the procedure. A total of 1,067 patients with attempted TAVR (mean age 78.4 ± 8.4 years; Society for Thoracic Surgery score 4.7 ± 3.4%) were found to have symptoms but less than severe AS. From baseline to postprocedure, mean gradient decreased (29.9 ± 4.9 vs 8.4 ± 4.8 mm Hg, p <0.001), and aortic valve area increased (1.2 ± 0.1 vs 2.2 ± 0.7 cm2, p <0.001). Clinical events included 30-day and 1-year all-cause mortality (1.5% and 9.6%), stroke (2.2% and 3.3%), and new pacemaker implantation (18.1% and 20.9%). There were statistically significant improvements in the New York Heart Association functional class and Kansas City Cardiomyopathy Questionnaire at 30 days and 1 year. In conclusion, patients with symptomatic but less than severe AS who underwent supra-annular, self-expanding TAVR experienced improved valve hemodynamics and quality of life measures 1 year after the procedure. Randomized studies of TAVR versus a control arm in symptomatic patients with less than severe AS are ongoing.