Recurrent stroke risk and cerebral microbleed burden in ischemic stroke and TIA

PubMed Central

Wilson, Duncan; Charidimou, Andreas; Ambler, Gareth; Fox, Zoe V.; Gregoire, Simone; Rayson, Phillip; Imaizumi, Toshio; Fluri, Felix; Naka, Hiromitsu; Horstmann, Solveig; Veltkamp, Roland; Rothwell, Peter M.; Kwa, Vincent I.H.; Thijs, Vincent; Lee, Yong-Seok; Kim, Young Dae; Huang, Yining; Wong, Ka Sing; Jäger, Hans Rolf

2016-01-01

Objective: To determine associations between cerebral microbleed (CMB) burden with recurrent ischemic stroke (IS) and intracerebral hemorrhage (ICH) risk after IS or TIA. Methods: We identified prospective studies of patients with IS or TIA that investigated CMBs and stroke (ICH and IS) risk during ≥3 months follow-up. Authors provided aggregate summary-level data on stroke outcomes, with CMBs categorized according to burden (single, 2–4, and ≥5 CMBs) and distribution. We calculated absolute event rates and pooled risk ratios (RR) using random-effects meta-analysis. Results: We included 5,068 patients from 15 studies. There were 115/1,284 (9.6%) recurrent IS events in patients with CMBs vs 212/3,781 (5.6%) in patients without CMBs (pooled RR 1.8 for CMBs vs no CMBs; 95% confidence interval [CI] 1.4–2.5). There were 49/1,142 (4.3%) ICH events in those with CMBs vs 17/2,912 (0.58%) in those without CMBs (pooled RR 6.3 for CMBs vs no CMBs; 95% CI 3.5–11.4). Increasing CMB burden increased the risk of IS (pooled RR [95% CI] 1.8 [1.0–3.1], 2.4 [1.3–4.4], and 2.7 [1.5–4.9] for 1 CMB, 2–4 CMBs, and ≥5 CMBs, respectively) and ICH (pooled RR [95% CI] 4.6 [1.9–10.7], 5.6 [2.4–13.3], and 14.1 [6.9–29.0] for 1 CMB, 2–4 CMBs, and ≥5 CMBs, respectively). Conclusions: CMBs are associated with increased stroke risk after IS or TIA. With increasing CMB burden (compared to no CMBs), the risk of ICH increases more steeply than that of IS. However, IS absolute event rates remain higher than ICH absolute event rates in all CMB burden categories. PMID:27590288

Validation of the pooled cohort risk score in an Asian population - a retrospective cohort study.

PubMed

Chia, Yook Chin; Lim, Hooi Min; Ching, Siew Mooi

2014-11-20

The Pooled Cohort Risk Equation was introduced by the American College of Cardiology (ACC) and American Heart Association (AHA) 2013 in their Blood Cholesterol Guideline to estimate the 10-year atherosclerotic cardiovascular disease (ASCVD) risk. However, absence of Asian ethnicity in the contemporary cohorts and limited studies to examine the use of the risk score limit the applicability of the equation in an Asian population. This study examines the validity of the pooled cohort risk score in a primary care setting and compares the cardiovascular risk using both the pooled cohort risk score and the Framingham General Cardiovascular Disease (CVD) risk score. This is a 10-year retrospective cohort study of randomly selected patients aged 40-79 years. Baseline demographic data, co-morbidities and cardiovascular (CV) risk parameters were captured from patient records in 1998. Pooled cohort risk score and Framingham General CVD risk score for each patient were computed. All ASCVD events (nonfatal myocardial infarction, coronary heart disease (CHD) death, fatal and nonfatal stroke) occurring from 1998-2007 were recorded. A total of 922 patients were studied. In 1998, mean age was 57.5 ± 8.8 years with 66.7% female. There were 47% diabetic patients and 59.9% patients receiving anti-hypertensive treatment. More than 98% of patients with pooled cohort risk score ≥7.5% had FRS >10%. A total of 45 CVD events occurred, 22 (7.2%) in males and 23 (3.7%) in females. The median pooled cohort risk score for the population was 10.1 (IQR 4.7-20.6) while the actual ASCVD events that occurred was 4.9% (45/922). Our study showed moderate discrimination with AUC of 0.63. There was good calibration with Hosmer-Lemeshow test χ2 = 12.6, P = 0.12. The pooled cohort risk score appears to overestimate CV risk but this apparent over-prediction could be a result of treatment. In the absence of a validated score in an untreated population, the pooled cohort risk score appears to be appropriate for use in a primary care setting.

Assessment of the cardiovascular safety of saxagliptin in patients with type 2 diabetes mellitus: pooled analysis of 20 clinical trials

PubMed Central

2014-01-01

Background It is important to establish the cardiovascular (CV) safety profile of novel antidiabetic drugs. Methods Pooled analyses were performed of 20 randomized controlled studies (N = 9156) of saxagliptin as monotherapy or add-on therapy in patients with type 2 diabetes mellitus (T2DM) as well as a subset of 11 saxagliptin + metformin studies. Adjudicated major adverse CV events (MACE; CV death, myocardial infarction [MI], and stroke) and investigator-reported heart failure were assessed, and incidence rates (IRs; events/100 patient-years) and IR ratios (IRRs; saxagliptin/control) were calculated (Mantel-Haenszel method). Results In pooled datasets, the IR point estimates for MACE and individual components of CV death, MI, and stroke favored saxagliptin, but the 95% CI included 1. IRR (95% CI) for MACE in the 20-study pool was 0.74 (0.45, 1.25). The Cox proportional hazard ratio (95% CI) was 0.75 (0.46, 1.21), suggesting no increased risk of MACE in the 20-study pool. In the 11-study saxagliptin + metformin pool, the IRR for MACE was 0.93 (0.44, 1.99). In the 20-study pool, the IRR for heart failure was 0.55 (0.27, 1.12). Conclusions Analysis of pooled data from 20 clinical trials in patients with T2DM suggests that saxagliptin is not associated with an increased CV risk. PMID:24490835

Dynamics of dissolved organic matter during four storm events in two forest streams: source, export, and implications for harmful disinfection byproduct formation.

PubMed

Yang, Liyang; Hur, Jin; Lee, Sonmin; Chang, Soon-Woong; Shin, Hyun-Sang

2015-06-01

Dynamics of river dissolved organic matter (DOM) during storm events have profound influences on the downstream aquatic ecosystem and drinking water safety. This study investigated temporal variations in DOM during four storm events in two forest headwater streams (the EH and JH brooks, South Korea) and the impacts on the disinfection byproducts (DBPs) formation potential. The within-event variations of most DOM quantity parameters were similar to the flow rate in the EH but not in the larger JH brook. The dissolved organic carbon (DOC) showed clockwise and counterclockwise hysteresis with the flow rate in the EH and JH brooks, respectively, indicating the importance of both flow path and DOM source pool size in determining the effects of storm events. The stream DOM became less aromatic/humified from the first to the last event in both brooks, probably due to the increasing fresh plant pool and the decreasing leaf litter pool during the course of rainy season. The DOC export during each event increased 1.3-2.7- and 1.1-7.0-fold by stormflows in the EH and JH brooks, respectively. The leaf litter and soil together was the major DOM source, particularly during early events. The enhanced DOM export probably increases the risks of DBPs formation in disinfection, as indicated by a strong correlation observed between DOC and trihalomethanes formation potential (THMFP). High correlations between two humic-like fluorescent components and THMFP further suggested the potential of assessing THMFP with in situ fluorescence sensors during storms.

Efficacy of self-expandable metal stents in management of benign biliary strictures and comparison with multiple plastic stents: a meta-analysis.

PubMed

Khan, Muhammad Ali; Baron, Todd H; Kamal, Faisal; Ali, Bilal; Nollan, Richard; Ismail, Mohammad Kashif; Tombazzi, Claudio; Artifon, Everson L A; Repici, Alessandro; Khashab, Mouen A

2017-07-01

Background and study aims  There is burgeoning interest in the utilization of covered self-expandable metal stents (CSEMSs) for managing benign biliary stricture (BBS). This systematic review and meta-analysis evaluated cumulative stricture resolution and recurrence rates using CSEMSs and compared performance of CSEMSs and multiple plastic stents (MPS) in BBS management. Method  Searches in several databases identified studies including ≥ 10 patients that utilized CSEMSs for BBS treatment. Weighted pooled rates were calculated for stricture resolution and recurrence. Pooled risk ratios (RRs) comparing CSEMSs with MPS were calculated for stricture resolution, stricture recurrence, and adverse events. Pooled difference in means was calculated to compare number of endoscopic retrograde cholangiopancreatographies (ERCPs) in each group.  Results  The meta-analysis included 22 studies with 1298 patients. Weighted pooled rate for BBS resolution with CSEMS was 83 % (95 % confidence limits [95 %CLs] 78 %, 87 %; I 2  = 72 %). On meta-regression analysis, resolution in chronic pancreatitis patients and post-orthotopic liver transplant patients were significant predictors of heterogeneity. Weighted pooled rate for stricture recurrence with CSEMSs was 16 % (11 %, 22 %). Overall rate of adverse events requiring intervention and/or hospitalization was 15 %. Four randomized controlled trials with 213 patients compared CSEMSs with MPS: the pooled RRs for stricture resolution, recurrence, and adverse events were 1.07 (0.97, 1.18), 0.88 (0.48, 1.63), and 1.16 (0.71, 1.88), respectively with no heterogeneity. Pooled difference in means for number of ERCPs was - 1.71 ( - 2.33, - 1.09) in favor of CSEMS. Conclusions  CSEMSs appear to have excellent efficacy in BBS management. They are as effective as MPS but require fewer ERCPs to achieve clinical success. © Georg Thieme Verlag KG Stuttgart · New York.

SAGE III L2 Solar Event Species Profiles (Binary)

Atmospheric Science Data Center

2016-06-14

... Search and Order:  Earthdata Search   FTP Access:  Data Pool V3  |  Data Pool V4 Parameters:  Aerosol ... Data Additional Info:  Data Format: Big Endian/IEEE Binary; Avg Size in MB: 0.044 SCAR-B Block:  ...

Adverse events associated with abacavir use in HIV-infected children and adolescents: a systematic review and meta-analysis.

PubMed

Jesson, Julie; Dahourou, Désiré L; Renaud, Françoise; Penazzato, Martina; Leroy, Valériane

2016-02-01

Concerns exist about the toxicity of drugs used in the implementation of large-scale antiretroviral programmes, and documentation of antiretroviral toxicity is essential. We did a systematic review and meta-analysis of adverse events among children and adolescents receiving regimens that contain abacavir, a widely used antiretroviral drug. We searched bibliographic databases and abstracts from relevant conferences from Jan 1, 2000, to March 1, 2015. All experimental and observational studies of HIV-infected patients aged 0-18 years who used abacavir, were eligible. Incidence of adverse outcomes in patients taking abacavir (number of new events in a period divided by population at risk at the beginning of the study) and relative risks (RR) compared with non-abacavir regimens were pooled with random effects models. Of 337 records and 21 conference abstracts identified, nine studies (eight full-text articles and one abstract) collected information about 2546 children, of whom 1769 (69%) were on abacavir regimens. Among children and adolescents taking abacavir, hypersensitivity reactions (eight studies) had a pooled incidence of 2·2% (95% CI 0·4-5·2); treatment switching or discontinuation (seven studies) pooled incidence was 10·9% (2·1-24·3); of grade 3-4 adverse events (six studies) pooled incidence was 9·9% (2·4-20·9); and adverse events other than hypersensitivity reaction (six studies) pooled incidence was 21·5% (2·8-48·4). Between-study inconsistency was significant for all outcomes (p<0·0001 for all inconsistencies). Incidence of death (four studies) was 3·3% (95% CI 1·5-5·6). In the three randomised clinical trials with comparative data, no increased risk of hypersensitivity reaction (pooled RR 1·08; 95% CI 0·19-6·15), grade 3 or 4 events (0·79 [0·44-1·42]), or death (1·72 [0·77-3·82]) was noted for abacavir relative to non-abacavir regimens. None of the reported deaths were related to abacavir. Abacavir-related toxicity occurs early after ART initiation and is manageable. Abacavir can be safely used for first-line or second-line antiretroviral regimens in children and adolescents, especially in sub-Saharan Africa were HLA B5701 genotype is rare. WHO. Copyright © 2016 Elsevier Ltd. All rights reserved.

78 FR 71476 - Health Insurance Providers Fee

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-29

...) entities. Another commenter suggested that the final regulations exclude high risk pools under section 1101... covered entity unless it provides health insurance for United States health risks in 2014. Because high... not be covered entities. In the event a high risk pool provides health insurance for United States...

Meta-Analysis of the Associations of p-Cresyl Sulfate (PCS) and Indoxyl Sulfate (IS) with Cardiovascular Events and All-Cause Mortality in Patients with Chronic Renal Failure.

PubMed

Lin, Cheng-Jui; Wu, Vincent; Wu, Pei-Chen; Wu, Chih-Jen

2015-01-01

Indoxyl sulfate (IS) and p-cresyl sulfate (PCS) are protein-bound uremic toxins that increase in the sera of patients with chronic kidney disease (CKD), and are not effectively removed by dialysis. The purpose of this meta-analysis was to investigate the relationships of PCS and IS with cardiovascular events and all-cause mortality in patients with CKD stage 3 and above. Medline, Cochrane, and EMBASE databases were searched until January 1, 2014 with combinations of the following keywords: chronic renal failure, end-stage kidney disease, uremic toxin, uremic retention, indoxyl sulfate, p-cresyl sulfate. Inclusion criteria were: 1) Patients with stage 1 to 5 CKD; 2) Prospective study; 3) Randomized controlled trial; 4) English language publication. The associations between serum levels of PCS and IS and the risks of all-cause mortality and cardiovascular events were the primary outcome measures. Of 155 articles initially identified, 10 prospective and one cross-sectional study with a total 1,572 patients were included. Free PCS was significantly associated with all-cause mortality among patients with chronic renal failure (pooled OR = 1.16, 95% CI = 1.03 to 1.30, P = 0.013). An elevated free IS level was also significantly associated with increased risk of all-cause mortality (pooled OR = 1.10, 95% CI = 1.03 to 1.17, P = 0.003). An elevated free PCS level was significantly associated with an increased risk of cardiovascular events among patients with chronic renal failure (pooled OR = 1.28, 95% CI = 1.10 to 1.50, P = 0.002), while free IS was not significantly associated with risk of cardiovascular events (pooled OR = 1.05, 95% CI = 0.98 to 1.13, P = 0.196). Elevated levels of PCS and IS are associated with increased mortality in patients with CKD, while PCS, but not IS, is associated with an increased risk of cardiovascular events.

Temperature and size variabilities of the Western Pacific Warm Pool

NASA Technical Reports Server (NTRS)

Yan, Xiao-Hai; Ho, Chung-Ru; Zheng, Quanan; Klemas, Vic

1992-01-01

Variabilities in sea-surface temperature and size of the Western Pacific Warm Pool were tracked with 10 years of satellite multichannel sea-surface temperature observations from 1982 to 1991. The results show that both annual mean sea-surface temperature and the size of the warm pool increased from 1983 to 1987 and fluctuated after 1987. Possible causes of these variations include solar irradiance variabilities, El Nino-Southern Oscillaton events, volcanic activities, and global warming.

Cardiovascular safety of linagliptin in type 2 diabetes: a comprehensive patient-level pooled analysis of prospectively adjudicated cardiovascular events.

PubMed

Rosenstock, Julio; Marx, Nikolaus; Neubacher, Dietmar; Seck, Thomas; Patel, Sanjay; Woerle, Hans-Juergen; Johansen, Odd Erik

2015-05-21

The cardiovascular (CV) safety of linagliptin was evaluated in subjects with type 2 diabetes (T2DM). Pre-specified patient-level pooled analysis of all available double-blind, randomized, controlled trials, ≥ 12 weeks' duration (19 trials, 9459 subjects) of linagliptin versus placebo/active treatment. Primary end point: composite of prospectively adjudicated CV death, non-fatal myocardial infarction, non-fatal stroke, and hospitalization for unstable angina (4P-MACE). Hospitalization for congestive heart failure (CHF) was also evaluated; adjudication of CHF was introduced during the phase 3 program (8 trials; 3314 subjects). 4P-MACE was assessed in placebo-controlled trials (subgroup of 18 trials; 7746 subjects). Investigator-reported events suggestive of CHF from 24 placebo-controlled trials (including trials <12 weeks' duration, 8778 subjects) were also analyzed. 5847 patients received linagliptin (5 mg: 5687, 10 mg: 160) and 3612 comparator (glimepiride: 775, voglibose: 162, placebo: 2675); cumulative exposure, 4421.3 and 3254.7 patient-years, respectively. 4P-MACE incidence rates: 13.4 per 1000 patient-years, linagliptin (60 events), 18.9, total comparators (62 events); overall hazard ratio (HR), 0.78 (95% confidence interval [CI], 0.55-1.12). HR for adjudicated hospitalization for CHF (n = 21): 1.04 (0.43-2.47). For placebo-controlled trials, 4P-MACE incidence rates: 14.9 per 1000 patient-years, linagliptin (43 events), 16.4, total comparators (29 events); overall HR, 1.09 (95% CI, 0.68-1.75). Occurrence of investigator-reported events suggestive of CHF was low for linagliptin- (26 events, 0.5%; serious: 16 events, 0.3%) and placebo-treated (8 events, 0.2%; serious: 6 events, 0.2%) patients. Linagliptin is not associated with increased CV risk versus pooled active comparators or placebo in patients with T2DM.

Use of Flood Seasonality in Pooling-Group Formation and Quantile Estimation: An Application in Great Britain

NASA Astrophysics Data System (ADS)

Formetta, Giuseppe; Bell, Victoria; Stewart, Elizabeth

2018-02-01

Regional flood frequency analysis is one of the most commonly applied methods for estimating extreme flood events at ungauged sites or locations with short measurement records. It is based on: (i) the definition of a homogeneous group (pooling-group) of catchments, and on (ii) the use of the pooling-group data to estimate flood quantiles. Although many methods to define a pooling-group (pooling schemes, PS) are based on catchment physiographic similarity measures, in the last decade methods based on flood seasonality similarity have been contemplated. In this paper, two seasonality-based PS are proposed and tested both in terms of the homogeneity of the pooling-groups they generate and in terms of the accuracy in estimating extreme flood events. The method has been applied in 420 catchments in Great Britain (considered as both gauged and ungauged) and compared against the current Flood Estimation Handbook (FEH) PS. Results for gauged sites show that, compared to the current PS, the seasonality-based PS performs better both in terms of homogeneity of the pooling-group and in terms of the accuracy of flood quantile estimates. For ungauged locations, a national-scale hydrological model has been used for the first time to quantify flood seasonality. Results show that in 75% of the tested locations the seasonality-based PS provides an improvement in the accuracy of the flood quantile estimates. The remaining 25% were located in highly urbanized, groundwater-dependent catchments. The promising results support the aspiration that large-scale hydrological models complement traditional methods for estimating design floods.

47 CFR 90.187 - Trunking in the bands between 150 and 512 MHz.

Code of Federal Regulations, 2012 CFR

2012-10-01

... that event, the burden of proving by clear and convincing evidence that the certified frequency... with any certified frequency coordinator for the pool (Public Safety or Industrial/Business) in which... relevant pool within one business day. For a period of sixty days thereafter, no application will be...

47 CFR 90.187 - Trunking in the bands between 150 and 512 MHz.

Code of Federal Regulations, 2011 CFR

2011-10-01

... that event, the burden of proving by clear and convincing evidence that the certified frequency... with any certified frequency coordinator for the pool (Public Safety or Industrial/Business) in which... relevant pool within one business day. For a period of sixty days thereafter, no application will be...

Molecular imaging of labile iron(II) pools in living cells with a turn-on fluorescent probe.

PubMed

Au-Yeung, Ho Yu; Chan, Jefferson; Chantarojsiri, Teera; Chang, Christopher J

2013-10-09

Iron is an essential metal for living organisms, but misregulation of its homeostasis at the cellular level can trigger detrimental oxidative and/or nitrosative stress and damage events. Motivated to help study the physiological and pathological consequences of biological iron regulation, we now report a reaction-based strategy for monitoring labile Fe(2+) pools in aqueous solution and living cells. Iron Probe 1 (IP1) exploits a bioinspired, iron-mediated oxidative C-O bond cleavage reaction to achieve a selective turn-on response to Fe(2+) over a range of cellular metal ions in their bioavailable forms. We show that this first-generation chemical tool for fluorescence Fe(2+) detection can visualize changes in exchangeable iron stores in living cells upon iron supplementation or depletion, including labile iron pools at endogenous, basal levels. Moreover, IP1 can be used to identify reversible expansion of labile iron pools by stimulation with vitamin C or the iron regulatory hormone hepcidin, providing a starting point for further investigations of iron signaling and stress events in living systems as well as future probe development.

AGU Hosts Networking Event for Female Scientists

NASA Astrophysics Data System (ADS)

McEntee, Chris

2013-01-01

At Fall Meeting this year I had the pleasure of cohosting a new event, a Networking Reception for Early Career Female Scientists and Students, with Jane Lubchenco, under secretary of Commerce for Oceans and Atmosphere and National Oceanic and Atmospheric Administration administrator, and Marcia McNutt, director of the U.S. Geological Survey. AGU recognizes the importance of having a diverse pool of new researchers who can enrich Earth and space sciences with their skills and innovation. That's why one of our four strategic goals is to help build the global talent pool and provide early-career scientists with networking opportunities like this one.

Expressions of Different-Trajectory Caused Motion Events in Chinese

ERIC Educational Resources Information Center

Paul, Jing Z.

2013-01-01

We perform motion events in all aspects of our daily life, from walking home to jumping into a pool, from throwing a frisbee to pushing a shopping cart. The fact that languages may encode such motion events in different fashions has raised intriguing questions regarding the typological classifications of natural languages in relation to…

Comparative coronary risks of apixaban, rivaroxaban and dabigatran: a meta-analysis and adjusted indirect comparison

PubMed Central

Loke, Yoon K; Pradhan, Shiva; Yeong, Jessica Ka-yan; Kwok, Chun Shing

2014-01-01

Aims There are concerns regarding increased risk of acute coronary syndrome with dabigatran. We aimed to assess whether alternative treatment options such as rivaroxaban or apixaban carry a similar risk as compared with dabigatran. Methods We searched MEDLINE and EMBASE for randomized controlled trials of apixaban, dabigatran or rivaroxaban against control (placebo, heparin or vitamin K antagonist). We pooled odds ratios (OR) for adverse coronary events (acute coronary syndrome or myocardial infarction) using fixed effect meta-analysis and assessed heterogeneity with I2. We conducted adjusted indirect comparisons to compare risk of adverse coronary events with apixaban or rivaroxaban vs. dabigatran. Results Twenty-seven randomized controlled trials met the inclusion criteria. Dabigatran was associated with a significantly increased risk of adverse coronary events in pooled analysis of nine trials (OR 1.45, 95% CI 1.14, 1.86). There was no signal for coronary risk with apixaban from nine trials (pooled OR 0.89, 95% CI 0.78, 1.03) or rivaroxaban from nine trials (pooled OR 0.81, 95% CI 0.72, 0.93). Overall, adjusted indirect comparison suggested that both apixaban (OR 0.61, 95% CI 0.44, 0.85) and rivaroxaban (OR 0.54; 95% CI 0.39, 0.76) were associated with lower coronary risk than dabigatran. Restricting the indirect comparison to a vitamin K antagonist as a common control, yielded similar findings, OR 0.57 (95% CI 0.39, 0.85) for apixaban vs. dabigatran and 0.53 (95% CI 0.37, 0.77) for rivaroxaban vs. dabigatran. Conclusions There are significant differences in the comparative safety of apixaban, rivaroxaban and dabigatran with regards to acute coronary adverse events. PMID:24617578

The distribution and public health consequences of releases of chemicals intended for pool use in 17 states, 2001-2009.

PubMed

Anderson, Ayana R; Welles, Wanda Lizak; Drew, James; Orr, Maureen F

2014-05-01

To keep swimming pool water clean and clear, consumers purchase, transport, store, use, and dispose of large amounts of potentially hazardous chemicals. Data about incidents due to the use of these chemicals and the resultant public health impacts are limited. The authors analyzed pool chemical release data from 17 states that participated in the Agency for Toxic Substances and Disease Registry's chemical event surveillance system during 2001-2009. In 400 pool chemical incidents, 60% resulted in injuries. Of the 732 injured persons, 67% were members of the public and 50% were under 18 years old. Incidents occurred most frequently in private residences (39%), but incidents with the most injured persons (34%) occurred at recreational facilities. Human error (71.9%) was the most frequent primary contributing factor, followed by equipment failure (22.8%). Interventions designed to mitigate the public health impact associated with pool chemical releases should target both private pool owners and public pool operators.

Efficacy and safety of 5-hydroxytryptamine 3 receptor antagonists in irritable bowel syndrome: A systematic review and meta-analysis of randomized controlled trials

PubMed Central

Tang, Yurong; Xiong, Wenjie; Shen, Xiaoxue; Jiang, Ling; Lin, Lin

2017-01-01

Aim We assessed the efficacy and safety of 5-hydroxytryptamine (5-HT3) receptor antagonists in adults with non-constipated irritable bowel syndrome (IBS) or diarrhea-predominant IBS (IBS-D). Methods We searched PubMed, MEDLINE, EMBASE, and the Cochrane Controlled Trials Register for randomized controlled trials (RCTs) involving adults with non-constipated IBS or IBS-D that compared 5-HT3 receptor antagonists with placebo or other conventional treatment. Dichotomous symptom data were pooled to obtain the relative risk (RR) and 95% confidence intervals (CIs) for improving global IBS symptoms, abdominal pain and abnormal bowel habits, or stool consistency symptoms after therapy, and adverse events, including constipation. Meta- analysis was performed with Mantel Haenszel method using Revman 5.3 software. Results We included 21 RCTs; 16 were high quality (Jadad score ≥ 4). The pooled RR of global IBS symptoms improved by 5-HT3 receptor antagonists versus placebo or mebeverine was 1.56 (95% CI: 1.43–1.71); alosetron, ramosetron, and cilansetron had similar treatment effects. The pooled RR of abdominal pain relieved by 5-HT3 receptor antagonists versus placebo was 1.33 (95% CI: 1.26–1.39). The pooled RR showed that 5-HT3 receptor antagonists improved abnormal bowel habits or stool consistency symptoms (RR = 1.63, 95% CI: 1.33, 1.99). The pooled RR of adverse events following 5-HT3 receptor antagonist treatment was 1.15 (95% CI: 1.08, 1.22). Subgroup analysis indicated that alosetron had a high rate of adverse effects (RR = 1.16, 95% CI: 1.08, 1.25); adverse events following ramosetron treatment were not statistically significantly different. 5-HT3 receptor antagonists were likelier to cause constipation: the pooled RR of constipation developing with 5-HT3 receptor antagonist versus placebo was 3.71 (95% CI: 2.98–4.61). However, constipation was likelier in patients with non-constipated IBS after taking 5-HT3 receptor antagonists than in patients with IBS-D only (non-constipated IBS and IBS-D: RR = 5.28 [95% CI: 3.93, 7.08] vs. IBS-D only 3.24 [2.54, 4.12]). Conclusions Ramosetron, cilansetron, ondansetron, and alosetron are effective for treating non-constipated IBS and IBS-D. Our systematic review found rare serious adverse events. PMID:28291778

A comparison of time dependent Cox regression, pooled logistic regression and cross sectional pooling with simulations and an application to the Framingham Heart Study.

PubMed

Ngwa, Julius S; Cabral, Howard J; Cheng, Debbie M; Pencina, Michael J; Gagnon, David R; LaValley, Michael P; Cupples, L Adrienne

2016-11-03

Typical survival studies follow individuals to an event and measure explanatory variables for that event, sometimes repeatedly over the course of follow up. The Cox regression model has been used widely in the analyses of time to diagnosis or death from disease. The associations between the survival outcome and time dependent measures may be biased unless they are modeled appropriately. In this paper we explore the Time Dependent Cox Regression Model (TDCM), which quantifies the effect of repeated measures of covariates in the analysis of time to event data. This model is commonly used in biomedical research but sometimes does not explicitly adjust for the times at which time dependent explanatory variables are measured. This approach can yield different estimates of association compared to a model that adjusts for these times. In order to address the question of how different these estimates are from a statistical perspective, we compare the TDCM to Pooled Logistic Regression (PLR) and Cross Sectional Pooling (CSP), considering models that adjust and do not adjust for time in PLR and CSP. In a series of simulations we found that time adjusted CSP provided identical results to the TDCM while the PLR showed larger parameter estimates compared to the time adjusted CSP and the TDCM in scenarios with high event rates. We also observed upwardly biased estimates in the unadjusted CSP and unadjusted PLR methods. The time adjusted PLR had a positive bias in the time dependent Age effect with reduced bias when the event rate is low. The PLR methods showed a negative bias in the Sex effect, a subject level covariate, when compared to the other methods. The Cox models yielded reliable estimates for the Sex effect in all scenarios considered. We conclude that survival analyses that explicitly account in the statistical model for the times at which time dependent covariates are measured provide more reliable estimates compared to unadjusted analyses. We present results from the Framingham Heart Study in which lipid measurements and myocardial infarction data events were collected over a period of 26 years.

Singular and combined effects of blowdown, salvage logging, and wildfire on forest floor and soil mercury pools.

PubMed

Mitchell, Carl P J; Kolka, Randall K; Fraver, Shawn

2012-08-07

A number of factors influence the amount of mercury (Hg) in forest floors and soils, including deposition, volatile emission, leaching, and disturbances such as fire. Currently the impact on soil Hg pools from other widespread forest disturbances such as blowdown and management practices like salvage logging are unknown. Moreover, ecological and biogeochemical responses to disturbances are generally investigated within a single-disturbance context, with little currently known about the impact of multiple disturbances occurring in rapid succession. In this study we capitalize on a combination of blowdown, salvage logging and fire events in the sub-boreal region of northern Minnesota to assess both the singular and combined effects of these disturbances on forest floor and soil total Hg concentrations and pools. Although none of the disturbance combinations affected Hg in mineral soil, we did observe significant effects on both Hg concentrations and pools in the forest floor. Blowdown increased the mean Hg pool in the forest floor by 0.76 mg Hg m(-2) (223%). Salvage logging following blowdown created conditions leading to a significantly more severe forest floor burn during wildfire, which significantly enhanced Hg emission. This sequence of combined events resulted in a mean loss of approximately 0.42 mg Hg m(-2) (68% of pool) from the forest floor, after conservatively accounting for potential losses via enhanced soil leaching and volatile emissions between the disturbance and sampling dates. Fire alone or blowdown followed by fire did not significantly affect the total Hg concentrations or pools in the forest floor. Overall, unexpected consequences for soil Hg accumulation and by extension, atmospheric Hg emission and risk to aquatic biota, may result when combined impacts are considered in addition to singular forest floor and soil disturbances.

Automated Detection of Obstructive Sleep Apnea Events from a Single-Lead Electrocardiogram Using a Convolutional Neural Network.

PubMed

Urtnasan, Erdenebayar; Park, Jong-Uk; Joo, Eun-Yeon; Lee, Kyoung-Joung

2018-04-23

In this study, we propose a method for the automated detection of obstructive sleep apnea (OSA) from a single-lead electrocardiogram (ECG) using a convolutional neural network (CNN). A CNN model was designed with six optimized convolution layers including activation, pooling, and dropout layers. One-dimensional (1D) convolution, rectified linear units (ReLU), and max pooling were applied to the convolution, activation, and pooling layers, respectively. For training and evaluation of the CNN model, a single-lead ECG dataset was collected from 82 subjects with OSA and was divided into training (including data from 63 patients with 34,281 events) and testing (including data from 19 patients with 8571 events) datasets. Using this CNN model, a precision of 0.99%, a recall of 0.99%, and an F 1 -score of 0.99% were attained with the training dataset; these values were all 0.96% when the CNN was applied to the testing dataset. These results show that the proposed CNN model can be used to detect OSA accurately on the basis of a single-lead ECG. Ultimately, this CNN model may be used as a screening tool for those suspected to suffer from OSA.

Systematic Review of Infrapopliteal Drug-Eluting Stents: A Meta-Analysis of Randomized Controlled Trials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Katsanos, Konstantinos, E-mail: katsanos@med.upatras.gr; Spiliopoulos, Stavros; Diamantopoulos, Athanasios

2013-06-15

IntroductionDrug-eluting stents (DES) have been proposed for the treatment of infrapopliteal arterial disease. We performed a systematic review to provide a qualitative analysis and quantitative data synthesis of randomized controlled trials (RCTs) assessing infrapopliteal DES.Materials and MethodsPubMed (Medline), EMBASE (Excerpta Medical Database), AMED (Allied and Complementary medicine Database), Scopus, CENTRAL (Cochrane Central Register of Controlled Trials), online content, and abstract meetings were searched in September 2012 for eligible RCTs according to the preferred reporting items for systematic reviews and meta-analyses selection process. Risk of bias was assessed using the Cochrane Collaboration's tool. Primary endpoint was primary patency defined as absencemore » of {>=}50 % vessel restenosis at 1 year. Secondary outcome measures included patient survival, limb amputations, change of Rutherford-Becker class, target lesion revascularization (TLR) events, complete wound healing, and event-free survival at 1 year. Risk ratio (RRs) were calculated using the Mantel-Haenszel fixed effects model, and number-needed-to-treat values are reported.ResultsThree RCTs involving 501 patients with focal infrapopliteal lesions were analyzed (YUKON-BTX, DESTINY, and ACHILLES trials). All three RCTs included relatively short and focal infrapopliteal lesions. At 1 year, there was clear superiority of infrapopliteal DES compared with control treatments in terms of significantly higher primary patency (80.0 vs. 58.5 %; pooled RR = 1.37, 95 % confidence interval [CI] = 1.18-1.58, p < 0.0001; number-needed-to-treat (NNT) value = 4.8), improvement of Rutherford-Becker class (79.0 vs. 69.6 %; pooled RR = 1.13, 95 % CI = 1.002-1.275, p = 0.045; NNT = 11.1), decreased TLR events (9.9 vs. 22.0 %; pooled RR = 0.45, 95 % CI = 0.28-0.73, p = 0.001; NNT = 8.3), improved wound healing (76.8 vs. 59.7 %; pooled RR = 1.29, 95 % CI = 1.02-1.62, p = 0.04; NNT = 5.9), and better overall event-free survival (72.2 vs. 57.3 %; pooled RR = 1.26, 95 % CI = 1.10-1.44, p = 0.0006; NNT = 6.7). Conclusion. DES for focal infrapopliteal lesions significantly inhibit vascular restenosis and thereby improve primary patency, decrease repeat procedures, improve wound healing, and prolong overall event-free survival.« less

Controls on Filling and Evacuation of Sediment in Waterfall Plunge Pools

NASA Astrophysics Data System (ADS)

Scheingross, J. S.; Lamb, M. P.

2014-12-01

Many waterfalls are characterized by the presence of deep plunge pools that experience periods of sediment fill and evacuation. These cycles of sediment fill are a first order control on the relative magnitude of lateral versus vertical erosion at the base of waterfalls, as vertical incision requires cover-free plunge pools to expose the bedrock floor, while lateral erosion can occur when pools are partially filled and plunge-pool walls are exposed. Currently, there exists no mechanistic model describing sediment transport through waterfall plunge pools, limiting our ability to predict waterfall retreat. To address this knowledge gap, we performed detailed laboratory experiments measuring plunge-pool sediment transport capacity (Qsc_pool) under varying waterfall and plunge-pool geometries, flow hydraulics, and sediment size. Our experimental plunge-pool sediment transport capacity measurements match well with a mechanistic model we developed which combines existing waterfall jet theory with a modified Rouse profile to predict sediment transport capacity as a function of water discharge and suspended sediment concentration at the plunge-pool lip. Comparing the transport capacity of plunge pools to lower gradient portions of rivers (Qsc_river) shows that, for transport limited conditions, plunge pools fill with sediment under modest water discharges when Qsc_river > Qsc_pool, and empty to bedrock under high discharges when Qsc_pool > Qsc_river. These results are consistent with field observations of sand-filled plunge pools with downstream boulder rims, implying filling and excavation of plunge pools over single-storm timescales. Thus, partial filling of waterfall plunge pools may provide a mechanism to promote lateral undercutting and retreat of waterfalls in homogeneous rock in which plunge-pool vertical incision occurs during brief large floods that expose bedrock, whereas lateral erosion may prevail during smaller events.

Terrestrial Carbon Fluxes from Deforestation in the Brazilian Amazon and Cerrado Regions Predicted from MODIS Satellite Data and Ecosystem Modeling

NASA Astrophysics Data System (ADS)

Klooster, S.; Potter, C.; Genovese, V.

2008-12-01

The NASA-CASA (Carnegie Ames Stanford Approach) simulation model based on satellite observations of monthly vegetation cover from the Moderate Resolution Imaging Spectroradiometer (MODIS) was used to estimate tropical forest and savanna (Cerrado) carbon pools for the Brazilian Amazon region over the period 2000-2004. Adjustments for mean age of forest stands were carried out across the region, resulting in a new mapping of aboveground biomass pools based on MODIS satellite data. Yearly maps of newly deforested lands from the Brazilian PRODES (Programa de calculo do desflorestamento da Amazonia ) project were combined with these NASA-CASA biomass predictions to generate seasonal budgets of potential carbon and nitrogen trace gas losses from biomass burning events. Simulations of plant residue and soil carbon decomposition were conducted in the NASA-CASA model during and following deforestation events to track the fate of aboveground biomass pools that were cut and burned each year across the region.

Limiting swimming pool outbreaks of cryptosporidiosis - the roles of regulations, staff, patrons and research.

PubMed

Ryan, Una; Lawler, Sheleigh; Reid, Simon

2017-02-01

Cryptosporidium is the leading cause of swimming pool outbreaks of gastroenteritis. Transmission occurs through the ingestion of oocysts that are passed in the faeces of an infected person or animal when an accidental faecal release event occurs. Cryptosporidium parasites present specific challenges for infection control as oocysts are highly resistant to chlorine levels used for pool disinfection, infected individuals can shed large numbers of oocysts, there is a long incubation period and shedding of oocysts occurs even after symptom resolution. The purposes of this review are to identify key barriers to limiting swimming pool-associated outbreaks of cryptosporidiosis and to outline needs for research and collaboration to advance co-ordinated management practices. We reviewed swimming pool-associated cryptosporidiosis outbreaks, disinfection teachniques, current regulations and the role of staff and patrons. Key barriers to limiting swimming pool-associated outbreaks of cryptosporidiosis are a lack of uniform national and international standards, poor adherence and understanding of regulations governing staff and patron behaviour, and low levels of public knowledge and awareness.

Hydrologic modeling to screen potential environmental management methods for malaria vector control in Niger

NASA Astrophysics Data System (ADS)

Gianotti, Rebecca L.; Bomblies, Arne; Eltahir, Elfatih A. B.

2009-08-01

This paper describes the first use of Hydrology-Entomology and Malaria Transmission Simulator (HYDREMATS), a physically based distributed hydrology model, to investigate environmental management methods for malaria vector control in the Sahelian village of Banizoumbou, Niger. The investigation showed that leveling of topographic depressions where temporary breeding habitats form during the rainy season, by altering pool basin microtopography, could reduce the pool persistence time to less than the time needed for establishment of mosquito breeding, approximately 7 days. Undertaking soil surface plowing can also reduce pool persistence time by increasing the infiltration rate through an existing pool basin. Reduction of the pool persistence time to less than the rainfall interstorm period increases the frequency of pool drying events, removing habitat for subadult mosquitoes. Both management approaches could potentially be considered within a given context. This investigation demonstrates that management methods that modify the hydrologic environment have significant potential to contribute to malaria vector control in water-limited, Sahelian Africa.

Bedload transport rates in a step-pool channel at near-bankfull flows

Treesearch

Daniel A. Marion

2001-01-01

This paper examines unit bedload transport rates (BTRs) at near-bankfull flows within a small step-pool channel in the Ouachita Mountains of central Arkansas. For this study, five runoff events with peak discharges between 0.25 and 1.34 cms (1.0- to 1.6-yr recurrence intervals) were produced in a natural channel using a streamflow simulation system. BTRs range from...

Fine-grained bed patch response to near-bankfull flows in a step-pool channel

Treesearch

Daniel A. Marion; Frank Weirich

1999-01-01

Fine-grained bed patches were monitored in a representative step-pool channel in the Arkansas Ouachita Mountains to assess their response to near-bankfull streamflow events. These patches are small, relatively well-sorted bed areas predominantly composed of gravel-size and smaller grains. They occupy 5.2 and 4.1 percent of the active and bankfull channel areas,...

Nonobstructive Coronary Artery Disease by Coronary CT Angiography Improves Risk Stratification and Allocation of Statin Therapy.

PubMed

Emami, Hamed; Takx, Richard A P; Mayrhofer, Thomas; Janjua, Sumbal; Park, Jakob; Pursnani, Amit; Tawakol, Ahmed; Lu, Michael T; Ferencik, Maros; Hoffmann, Udo

2017-09-01

This study sought to determine prognostic value of nonobstructive coronary artery disease (CAD) for atherosclerotic cardiovascular disease (ASCVD) events and to determine whether incorporation of this information into the pooled cohort equation reclassifies recommendations for statin therapy as defined by the 2013 guidelines for cholesterol management of the American College of Cardiology and American Heart Association (ACC/AHA). Detection of nonobstructive CAD by coronary computed tomography angiography may improve risk stratification and permit individualized and more appropriate allocation of statin therapy. This study determined the pooled hazard ratio of nonobstructive CAD for ASCVD events from published studies and incorporated this information into the ACC/AHA pooled cohort equation. The study calculated revised sex- and ethnicity-based 10-year ASCVD risk and determined boundaries corresponding to the original 7.5% risk for ASCVD events. It also assessed reclassification for statin eligibility by incorporating the results from meta-analysis to individual patients from a separate cohort. This study included 2 studies (2,295 subjects; 66% male; prevalence of nonobstructive CAD, 47%; median follow-up, 49 months; 67 ASCVD events). The hazard ratio of nonobstructive CAD for ASCVD events was 3.2 (95% confidence interval: 1.5 to 6.7). Incorporation of this information into the pooled cohort equation resulted in reclassification toward statin eligibility in individuals with nonobstructive CAD, with an original ASCVD score of 3.0% and 5.9% or higher in African-American women and men and a score of 4.4% and 4.6% or higher in Caucasian women and men, respectively. The absence of nonobstructive CAD resulted in reclassification toward statin ineligibility if the original ASCVD score was as 10.0% and 17.9% or lower in African-American women and men and 13.7% and 14.3% or lower in Caucasian women and men, respectively. Reclassification is observed in 14% of patients. Detection of nonobstructive CAD by coronary computed tomography angiography improves risk stratification and permits individualized and more appropriate allocation of statin therapy across sex and ethnicity groups. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Peroral endoscopic myotomy for the treatment of esophageal achalasia: systematic review and pooled analysis.

PubMed

Patel, K; Abbassi-Ghadi, N; Markar, S; Kumar, S; Jethwa, P; Zaninotto, G

2016-10-01

Peroral endoscopic myotomy (POEM) is a novel approach to performing esophageal myotomy for the treatment of achalasia. This review aims to assess subjective and objective metrics of achalasia treatment efficacy, perioperative adverse events and the incidence of postoperative gastroesophageal reflux disease in patients treated with POEM. Secondary aims include a pooled analysis comparison of the clinical outcomes and procedural safety of POEM versus laparoscopic Heller's myotomy (LHM). A systematic review of the literature, up to and including January 15, 2015, was conducted for studies reporting POEM outcomes. Studies comparing POEM to LHM were also included for the purpose of pooled analysis. Outcomes from 1122 POEM patients, from 22 studies, are reported in this systematic review. Minor operative adverse events included capno/pneumo-peritoneum (30.6%), capno/pneumo-thorax (11.0%) and subcutaneous emphysema (31.6%). Major operative adverse events included mediastinal leak (0.3%), postoperative bleeding (1.1%) and a single mortality (0.09%). There was an improvement in lower esophageal sphincter pressure and timed barium esophagram column height of 66% and 80% post-POEM, respectively. Symptom improvement was demonstrated with a pre- and post-POEM Eckardt score ± standard deviation of 6.8 ± 1.0 and 1.2 ± 0.6, respectively. Pre- and post-POEM endoscopy showed esophagitis in 0% and 19% of patients, respectively. The median (interquartile range) points scored for study quality was 15 (14-16) out of total of 32. Pooled analysis of three comparative studies between LHM and POEM showed similar results for adverse events, perforation rate, operative time and a nonsignificant trend toward a reduced length of hospital stay in the POEM group. In conclusion, POEM is a safe and effective treatment for achalasia, showing significant improvements in objective metrics and achalasia-related symptoms. Randomized comparative studies of LHM and POEM are required to determine the most effective treatment modality for achalasia. © 2015 International Society for Diseases of the Esophagus.

Community Response to a Heavy Precipitation Event in High Temperature, Chemosynthetic Biofilms and Sediments

NASA Astrophysics Data System (ADS)

Meyer-Dombard, D. R.; Loiacono, S. T.; Shock, E.

2012-12-01

Coordinated analysis of the "Bison Pool" (BP) Environmental Genome and a complementary contextual geochemical dataset of ~75 parameters revealed biogeochemical cycling and metabolic and microbial community shifts in a Yellowstone National Park hot spring ecosystem (1). The >22m outflow of BP is a gradient of decreasing temperature, increasing dissolved oxygen, and changing availability of nutrients. Microbial life at BP transitions from a 92°C chemosynthetic community in the BP source pool to a 56°C photosynthetic mat community. Metagenomic data at BP showed the potential for both heterotrophic and autotrophic carbon metabolism (rTCA and acetyl-CoA cycles) in the highest temperature, chemosynthetic regions (1). This region of the outflow is dominated by Aquificales and Pyrococcus relatives, with smaller contributions of heterotrophic Bacteria. Following a 2h heavy precipitation event we observed an influx of exogenous organic material into the source pool supplied from the meadow surrounding the BP area. We sampled biomass and fluid at several locations within the outflow immediately following the event, and on several occasions for the next eight days. Elemental analysis and carbon and nitrogen isotopic analyses were conducted on biomass and sediment, and dissolved organic and inorganic carbon content and δ13C of fluids were analyzed. DNA and RNA were extracted, and following RT-PCR, nitrogen cycle functional gene expression was evaluated. Previous work at BP has shown that chemosynthetic biomass may carry isotopic signatures of fractionation during carbon fixation, via the acetyl-CoA and rTCA cycles (2). However, the addition of exogenous organic carbon during the rain event had an immediate and dramatic effect on the sediments and biofilms in the chemosynthetic zone of the outflow. Dissolved organic carbon was the highest measured in six years. Chemosynthetic biomass responded by incorporating the organic carbon. Carbon isotopic signatures in chemosynthetic biomass at "Bison Pool" have been previously measured at ~ -4‰ (2). However, immediately following the event, carbon in biomass was measured at ~ -25‰ (values similar to local soil and bison excrement). Biomass closest to the source of "Bison Pool" returned to ~ -4‰ within a few days, but biomass ~ 3m downstream was still ~ -14‰ eight days after the event. Carbon isotopic signatures of the dissolved inorganic carbon (DIC) were depleted relative to values measured in 2005-2009, possibly a result of a combination of added DIC in rain and heterotrophic waste produced using the exogenous depleted carbon; this depleted DIC persisted for the full study period. These results suggest that a shift from autotrophic to heterotrophic metabolism may occur following every significant precipitation event at BP, and support previous observations concerning potential periodic eutrophic conditions in this ecosystem (3). 1 Swingley, W.D. et al., PLoS ONE, 7(6): e38108. 2 Havig et al., 2011. JGR Biogeosciences, 116, G01005. 3 Loiacono, S.T. et al., 2012. EM, 14(5): 1272-1283.

Neuropsychiatric safety with liraglutide 3.0 mg for weight management: Results from randomized controlled phase 2 and 3a trials.

PubMed

O'Neil, Patrick M; Aroda, Vanita R; Astrup, Arne; Kushner, Robert; Lau, David C W; Wadden, Thomas A; Brett, Jason; Cancino, Ana-Paula; Wilding, John P H

2017-11-01

Liraglutide, a GLP-1 receptor agonist, regulates appetite via receptors in the brain. Because of concerns regarding the potential of centrally-acting anti-obesity medications to affect mental health, pooled neuropsychiatric safety data from all phase 2 and 3a randomized, double-blind trials with liraglutide 3.0 mg were evaluated post hoc. Data from the liraglutide weight-management programme were pooled. Across trials, individuals with a body mass index ≥30 or ≥27 kg/m 2 with weight-related comorbidities were randomized to once-daily subcutaneous liraglutide 3.0 mg (n = 3384) or placebo (n = 1941), both with a 500 kcal/d deficit diet, plus exercise. Adverse events related to neuropsychiatric safety were collected in all trials. Additionally, in the phase 3a trials, validated mental-health questionnaires were prospectively and systematically administered. In the pooled analysis of 5325 randomized and exposed individuals, rates of depression (2.1 vs 2.1 events/100 person-years) and anxiety (1.9 vs 1.7 events/100 person-years) through adverse event reporting were similarly low in liraglutide and placebo groups. Nine (0.3%) individuals receiving liraglutide and 2 (0.1%) receiving placebo reported adverse events of suicidal ideation or behaviour. In phase 3a trials, mean baseline Patient Health Questionnaire-9 scores of 2.8 ± 3.0 vs 2.9 ± 3.1 for liraglutide vs placebo improved to 1.8 ± 2.7 vs 1.9 ± 2.7, respectively, at treatment end; 34/3291 individuals (1.0%) receiving liraglutide 3.0 mg vs 19/1843 (1.0%) receiving placebo reported suicidal ideation on the Columbia-Suicide Severity Rating Scale. Results of this exploratory pooled analysis provide no cause for concern regarding the neuropsychiatric safety of treatment with liraglutide 3.0 mg in patients similar to those included in the examined trials. Although there was a small numerical imbalance in suicidal ideation with liraglutide through adverse event reporting, no between-treatment imbalances in suicidal ideation/behaviour or depression were noted through prospective questionnaire assessments. © 2017 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Assessing the role of natural disturbance and forest management on dead wood dynamics in mixed-species stands of central Maine, USA

Treesearch

Joshua J. Puhlick; Aaron R. Weiskittel; Shawn Fraver; Matthew B. Russell; Laura S. Kenefic

2016-01-01

Dead wood pools are strongly influenced by natural disturbance events, stand development processes, and forest management activities. However, the relative importance of these influences can vary over time. In this study, we evaluate the role of these factors on dead wood biomass pools across several forest management alternatives after 60 years of treatment on the...

ASCANs Helms and Gregory swim in pool during Elgin AFB survival training

NASA Image and Video Library

1990-09-20

1990 Group 13 Astronaut Candidates (ASCANs) Susan J. Helms (foreground) and William G. Gregory, wearing helmets and flight suits, swim in pool at Elgin Air Force Base (AFB) in Pensacola, Florida, during water survival exercises. The training familiarized the candidates with survival techniques necessary in the event of a water landing. ASCANs participated in the exercises from 08-14-90 through 08-17-90.

Intervention Associated Acute Kidney Injury and Long-Term Cardiovascular Outcomes.

PubMed

Saratzis, Athanasios; Harrison, Seamus; Barratt, Jonathan; Sayers, Robert D; Sarafidis, Pantelis A; Bown, Matthew J

2015-01-01

Acute kidney injury (AKI) has been associated with all-cause short- and long-term mortality. However, its association with cardiovascular (CV) events remains unclear. We sought to investigate this in patients undergoing open (OAR) or endovascular (EVAR) abdominal aortic aneurysm repair, as they are likely to develop both AKI and CV morbidity. A meta-analysis was subsequently performed to confirm this in other CV-interventions. AKI-incidence was assessed in a multicentre-cohort of 1,068 patients undergoing EVAR (947 individuals) or OAR electively using the 'Acute Kidney Injury Network' criteria. A composite-endpoint was used, consisting of non-fatal myocardial infarction (MI), stroke, vascular event, hospitalisation due to heart failure and CV death. A systematic literature review identified studies reporting AKI-incidence and CV events. Risk ratios (RRs) at 1 and 5 years were combined using meta-analysis. During a median follow-up of 62 months (range 11-121), AKI was associated with CV events on adjusted (for CV risk-factors) analyses (Incidence 36% of EVAR, 32% of OAR patients; hazard ratio 1.73, 95% CI 1.06-3.39, p=0.03) for the overall population. In the meta-analysis, 7 studies reported incidence of MI on 23,936 patients 1-year after coronary intervention (PCI) with a pooled RR of 1.76 (95% CI 1.45-2.83, p<0.001); at 2 years, 3 studies reported MI incidence on 17,773 patients after PCI with a pooled RR of 1.34 (95% CI 1.10-1.63, p=0.003). MI-incidence was reported 5 years after cardiac surgery by 3 studies (33,701 patients) with a pooled RR of 1.60 (95% CI 1.43-1.81). AKI is associated with long-term CV events after surgery or endovascular intervention. © 2015 S. Karger AG, Basel.

Saltmarsh pool and tidal creek morphodynamics: Dynamic equilibrium of northern latitude saltmarshes?

NASA Astrophysics Data System (ADS)

Wilson, Carol A.; Hughes, Zoe J.; FitzGerald, Duncan M.; Hopkinson, Charles S.; Valentine, Vinton; Kolker, Alexander S.

2014-05-01

Many saltmarsh platforms in New England and other northern climates (e.g. Canada, northern Europe) exhibit poor drainage, creating waterlogged regions where short-form Spartina alterniflora dominates and stagnant pools that experience tidal exchange only during spring tides and storm-induced flooding events. The processes related to pool formation and tidal creek incision (via headward erosion) that may eventually drain these features are poorly understood, however it has been suggested that an increase in pool occurrence in recent decades is due to waterlogging stress from sea-level rise. We present evidence here that saltmarshes in Plum Island Estuary of Massachusetts are keeping pace with sea-level rise, and that the recent increase in saltmarsh pool area coincides with changes in drainage density from a legacy of anthropogenic ditching (reversion to natural drainage conditions). Gradients, in addition to elevation and hydroperiod, are critical for saltmarsh pool formation. Additionally, elevation and vegetative changes associated with pool formation, creek incision, subsequent drainage of pools, and recolonization by S. alterniflora are quantified. Pool and creek dynamics were found to be cyclic in nature, and represent platform elevation in dynamic equilibrium with sea level whereby saltmarsh elevation may be lowered (due to degradation of organic matter and formation of a pool), however may be regained on short timescales (101-2 yr) with creek incision into pools and restoration of tidal exchange. Rapid vertical accretion is associated with sedimentation and S. alterniflora plant recolonization.

Refuge habitats for fishes during seasonal drying in an intermittent stream: movement, survival and abundance of three minnow species

USGS Publications Warehouse

Hodges, S.W.; Magoulick, Daniel D.

2011-01-01

Drought and summer drying can be important disturbance events in many small streams leading to intermittent or isolated habitats. We examined what habitats act as refuges for fishes during summer drying, hypothesizing that pools would act as refuge habitats. We predicted that during drying fish would show directional movement into pools from riffle habitats, survival rates would be greater in pools than in riffles, and fish abundance would increase in pool habitats. We examined movement, survival and abundance of three minnow species, bigeye shiner (Notropis boops), highland stoneroller (Campostoma spadiceum) and creek chub (Semotilus atromaculatus), during seasonal stream drying in an Ozark stream using a closed robust multi-strata mark-recapture sampling. Population parameters were estimated using plausible models within program MARK, where a priori models are ranked using Akaike's Information Criterion. Creek chub showed directional movement into pools and increased survival and abundance in pools during drying. Highland stonerollers showed strong directional movement into pools and abundance increased in pools during drying, but survival rates were not significantly greater in pools than riffles. Bigeye shiners showed high movement rates during drying, but the movement was non-directional, and survival rates were greater in riffles than pools. Therefore, creek chub supported our hypothesis and pools appear to act as refuge habitats for this species, whereas highland stonerollers partly supported the hypothesis and bigeye shiners did not support the pool refuge hypothesis. Refuge habitats during drying are species dependent. An urgent need exists to further understand refuge habitats in streams given projected changes in climate and continued alteration of hydrological regimes.

The Impact of Warm Pool El Nino Events on Antarctic Ozone

NASA Technical Reports Server (NTRS)

Hurwitz, Margaret M.; Newman, P. A.; Song, In-Sun; Frith, Stacey M.

2011-01-01

Warm pool El Nino (WPEN) events are characterized by positive sea surface temperature (SST) anomalies in the central equatorial Pacific in austral spring and summer. Previous work found an enhancement in planetary wave activity in the South Pacific in austral spring, and a warming of 3-5 K in the Antarctic lower stratosphere during austral summer, in WPEN events as compared with ENSO neutral. In this presentation, we show that weakening of the Antarctic vortex during WPEN affects the structure and magnitude of high-latitude total ozone. We use total ozone data from TOMS and OMI, as well as station data from Argentina and Antarctica, to identify shifts in the longitudinal location of the springtime ozone minimum from its climatological position. In addition, we examine the sensitivity of the WPEN-related ozone response to the phase of the quasi-biennial oscillation (QBO). We then compare the observed response to WPEN events with Goddard Earth Observing System chemistry-climate model, version 2 (GEOS V2 CCM) simulations. Two, 50-year time-slice simulations are forced by annually repeating SST and sea ice climatologies, one set representing observed WPEN events and the second set representing neutral ENSO events, in a present-day climate. By comparing the two simulations, we isolate the impact of WPEN events on lower stratospheric ozone, and furthermore, examine the sensitivity of the WPEN ozone response to the phase of the QBO.

The effects of the Indo-Pacific warm pool on the stratosphere

NASA Astrophysics Data System (ADS)

Zhou, Xin; Li, Jianping; Xie, Fei; Ding, Ruiqiang; Li, Yanjie; Zhao, Sen; Zhang, Jiankai; Li, Yang

2017-03-01

Sea surface temperature (SST) in the Indo-Pacific warm pool (IPWP) plays a key role in influencing East Asian climate, and even affects global-scale climate change. This study defines IPWP Niño and IPWP Niña events to represent the warm and cold phases of IPWP SST anomalies, respectively, and investigates the effects of these events on stratospheric circulation and temperature. Results from simulations forced by observed SST anomalies during IPWP Niño and Niña events show that the tropical lower stratosphere tends to cool during IPWP Niño events and warm during IPWP Niña events. The responses of the northern and southern polar vortices to IPWP Niño events are fairly symmetric, as both vortices are significantly warmed and weakened. However, the responses of the two polar vortices to IPWP Niña events are of opposite sign: the northern polar vortex is warmed and weakened, but the southern polar vortex is cooled and strengthened. These features are further confirmed by composite analysis using reanalysis data. A possible dynamical mechanism connecting IPWP SST to the stratosphere is suggested, in which IPWP Niño and Niña events excite teleconnections, one similar to the Pacific-North America pattern in the Northern Hemisphere and a Rossby wave train in the Southern Hemisphere, which project onto the climatological wave in the mid-high latitudes, intensifying the upward propagation of planetary waves into the stratosphere and, in turn, affecting the polar vortex.

Reporting of Adverse Events in Published and Unpublished Studies of Health Care Interventions: A Systematic Review

PubMed Central

Golder, Su; Wright, Kath

2016-01-01

Background We performed a systematic review to assess whether we can quantify the underreporting of adverse events (AEs) in the published medical literature documenting the results of clinical trials as compared with other nonpublished sources, and whether we can measure the impact this underreporting has on systematic reviews of adverse events. Methods and Findings Studies were identified from 15 databases (including MEDLINE and Embase) and by handsearching, reference checking, internet searches, and contacting experts. The last database searches were conducted in July 2016. There were 28 methodological evaluations that met the inclusion criteria. Of these, 9 studies compared the proportion of trials reporting adverse events by publication status. The median percentage of published documents with adverse events information was 46% compared to 95% in the corresponding unpublished documents. There was a similar pattern with unmatched studies, for which 43% of published studies contained adverse events information compared to 83% of unpublished studies. A total of 11 studies compared the numbers of adverse events in matched published and unpublished documents. The percentage of adverse events that would have been missed had each analysis relied only on the published versions varied between 43% and 100%, with a median of 64%. Within these 11 studies, 24 comparisons of named adverse events such as death, suicide, or respiratory adverse events were undertaken. In 18 of the 24 comparisons, the number of named adverse events was higher in unpublished than published documents. Additionally, 2 other studies demonstrated that there are substantially more types of adverse events reported in matched unpublished than published documents. There were 20 meta-analyses that reported the odds ratios (ORs) and/or risk ratios (RRs) for adverse events with and without unpublished data. Inclusion of unpublished data increased the precision of the pooled estimates (narrower 95% confidence intervals) in 15 of the 20 pooled analyses, but did not markedly change the direction or statistical significance of the risk in most cases. The main limitations of this review are that the included case examples represent only a small number amongst thousands of meta-analyses of harms and that the included studies may suffer from publication bias, whereby substantial differences between published and unpublished data are more likely to be published. Conclusions There is strong evidence that much of the information on adverse events remains unpublished and that the number and range of adverse events is higher in unpublished than in published versions of the same study. The inclusion of unpublished data can also reduce the imprecision of pooled effect estimates during meta-analysis of adverse events. PMID:27649528

Efficacy of Second Generation Direct-Acting Antiviral Agents for Treatment Naïve Hepatitis C Genotype 1: A Systematic Review and Network Meta-Analysis

PubMed Central

Sobhonslidsuk, Abhasnee; Thakkinstian, Ammarin; Teerawattananon, Yot

2015-01-01

Background The treatment of hepatitis C (HCV) infections has significantly changed in the past few years due to the introduction of direct-acting antiviral agents (DAAs). DAAs could improve the sustained virological response compared to pegylated interferon with ribavirin (PR). However, there has been no evidence from randomized controlled trials (RCTs) that directly compare the efficacy among the different regimens of DAAs. Aim Therefore, we performed a systematic review and network meta-analysis aiming to compare the treatment efficacy between different DAA regimens for treatment naïve HCV genotype 1. Methods Medline and Scopus were searched up to 25th May 2015. RCTs investigating the efficacy of second generation DAA regimens for treatment naïve HCV genotype 1 were eligible for the review. Due to the lower efficacy and more side effects of first generation DAAs, this review included only second generation DAAs approved by the US or EU Food and Drug Administration, that comprised of simeprevir (SMV), sofosbuvir (SOF), daclatasvir (DCV), ledipasvir (LDV), and paritaprevir/ritonavir/ombitasvir plus dasabuvir (PrOD). Primary outcomes were sustained virological response at weeks 12 (SVR12) and 24 (SVR24) after the end of treatment and adverse drug events (i.e. serious adverse events, anemia, and fatigue). Efficacy of all treatment regimens were compared by applying a multivariate random effect meta-analysis. Incidence rates of SVR12 and SVR24, and adverse drug events of each treatment regimen were pooled using ‘pmeta’ command in STATA program. Results Overall, 869 studies were reviewed and 16 studies were eligible for this study. Compared with the PR regimen, SOF plus PR, SMV plus PR, and DVC plus PR regimens yielded significantly higher probability of having SVR24 with pooled risk ratios (RR) of 1.98 (95% CI 1.24, 3.14), 1.46 (95% CI: 1.22, 1.75), and 1.68 (95% CI: 1.14, 2.46), respectively. Pooled incidence rates of SVR12 and SVR24 in all treatment regimens without PR, i.e. SOF plus LDV with/without ribavirin, SOF plus SMV with/without ribavirin, SOF plus DCV with/without ribavirin, and PrOD with/without ribavirin, (pooled incidence of SVR12 ranging from 93% to 100%, and pooled incidence of SVR24 ranging from 89% to 96%) were much higher than the pooled incidence rates of SVR12 (51%) and SVR24 (48%) in PR alone. In comparing SOF plus LDV with ribavirin and SOF plus LDV without ribavirin, the chance of having SVR12 was not significantly different between these two regimens, with the pooled RR of 0.99 (95% CI: 0.97, 1.01). Regarding adverse drug events, risk of serious adverse drug events, anemia and fatigue were relatively higher in treatment regimens with PR than the treatment regimens without PR. The main limitation of our study is that a subgroup analysis according to dosages and duration of treatment could not be performed. Therefore, the dose and duration of recommended treatment have been suggested in range and not in definite value. Conclusions Both DAA plus PR and dual DAA regimens should be included in the first line drug for treatment naïve HCV genotype 1 because of the significant clinical benefits over PR alone. However, due to high drug costs, an economic evaluation should be conducted in order to assess the value of the investment when making coverage decisions. PMID:26720298

Refuge habitats for fishes during seasonal drying in an intermittent stream: Movement, survival and abundance of three minnow species

USGS Publications Warehouse

Hodges, S.W.; Magoulick, D.D.

2011-01-01

Drought and summer drying can be important disturbance events in many small streams leading to intermittent or isolated habitats. We examined what habitats act as refuges for fishes during summer drying, hypothesizing that pools would act as refuge habitats. We predicted that during drying fish would show directional movement into pools from riffle habitats, survival rates would be greater in pools than in riffles, and fish abundance would increase in pool habitats. We examined movement, survival and abundance of three minnow species, bigeye shiner (Notropis boops), highland stoneroller (Campostoma spadiceum) and creek chub (Semotilus atromaculatus), during seasonal stream drying in an Ozark stream using a closed robust multi-strata mark-recapture sampling. Population parameters were estimated using plausible models within program MARK, where a priori models are ranked using Akaike's Information Criterion. Creek chub showed directional movement into pools and increased survival and abundance in pools during drying. Highland stonerollers showed strong directional movement into pools and abundance increased in pools during drying, but survival rates were not significantly greater in pools than riffles. Bigeye shiners showed high movement rates during drying, but the movement was non-directional, and survival rates were greater in riffles than pools. Therefore, creek chub supported our hypothesis and pools appear to act as refuge habitats for this species, whereas highland stonerollers partly supported the hypothesis and bigeye shiners did not support the pool refuge hypothesis. Refuge habitats during drying are species dependent. An urgent need exists to further understand refuge habitats in streams given projected changes in climate and continued alteration of hydrological regimes. ?? 2011 Springer Basel AG (outside the USA).

Testing Domestication Scenarios of Lima Bean (Phaseolus lunatus L.) in Mesoamerica: Insights from Genome-Wide Genetic Markers

PubMed Central

Chacón-Sánchez, María I.; Martínez-Castillo, Jaime

2017-01-01

Plant domestication can be seen as a long-term process that involves a complex interplay among demographic processes and evolutionary forces. Previous studies have suggested two domestication scenarios for Lima bean in Mesoamerica: two separate domestication events, one from gene pool MI in central-western Mexico and another one from gene pool MII in the area Guatemala-Costa Rica, or a single domestication from gene pool MI in central-western Mexico followed by post-domestication gene flow with wild populations. In this study we evaluated the genetic structure of the wild gene pool and tested these two competing domestication scenarios of Lima bean in Mesoamerica by applying an ABC approach to a set of genome-wide SNP markers. The results confirm the existence of three gene pools in wild Lima bean, two Mesoamerican gene pools (MI and MII) and the Andean gene pool (AI), and suggest the existence of another gene pool in central Colombia. The results indicate that although both domestication scenarios may be supported by genetic data, higher statistical support was given to the single domestication scenario in central-western Mexico followed by admixture with wild populations. Domestication would have involved strong founder effects reflected in loss of genetic diversity and increased LD levels in landraces. Genomic regions affected by selection were detected and these may harbor candidate genes related to domestication. PMID:28955351

Mass effects meet species sorting: transformations of microbial assemblages in epiphreatic subsurface karst water pools.

PubMed

Shabarova, Tanja; Widmer, Franco; Pernthaler, Jakob

2013-09-01

We investigated the transformations of the microbial communities in epiphreatic karst cave pools with different flooding frequencies. Fingerprinting of 16S rRNA genes was combined with microscopic and sequence analysis to examine if source water would transport comparable microbial inocula into the pools at consecutive flood events, and to assess possible effects of residence time on the microbial assemblages during stagnant periods. Variability in the concentrations of dissolved organic carbon and conductivity indicated differences between floods and changes of pool water over time. High numbers of Betaproteobacteria affiliated with Methylophilaceae and Comamonadaceae were introduced into the pools during floodings. While the former persisted in the pools, the latter exhibited considerable microdiversification. These Betaproteobacteria might thus represent core microbial groups in karst water. A decrease in the estimated total diversity of the remaining bacterial taxa was apparent after a few weeks of residence: Some were favoured by stagnant conditions, whereas the majority was rapidly outcompeted. Thus, the microbial communities consisted of different components governed by complementary assembly mechanisms (dispersal versus environmental filtering) upon introduction into the pools. High overlap of temporary and persistent community members between samplings from two winters, moreover, reflected the seasonal recurrence of the studied microbial assemblages. © 2013 John Wiley & Sons Ltd and Society for Applied Microbiology.

Can the GEOS CCM Simulate the Temperature Response to Warm Pool El Nino Events in the Antarctic Stratosphere?

NASA Technical Reports Server (NTRS)

Hurwitz, M. M.; Song, I.-S.; Oman, L. D.; Newman, P. A.; Molod, A. M.; Frith, S. M.; Nielsen, J. E.

2010-01-01

"Warm pool" (WP) El Nino events are characterized by positive sea surface temperature (SST) anomalies in the central equatorial Pacific. During austral spring. WP El Nino events are associated with an enhancement of convective activity in the South Pacific Convergence Zone, provoking a tropospheric planetary wave response and thus increasing planetary wave driving of the Southern Hemisphere stratosphere. These conditions lead to higher polar stratospheric temperatures and to a weaker polar jet during austral summer, as compared with neutral ENSO years. Furthermore, this response is sensitive to the phase of the quasi-biennial oscillation (QBO): a stronger warming is seen in WP El Nino events coincident with the easterly phase of the quasi-biennial oscillation (QBO) as compared with WP El Nino events coincident with a westerly or neutral QBO. The Goddard Earth Observing System (GEOS) chemistry-climate model (CCM) is used to further explore the atmospheric response to ENSO. Time-slice simulations are forced by composited SSTs from observed WP El Nino and neutral ENSO events. The modeled eddy heat flux, temperature and wind responses to WP El Nino events are compared with observations. A new gravity wave drag scheme has been implemented in the GEOS CCM, enabling the model to produce a realistic, internally generated QBO. By repeating the above time-slice simulations with this new model version, the sensitivity of the WP El Nino response to the phase of the quasi-biennial oscillation QBO is estimated.

Can the GEOS CCM Simulate the Temperature Response to Warm Pool El Nino Events in the Antarctic Stratosphere?

NASA Technical Reports Server (NTRS)

Hurwitz, M. M.; Song, I.-S.; Oman, L. D.; Newman, P. A.; Molod, A. M.; Frith, S. M.; Nielsen, J. E.

2011-01-01

"Warm pool" (WP) El Nino events are characterized by positive sea surface temperature (SST) anomalies in the central equatorial Pacific. During austral spring, WP El Nino events are associated with an enhancement of convective activity in the South Pacific Convergence Zone, provoking a tropospheric planetary wave response and thus increasing planetary wave driving of the Southern Hemisphere stratosphere. These conditions lead to higher polar stratospheric temperatures and to a weaker polar jet during austral summer, as compared with neutral ENSO years. Furthermore, this response is sensitive to the phase of the quasi-biennial oscillation (QBO): a stronger warming is seen in WP El Nino events coincident with the easterly phase of the quasi-biennial oscillation (QBO) as compared with WP El Nino events coincident with a westerly or neutral QBO. The Goddard Earth Observing System (GEOS) chemistry-climate model (CCM) is used to further explore the atmospheric response to ENSO. Time-slice simulations are forced by composited SSTs from observed NP El Nino and neutral ENSO events. The modeled eddy heat flux, temperature and wind responses to WP El Nino events are compared with observations. A new gravity wave drag scheme has been implemented in the GEOS CCM, enabling the model to produce e realistic, internally generated QBO. By repeating the above time-slice simulations with this new model version, the sensitivity of the WP El Nino response to the phase of the quasi-biennial oscillation QBO is estimated.

First Observation of Rock Motion on Racetrack Playa, Death Valley National Park—Role of a Persistent Pool, Sun, Zephyrs, Windowpane Ice, and Tugboats

NASA Astrophysics Data System (ADS)

Norris, R. D.; Norris, J. M.

2014-12-01

Trails in the mud-cracked surface of Racetrack Playa have been scored by hundreds of rocks up to 320 kg, but the mechanism of movement is debated. In Winter 2013-2014, we observed rocks in motion associated with a transient pool formed by winter precipitation. The pond was 7 cm deep on the southern edge of the playa, tapering to a mud flat to the north. Freezing during cold winter nights formed floating "windowpane" ice 3-5 mm thick. Rocks repeatedly moved on sunny days under light winds of 3-5 m/second, as the ice broke up near midday and was set into motion by wind stress on melt pools and the ice surface. Ice panels shoved rocks along the mud like a tugboat, sometimes forming moving imbricated ice piles upstream of the rocks and in other cases moving faster than the rocks and forming brash-filled leads downstream. GPS units mounted in experimental rocks recorded a creeping pace of 2-6 m/minute, a speed that made it difficult to observe trail formation visually. The 2013-2014 pond formed on November 20-24 and persisted through early February 2014. During this time rocks were observed moving at least five times, and studies of "stiz marks" formed by rocks at the ends of trail segments show that there were likely 3-5 additional move events. Observed travel times ranged from a few seconds to 16 minutes. In one event, two experimental rocks 153 m apart began moving simultaneously and traveled 64.1 and 65.6 m respectively, ultimately moving 157-162 m in subsequent events. Rock motion depends on the creation of winter pools sufficiently deep to allow the formation of floating ice and exposed to the light winds and sun needed for ice breakup. The combination of these events is extremely rare, leading to highly episodic trail formation. Our observations differ from previous hypotheses in that the rocks were moved by thinner ice, at slower speeds, and by lighter winds than predicted.

Posttraumatic stress disorder in critical illness survivors: a metaanalysis.

PubMed

Parker, Ann M; Sricharoenchai, Thiti; Raparla, Sandeep; Schneck, Kyle W; Bienvenu, O Joseph; Needham, Dale M

2015-05-01

To conduct a systematic review and metaanalysis of the prevalence, risk factors, and prevention/treatment strategies for posttraumatic stress disorder symptoms in critical illness survivors. PubMed, Embase, CINAHL, PsycINFO, and Cochrane Library from inception through March 5, 2014. Eligible studies met the following criteria: 1) adult general/nonspecialty ICU, 2) validated posttraumatic stress disorder instrument greater than or equal to 1 month post-ICU, and 3) sample size greater than or equal to 10 patients. Duplicate independent review and data abstraction from all eligible titles/abstracts/full-text articles. The search identified 2,817 titles/abstracts, with 40 eligible articles on 36 unique cohorts (n = 4,260 patients). The Impact of Event Scale was the most common posttraumatic stress disorder instrument. Between 1 and 6 months post-ICU (six studies; n = 456), the pooled mean (95% CI) Impact of Event Scale score was 20 (17-24), and the pooled prevalences of clinically important posttraumatic stress disorder symptoms (95% CI) were 25% (18-34%) and 44% (36-52%) using Impact of Event Scale thresholds greater than or equal to 35 and greater than or equal to 20, respectively. Between 7 and 12 months post-ICU (five studies; n = 698), the pooled mean Impact of Event Scale score was 17 (9-24), and pooled prevalences of posttraumatic stress disorder symptoms were 17% (10-26%) and 34% (22-50%), respectively. ICU risk factors for posttraumatic stress disorder symptoms included benzodiazepine administration and post-ICU memories of frightening ICU experiences. Posttraumatic stress disorder symptoms were associated with worse quality of life. In European-based studies: 1) an ICU diary was associated with a significant reduction in posttraumatic stress disorder symptoms, 2) a self-help rehabilitation manual was associated with significant posttraumatic stress disorder symptom reduction at 2 months, but not 6 months; and 3) a nurse-led ICU follow-up clinic did not reduce posttraumatic stress disorder symptoms. Clinically important posttraumatic stress disorder symptoms occurred in one fifth of critical illness survivors at 1-year follow-up, with higher prevalence in those who had comorbid psychopathology, received benzodiazepines, and had early memories of frightening ICU experiences. In European studies, ICU diaries reduced posttraumatic stress disorder symptoms.

Habitat ephemerality and hatching fractions of a diapausing anostracan (Crustacea: Branchiopoda)

Treesearch

Marie A. Simovich; Thomas E. Philippi; Ellen T. Bauder; Jacob A. Moorad

2005-01-01

Diapause allows aquatic organisms to survive periods of drydown in intermittent pools. However, often not all of the individuals hatch in response to a filling event. This prolonged diapause can be a bet-hedging adaptation to unpredictability in the duration of filling events. Under the simplest bet-hedging model of selection on prolonged diapause, the fraction of eggs...

ASCAN Ochoa floats in pool during Elgin AFB water survival training

NASA Technical Reports Server (NTRS)

1990-01-01

1990 Group 13 Astronaut Candidate (ASCAN) Ellen Ochoa, wearing helmet and flight suit, climbs into a single person life raft while floating in a pool at Elgin Air Force Base (AFB) in Pensacola, Florida, during water survival exercises. Ochoa's underarm flotation device holds her above the water as she pulls herself into the life raft. The training familiarized the candidates with survival techniques necessary in the event of a water landing. ASCANs participated in the exercises from 08-14-90 through 08-17-90.

Cold weather effects on Dresden Unit 1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Anagnostopoulos, H.

1995-03-01

Dresden Unit 1 is in the final stages of a decommissioning effort directed at preparing the unit to enter a SAFSTOR status. Following an extended sub-zero cold wave, about 55,000 gallons of water were discovered in the lowest elevation of the spherical reactor enclosure. Cold weather had caused the freezing and breaking of several service water lines that had not been completely isolated. Two days later, at a regularly scheduled decommissioning meeting, the event was communicated to the decommissioning team, who quickly recognized the potential for freezing of a 42 inches diameter Fuel Transfer Tube that connects the sphere tomore » the Spent Fuel Pool. The team directed that the pool gates between the adjacent Spent Fuel Pool and the Fuel Transfer Pool be installed, and a portable source of heat was installed on the Fuel Transfer Tube. It was later determined that, with the fuel pool gates removed, and with a worst case freeze break at the 502 elevation on the Fuel Transfer Tube (in the Sphere), the fuel in the Spent Fuel Pool could be uncovered to a level 3 below the top of active fuel.« less

The efficacy and safety of alectinib in the treatment of ALK+ NSCLC: a systematic review and meta-analysis

PubMed Central

Chen, Yuqing; Qian, Ruolan; Liu, Sihan; You, Danming; Zhang, Jian; Luo, Peng

2018-01-01

Background Alectinib is a second-generation anaplastic lymphoma kinase (ALK) inhibitor approved by the US Food and Drug Administration to treat crizotinib-refractory non-small cell lung cancer. We performed this meta-analysis to synthesize the results of different clinical trials to evaluate the efficacy and safety of alectinib. Methods A search of 3 databases, including PubMed, Web of Science, and the Cochrane Library, was performed from the inception of each database through September 5, 2017. We have pooled the overall response rate (ORR), disease control rate, progression-free survival, and intracranial ORR to evaluate the efficacy of alectinib. Discontinuation rate, rate of dose reduction or interruption due to adverse events as well as the incidence of several adverse events were aggregated to evaluate its safety. Results A total of 8 studies with 626 patients have been included in our study. The pooled efficacy parameters are as follows: ORR 70% (95% CI: 57% to 82%), disease control rate 88% (95% CI: 82% to 94%), progression-free survival 9.36 months (95% CI: 7.38% to 11.34%), and intracranial ORR 52% (95% CI: 45% to 59%). ALK inhibitor-naïve patients tend to have better responses than crizotinib-pretreated patients. The aggregate discontinuation rate is 7% (95% CI: 4% to 10%), and the pooled rate of dose reduction or interruption is 33% (95% CI: 24% to 42%). The incidences of most adverse events were relatively low, while the incidences of 2 frequently reported adverse events, myalgia (18%) and anemia (25%), were even higher than with the first-generation ALK inhibitor crizotinib. Conclusion Generally, alectinib is a drug with preferable efficacy and tolerable adverse effects, and it is suitable for the treatment of intracranial metastases. PMID:29535535

The efficacy and safety of alectinib in the treatment of ALK+ NSCLC: a systematic review and meta-analysis.

PubMed

Fan, Junsheng; Xia, Zengfei; Zhang, Xiaoli; Chen, Yuqing; Qian, Ruolan; Liu, Sihan; You, Danming; Zhang, Jian; Luo, Peng

2018-01-01

Alectinib is a second-generation anaplastic lymphoma kinase (ALK) inhibitor approved by the US Food and Drug Administration to treat crizotinib-refractory non-small cell lung cancer. We performed this meta-analysis to synthesize the results of different clinical trials to evaluate the efficacy and safety of alectinib. A search of 3 databases, including PubMed, Web of Science, and the Cochrane Library, was performed from the inception of each database through September 5, 2017. We have pooled the overall response rate (ORR), disease control rate, progression-free survival, and intracranial ORR to evaluate the efficacy of alectinib. Discontinuation rate, rate of dose reduction or interruption due to adverse events as well as the incidence of several adverse events were aggregated to evaluate its safety. A total of 8 studies with 626 patients have been included in our study. The pooled efficacy parameters are as follows: ORR 70% (95% CI: 57% to 82%), disease control rate 88% (95% CI: 82% to 94%), progression-free survival 9.36 months (95% CI: 7.38% to 11.34%), and intracranial ORR 52% (95% CI: 45% to 59%). ALK inhibitor-naïve patients tend to have better responses than crizotinib-pretreated patients. The aggregate discontinuation rate is 7% (95% CI: 4% to 10%), and the pooled rate of dose reduction or interruption is 33% (95% CI: 24% to 42%). The incidences of most adverse events were relatively low, while the incidences of 2 frequently reported adverse events, myalgia (18%) and anemia (25%), were even higher than with the first-generation ALK inhibitor crizotinib. Generally, alectinib is a drug with preferable efficacy and tolerable adverse effects, and it is suitable for the treatment of intracranial metastases.

Analysis of number needed to treat for droxidopa in patients with symptomatic neurogenic orthostatic hypotension.

PubMed

François, Clément; Rowse, Gerald J; Hewitt, L Arthur; Vo, Pamela; Hauser, Robert A

2016-08-18

Droxidopa is an orally active prodrug that significantly improved dizziness/lightheadedness measured using the Orthostatic Hypotension Symptom Assessment (OHSA) Item 1 in patients with neurogenic orthostatic hypotension (nOH) caused by primary autonomic failure (Parkinson disease, multiple system atrophy, and pure autonomic failure), dopamine β-hydroxylase deficiency, or nondiabetic autonomic neuropathy. The efficacy and safety of droxidopa were assessed by determining the number needed to treat (NNT) and the number needed to harm (NNH). Data collected in randomized, placebo-controlled clinical studies in adults with a clinical diagnosis of symptomatic nOH were pooled for efficacy and safety analyses. NNT and NNH were calculated as reciprocals of the risk difference (difference in event rates) for droxidopa versus placebo. The NNT for droxidopa for improvement in OHSA Item 1 was <10. The NNH for adverse events (AEs) leading to discontinuation in the pooled studies was 81. The likelihood of being helped or harmed (LHH) calculated from pooled analysis of the NNT for ≥2 units of improvement in OHSA Item 1 score and the NNH for discontinuations due to AEs were 7.8, 8.8, 3.1, and 3.5 for weeks 1, 2, 4, and 8 after randomization, respectively. Droxidopa is efficacious for treatment of nOH, with an NNT below 10 and an acceptable tolerability profile with NNH ranging from 23 to 302 in the pooled analysis of frequently occurring AEs. Based on the LHH for the pooled analysis at week 1, droxidopa is 7.8 times more likely than placebo to show a clinical benefit than result in discontinuation because of an AE. ClinicalTrials.gov identifiers: NCT00782340 , first received October 29, 2008; NCT00633880 , first received March 5, 2008; and NCT01176240 , first received July 30, 2010.

Addition of bevacizumab to fluorouracil-based first-line treatment of metastatic colorectal cancer: pooled analysis of cohorts of older patients from two randomized clinical trials.

PubMed

Kabbinavar, Fairooz F; Hurwitz, Herbert I; Yi, Jing; Sarkar, Somnath; Rosen, Oliver

2009-01-10

Colorectal cancer (CRC) occurs predominantly in older persons. To provide more statistical power to assess risk/benefit in older patients, we examined the clinical benefit of bevacizumab (BV) plus fluorouracil-based chemotherapy in first-line metastatic CRC (mCRC) treatment in patients aged > or = 65 years, using data pooled from two placebo-controlled studies. Pooled efficacy data for 439 patients > or = 65 years old randomized to BV plus chemotherapy (n = 218) or placebo plus chemotherapy (n = 221) in study 1 and study 2 were retrospectively analyzed on an intent-to-treat basis for overall survival (OS), progression-free survival (PFS), and objective response. Safety analysis was based on reports of targeted adverse events in treated patients. Median OS with BV plus chemotherapy was 19.3 v 14.3 months with placebo plus chemotherapy (hazard ratio [HR] = 0.70; 95% CI, 0.55 to 0.90; P = .006). Patients treated with BV plus chemotherapy had a median PFS of 9.2 v 6.2 months for placebo plus chemotherapy patients (HR = 0.52; 95% CI, 0.40 to 0.67; P < .0001). The objective response rate was 34.4% with BV plus chemotherapy versus 29.0% with placebo plus chemotherapy (difference not statistically significant). Rates of BV-associated adverse events in the pooled BV plus chemotherapy group were consistent with those reported in the overall populations for the two studies. Analysis of pooled patient cohorts age >/= 65 years from two similar trials in mCRC indicates that adding bevacizumab to fluorouracil-based chemotherapy improved OS and PFS, similar to the benefits in younger patients. Also, the risks of treatment do not seem to exceed those in younger patients with mCRC.

Comparison of mesalazine and balsalazide in induction and maintenance of remission in patients with ulcerative colitis: a meta-analysis.

PubMed

Rahimi, Roja; Nikfar, Shekoufeh; Rezaie, Ali; Abdollahi, Mohammad

2009-04-01

5-Aminosalicylates are the standard treatment for induction and maintenance of remission in mild-to-moderate ulcerative colitis. In recent years, the 5-aminosalicylic acid-containing pro-drug balsalazide has been the focus of attention. To compare the efficacy and tolerance of balsalazide and mesalazine by meta-analysis. Pubmed, Embase, Scopus, Web of Science, and the Cochrane Central Register of Controlled Trials were searched for studies comparing the efficacy and/or tolerance of balsalazide with mesalazine in the management of UC. The search terms were: "mesalazine" or "5-aminosalicylic acid" and "balsalazide" and "ulcerative colitis." Data were collected from 1966 to 2007 (up to February). There was no language restriction. "Symptomatic remission," "complete remission," "relapse rate," "total adverse events," and "withdrawals because of adverse events" were the key outcomes of interest. Six randomized placebo-controlled clinical trials met our criteria and were included in the meta-analysis. In these "symptomatic remission," "complete remission," "relapse rate," "total adverse events," and "withdrawals because of adverse events" were evaluated in three, three, two, five, and six of the trials, respectively. They included 653 patients consisting of 55.4% men and 44.6% women randomized to receive either balsalazide or mesalazine. Pooling of three trials for symptomatic remission yielded a significant relative risk (RR) of 1.23 (95% confidence interval of 1.03-1.47, P = 0.02). The summary RR for complete remission in three trials was 1.3 (95% CI of 1.002-1.68, P = 0.048). Pooling of two trials for the outcome of relapse yielded a non-significant RR of 0.77 (95% CI of 0.56-1.07, P = 0.12). Pooling five studies from which data for any adverse events were extracted, yielded a non-significant RR of 0.87 (95% CI of 0.75-1.001, P = 0.53). The summary RR for withdrawals because of adverse events in six trials was 0.69, a non-significant RR (95% CI of 0.37-1.29, P = 0.24). Balsalazide is more effective than mesalazine in induction of remission, but balsalazide has no benefit compared with mesalazine in preventing relapse in the population selected. The number of patients with any adverse events and withdrawals because of severe adverse events is similar for mesalazine and balsalazide.

AP1000{sup R} nuclear power plant safety overview for spent fuel cooling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gorgemans, J.; Mulhollem, L.; Glavin, J.

2012-07-01

The AP1000{sup R} plant is an 1100-MWe class pressurized water reactor with passive safety features and extensive plant simplifications that enhance construction, operation, maintenance, safety and costs. The AP1000 design uses passive features to mitigate design basis accidents. The passive safety systems are designed to function without safety-grade support systems such as AC power, component cooling water, service water or HVAC. Furthermore, these passive features 'fail safe' during a non-LOCA event such that DC power and instrumentation are not required. The AP1000 also has simple, active, defense-in-depth systems to support normal plant operations. These active systems provide the first levelmore » of defense against more probable events and they provide investment protection, reduce the demands on the passive features and support the probabilistic risk assessment. The AP1000 passive safety approach allows the plant to achieve and maintain safe shutdown in case of an accident for 72 hours without operator action, meeting the expectations provided in the U.S. Utility Requirement Document and the European Utility Requirements for passive plants. Limited operator actions are required to maintain safe conditions in the spent fuel pool via passive means. In line with the AP1000 approach to safety described above, the AP1000 plant design features multiple, diverse lines of defense to ensure spent fuel cooling can be maintained for design-basis events and beyond design-basis accidents. During normal and abnormal conditions, defense-in-depth and other systems provide highly reliable spent fuel pool cooling. They rely on off-site AC power or the on-site standby diesel generators. For unlikely design basis events with an extended loss of AC power (i.e., station blackout) or loss of heat sink or both, spent fuel cooling can still be provided indefinitely: - Passive systems, requiring minimal or no operator actions, are sufficient for at least 72 hours under all possible pool heat load conditions. - After 3 days, several different means are provided to continue spent fuel cooling using installed plant equipment as well as off-site equipment with built-in connections. Even for beyond design basis accidents with postulated pool damage and multiple failures in the passive safety-related systems and in the defense-in-depth active systems, the AP1000 multiple spent fuel pool spray and fill systems provide additional lines of defense to prevent spent fuel damage. (authors)« less

Pre-trained D-CNN models for detecting complex events in unconstrained videos

NASA Astrophysics Data System (ADS)

Robinson, Joseph P.; Fu, Yun

2016-05-01

Rapid event detection faces an emergent need to process large videos collections; whether surveillance videos or unconstrained web videos, the ability to automatically recognize high-level, complex events is a challenging task. Motivated by pre-existing methods being complex, computationally demanding, and often non-replicable, we designed a simple system that is quick, effective and carries minimal overhead in terms of memory and storage. Our system is clearly described, modular in nature, replicable on any Desktop, and demonstrated with extensive experiments, backed by insightful analysis on different Convolutional Neural Networks (CNNs), as stand-alone and fused with others. With a large corpus of unconstrained, real-world video data, we examine the usefulness of different CNN models as features extractors for modeling high-level events, i.e., pre-trained CNNs that differ in architectures, training data, and number of outputs. For each CNN, we use 1-fps from all training exemplar to train one-vs-rest SVMs for each event. To represent videos, frame-level features were fused using a variety of techniques. The best being to max-pool between predetermined shot boundaries, then average-pool to form the final video-level descriptor. Through extensive analysis, several insights were found on using pre-trained CNNs as off-the-shelf feature extractors for the task of event detection. Fusing SVMs of different CNNs revealed some interesting facts, finding some combinations to be complimentary. It was concluded that no single CNN works best for all events, as some events are more object-driven while others are more scene-based. Our top performance resulted from learning event-dependent weights for different CNNs.

Differing predictive relationships between baseline LDL-C, systolic blood pressure, and cardiovascular outcomes.

PubMed

Deedwania, Prakash C; Pedersen, Terje R; DeMicco, David A; Breazna, Andrei; Betteridge, D John; Hitman, Graham A; Durrington, Paul; Neil, Andrew

2016-11-01

Traditional cardiovascular risk factors, such as hypertension and dyslipidemia, predispose individuals to cardiovascular disease, particularly patients with diabetes. We investigated the predictive value of baseline systolic blood pressure (SBP) and low-density lipoprotein cholesterol (LDL-C) on the risk of vascular outcomes in a large population of patients at high risk of future cardiovascular events. Data were pooled from the TNT (Treating to New Targets), CARDS (Collaborative Atorvastatin Diabetes Study), and IDEAL (Incremental Decrease in End-Points Through Aggressive Lipid Lowering) trials and included a total of 21,727 patients (TNT: 10,001; CARDS: 2838; IDEAL: 8888). The effect of baseline SBP and LDL-C on cardiovascular events, coronary events, and stroke was evaluated using a multivariate Cox proportional-hazards model. Overall, risk of cardiovascular events was significantly higher for patients with higher baseline SBP or LDL-C. Higher baseline SBP was significantly predictive of stroke but not coronary events. Conversely, higher baseline LDL-C was significantly predictive of coronary events but not stroke. Results from the subgroup with diabetes (5408 patients; TNT: 1501; CARDS: 2838; IDEAL: 1069) were broadly consistent with those of the total cohort: baseline SBP and LDL-C were significantly predictive of cardiovascular events overall, with the association to LDL-C predominantly related to an effect on coronary events. However, baseline SBP was not predictive of either coronary or stroke events in the pooled diabetic population. In this cohort of high-risk patients, baseline SBP and LDL-C were significantly predictive of cardiovascular outcomes, but this effect may differ between the cerebrovascular and coronary systems. NCT00327691 (TNT); NCT00327418 (CARDS); NCT00159835 (IDEAL). Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A meta-analysis of the risk of total cardiovascular events of isosmolar iodixanol compared with low-osmolar contrast media.

PubMed

Zhang, Bu-Chun; Wu, Qiang; Wang, Cheng; Li, Dong-Ye; Wang, Zhi-Rong

2014-04-01

The iso-osmolar contrast agent iodixanol may be associated with a lower incidence of cardiac events than low-osmolar contrast media (LOCM), but previous trials have yielded mixed results. To compare the risk of total cardiovascular events of the iso-osmolar contrast medium, iodixanol, to LOCM. Medical literature databases were searched to identify comparisons between iodixanol and LOCM with cardiovascular events as a primary endpoint. A random-effects model was used to obtain pooled odds ratio (OR) for within-hospital and 30-day events. A total of 2 prospective cross-sectional studies and 11 randomized controlled trials (RCTs) (covering 6859 subjects) met our criteria. There was no significant difference in the incidence of within-hospital and 30-day cardiovascular events when iodixanol was compared with LOCM, with pooled OR of 0.72 (95%CI 0.49-1.06, p=0.09) and 1.19 (95%CI 0.70-2.02, p=0.53), respectively. Subgroup analysis showed no relative difference when iodixanol was compared with ioxaglate (OR=0.92, 95%CI 0.50-1.70, p=0.80) and iohexol (OR=0.75, 95%CI 0.48-1.17, p=0.21). However, a reduction in the within-hospital cardiovascular events was observed when iodixanol was compared with LOCM in the RCT subgroup (OR=0.65, 95%CI 0.44-0.96, p=0.03). Sensitivity analyses revealed that three studies had a strong impact on the association of within-hospital cardiovascular events between iodixanol and LOCM. Meta-regression analysis failed to account for heterogeneity. No publication bias was detected. This meta-analysis demonstrates that there is no conclusive evidence that iodixanol is superior to LOCM overall with regard to fewer cardiovascular events. Copyright © 2014. Published by Elsevier Ltd.

Visualization of hump formation in high-speed gas metal arc welding

NASA Astrophysics Data System (ADS)

Wu, C. S.; Zhong, L. M.; Gao, J. Q.

2009-11-01

The hump bead is a typical weld defect observed in high-speed welding. Its occurrence limits the improvement of welding productivity. Visualization of hump formation during high-speed gas metal arc welding (GMAW) is helpful in the better understanding of the humping phenomena so that effective measures can be taken to suppress or decrease the tendency of hump formation and achieve higher productivity welding. In this study, an experimental system was developed to implement vision-based observation of the weld pool behavior during high-speed GMAW. Considering the weld pool characteristics in high-speed welding, a narrow band-pass and neutral density filter was equipped for the CCD camera, the suitable exposure time was selected and side view orientation of the CCD camera was employed. The events that took place at the rear portion of the weld pools were imaged during the welding processes with and without hump bead formation, respectively. It was found that the variation of the weld pool surface height and the solid-liquid interface at the pool trailing with time shows some useful information to judge whether the humping phenomenon occurs or not.

Surveillance for waterborne disease outbreaks and other health events associated with recreational water --- United States, 2007--2008.

PubMed

Hlavsa, Michele C; Roberts, Virginia A; Anderson, Ayana R; Hill, Vincent R; Kahler, Amy M; Orr, Maureen; Garrison, Laurel E; Hicks, Lauri A; Newton, Anna; Hilborn, Elizabeth D; Wade, Timothy J; Beach, Michael J; Yoder, Jonathan S

2011-09-23

Since 1978, CDC, the U.S. Environmental Protection Agency, and the Council of State and Territorial Epidemiologists have collaborated on the Waterborne Disease and Outbreak Surveillance System (WBDOSS) for collecting and reporting data on waterborne disease outbreaks associated with recreational water. This surveillance system is the primary source of data concerning the scope and health effects of waterborne disease outbreaks in the United States. In addition, data are collected on other select recreational water--associated health events, including pool chemical--associated health events and single cases of Vibrio wound infection and primary amebic meningoencephalitis (PAM). Data presented summarize recreational water--associated outbreaks and other health events that occurred during January 2007--December 2008. Previously unreported data on outbreaks that have occurred since 1978 also are presented. The WBDOSS database includes data on outbreaks associated with recreational water, drinking water, water not intended for drinking (excluding recreational water), and water use of unknown intent. Public health agencies in the states, the District of Columbia, U.S. territories, and Freely Associated States are primarily responsible for detecting and investigating waterborne disease outbreaks and voluntarily reporting them to CDC using a standard form. Only data on outbreaks associated with recreational water are summarized in this report. Data on other recreational water--associated health events reported to CDC, the Agency for Toxic Substances and Disease Registry (ATSDR), and the U.S. Consumer Product Safety Commission (CPSC) also are summarized. A total of 134 recreational water--associated outbreaks were reported by 38 states and Puerto Rico for 2007--2008. These outbreaks resulted in at least 13,966 cases. The median outbreak size was 11 cases (range: 2--5,697 cases). A total of 116 (86.6%) outbreaks were associated with treated recreational water (e.g., pools and interactive fountains) and resulted in 13,480 (96.5%) cases. Of the 134 outbreaks, 81 (60.4%) were outbreaks of acute gastrointestinal illness (AGI); 24 (17.9%) were outbreaks of dermatologic illnesses, conditions, or symptoms; and 17 (12.7%) were outbreaks of acute respiratory illness. Outbreaks of AGI resulted in 12,477 (89.3%) cases. The etiology was laboratory-confirmed for 105 (78.4%) of the 134 outbreaks. Of the 105 outbreaks with a laboratory-confirmed etiology, 68 (64.8%) were caused by parasites, 22 (21.0%) by bacteria, five (4.8%) by viruses, nine (8.6%) by chemicals or toxins, and one (1.0%) by multiple etiology types. Cryptosporidium was confirmed as the etiologic agent of 60 (44.8%) of 134 outbreaks, resulting in 12,154 (87.0%) cases; 58 (96.7%) of these outbreaks, resulting in a total of 12,137 (99.9%) cases, were associated with treated recreational water. A total of 32 pool chemical--associated health events that occurred in a public or residential setting were reported to WBDOSS by Maryland and Michigan. These events resulted in 48 cases of illness or injury; 26 (81.3%) events could be attributed at least partially to chemical handling errors (e.g., mixing incompatible chemicals). ATSDR's Hazardous Substance Emergency Events Surveillance System received 92 reports of hazardous substance events that occurred at aquatic facilities. More than half of these events (55 [59.8%]) involved injured persons; the most frequently reported primary contributing factor was human error. Estimates based on CPSC's National Electronic Injury Surveillance System (NEISS) data indicate that 4,574 (95% confidence interval [CI]: 2,703--6,446) emergency department (ED) visits attributable to pool chemical--associated injuries occurred in 2008; the most frequent diagnosis was poisoning (1,784 ED visits [95% CI: 585--2,984]). NEISS data indicate that pool chemical--associated health events occur frequently in residential settings. A total of 236 Vibrio wound infections were reported to be associated with recreational water exposure; 36 (48.6%) of the 74 hospitalized vibriosis patients and six (66.7%) of the nine vibriosis patients who died had V. vulnificus infections. Eight fatal cases of PAM occurred after exposure to warm untreated freshwater. The 134 recreational water--associated outbreaks reported for 2007--2008 represent a substantial increase over the 78 outbreaks reported for 2005--2006 and the largest number of outbreaks ever reported to WBDOSS for a 2-year period. Outbreaks, especially the largest ones, were most frequently associated with treated recreational water and characterized by AGI. Cryptosporidium remains the leading etiologic agent. Pool chemical--associated health events occur frequently but are preventable. Data on other select recreational water--associated health events further elucidate the epidemiology of U.S. waterborne disease by highlighting less frequently implicated types of recreational water (e.g., oceans) and detected types of recreational water--associated illness (i.e., not AGI). CDC uses waterborne disease outbreak surveillance data to 1) identify the types of etiologic agents, recreational water venues, and settings associated with waterborne disease outbreaks; 2) evaluate the adequacy of regulations and public awareness activities to promote healthy and safe swimming; and 3) establish public health priorities to improve prevention efforts, guidelines, and regulations at the local, state, and federal levels.

Marsh Pool and Tidal Creek Morphodynamics: Dynamic Equilibrium of New England Saltmarshes?

NASA Astrophysics Data System (ADS)

Wilson, C.; FitzGerald, D. M.; Hughes, Z. J.

2012-12-01

Under natural conditions, high saltmarsh platforms in New England exhibit poor drainage, creating waterlogged pannes (where short-form Spartina alterniflora dominates) and stagnant pools that experience tidal exchange only during spring tides and storm-induced flooding events. It is well accepted that a legacy of ditching practices (either for agriculture or mosquito control purposes) provide "overdrainage" of saltmarshes (after Redfield, 1972) and a shift in biogeochemical conditions: lowering of groundwater tables, aeration of soil, and decrease in preserved belowground biomass. Analysis of historical imagery in the Plum Island Estuary of Massachusetts reveals closure and decrease in length of anthropogenic ditches in recent decades is closely linked to marsh pool evolution. Field analyses including stratigraphic transects and elevation surveys suggest these marshes are reverting to natural drainage conditions. Further, an important dynamic interaction exists between saltmarsh pools and natural tidal creeks: creeks incise into pool areas, causing drainage of the pools, and formation of an unvegetated mudflat which can be rapidly recolonized by halophytic Spartina alterniflora vegetation. It was determined that pool and creek dynamics are cyclic in nature. The marsh platform is in dynamic equilibrium with respect to elevation and sea-level whereby marsh elevation may be lost (due to degradation of organic matter and formation of a pool) however may be regained (by creek incision into pools, restoration of tidal exchange, and rapid vertical accretion with Spartina alterniflora recolonization. Since vertical accretion in saltmarshes is a function of both organic and inorganic contributions to the marsh subsurface, it is hypothesized that cannibalization of existing muds is supplying inorganic material in this sediment starved system.

Purpose in Life and Its Relationship to All-Cause Mortality and Cardiovascular Events: A Meta-Analysis.

PubMed

Cohen, Randy; Bavishi, Chirag; Rozanski, Alan

2016-01-01

To assess the net impact of purpose in life on all-cause mortality and cardiovascular events. The electronic databases PubMed, Embase, and PsycINFO were systematically searched through June 2015 to identify all studies investigating the relationship between purpose in life, mortality, and cardiovascular events. Articles were selected for inclusion if, a) they were prospective, b) evaluated the association between some measure of purpose in life and all-cause mortality and/or cardiovascular events, and c) unadjusted and/or adjusted risk estimates and confidence intervals (CIs) were reported. Ten prospective studies with a total of 136,265 participants were included in the analysis. A significant association was observed between having a higher purpose in life and reduced all-cause mortality (adjusted pooled relative risk = 0.83 [CI = 0.75-0.91], p < .001) and cardiovascular events (adjusted pooled relative risk = 0.83 [CI = 0.75-0.92], p = .001). Subgroup analyses by study country of origin, questionnaire used to measure purpose in life, age, and whether or not participants with baseline cardiovascular disease were included in the study all yielded similar results. Possessing a high sense of purpose in life is associated with a reduced risk for all-cause mortality and cardiovascular events. Future research should focus on mechanisms linking purpose in life to health outcomes, as well as interventions to assist individuals identified as having a low sense of purpose in life.

Safety and efficacy of apixaban versus warfarin in patients with end-stage renal disease: Meta-analysis.

PubMed

Chokesuwattanaskul, Ronpichai; Thongprayoon, Charat; Tanawuttiwat, Tanyanan; Kaewput, Wisit; Pachariyanon, Pavida; Cheungpasitporn, Wisit

2018-06-01

At the present, apixaban is the only nonvitamin K oral anticoagulant approved by the Food and Drug Administration for use with patients with creatinine clearance <15 mL/min or end-stage renal disease (ESRD). However, the recommendations are based on pharmacokinetic and pharmacodynamic data and there was lack of clinical trial evidence. We aimed to assess safety and efficacy of apixaban in patients with advanced chronic kidney disease (CKD) or ESRD. Databases were searched through November 2017. Studies that reported incidence or odd ratios of bleeding complications or thromboembolic events in the use of apixaban in patients with CKD stage 4-5 or ESRD on dialysis were included. Effect estimates from the individual study were extracted and combined using random-effect, generic inverse variance method of DerSimonian and Laird. Five studies were included into the analysis consisting of 43,850 patients in observational cohort studies. The majority of patients (87%) used apixaban for atrial fibrillation. The pooled estimated incidence of any bleeding complications on apixaban was 17.4% (95% confidence interval [CI]: 13.0%-23.0%). Compared to warfarin, apixaban was significantly associated with reduced risk of major bleeding (pooled odds ratio [OR], 0.42; 95% CI, 0.28-0.61). In studies in ESRD patients on dialysis, the pooled OR of major bleeding was 0.27 (95% CI, 0.07-0.95). There was no significant difference in risk of thromboembolic events in advanced CKD or ESRD patients on apixaban versus vitamin K antagonists (pooled OR, 0.56; 95% CI, 0.23-1.39). Among patients with advanced CKD and ESRD, the use of apixaban was associated with lower risk of major bleeding compared to warfarin, and was found to be relatively effective with no excess risk of thromboembolic events. © 2018 Wiley Periodicals, Inc.

Effects of education and income on cardiovascular outcomes: A systematic review and meta-analysis.

PubMed

Khaing, Win; Vallibhakara, Sakda A; Attia, John; McEvoy, Mark; Thakkinstian, Ammarin

2017-07-01

Objective Previous studies have reported discrepancy effects of education and income on cardiovascular diseases. This systematic review and meta-analysis was therefore conducted which aimed to summarize effects of education and income on cardiovascular diseases. Methods Studies were identified from Medline and Scopus until July 2016. Cohorts were eligible if they assessed associations between education/income and cardiovascular diseases, had at least one outcome including coronary artery diseases, cardiovascular events, strokes and cardiovascular deaths. A multivariate meta-analysis was applied to pool risk effects of these social determinants. Results Among 72 included cohorts, 39, 19, and 14 were studied in Europe, USA, and Asia. Pooled risk ratios of low and medium versus high education were 1.36 (95% confidence interval: 1.11-1.66) and 1.21 (1.06-1.40) for coronary artery diseases, 1.50 (1.17-1.92) and 1.27 (1.09-1.48) for cardiovascular events, 1.23 (1.06-1.43) and 1.17 (1.01-1.35) for strokes, and 1.39 (1.26-1.54) and 1.21 (1.12-1.30) for cardiovascular deaths. The effects of education on all cardiovascular diseases were still present in US and Europe settings, except in Asia this was present only for cardiovascular deaths. Effects of low and medium income versus high on these corresponding cardiovascular diseases were 1.49 (1.16-1.91) and 1.27 (1.10-1.47) for coronary artery diseases, 1.17 (0.96-1.44) and 1.05 (0.98-1.13) for cardiovascular events, 1.30 (0.99-1.72) and 1.24 (1.00-1.53) for strokes, and 1.76 (1.45-2.14) and 1.34 (1.17-1.54) for cardiovascular deaths. Conclusion Social determinants are risk factors of cardiovascular diseases in developed countries, although high heterogeneity in pooling. Data in Asia countries are still needed to update pooling.

ECS Maintenance Wed. 12/28

Atmospheric Science Data Center

2016-12-27

Date(s):  Wednesday, December 28, 2016 Time:  12 am - 12 pm EDT Event Impact:  The Data Pool, MISR order and browse tools, TAD, TES and MOPITT Search and Subset Applications, and Reverb will be unavailable...

Maintenance Downtime April 23, 2014

Atmospheric Science Data Center

2014-04-23

Date(s):  Wednesday, April 23, 2014 Time:  7:00 am - 5:00 pm EDT Event ... Due to scheduled maintenance Wednesday, April 23, 2014: The Data Pool, MISR order and browse tools, TES and MOPITT Search ...

Physical and chemical differences between natural and artificial pools in blanket peatlands

NASA Astrophysics Data System (ADS)

Turner, Ed; Baird, Andy; Billett, Mike; Chapman, Pippa; Dinsmore, Kerry; Holden, Joseph

2014-05-01

Natural pools are common features of many northern peatlands. Numerous artificial pools are being created behind dams installed during drain-blocking, a common peatland restoration technique, significantly increasing the area of open water. Natural pools are known to be major sources of GHGs (e.g. Hamilton et al. 1994), but the reasons they are such 'hotspots' is poorly understood. We hypothesize that pools act as 'biochemical reactors' of particulate and dissolved organic carbon (POC and DOC) transported from surrounding peat that is processed into a range of products including CH4 and CO2. Therefore, understanding the processes operating in both natural and artificial pool systems is fundamental to elucidating this hypothesis. Water levels and temperature have been continuously monitored at six natural and six artificial pools within the 'Flow Country' blanket peatland in northern Scotland since May 2013. Bi-weekly sampling of waters from pools, peat matrix through-flow (via piezometers) and surface flow has been conducted for analysis of DOC, POC, DIC, CH4diss and CO2diss, together with GHG flux measurements from pool surfaces and adjacent peat. We show that, to date, pool water levels rapidly respond to rainfall, although artificial pools appear to respond with greater magnitude. For example, over the course of same rainfall event (20-23 June 2013), natural and artificial pool levels increased between 5.3 and 9.8 cm, and 12.5 and 22.6 cm respectively. Temperature measured at c. 5 cm from the base of each pool shows distinct diurnal fluctuations, which are of greater magnitude in all but one of the natural pools compared to the artificial pools: over the same period (20-23 July 2013), the maximum diurnal variation at the artificial pool site was 5.1 °C compared to 9.2 °C within the natural pools. Vegetation cover is generally higher in artificial pools and may have a moderating effect on variations in pool temperature. Results of pool-water DOC analysis from regular sampling at the study site and a wider regional survey indicate DOC concentrations are consistently higher in artificial pools. The implications of these preliminary results in relation to the carbon cycle and GHGs of blanket peatlands are briefly discussed. Hamilton, J. D., Kelly, C. A., Rudd, J. W. M., Hesslein, R. H. and Roulet, N. T. (1994) Flux to the atmosphere of CH4 and CO2 from wetland ponds on the Hudson Bay lowlands (HBLs). Journal of Geophysical Research 99, 1495-1510.

Evolution of a small hydrothermal eruption episode through a mud pool of varying depth and rheology, White Island, NZ

NASA Astrophysics Data System (ADS)

Edwards, M. J.; Kennedy, B. M.; Jolly, A. D.; Scheu, B.; Jousset, P.

2017-02-01

White Island volcano, New Zealand was a host to multiple hydrothermal eruptive episodes within a mud-sulphur pool in 2013. Although hydrothermal activity is common at White Island, past events have largely gone undescribed in favour of the larger phreatomagmatic and magmatic eruptions. Here, we detail the first and longest hydrothermal episode of 2013, lasting from 15 January to 7 February using video and photo analysis from tour operators and staff responsible for monitoring the volcano. Differences in the dominant bubble burst style across this episode led to the classification of four distinct eruption regimes: (1) multiple irregular bursts on the pool surface, (2) larger distinct symmetric hemispheres with starbursts and/or followed by mud heaves, (3) no initial pool surface deformation but a vertical steam jet followed by a sometimes large directed mud heave and (4) no lake and continuous pulsating dry ash and block venting. The progression through these regimes is associated with a lowering lake level and a concomitantly increasing viscosity of the pool, which initially comprises a low viscosity muddy water, and partially evaporates to yield a shallow layer of high viscosity mud that ends with the complete drying up of the mud pool. Formation of primary mud hemispheres or gas jets is followed by heaves or secondary upheaval events. The heights of these heaves are used as a measure of explosivity. Heights increase from ˜8 m during regime 1 on 15 January to ˜102 m during regime 3 on 28 January. Venting of dry mud during regime 4 developed on 29 January before a regression back to regime 1 took place on 7 February as the pool re-established. Through observations of the shapes of ejected mud clots, we propose that the increasing explosivity of higher number regimes is primarily due to increasing slug bubble lengths teamed with increasing mud pool viscosity. We attribute a lesser control to the decreasing depth of the pool during its progressive desiccation, which may in turn influence the bubble burst depth. Occasionally, visible yellowing of the steam/gas plume led us to suggest that elemental sulphur may also be present in the conduit and may also play a role in regulating bubble release dynamics. Although, evidence for magmatic/phreatomagmatic eruptions was present during eruptions later in 2013, we found no evidence for juvenile magma in the January-February eruption episode described here. However, we concur with other investigators that magma was probably intruded to shallow levels and may have driven heat and gas flux. Our explanation for the correlation of pool depth, mud viscosity and eruption regime is based on a conceptual model in which a pool is perched above a two phase hydrothermal system and is sensitive to changes in the heat and gas flux from shallow magma. The variable release of gas and thermal perturbations in the course of the January-February eruptive episode impacted the pool level, the water to sediment ratio in the pool, and thus its viscosity, and in turn modulated the eruption regime. The varying degree of explosivity throughout this episode calls for a new consideration of pool properties in assessing eruption hazards at this frequently visited volcano. We additionally emphasise that ballistic hazards from small eruptions exist coupled with a range of seismic signals and that the hazard was greatest during infrasound tremor.

Effects of Recombinant Human Growth Hormone for Osteoporosis: Systematic Review and Meta-Analysis.

PubMed

Atkinson, Hayden F; Moyer, Rebecca F; Yacoub, Daniel; Coughlin, Dexter; Birmingham, Trevor B

2017-03-01

Our objective was to evaluate the efficacy of recombinant human growth hormone (GH) on bone mineral density (BMD) in persons age 50 and older, with normal pituitary function, with or at risk for developing osteoporosis. We systematically reviewed randomized clinical trials (RCTs), searching six databases, and conducted meta-analyses to examine GH effects on BMD of the lumbar spine and femoral neck. Data for fracture incidence, bone metabolism biomarkers, and adverse events were also extracted and analysed. Thirteen RCTs met the eligibility criteria. Pooled effect sizes suggested no significant GH effect on BMD. Pooled effect sizes were largest, but nonsignificant, when compared to placebo. GH had a significant effect on several bone metabolism biomarkers. A significantly higher rate of adverse events was observed in the GH groups. Meta-analysis of RCTs suggests that GH treatment for persons with or at risk for developing osteoporosis results in very small, nonsignificant increases in BMD.

Association of kidney stones with atherosclerotic cardiovascular disease among adults in the United States: Considerations by race-ethnicity.

PubMed

Glover, LaShaunta M; Bass, Martha Ann; Carithers, Teresa; Loprinzi, Paul D

2016-04-01

There is a paucity of research examining the relationship between kidney stones and risk of cardiovascular disease while considering individuals of different race-ethnicities. The purpose of this study was to examine the association between history of kidney stones and increased odds of atherosclerotic cardiovascular disease (via the Pooled Cohort Equations) across race-ethnicity groups. 5571 participants aged 40-79 from the 2007-2012 cycles of the NHANES were used for this study. A history of kidney stones was collected from survey data. Predicted odds of having a 10-year atherosclerotic cardiovascular disease (ASCVD) event was assessed from the Pooled Cohort Equations. After adjustments, having kidney stones was not associated with an increase odds of having an ASCVD event within the next 10-years (OR 1.03; 95% CI: 0.58-1.82, P=0.91). However, among non-Hispanic blacks, those with kidney stones had a 2.24 increased odds (OR 2.24; 95% CI: 1.08-4.66; P=0.03) of having an ASCVD event within the next 10-years when compared to non-Hispanic blacks with no history of a kidney stone. Kidney stones were associated with 10-year risk of a future ASCVD event among non-Hispanic blacks. Copyright © 2016 Elsevier Inc. All rights reserved.

STS-65 Mission Specialist Chiao in EMU prepares for WETF contingency EVA

NASA Technical Reports Server (NTRS)

1994-01-01

STS-65 Mission Specialist Leroy Chiao, fully suited in an extravehicular mobility unit (EMU) and helmet, stands on a platform suspended via an overhead crane as he is lowered into a 25-feet deep pool at the Johnson Space Center's (JSC's) Weightless Environment Training Facility (WETF) Bldg 29. Chiao prepares to be immersed in the pool to practice door and latch contingency extravehicular activity (EVA) procedures. Although no spacewalk is planned for the STS-65 International Microgravity Laboratory 2 (IML-2) mission, NASA always trains some of each mission's crewmembers to perform in-space tasks that would be required in the event of remote system failure. For 14 years, the WETF pool has been used to train astronauts for spacewalks and to evaluate certain hardware and procedures. Chiao's EMU is weighted to enable the astronaut to achieve neutral buoyancy once in the tank. SCUBA-equipped divers already in the pool guide the platform into the water.

Measurement of patient safety: a systematic review of the reliability and validity of adverse event detection with record review

PubMed Central

Hanskamp-Sebregts, Mirelle; Zegers, Marieke; Vincent, Charles; van Gurp, Petra J; de Vet, Henrica C W; Wollersheim, Hub

2016-01-01

Objectives Record review is the most used method to quantify patient safety. We systematically reviewed the reliability and validity of adverse event detection with record review. Design A systematic review of the literature. Methods We searched PubMed, EMBASE, CINAHL, PsycINFO and the Cochrane Library and from their inception through February 2015. We included all studies that aimed to describe the reliability and/or validity of record review. Two reviewers conducted data extraction. We pooled κ values (κ) and analysed the differences in subgroups according to number of reviewers, reviewer experience and training level, adjusted for the prevalence of adverse events. Results In 25 studies, the psychometric data of the Global Trigger Tool (GTT) and the Harvard Medical Practice Study (HMPS) were reported and 24 studies were included for statistical pooling. The inter-rater reliability of the GTT and HMPS showed a pooled κ of 0.65 and 0.55, respectively. The inter-rater agreement was statistically significantly higher when the group of reviewers within a study consisted of a maximum five reviewers. We found no studies reporting on the validity of the GTT and HMPS. Conclusions The reliability of record review is moderate to substantial and improved when a small group of reviewers carried out record review. The validity of the record review method has never been evaluated, while clinical data registries, autopsy or direct observations of patient care are potential reference methods that can be used to test concurrent validity. PMID:27550650

Placebo and nocebo reactions in randomized trials of pharmacological treatments for persistent depressive disorder. A meta-regression analysis.

PubMed

Meister, Ramona; Jansen, Alessa; Härter, Martin; Nestoriuc, Yvonne; Kriston, Levente

2017-06-01

We aimed to investigate placebo and nocebo reactions in randomized controlled trials (RCT) of pharmacological treatments for persistent depressive disorder (PDD). We conducted a systematic electronic search and included RCTs investigating antidepressants for the treatment of PDD. Outcomes were the number of patients experiencing response and remission in placebo arms (=placebo reaction). Additional outcomes were the incidence of patients experiencing adverse events and related discontinuations in placebo arms (=nocebo reaction). A priori defined effect modifiers were analyzed using a series of meta-regression analyses. Twenty-three trials were included in the analyses. We found a pooled placebo response rate of 31% and a placebo remission rate of 22%. The pooled adverse event rate and related discontinuations were 57% and 4%, respectively. All placebo arm outcomes were positively associated with the corresponding medication arm outcomes. Placebo response rate was associated with a greater proportion of patients with early onset depression, a smaller chance to receive placebo and a larger sample size. The adverse event rate in placebo arms was associated with a greater proportion of patients with early onset depression, a smaller proportion of females and a more recent publication. Pooled placebo and nocebo reaction rates in PDD were comparable to those in episodic depression. The identified effect modifiers should be considered to assess unbiased effects in RCTs, to influence placebo and nocebo reactions in practice. Limitations result from the methodology applied, the fact that we conducted only univariate analyses, and the number and quality of included trials. Copyright © 2017 Elsevier B.V. All rights reserved.

SAGE III L2 Lunar Event Species Profiles (Binary)

Atmospheric Science Data Center

2017-10-27

... Search and Order:  Earthdata Search   FTP Access:  Data Pool Parameters:  Chlorine Dioxide Nitrogen Dioxide ... Data Additional Info:  Data Format: Big Endian/IEEE Binary; Avg Size in MB: 0.017 SCAR-B Block:  ...

Further Insight into the Cardiovascular Risk Calculator Controversy: The Roles of Statins, Revascularizations, and Under-Ascertainment in the Women's Health Study

PubMed Central

Cook, Nancy R.; Ridker, Paul M

2015-01-01

Importance While the Pooled Cohort Equations from the recent ACC/AHA Guideline on the Assessment of Cardiovascular Risk have over-estimated cardiovascular risk in multiple external cohorts, the reasons for the discrepancy are unclear. Objective To determine whether increased use of statins over time, incident coronary revascularization procedures, or under-ascertainment of vascular events explain over-estimation of risk in a more contemporary population. Design, Setting, and Participants 27,542 women aged 45-79 with complete ascertainment of plasma lipids and other risk factors from the Women's Health Study (WHS), a nationwide cohort of US women free of cardiovascular disease, cancer or other major illness at baseline in 1992-95. Women were followed for a median of 10 years. Main Outcomes and Measures Atherosclerotic cardiovascular disease (ASCVD), defined as any myocardial infarction, any stroke, or death due to cardiovascular cause. Results 632 women experienced an ASCVD event over follow-up. The average predicted risk from the Pooled Cohort Equations was 3.6% over 10 years, compared to an actual observed risk of 2.2%. Predicted rates were 90% higher than the observed rates in the 0-<5% and 5-<7.5% risk groups and 40% higher in the 7.5-<10% and 10%+ risk groups. Rates of statin use and revascularizations increased over follow-up time and by risk group, and in sensitivity analyses, we estimated the hypothetical rates if no women were on statins or underwent revascularization procedures. After adjustment for intervention effects of statins and revascularization as well as hypothetical confounding by indication, predicted rates remained 80% higher than observed rates in the lower two risk groups and 30% higher in the upper two risk groups. Under-ascertainment is unlikely since follow-up rates in the WHS were 97%, and overall we would need 60% more events to match the numbers predicted using the Pooled Cohort Equations. Conclusions and Relevance Neither statin use, revascularization procedures, nor under-ascertainment of events explain the discrepancy between observed rates of ASCVD in the WHS and those predicted by the ACC/AHA Pooled Cohort Equations. Other explanations include changing patterns of risk within more contemporary populations. PMID:25285455

A meta-analysis of clinical and radiographic outcomes of posterior horn medial meniscus root repairs.

PubMed

Chung, Kyu Sung; Ha, Jeong Ku; Ra, Ho Jong; Kim, Jin Goo

2016-05-01

Although interest in medial meniscus posterior root tear (MMPRT) repair has increased, few case series have been reported. This meta-analysis aimed to examine the clinical and radiological effects of MMPRT repair by pooling pre- and post-operative data from case-series reports. A literature search was performed using MEDLINE/PubMed, the Cochrane Central Register of Controlled Trials, and EMBASE databases. Pre- and post-operative data were pooled to investigate the effects of MMPRT repair, including the Lysholm score improvement, meniscal extrusion (mm) reduction, progression of the Kellgren-Lawrence (K-L) grade, and cartilage status according to the Outerbridge classification. Treatment effects included paired standardized mean differences (difference in the pre- and post-operative mean outcomes divided by the standard deviation) for the Lysholm score and meniscal extrusion, as well as the pooled event rates of progression of K-L grade and cartilage status. As treatment effects, the Lysholm score increased by as much as 3.675 (P < 0.001), whereas meniscus extrusion was not reduced (n.s.). The overall pooled event rates of progression of K-L grade and cartilage status were 10.6 and 17.3 % (P < 0.001), respectively. According to the current literature, MMPRT repair resulted in significant improvements in the post-operative clinical subjective scores compared with the preoperative status. However, meniscus extrusion was not reduced. Considering the occurrence of progression of K-L grade and cartilage status, it did not prevent the progression of arthrosis completely. Based on these results, repair results in favourable outcomes for MMPRT. Meta-analysis, Level IV.

Response of the Antarctic Stratosphere to Warm Pool EI Nino Events in the GEOS CCM

NASA Technical Reports Server (NTRS)

Hurwitz, Margaret M.; Song, In-Sun; Oman, Luke D.; Newman, Paul A.; Molod, Andrea M.; Frith, Stacey M.; Nielsen, J. Eric

2011-01-01

A new type of EI Nino event has been identified in the last decade. During "warm pool" EI Nino (WPEN) events, sea surface temperatures (SSTs) in the central equatorial Pacific are warmer than average. The EI Nino signal propagates poleward and upward as large-scale atmospheric waves, causing unusual weather patterns and warming the polar stratosphere. In austral summer, observations show that the Antarctic lower stratosphere is several degrees (K) warmer during WPEN events than during the neutral phase of EI Nino/Southern Oscillation (ENSO). Furthermore, the stratospheric response to WPEN events depends of the direction of tropical stratospheric winds: the Antarctic warming is largest when WPEN events are coincident with westward winds in the tropical lower and middle stratosphere i.e., the westward phase of the quasi-biennial oscillation (QBO). Westward winds are associated with enhanced convection in the subtropics, and with increased poleward wave activity. In this paper, a new formulation of the Goddard Earth Observing System Chemistry-Climate Model, Version 2 (GEOS V2 CCM) is used to substantiate the observed stratospheric response to WPEN events. One simulation is driven by SSTs typical of a WPEN event, while another simulation is driven by ENSO neutral SSTs; both represent a present-day climate. Differences between the two simulations can be directly attributed to the anomalous WPEN SSTs. During WPEN events, relative to ENSO neutral, the model simulates the observed increase in poleward planetary wave activity in the South Pacific during austral spring, as well as the relative warming of the Antarctic lower stratosphere in austral summer. However, the modeled response to WPEN does not depend on the phase of the QBO. The modeled tropical wind oscillation does not extend far enough into the lower stratosphere and upper troposphere, likely explaining the model's insensitivity to the phase of the QBO during WPEN events.

Sensitivity of the Atmospheric Response to Warm Pool El Nino Events to Modeled SSTs and Future Climate Forcings

NASA Technical Reports Server (NTRS)

Hurwitz, Margaret M.; Garfinkel, Chaim I.; Newman, Paul A.; Oman, Luke D.

2013-01-01

Warm pool El Nino (WPEN) events are characterized by positive sea surface temperature (SST) anomalies in the central equatorial Pacific. Under present-day climate conditions, WPEN events generate poleward propagating wavetrains and enhance midlatitude planetary wave activity, weakening the stratospheric polar vortices. The late 21st century extratropical atmospheric response to WPEN events is investigated using the Goddard Earth Observing System Chemistry-Climate Model (GEOSCCM), version 2. GEOSCCM simulations are forced by projected late 21st century concentrations of greenhouse gases (GHGs) and ozone-depleting substances (ODSs) and by SSTs and sea ice concentrations from an existing ocean-atmosphere simulation. Despite known ocean-atmosphere model biases, the prescribed SST fields represent a best estimate of the structure of late 21st century WPEN events. The future Arctic vortex response is qualitatively similar to that observed in recent decades but is weaker in late winter. This response reflects the weaker SST forcing in the Nino 3.4 region and subsequently weaker Northern Hemisphere tropospheric teleconnections. The Antarctic stratosphere does not respond to WPEN events in a future climate, reflecting a change in tropospheric teleconnections: The meridional wavetrain weakens while a more zonal wavetrain originates near Australia. Sensitivity simulations show that a strong poleward wavetrain response to WPEN requires a strengthening and southeastward extension of the South Pacific Convergence Zone; this feature is not captured by the late 21st century modeled SSTs. Expected future increases in GHGs and decreases in ODSs do not affect the polar stratospheric responses to WPEN.

Proton pump inhibitor monotherapy and the risk of cardiovascular events in patients with gastro-esophageal reflux disease: a meta-analysis.

PubMed

Sun, S; Cui, Z; Zhou, M; Li, R; Li, H; Zhang, S; Ba, Y; Cheng, G

2017-02-01

Proton pump inhibitors (PPIs) are commonly used as potent gastric acid secretion antagonists for gastro-esophageal disorders and their overall safety in patients with gastro-esophageal reflux disease (GERD) is considered to be good and they are well-tolerated. However, recent studies have suggested that PPIs may be a potential independent risk factor for cardiovascular adverse events. The aim of our meta-analysis was to examine the association between PPI monotherapy and cardiovascular events in patients with GERD. A literature search involved examination of relevant databases up to July 2015 including PubMed, Cochrane Library, EMBASE, and ClinicalTrial.gov, as well as selected randomized controlled trials (RCTs) reporting cardiovascular events with PPI exposure in GERD patients. In addition, the pooled risk ratio (RR) and heterogeneity were assessed based on a fixed effects model of the meta-analysis and the I 2 statistic, respectively. Seventeen RCTs covering 7540 patients were selected. The pooled data suggested that the use of PPIs was associated with a 70% increased cardiovascular risk (RR=1.70, 95% CI: [1.13-2.56], P=.01, I 2 =0%). Furthermore, higher risks of adverse cardiovascular events in the omeprazole subgroup (RR=3.17, 95% CI: [1.43-7.03], P=.004, I 2 =25%) and long-term treatment subgroup (RR=2.33, 95% CI: [1.33-4.08], P=.003, I 2 =0%) were found. PPI monotherapy can be a risk factor for cardiovascular adverse events. Omeprazole could significantly increase the risk of cardiovascular events and, so, should be used carefully. © 2016 John Wiley & Sons Ltd.

Data Assimilation to Improve CMAQ Model Estimates of Particulate Matter Pollution during Wintertime Persistent Cold Air Pool Events in Salt Lake City, Utah

NASA Astrophysics Data System (ADS)

Ivey, C. E.; Balachandran, S.; Russell, A. G.; Hu, Y.; Holmes, H.

2017-12-01

More than one million people live in Salt Lake Valley, Utah, where wintertime pollution reaches unhealthy levels due to the unique meteorology and orography of the region. Persistent cold air pool (PCAP) events occur when high pressure ridges create stagnant conditions over a valley, which hampers large-scale advection and reduces surface wind speeds. During PCAP periods the fraction of incoming solar radiation that reaches the valley floor is also reduced, leading to temperature inversions that allow pollution to build. Pollution levels continue to climb until a washout event removes the pollutants from the valley. Washout events include high winds or precipitation events with advection or wet deposition related removal processes, respectively. In this work, novel data assimilation and source apportionment techniques are applied for January and February 2007 to analyze CMAQ-modeled source composition and source impacts for the Salt Lake Valley during PCAP events. First, a hybrid source-oriented apportionment model is applied over continental U.S. to determine observation and model-based impacts from 20 sources, including agricultural activities, fossil fuel combustion, dust, and metals processing. Then, a secondary bias correction method is applied to better quantify the source impacts on secondary PM2.5, which constitutes the majority of the PM2.5 mass. Revised concentrations reflect what was previously reported in studies of PCAP pollution in the Salt Lake Valley, where the dominant aerosol was found to be ammonium nitrate. Further, gasoline and natural gas combustion were found to be the greatest contributing sources to aerosol concentrations during the PCAP events. The benefit of the data assimilation methods is the availability of spatially and temporally resolved model estimates of source impacts that better reflect observed concentrations.

The HEART score for early rule out of acute coronary syndromes in the emergency department: a systematic review and meta-analysis.

PubMed

Van Den Berg, Patricia; Body, Richard

2018-03-01

The objective of this systematic review was to summarise the current evidence on the diagnostic accuracy of the HEART score for predicting major adverse cardiac events in patients presenting with undifferentiated chest pain to the emergency department. Two investigators independently searched Medline, Embase and Cochrane databases between 2008 and May 2016 identifying eligible studies providing diagnostic accuracy data on the HEART score for predicting major adverse cardiac events as the primary outcome. For the 12 studies meeting inclusion criteria, study characteristics and diagnostic accuracy measures were systematically extracted and study quality assessed using the QUADAS-2 tool. After quality assessment, nine studies including data from 11,217 patients were combined in the meta-analysis applying a generalised linear mixed model approach with random effects assumption (Stata 13.1). In total, 15.4% of patients (range 7.3-29.1%) developed major adverse cardiac events after a mean of 6 weeks' follow-up. Among patients categorised as 'low risk' and suitable for early discharge (HEART score 0-3), the pooled incidence of 'missed' major adverse cardiac events was 1.6%. The pooled sensitivity and specificity of the HEART score for predicting major adverse cardiac events were 96.7% (95% confidence interval (CI) 94.0-98.2%) and 47.0% (95% CI 41.0-53.5%), respectively. Patients with a HEART score of 0-3 are at low risk of incident major adverse cardiac events. As 3.3% of patients with major adverse cardiac events are 'missed' by the HEART score, clinicians must ask whether this risk is acceptably low for clinical implementation.

Vascular protection in peripheral artery disease: systematic review and modelling study.

PubMed

Hackam, D G; Sultan, N M; Criqui, M H

2009-07-01

To ascertain the effectiveness of medical therapy for reducing risk in peripheral artery disease (PAD) and to model the potential impact of combining multiple efficacious approaches. 17 electronic databases, reference lists of primary studies, clinical practice guidelines, review articles, trial registries and conference proceedings from cardiology, vascular surgery and atherosclerosis meetings were screened. Eligible studies were randomized trials or meta-analyses of randomized trials of medical therapy for PAD which reported major cardiovascular events (myocardial infarction, stroke and cardiovascular death). Baseline event rates for modelling analyses were derived from published natural history cohorts. Overall, three strategies had persuasive evidence for reducing risk in PAD: antiplatelet agents (pooled RRR 26%, 95% CI 10 to 42), statins (pooled RRR 26%, 95% CI 18 to 33) and angiotensin-converting enzyme inhibitors (individual trial RRR 25%, 95% CI 8 to 39). The estimated cumulative relative risk reduction for all three strategies was 59% (CI 32 to 76). Given a 5-year major cardiovascular event rate of 25%, the corresponding absolute risk reduction and number needed to treat to prevent one event were 15% (CI 8 to 19) and 7 (CI 5 to 12), respectively. Population level analyses suggest that increased uptake of these modalities could prevent more than 200 000 events in patients with PAD each year. The use of multiple efficacious strategies has the potential to substantially reduce the cardiovascular burden of PAD. However, these data should be regarded as hypothetical, since they are based on mathematical modelling rather than factorial randomized trials.

Where children and adolescents drown in Queensland: a population-based study.

PubMed

Wallis, Belinda A; Watt, Kerrianne; Franklin, Richard C; Nixon, James W; Kimble, Roy M

2015-11-26

This retrospective population-based study examined drowning location by the site of immersion for both fatal and non-fatal drowning events in Queensland. Drowning location is not routinely collected, and this study used data linkage to identify drowning sites. The resulting enhanced quality data quantify drowning incidence for specific locations by geographic region, age group and by severity for the first time. Linked data were accessed from the continuum of care (prehospital, emergency, hospital admission and death data) on fatal and non-fatal drowning episodes in children aged 0-19 years in Queensland for the years 2002-2008 inclusive. Drowning locations ranked in order of overall incidence were pools, inland water, coastal water, baths and other man-made water hazards. Swimming pools produced the highest incidence rates (7.31/100,000) for overall drowning events and were more often privately owned pools and in affluent neighbourhoods. Toddlers 0-4 years were most at risk around pools (23.94/100,000), and static water bodies such as dams and buckets-the fatality ratios were highest at these 2 locations for this age group. Children 5-14 years incurred the lowest incidence rates regardless of drowning location. Adolescents 15-19 years were more frequently involved in a drowning incident on the coast shoreline, followed by inland dynamic water bodies. Linked data have resulted in the most comprehensive data collection on drowning location and severity to date for children in the state of Queensland. Most mortality and morbidity could have been prevented by improving water safety through engaged supervision around pools and bath time, and a heightened awareness of buckets and man-made water hazards around the farm home for young children. These data provide a different approach to inform prevention strategies. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Where children and adolescents drown in Queensland: a population-based study

PubMed Central

Wallis, Belinda A; Watt, Kerrianne; Franklin, Richard C; Nixon, James W; Kimble, Roy M

2015-01-01

Objective This retrospective population-based study examined drowning location by the site of immersion for both fatal and non-fatal drowning events in Queensland. Drowning location is not routinely collected, and this study used data linkage to identify drowning sites. The resulting enhanced quality data quantify drowning incidence for specific locations by geographic region, age group and by severity for the first time. Design Linked data were accessed from the continuum of care (prehospital, emergency, hospital admission and death data) on fatal and non-fatal drowning episodes in children aged 0–19 years in Queensland for the years 2002–2008 inclusive. Results Drowning locations ranked in order of overall incidence were pools, inland water, coastal water, baths and other man-made water hazards. Swimming pools produced the highest incidence rates (7.31/100 000) for overall drowning events and were more often privately owned pools and in affluent neighbourhoods. Toddlers 0–4 years were most at risk around pools (23.94/100 000), and static water bodies such as dams and buckets—the fatality ratios were highest at these 2 locations for this age group. Children 5–14 years incurred the lowest incidence rates regardless of drowning location. Adolescents 15–19 years were more frequently involved in a drowning incident on the coast shoreline, followed by inland dynamic water bodies. Conclusions Linked data have resulted in the most comprehensive data collection on drowning location and severity to date for children in the state of Queensland. Most mortality and morbidity could have been prevented by improving water safety through engaged supervision around pools and bath time, and a heightened awareness of buckets and man-made water hazards around the farm home for young children. These data provide a different approach to inform prevention strategies. PMID:26610762

Management Modalities for Traumatic Macular Hole: A Systematic Review and Single-Arm Meta-Analysis.

PubMed

Gao, Min; Liu, Kun; Lin, Qiurong; Liu, Haiyun

2017-02-01

The purposes of this study were to (i) determine macular hole (MH) closure rates and visual outcomes by comparing two methods of managing traumatic MH (TMH)-an event resulting in severe loss of visual acuity (VA); (ii) characterize patients who undergo spontaneous TMH closure; (iii) determine which TMH patients should be observed before resorting to surgical repair; and (iv) elucidate factors that influence postoperative visual outcomes. Studies (n=10) of patients who were managed by surgery or observation for TMH were meta-analyzed retrospectively. Management modalities included surgical repair (surgery group) and observation for spontaneous hole closure (observation group). In addition, a 12-case series of articles (1990-2014) on spontaneous hole closure was statistically summarized. SAS and Comprehensive Meta-Analysis (CMA) (version 3.0) were used for analysis. For surgery group patients, the fixed-model pooled event rate for hole closure was 0.919 (range, 0.861-0.954) and for observation group patients, 0.368 (range, 0.236-0.448). The random-model pooled event rate for improvement of visual acuity (VA) for surgery group patients was 0.748 (range, 0.610-0.849) and for observation group patients, 0.505 (range, 0.397-0.613). For patients in both groups, the mean age of spontaneous closure was 18.71±10.64 years; mean size of TMHs, 0.18±0.06 decimal degrees (DD); and mean time for hole closure, 3.38±3.08 months. The pooled event rate for visual improvement was 0.748 (0.610-0.849). Hole closure and VA improvement rates of surgery group patients were significantly higher than those for observation group patients. Patients of ≤ 24 years of age with MH sizes of ≤ 0.2DD were more likely to achieve spontaneous hole closure. The interval of time from injury to surgery was statistically significantly associated with the level of visual improvement.

Stroke prevention in atrial fibrillation: pooled analysis of SPORTIF III and V trials.

PubMed

Albers, Gregory W

2004-12-01

This article will review 2 clinical trials that recently compared the safety and efficacy of the oral direct thrombin inhibitor ximelagatran (fixed dose, 36 mg twice daily) with warfarin (adjusted dose, target international normalized ratio [INR] 2.0-3.0) in patients with nonvalvular atrial fibrillation and at least 1 risk factor for stroke. These noninferiority trials involved 7329 patients and a mean exposure to study drug of 18.5 months. The Stroke Prevention Using Oral Thrombin Inhibitor in Atrial Fibrillation (SPORTIF) III (open-label, N = 3407) and V trials (double-blind, N = 3922) were designed for pooled analysis, and the data showed the efficacy of ximelagatran therapy was comparable (noninferior) with extremely well-controlled warfarin therapy in preventing stroke and systemic embolic events; the primary event rates were 1.65% per year and 1.62% per year in the warfarin and ximelagatran groups, respectively (P = .941). In patients with a history of stroke or transient ischemic attack (about 20% of the SPORTIF population), the event rates were 3.27% per year and 2.83% per year in the warfarin and ximelagatran groups, respectively (P = .625). The distribution of stroke subtypes was similar in the 2 treatment groups. Intracranial hemorrhage occurred at a rate of 0.20% per year with warfarin and 0.11% per year with ximelagatran. Combined rates of minor and major bleeding were significantly lower with ximelagatran than with warfarin (32% per year vs 39% per year; P < .0001). The myocardial infarction rates were the same in the pooled database (no difference between agents). The aspirin data will be the subject of two substudy papers. Oral ximelagatran administered without coagulation monitoring or dose adjustment was as effective as well-controlled, adjusted-dose warfarin for prevention of stroke and systemic embolic events and was associated with significantly less total bleeding. This oral direct thrombin inhibitor is a potentially promising treatment option for the prevention of thromboembolism.

Observations of Cold Pool Properties during GoAmazon2014/5

NASA Astrophysics Data System (ADS)

Mayne, S. L.; Schumacher, C.; MacDonald, L.; Turner, D. D.

2017-12-01

Convectively generated cold pools are instrumental in both the development of the sub-cloud layer and the organization of deep convection. Despite this, analyses of cold pools in the tropics are constrained by a lack of observational data; insight into the phenomena therefore relies heavily on numerical models. GoAmazon2014/5, a 2-year DOE-sponsored field campaign centered on Manacapuru, Brazil in the central Amazon, provides a unique opportunity to characterize tropical cold pools and allows for the comparison of observational data with theoretical results from model cold pool simulations and parameterizations. This investigation analyzes radar, disdrometer, and profiler measurements at the DOE mobile facility site to study tropical cold pool characteristics. The Brazilian military (SIPAM) operational S-band radar in Manaus is used to provide a broad context of convective systems, while measurements from Parsivel disdrometers are used to assess drop-size distributions (DSDs) at the surface. A unique aspect of this research is the use of the Atmospheric Emitted Radiance Interferometer (AERI) instrument, which utilizes down-welling IR measurements to obtain vertical profiles of thermodynamic quantities such as temperature and water vapor in the lowest few km of the atmosphere. Combined with surface observations and sounding data, these datasets will result in a thorough investigation of the horizontal and vertical characteristics of cold pools over the tropical rain forest. Preliminary analyses of 20 events reveal a mean cold pool height of 220 m and a mean radius of approximately 8.5 km. The average cold pool experienced a temperature (specific humidity) decrease of approximately 1 K (0.4 g/kg) at the surface. The temperature decrease is consistent with modeling studies and limited observations from previous studies over the tropics. The small decrease in specific humidity is attributed to the high moisture content within the cold pools. AERI retrievals of potential temperature and specific humidity profiles show promising similarities with theoretical results produced using the cold pool parameterization presented by Del Genio et al. (2015); however, results are sensitive to both the mass of air injected into the cold pool after its formation, and the thermodynamic characteristics of the downdraft.

Nuclear Power - Post Fukushima

NASA Astrophysics Data System (ADS)

Reyes, Jose, Jr.

2011-10-01

The extreme events that led to the prolonged power outage at the Fukushima Daiicchi nuclear plant have highlighted the importance of assuring a means for stable long term cooling of the nuclear fuel and containment following a complete station blackout. Legislative bodies, regulatory agencies and industry are drawing lessons from those events and considering what changes, if any, are needed to nuclear power, post Fukushima. The enhanced safety of a new class of reactor designed by NuScale Power is drawing significant attention in light of the Fukushima events. During normal operation, each NuScale containment is fully immersed in a water-filled stainless steel lined concrete pool that resides underground. The pool, housed in a Seismic Category I building, is large enough to provided 30 days of core and containment cooling without adding water. After 30 days, the decay heat generations coupled with thermal radiation heat transfer is completely adequate to remove core decay heat for an unlimited period of time. These passive power systems can perform their function without requiring an external supply of water of power. An assessment of the NuScale passive systems is being performed through a comprehensive test program that includes the NuScale integral system test facility at Oregon State University

Predictive value for cardiovascular events of common carotid intima media thickness and its rate of change in individuals at high cardiovascular risk - Results from the PROG-IMT collaboration.

PubMed

Lorenz, Matthias W; Gao, Lu; Ziegelbauer, Kathrin; Norata, Giuseppe Danilo; Empana, Jean Philippe; Schmidtmann, Irene; Lin, Hung-Ju; McLachlan, Stela; Bokemark, Lena; Ronkainen, Kimmo; Amato, Mauro; Schminke, Ulf; Srinivasan, Sathanur R; Lind, Lars; Okazaki, Shuhei; Stehouwer, Coen D A; Willeit, Peter; Polak, Joseph F; Steinmetz, Helmuth; Sander, Dirk; Poppert, Holger; Desvarieux, Moise; Ikram, M Arfan; Johnsen, Stein Harald; Staub, Daniel; Sirtori, Cesare R; Iglseder, Bernhard; Beloqui, Oscar; Engström, Gunnar; Friera, Alfonso; Rozza, Francesco; Xie, Wuxiang; Parraga, Grace; Grigore, Liliana; Plichart, Matthieu; Blankenberg, Stefan; Su, Ta-Chen; Schmidt, Caroline; Tuomainen, Tomi-Pekka; Veglia, Fabrizio; Völzke, Henry; Nijpels, Giel; Willeit, Johann; Sacco, Ralph L; Franco, Oscar H; Uthoff, Heiko; Hedblad, Bo; Suarez, Carmen; Izzo, Raffaele; Zhao, Dong; Wannarong, Thapat; Catapano, Alberico; Ducimetiere, Pierre; Espinola-Klein, Christine; Chien, Kuo-Liong; Price, Jackie F; Bergström, Göran; Kauhanen, Jussi; Tremoli, Elena; Dörr, Marcus; Berenson, Gerald; Kitagawa, Kazuo; Dekker, Jacqueline M; Kiechl, Stefan; Sitzer, Matthias; Bickel, Horst; Rundek, Tatjana; Hofman, Albert; Mathiesen, Ellisiv B; Castelnuovo, Samuela; Landecho, Manuel F; Rosvall, Maria; Gabriel, Rafael; de Luca, Nicola; Liu, Jing; Baldassarre, Damiano; Kavousi, Maryam; de Groot, Eric; Bots, Michiel L; Yanez, David N; Thompson, Simon G

2018-01-01

Carotid intima media thickness (CIMT) predicts cardiovascular (CVD) events, but the predictive value of CIMT change is debated. We assessed the relation between CIMT change and events in individuals at high cardiovascular risk. From 31 cohorts with two CIMT scans (total n = 89070) on average 3.6 years apart and clinical follow-up, subcohorts were drawn: (A) individuals with at least 3 cardiovascular risk factors without previous CVD events, (B) individuals with carotid plaques without previous CVD events, and (C) individuals with previous CVD events. Cox regression models were fit to estimate the hazard ratio (HR) of the combined endpoint (myocardial infarction, stroke or vascular death) per standard deviation (SD) of CIMT change, adjusted for CVD risk factors. These HRs were pooled across studies. In groups A, B and C we observed 3483, 2845 and 1165 endpoint events, respectively. Average common CIMT was 0.79mm (SD 0.16mm), and annual common CIMT change was 0.01mm (SD 0.07mm), both in group A. The pooled HR per SD of annual common CIMT change (0.02 to 0.43mm) was 0.99 (95% confidence interval: 0.95-1.02) in group A, 0.98 (0.93-1.04) in group B, and 0.95 (0.89-1.04) in group C. The HR per SD of common CIMT (average of the first and the second CIMT scan, 0.09 to 0.75mm) was 1.15 (1.07-1.23) in group A, 1.13 (1.05-1.22) in group B, and 1.12 (1.05-1.20) in group C. We confirm that common CIMT is associated with future CVD events in individuals at high risk. CIMT change does not relate to future event risk in high-risk individuals.

The safety profile of parecoxib for the treatment of postoperative pain: a pooled analysis of 28 randomized, double-blind, placebo-controlled clinical trials and a review of over 10 years of postauthorization data

PubMed Central

Schug, Stephan A; Parsons, Bruce; Li, Chunming; Xia, Feng

2017-01-01

Background Nonselective, nonsteroidal anti-inflammatory drugs (NSAIDs) and selective cyclooxygenase-2 (COX-2) inhibitors are associated with safety issues including cardiovascular, renal, and gastrointestinal (GI) events. Objective To examine the safety of parecoxib, a COX-2 inhibitor, for the management of postoperative pain. Design Pooled analysis of 28 placebo-controlled trials of parecoxib and review of postauthorization safety data. Main outcome measures Prespecified safety events commonly associated with COX-2 inhibitors and/or NSAIDs. In the clinical trial analysis, the frequency of each event was compared between treatment groups using a chi-square test. In the postauthorization review, the number of confirmed cases, along with outcome, was presented for each event. Results In the clinical trial analysis, GI-related events occurred in ~0.2% of patients in the parecoxib and placebo groups. Renal failure and impairment was similar between parecoxib (1.0%) and placebo (0.9%). The occurrence of arterial (parecoxib=0.3%; placebo=0.2%) and venous (parecoxib=0.2%; placebo=0.1%) cardiovascular embolic and thrombotic events was similar between groups. Hypersensitivity reactions including anaphylactic reactions (parecoxib=8.7%; placebo=8.6%), hypotension (parecoxib=2.6%; placebo=2.1%), angioedema (parecoxib=2.5%; placebo=2.8%), and severe cutaneous adverse reactions (0% in both groups) were similar between groups. Incision site or other skin/tissue infections occurred in <0.1% of patients in both groups. The occurrence of these events (total reports/serious reports) in the postauthorization database, based on 69,567,300 units of parecoxib, was as follows: GI ulceration-related events (35/35), renal failure and impairment (77/68), cardiovascular embolic and thrombotic events (66/64), hypersensitivity reactions including hypotension-related events (32/25) and severe cutaneous adverse events (17/17), and masking signs of inflammation (18/18). A majority of reported outcomes were classified as recovered or recovering. Conclusions Potentially serious safety events occur infrequently with parecoxib, which high-lights its safety in patients with postoperative pain. PMID:29066931

The safety profile of parecoxib for the treatment of postoperative pain: a pooled analysis of 28 randomized, double-blind, placebo-controlled clinical trials and a review of over 10 years of postauthorization data.

PubMed

Schug, Stephan A; Parsons, Bruce; Li, Chunming; Xia, Feng

2017-01-01

Nonselective, nonsteroidal anti-inflammatory drugs (NSAIDs) and selective cyclooxygenase-2 (COX-2) inhibitors are associated with safety issues including cardiovascular, renal, and gastrointestinal (GI) events. To examine the safety of parecoxib, a COX-2 inhibitor, for the management of postoperative pain. Pooled analysis of 28 placebo-controlled trials of parecoxib and review of postauthorization safety data. Prespecified safety events commonly associated with COX-2 inhibitors and/or NSAIDs. In the clinical trial analysis, the frequency of each event was compared between treatment groups using a chi-square test. In the postauthorization review, the number of confirmed cases, along with outcome, was presented for each event. In the clinical trial analysis, GI-related events occurred in ~0.2% of patients in the parecoxib and placebo groups. Renal failure and impairment was similar between parecoxib (1.0%) and placebo (0.9%). The occurrence of arterial (parecoxib=0.3%; placebo=0.2%) and venous (parecoxib=0.2%; placebo=0.1%) cardiovascular embolic and thrombotic events was similar between groups. Hypersensitivity reactions including anaphylactic reactions (parecoxib=8.7%; placebo=8.6%), hypotension (parecoxib=2.6%; placebo=2.1%), angioedema (parecoxib=2.5%; placebo=2.8%), and severe cutaneous adverse reactions (0% in both groups) were similar between groups. Incision site or other skin/tissue infections occurred in <0.1% of patients in both groups. The occurrence of these events (total reports/serious reports) in the postauthorization database, based on 69,567,300 units of parecoxib, was as follows: GI ulceration-related events (35/35), renal failure and impairment (77/68), cardiovascular embolic and thrombotic events (66/64), hypersensitivity reactions including hypotension-related events (32/25) and severe cutaneous adverse events (17/17), and masking signs of inflammation (18/18). A majority of reported outcomes were classified as recovered or recovering. Potentially serious safety events occur infrequently with parecoxib, which high-lights its safety in patients with postoperative pain.

Eighty routes to a ribonucleotide world; dispersion and stringency in the decisive selection.

PubMed

Yarus, Michael

2018-05-21

We examine the initial emergence of genetics; that is, of an inherited chemical capability. The crucial actors are ribonucleotides, occasionally meeting in a prebiotic landscape. Previous work identified six influential variables during such random ribonucleotide pooling. Geochemical pools can be in periodic danger (e.g., from tides) or constant danger (e.g., from unfavorable weather). Such pools receive Gaussian nucleotide amounts sporadically, at random times, or get varying substrates simultaneously. Pools use cross-templated RNA synthesis (5'-5' product from 5'-3' template) or para-templated (5'-5' product from 5'-5' template) synthesis. Pools can undergo mild or strong selection, and be recently initiated (early) or late in age. Considering > 80 combinations of these variables, selection calculations identify a superior route. Most likely, an early, sporadically fed, cross-templating pool in constant danger, receiving ≥ 1 mM nucleotides while under strong selection for a coenzyme-like product will host selection of the first encoded biochemical functions. Predominantly templated products emerge from a critical event, the starting bloc selection, which exploits inevitable differences among early pools. Favorable selection has a simple rationale; it is increased by product dispersion (sd/mean), by selection intensity (mild or strong), or by combining these factors as stringency, reciprocal fraction of pools selected (1/sfsel). To summarize: chance utility, acting via a preference for disperse, templated coenzyme-like dinucleotides, uses stringent starting bloc selection to quickly establish majority encoded/genetic expression. Despite its computational origin, starting bloc selection is largely independent of specialized assumptions. This ribodinucleotide route to inheritance may also have facilitated 5'-3' chemical RNA replication. Published by Cold Spring Harbor Laboratory Press for the RNA Society.

A new pooling strategy for high-throughput screening: the Shifted Transversal Design

PubMed Central

Thierry-Mieg, Nicolas

2006-01-01

Background In binary high-throughput screening projects where the goal is the identification of low-frequency events, beyond the obvious issue of efficiency, false positives and false negatives are a major concern. Pooling constitutes a natural solution: it reduces the number of tests, while providing critical duplication of the individual experiments, thereby correcting for experimental noise. The main difficulty consists in designing the pools in a manner that is both efficient and robust: few pools should be necessary to correct the errors and identify the positives, yet the experiment should not be too vulnerable to biological shakiness. For example, some information should still be obtained even if there are slightly more positives or errors than expected. This is known as the group testing problem, or pooling problem. Results In this paper, we present a new non-adaptive combinatorial pooling design: the "shifted transversal design" (STD). It relies on arithmetics, and rests on two intuitive ideas: minimizing the co-occurrence of objects, and constructing pools of constant-sized intersections. We prove that it allows unambiguous decoding of noisy experimental observations. This design is highly flexible, and can be tailored to function robustly in a wide range of experimental settings (i.e., numbers of objects, fractions of positives, and expected error-rates). Furthermore, we show that our design compares favorably, in terms of efficiency, to the previously described non-adaptive combinatorial pooling designs. Conclusion This method is currently being validated by field-testing in the context of yeast-two-hybrid interactome mapping, in collaboration with Marc Vidal's lab at the Dana Farber Cancer Institute. Many similar projects could benefit from using the Shifted Transversal Design. PMID:16423300

Investigation of wintertime cold-air pools and aerosol layers in the Salt Lake Valley using a lidar ceilometer

NASA Astrophysics Data System (ADS)

Young, Joseph Swyler

This thesis investigates the utility of lidar ceilometers, a type of aerosol lidar, in improving the understanding of meteorology and air quality in persistent wintertime stable boundary layers, or cold-air pools, that form in urbanized valley and basin topography. This thesis reviews the scientific literature to survey the present knowledge of persistent cold-air pools, the operating principles of lidar ceilometers, and their demonstrated utility in meteorological investigations. Lidar ceilometer data from the Persistent Cold-Air Pool Study (PCAPS) are then used with meteorological and air quality data from other in situ and remote sensing equipment to investigate cold-air pools that formed in Utah's Salt Lake Valley during the winter of 2010-2011. The lidar ceilometer is shown to accurately measure aerosol layer depth and aerosol loading, when compared to visual observations. A linear relationship is found between low-level lidar backscatter and surface particulate measurements. Convective boundary layer lidar analysis techniques applied to cold-air pool ceilometer profiles can detect useful layer characteristics. Fine-scale waves are observed and analyzed within the aerosol layer, with emphasis on Kelvin-Helmholz waves. Ceilometer aerosol backscatter profiles are analyzed to quantify and describe mixing processes in persistent cold-air pools. Overlays of other remote and in-situ observations are combined with ceilometer particle backscatter to describe specific events during PCAPS. This analysis describes the relationship between the aerosol layer and the valley inversion as well as interactions with large-scale meteorology. The ceilometer observations of hydrometers are used to quantify cloudiness and precipitation during the project, observing that 50% of hours when a PCAP was present had clouds or precipitation below 5 km above ground level (AGL). Then, combining an objective technique for determining hourly aerosol layer depths and correcting this subjectively during periods with low clouds or precipitation, a time series of aerosol depths was obtained. The mean depth of the surface-based aerosol layer during PCAP events was 1861 m MSL with a standard deviation of 135 m. The aerosol layer depth, given the approximate 1300 m altitude of the valley floor, is thus about 550 m, about 46% of the basin depth. The aerosol layer is present during much of the winter and is removed only during strong or prolonged precipitation periods or when surface winds are strong. Nocturnal fogs that formed near the end of high-stability PCAP episodes had a limited effect on aerosol layer depth. Aerosol layer depth was relatively invariant during the winter and during the persistent cold-air pools, while PM10 concentrations at the valley floor varied with bulk atmospheric stability associated primarily with passage of large-scale high- and low-pressure weather systems. PM10 concentrations also increased with cold-air pool duration. Mean aerosol loading in the surface-based aerosol layer, as determined from ceilometer backscatter coefficients, showed weaker variations than those of surface PM10 concentrations, suggesting that ineffective vertical mixing and aerosol layering are present in the cold-air pools. This is supported by higher time-resolution backscatter data, and it distinguishes the persistent cold-air pools from well-mixed convective boundary layers where ground-based air pollution concentrations are closely related to time-dependent convective boundary layer/aerosol depths. These results are discussed along with recommendations for future explorations of the ceilometer and cold-air pool topics.

A retrospective, pooled data analysis of the safety of pegaptanib sodium in the treatment of age-related macular degeneration in subjects with or without diabetes mellitus.

PubMed

Dombi, Theresa; Kwok, Kenneth K; Sultan, Marla B

2012-08-08

To evaluate the safety of pegaptanib sodium 0.3 mg intravitreal injection in the treatment of neovascular age-related macular degeneration in subjects with or without diabetes mellitus. A pooled, retrospective, analysis was conducted of data from 9 sponsor-administered, randomized, open-label trials. Subjects who received pegaptanib by randomization or change in dose assignment, crossover design, or protocol amendment, were included. Reports of endophthalmitis, increased intraocular pressure, retinal injury, intraocular hemorrhage, traumatic cataract, hypersensitivity reactions, stroke, myocardial infarction, and other arterial thromboembolic events defined by the Antiplatelet Trialists' Collaboration were identified by Medical Dictionary for Regulatory Activities preferred terms. Adverse events were summarized from the first injection to 42 days after the last injection. The incidence of adverse events was stratified by the presence/absence of diabetes. Of 1,586 subjects enrolled, 165 (10.4%) had a history of diabetes mellitus and 1,421 (89.6%) did not. The 2 populations were similar at baseline. Based on the comparison of prespecified ocular, hypersensitivity, and Antiplatelet Trialists' Collaboration event terms, the safety review did not identify any notable differences between the 2 populations. This retrospective analysis found no increased safety risk resulting from treatment with pegaptanib 0.3 mg in individuals with neovascular age-related macular degeneration and concomitant diabetes mellitus.

Thromboembolic Events After Vitamin K Antagonist Reversal With 4-Factor Prothrombin Complex Concentrate: Exploratory Analyses of Two Randomized, Plasma-Controlled Studies.

PubMed

Milling, Truman J; Refaai, Majed A; Goldstein, Joshua N; Schneider, Astrid; Omert, Laurel; Harman, Amy; Lee, Martin L; Sarode, Ravi

2016-01-01

We evaluated thromboembolic events after vitamin K antagonist reversal in post hoc analyses of pooled data from 2 randomized trials comparing 4-factor prothrombin complex concentrate (4F-PCC) (Beriplex/Kcentra) with plasma. Unblinded investigators identified thromboembolic events, using standardized terms (such as "myocardial infarction," "deep vein thrombosis," "pulmonary embolism," and "ischemic stroke"). A blinded safety adjudication board reviewed serious thromboembolic events, as well as those referred by an independent unblinded data and safety monitoring board. We descriptively compared thromboembolic event and patient characteristics between treatment groups and included detailed patient-level outcome descriptions. We did not power the trials to assess safety. We enrolled 388 patients (4F-PCC: n=191; plasma: n=197) in the trials. Thromboembolic events occurred in 14 of 191 patients (7.3%) in the 4F-PCC group and 14 of 197 (7.1%) in the plasma group (risk difference 0.2%; 95% confidence interval -5.5% to 6.0%). Investigators reported serious thromboembolic events in 16 patients (4F-PCC: n=8; plasma: n=8); the data and safety monitoring board referred 2 additional myocardial ischemia events (plasma group) to the safety adjudication board for review. The safety adjudication board judged serious thromboembolic events in 10 patients (4F-PCC: n=4; plasma: n=6) as possibly treatment related. There were 8 vascular thromboembolic events in the 4F-PCC group versus 4 in the plasma group, and 1 versus 6 cardiac events, respectively. Among patients with thromboembolic events, 3 deaths occurred in each treatment group. All-cause mortality for the pooled population was 13 per group. We observed no relationship between thromboembolic event occurrence and factor levels transiently above the upper limit of normal; there were no notable differences in median factor or proteins C and S levels up to 24 hours postinfusion start in patients with and without thromboembolic events. The incidence of thromboembolic events after vitamin K antagonist reversal with 4F-PCC or plasma was similar and independent of coagulation factor levels; small differences in the number of thromboembolic event subtypes were observed between treatment groups. Copyright © 2015 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

Upper Ocean Response to the Atmospheric Cold Pools Associated With the Madden-Julian Oscillation

NASA Astrophysics Data System (ADS)

Pei, Suyang; Shinoda, Toshiaki; Soloviev, Alexander; Lien, Ren-Chieh

2018-05-01

Atmospheric cold pools are frequently observed during the Madden-Julian Oscillation events and play an important role in the development and organization of large-scale convection. They are generally associated with heavy precipitation and strong winds, inducing large air-sea fluxes and significant sea surface temperature (SST) fluctuations. This study provides a first detailed investigation of the upper ocean response to the strong cold pools associated with the Madden-Julian Oscillation, based on the analysis of in situ data collected during the Dynamics of the Madden-Julian Oscillation (DYNAMO) field campaign and one-dimensional ocean model simulations validated by the data. During strong cold pools, SST drops rapidly due to the atmospheric cooling in a shoaled mixed layer caused by the enhanced near-surface salinity stratification generated by heavy precipitation. Significant contribution also comes from the component of surface heat flux produced by the cold rain temperature. After the period of heavy rain, while net surface cooling remains, SST gradually recovers due to the enhanced entrainment of warmer waters below the mixed layer.

Swimming Pool Electrical Injuries: Steps Toward Prevention.

PubMed

Tashiro, Jun; Burnweit, Cathy A

2017-01-09

Electrical injuries in swimming pools are an important pediatric public health concern. We sought to (1) improve our understanding of the clinical presentation and outcomes following and (2) describe the epidemiology of swimming pool electrical injuries in the United States. We reviewed 4 cases of pediatric (<18 y old) electrical injury from a single, urban level 1 pediatric trauma center. We also queried the National Electronic Injury Surveillance System (NEISS) for emergency department visits due to electrical injury associated with swimming pools, occurring between 1991 and 2013. Overall, 566 cases were reported, with a mean (SD) age of 9.2 (4.1) years. Patients were mostly treated and released from the emergency department (91.8%), whereas 8.2% were hospitalized. When stated, injuries occurred most frequently at home (57.0%), followed by public (23.9%) and sports facilities (19.1%). Electrical outlets or receptacles (39.8%) were most commonly implicated, followed by electrical system doors (18.2%), electric wiring systems (17.0%), thermostats (16.3%), hair dryers (4.6%), and radios (4.1%). Pediatric cases represented 48.4% of swimming pool-related electrical injuries reported to NEISS. Electrical injuries occurring in and around swimming pools remain an important source of morbidity and mortality. Although NEISS monitors sentinel events, current efforts at preventing such cases are less than adequate. All electrical outlets near swimming pools should be properly wired with ground fault circuit interrupter devices. Possible approaches to increasing safe electrical device installation are through strengthening public awareness and education of the potential for injury, as well as changes to current inspection regulations.

Methylmercury in flood-control impoundments and natural waters of northwestern Minnesota, 1997-99

USGS Publications Warehouse

Brigham, M.E.; Krabbenhoft, D.P.; Olson, M.L.; DeWild, J.F.

2002-01-01

We studied methylmercury (MeHg) and total mercury (HgT) in impounded and natural surface waters in northwestern Minnesota, in settings ranging from agricultural to undeveloped. In a recently constructed (1995) permanent-pool impoundment, MeHg levels typically increased from inflow to outflow during 1997; this trend broke down from late 1998 to early 1999. MeHg levels in the outflow reached seasonal maxima in mid-summer (maximum of 1.0 ng L−1 in July 1997) and late-winter (maximum of 6.6 ng L−1 in February 1999), and are comparable to high levels observed in new hydroelectric reservoirs in Canada. Spring and autumn MeHg levels were typically about 0.1–0.2 ng L−1. Overall, MeHg levels in both the inflow (a ditch that drains peatlands) and outflow were significantly higher than in three nearby reference natural lakes. Eleven older permanent-pool impoundments and six natural lakes in northwestern Minnesota were sampled five times. The impoundments typically had higher MeHg levels (0.071–8.36 ng L−1) than natural lakes. Five of six lakes MeHg levels typical of uncontaminated lakes (0.014–1.04 ng L−1) with highest levels in late winter, whereas a hypereutrophic lake had high levels (0.37–3.67 ng L−1) with highest levels in mid-summer. Seven temporary-pool impoundments were sampled during summer high-flow events. Temporary-pool impoundments that retained water for about 10–15 days after innundation yielded pronounced increases in MeHg from inflow to outflow, in one case reaching 4.6 ng L−1, which was about 2 ng L−1 greater than the mean inflow concentration during the runoff event.

Epidemiology of pediatric functional abdominal pain disorders: a meta-analysis.

PubMed

Korterink, Judith J; Diederen, Kay; Benninga, Marc A; Tabbers, Merit M

2015-01-01

We aimed to review the literature regarding epidemiology of functional abdominal pain disorders in children and to assess its geographic, gender and age distribution including associated risk factors of developing functional abdominal pain. The Cochrane Library, MEDLINE, EMBASE, CINAHL and PsychInfo databases were systematically searched up to February 2014. Study selection criteria included: (1) studies of birth cohort, school based or general population samples (2) containing data concerning epidemiology, prevalence or incidence (3) of children aged 4-18 years (4) suffering from functional abdominal pain. Quality of studies was rated by a self-made assessment tool. A random-effect meta-analysis model was used to estimate the prevalence of functional abdominal pain in childhood. A total of 58 articles, including 196,472 children were included. Worldwide pooled prevalence for functional abdominal pain disorders was 13.5% (95% CI 11.8-15.3), of which irritable bowel syndrome was reported most frequently (8.8%, 95% CI 6.2-11.9). The prevalence across studies ranged widely from 1.6% to 41.2%. Higher pooled prevalence rates were reported in South America (16.8%) and Asia (16.5%) compared to Europe (10.5%). And a higher pooled prevalence was reported when using the Rome III criteria (16.4%, 95% CI 13.5-19.4). Functional abdominal pain disorders are shown to occur significantly more in girls (15.9% vs. 11.5%, pooled OR 1.5) and is associated with the presence of anxiety and depressive disorders, stress and traumatic life events. Functional abdominal pain disorders are a common problem worldwide with irritable bowel syndrome as most encountered abdominal pain-related functional gastrointestinal disorder. Female gender, psychological disorders, stress and traumatic life events affect prevalence.

Epidemiology of Pediatric Functional Abdominal Pain Disorders: A Meta-Analysis

PubMed Central

Korterink, Judith J.; Diederen, Kay; Benninga, Marc A.; Tabbers, Merit M.

2015-01-01

Objective We aimed to review the literature regarding epidemiology of functional abdominal pain disorders in children and to assess its geographic, gender and age distribution including associated risk factors of developing functional abdominal pain. Methods The Cochrane Library, MEDLINE, EMBASE, CINAHL and PsychInfo databases were systematically searched up to February 2014. Study selection criteria included: (1) studies of birth cohort, school based or general population samples (2) containing data concerning epidemiology, prevalence or incidence (3) of children aged 4-18 years (4) suffering from functional abdominal pain. Quality of studies was rated by a self-made assessment tool. A random-effect meta-analysis model was used to estimate the prevalence of functional abdominal pain in childhood. Results A total of 58 articles, including 196,472 children were included. Worldwide pooled prevalence for functional abdominal pain disorders was 13.5% (95% CI 11.8-15.3), of which irritable bowel syndrome was reported most frequently (8.8%, 95% CI 6.2-11.9). The prevalence across studies ranged widely from 1.6% to 41.2%. Higher pooled prevalence rates were reported in South America (16.8%) and Asia (16.5%) compared to Europe (10.5%). And a higher pooled prevalence was reported when using the Rome III criteria (16.4%, 95% CI 13.5-19.4). Functional abdominal pain disorders are shown to occur significantly more in girls (15.9% vs. 11.5%, pooled OR 1.5) and is associated with the presence of anxiety and depressive disorders, stress and traumatic life events. Conclusion Functional abdominal pain disorders are a common problem worldwide with irritable bowel syndrome as most encountered abdominal pain-related functional gastrointestinal disorder. Female gender, psychological disorders, stress and traumatic life events affect prevalence. PMID:25992621

Interfacial heat transfer in multiphase molten pools with gas injection

NASA Astrophysics Data System (ADS)

Bilbao Y Leon, Rosa Marina

1998-12-01

In the very unlikely event of a severe reactor accident involving core meltdown and pressure vessel failure, it is vital to identify the circumstances that would allow the molten core material to cool down and resolidify, bringing core debris to a safe and stable state. In this type of accident, the molten material which escapes from the reactor pressure vessel will accumulate as a molten pool in the reactor cavity below. To achieve coolability of the corium in this configuration it has been proposed to flood the cavity with water from above forming a layered structure where upward heat loss from the molten pool to the water will cause the core material to quench and solidify. The effectiveness of this procedure depends largely on the rate of upward heat loss as well as on the formation and stability of an upper crust. In this situation the molten pool becomes a three phase mixture: the solid and liquid slurry formed by the molten pool cooled to a temperature below the temperature of liquidus, agitated by the gases formed in the concrete ablation process. The present work quantifies the partition of the heat losses upward and downward considering the influence of the solid fraction in the pool and the viscosity effects, and the rate of heat loss through a solid layer. To complete this task a intermediate scale experimental test section has been designed and built at the University of Wisconsin - Madison, in which simulant materials are used to model the process of heat and mass transfer which involves the molten pool, the solid layer atop and the coolant layer above. The design includes volumetric heating, gas injection from the bottom and solids within the pool. New experimental results showing the heat transfer behavior for pools with different viscosities and various solid fractions are presented. The current results indicate a power split which favors heat transfer upward to the coolant simulant above by a 2:1 or 3:1 ratio. In addition, the power split is unaffected by the viscosity of the pool, the solid fractions in the pool and the superficial velocity.

76 FR 66637 - Prohibited Transaction Exemption Procedures; Employee Benefit Plans

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-27

... independent fiduciary. In all events, the burden is on the applicant to demonstrate the independence of the... interest, pooled fund, qualified appraisal report, qualified independent appraiser, and qualified independent fiduciary. Definition of ``Affiliate''--Section 2570.31(a) of the proposed rule specifically...

Contrasting Effects of Central Pacific and Eastern Pacific El Nino on Stratospheric Water Vapor

NASA Technical Reports Server (NTRS)

Garfinkel, Chaim I.; Hurwitz, Margaret M.; Oman, Luke D.; Waugh, Darryn W.

2013-01-01

Targeted experiments with a comprehensive chemistry-climate model are used to demonstrate that seasonality and the location of the peak warming of sea surface temperatures dictate the response of stratospheric water vapor to El Nino. In spring, El Nino events in which sea surface temperature anomalies peak in the eastern Pacific lead to a warming at the tropopause above the warm pool region, and subsequently to more stratospheric water vapor (consistent with previous work). However, in fall and in early winter, and also during El Nino events in which the sea surface temperature anomaly is found mainly in the central Pacific, the response is qualitatively different: temperature changes in the warm pool region are nonuniform and less water vapor enters the stratosphere. The difference in water vapor in the lower stratosphere between the two variants of El Nino approaches 0.3 ppmv, while the difference between the winter and spring responses exceeds 0.5 ppmv.

Canadian astronaut Marc Garneau during emergency bailout training

NASA Image and Video Library

1993-10-07

S93-45726 (7 Oct. 1993) --- Canadian astronaut candidate Marc Garneau, later named as a mission specialist for NASA's STS-77 mission, participates in emergency bailout training at the Johnson Space Center (JSC). Garneau was in the 1992 class of Astronaut Candidates (ASCAN). Wearing full parachute gear following a simulated parachute drop, Garneau has deployed a small life raft in a 25-feet deep pool in JSC's Weightless Environment Training Facility (WET-F). This portion of an astronaut's training is to prepare him or her for proper measures to take in the event of bailout over water. Garneau is assisted here by one of several SCUBA-equipped divers in the pool.

Interventions for non-metastatic squamous cell carcinoma of the skin: systematic review and pooled analysis of observational studies.

PubMed

Lansbury, Louise; Bath-Hextall, Fiona; Perkins, William; Stanton, Wendy; Leonardi-Bee, Jo

2013-11-04

To assess the effects of treatments for non-metastatic invasive squamous cell carcinoma (SCC) of the skin using evidence from observational studies, given the paucity of evidence from randomised controlled trials. Systematic review of observational studies. Medline, Embase, to December 2012. Observational studies of interventions for primary, non-metastatic, invasive, SCC of the skin that reported recurrence during follow-up, quality of life, initial response to treatment, adverse events, cosmetic appearance, or death from disease. Studies were excluded if data for primary cutaneous SCC was not separable from other data. Data were extracted independently by two reviewers. Meta-analysis was performed where appropriate using a random effects model to estimate the pooled proportion of an event with 95% confidence intervals. 118 publications were included, covering seven treatment modalities. Pooled estimates of recurrence of SCCs were lowest after cryotherapy (0.8% (95% confidence interval 0.1% to 2%)) and curettage and electrodesiccation (1.7% (0.5% to 3.4%)), but most treated SCCs were small, low risk lesions. After Mohs micrographic surgery, the pooled estimate of local recurrence during variable follow-up periods from 10 studies was 3.0% (2.2% to 3.9%), which was non-significantly lower than the pooled average local recurrence of 5.4% (2.5% to 9.1%) after standard surgical excision (12 studies), and 6.4% (3.0% to 11.0%) after external radiotherapy (7 studies). After an apparently successful initial response of SCCs to photodynamic therapy, pooled average recurrence of 26.4% (12.3% to 43.7%; 8 studies) was significantly higher than other treatments. Evidence was limited for laser treatment (1 study) and for topical and systemic treatments (mostly single case reports or small non-comparative series with limited follow-up). Many observational studies have looked at different treatment modalities for SCC, but the evidence base for the effectiveness of these interventions is poor. Comparison of outcomes after different treatments should be interpreted cautiously owing to biases inherent in the types of study included, and lack of direct comparisons to enable the estimation of relative treatment effect. Further evidence is needed to develop a prognostic model and stratify individuals at high risk of developing SCC, to improve the evidence base for this common cancer and to optimise clinical management. International Prospective Register of Systematic Reviews (PROSPERO) registration number CRD42011001450.

Screening for Cardiovascular Disease Risk With Electrocardiography: US Preventive Services Task Force Recommendation Statement.

PubMed

Curry, Susan J; Krist, Alex H; Owens, Douglas K; Barry, Michael J; Caughey, Aaron B; Davidson, Karina W; Doubeni, Chyke A; Epling, John W; Kemper, Alex R; Kubik, Martha; Landefeld, C Seth; Mangione, Carol M; Silverstein, Michael; Simon, Melissa A; Tseng, Chien-Wen; Wong, John B

2018-06-12

Cardiovascular disease (CVD), which encompasses atherosclerotic conditions such as coronary heart disease, cerebrovascular disease, and peripheral arterial disease, is the most common cause of death among adults in the United States. Treatment to prevent CVD events by modifying risk factors is currently informed by CVD risk assessment with tools such as the Framingham Risk Score or the Pooled Cohort Equations, which stratify individual risk to inform treatment decisions. To update the 2012 US Preventive Services Task Force (USPSTF) recommendation on screening for coronary heart disease with electrocardiography (ECG). The USPSTF reviewed the evidence on whether screening with resting or exercise ECG improves health outcomes compared with the use of traditional CVD risk assessment alone in asymptomatic adults. For asymptomatic adults at low risk of CVD events (individuals with a 10-year CVD event risk less than 10%), it is very unlikely that the information from resting or exercise ECG (beyond that obtained with conventional CVD risk factors) will result in a change in the patient's risk category as assessed by the Framingham Risk Score or Pooled Cohort Equations that would lead to a change in treatment and ultimately improve health outcomes. Possible harms are associated with screening with resting or exercise ECG, specifically the potential adverse effects of subsequent invasive testing. For asymptomatic adults at intermediate or high risk of CVD events, there is insufficient evidence to determine the extent to which information from resting or exercise ECG adds to current CVD risk assessment models and whether information from the ECG results in a change in risk management and ultimately reduces CVD events. As with low-risk adults, possible harms are associated with screening with resting or exercise ECG in asymptomatic adults at intermediate or high risk of CVD events. The USPSTF recommends against screening with resting or exercise ECG to prevent CVD events in asymptomatic adults at low risk of CVD events. (D recommendation) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening with resting or exercise ECG to prevent CVD events in asymptomatic adults at intermediate or high risk of CVD events. (I statement).

Single Intravenous Dose of Oritavancin for Treatment of Acute Skin and Skin Structure Infections Caused by Gram-Positive Bacteria: Summary of Safety Analysis from the Phase 3 SOLO Studies.

PubMed

Corey, G Ralph; Loutit, Jeffery; Moeck, Greg; Wikler, Matthew; Dudley, Michael N; O'Riordan, William

2018-04-01

Oritavancin is a lipoglycopeptide with bactericidal activity against Gram-positive organisms. Its rapid concentration-dependent bactericidal activity and long elimination half-life allow single-dose treatment of acute bacterial skin and skin structure infections (ABSSSI). SOLO I and SOLO II were randomized, double-blind studies evaluating the efficacy and safety of a single 1,200-mg intravenous (i.v.) dose of oritavancin versus twice-daily i.v. vancomycin for 7 to 10 days in ABSSSI patients. Safety data from both studies were pooled for safety analysis. The database comprised pooled safety data for 976 oritavancin-treated patients and 983 vancomycin-treated patients. The incidences of adverse events, serious adverse events, and discontinuations due to adverse events were similar for oritavancin (55.3, 5.8, and 3.7%, respectively) and vancomycin (56.9, 5.9, and 4.2%, respectively). The median time to onset (3.8 days versus 3.1 days, respectively) and the duration (3.0 days for both groups) of adverse events were also similar between the two groups. The most frequently reported events were nausea, headache, and vomiting. Greater than 90% of all events were mild or moderate in severity. There were slightly more infections and infestations, abscesses or cellulitis, and hepatic and cardiac adverse events in the oritavancin group; however, more than 80% of these events were mild or moderate. Subgroup analyses did not identify clinically meaningful differences in the incidence of adverse events attributed to oritavancin. A single 1,200-mg dose of oritavancin was well tolerated and had a safety profile similar to that of twice-daily vancomycin. The long elimination half-life of oritavancin compared to that of vancomycin did not result in a clinically meaningful delay to the onset or prolongation of adverse events. (This study has been registered at ClinicalTrials.gov under registration no. NCT01252719 and NCT01252732.). Copyright © 2018 American Society for Microbiology.

Geomorphic and hydraulic Analyses of In-stream Step-pool Structures (I)

NASA Astrophysics Data System (ADS)

Kuo, W. C.; Hu, Y. L.; Wang, H. W.

2016-12-01

Longitudinal stair-like structures, such as alternating steps and pools, are found commonly in steep mountain streams. In a way to mimic the natural characteristics, many implementations of constructing artificial step structures have long been found in field practice to stabilize streambeds and enhance aquatic systems. To better understand how constructed step-pool systems form and function, this paper discusses the hydraulic and geomorphic factors based on flume experiments, and further compare to our field observations in Chijiawan Creek in Taiwan. We constructed a 2.9-m-long, 0.15-wide, and 0.3-m-high acrylic walled recirculating channel and conducted experiments to understand the formation, hydraulic features, and channel stability of step-pools of scenarios considering different channel slopes, discharges, feeding sediments. The results indicated that the keystones played a crucial role in stabilizing step-pool structures. The grain sizes of keystones from the experiments ranged approximately from one-third to one-tenth of channel width, while those from the field observations were about one-ninth to two-ninths. While the experimental discharge increased from 0.0012 cms to 0.006 cms, the flow transformed from nappe flow to skimming flow and the difference of average velocity between steps and pools reduced 30%. Besides, experiments showed that the step-pool structures failed immediately after keystones destroyed at a sediment transportation rate about 1.5 times of sediment feeding rate. It highlights the step-pools and channel stability is highly related to keystones. We further found the step-pools were buried at the experimental cases with coarse sediment fed upstream, similar to our field observations in Chijiawan Creek, with an approximately 1 3m deposition after Typhoon Soudelor, a 5-year event. The results obtained in this study would serve as a basis for ongoing discussions on how constructed step-pool structures would function and fail. More efforts of field investigations, flume experiments, and field experiments in helping developing specific recommendations and providing scientific insights for not only in Taiwan but around the world are still in need.

NUCLEAR REACTOR CONTROL SYSTEM

DOEpatents

Epler, E.P.; Hanauer, S.H.; Oakes, L.C.

1959-11-01

A control system is described for a nuclear reactor using enriched uranium fuel of the type of the swimming pool and other heterogeneous nuclear reactors. Circuits are included for automatically removing and inserting the control rods during the course of normal operation. Appropriate safety circuits close down the nuclear reactor in the event of emergency.

Have Tropical Cyclones Been Feeding More Extreme Rainfall?

NASA Technical Reports Server (NTRS)

Lau, K.-M.; Zhou, Y. P.; Wu, H.-T.

2008-01-01

We have conducted a study of the relationship between tropical cyclone (TC) and extreme rain events using GPCP and TRMM rainfall data, and storm track data for July through November (JASON) in the North Atlantic (NAT) and the western North Pacific (WNP). Extreme rain events are defined in terms of percentile rainrate, and TC-rain by rainfall associated with a named TC. Results show that climatologically, 8% of rain events and 17% of the total rain amount in NAT are accounted by TCs, compared to 9% of rain events and 21% of rain amount in WNP. The fractional contribution of accumulated TC-rain to total rain, Omega, increases nearly linearly as a function of rainrate. Extending the analyses using GPCP pentad data for 1979-2005, and for the post-SSM/I period (1988-2005), we find that while there is no significant trend in the total JASON rainfall over NAT or WNP, there is a positive significant trend in heavy rain over both basins for the 1979-2005 period, but not for the post-SSM/I period. Trend analyses of Omega for both periods indicate that TCs have been feeding increasingly more to rainfall extremes in NAT, where the expansion of the warm pool area can explain slight more than 50% of the change in observed trend in total TC rainfall. In WNP, trend signals for Omega are mixed, and the long-term relationship between TC rain and warm pool areas are strongly influenced by interannual and interdecadal variability.

Patent foramen ovale transcatheter closure vs. medical therapy on recurrent vascular events: a systematic review and meta-analysis of randomized controlled trials.

PubMed

Rengifo-Moreno, Pablo; Palacios, Igor F; Junpaparp, Parichart; Witzke, Christian F; Morris, D Lynn; Romero-Corral, Abel

2013-11-01

In patients with cryptogenic stroke, transcatheter (TC) closure of a patent foramen ovale (PFO) has not been shown to better prevent recurrent vascular events than medical therapy. However, randomized controlled trials (RCT) to date have included few vascular events, and lack of power has been raised as an important concern. To conduct a systematic review and meta-analysis of existing RCT published studies assessing the recurrence of vascular events after TC PFO closure when compared to medical therapy. Using the search terms "patent foramen ovale", "PFO", "stroke", "percutaneous closure" and "transcatheter closure", Medline, Pubmed, Embase, and Cochrane databases were reviewed from inception through April 2013, with no language restrictions. Only studies in adult humans were considered. Additional references were obtained from the bibliographies of studies reviewed. The following criteria were used for study selection: 1) randomized controlled trial, 2) subjects were adult patients with cryptogenic stroke who were randomized to TC PFO closure or medical treatment (antiplatelet therapy and/or anticoagulation), and 3) reported outcomes included cardiac death, all death, stroke, transient ischemic attack, and peripheral embolism. Methodological and descriptive data, adverse events (including raw data and risk estimates), as well as procedural success and complications were abstracted in duplicate from each study independently, and agreement was tested. We followed rigorously the recommended guidelines for reporting and conducting and assessing quality of meta-analysis of RCT. The primary endpoints pre-specified in advance were recurrent vascular events, and composite endpoint of death, and recurrent vascular events. Three studies were identified as meeting selection criteria. These included a total of 2,303 patients, with 1,150 patients randomized to TC PFO closure and 1,153 patients randomized to medical therapy. Mean follow-up was 3.5 years. Baseline characteristics (age, sex, and cardiovascular risk factors) were similar across studies. Intention-to-treat analyses showed a statistically significant risk reduction in stroke and/or transient ischemic attack in the TC PFO closure group when compared to medical treatment, pooled HR = 0.59, 95%CI (0.36-0.97), P = 0.04. The combined outcome of death, and vascular events, showed a borderline statistically significant benefit for TC PFO closure when compared to medical treatment, pooled HR = 0.67, 95%CI (0.44-1.00), P = 0.05 Subjects with a substantial PFO shunt seem to benefit the most with TC PFO closure, pooled HR = 0.35, 95%CI (0.12-1.03), P = 0.06, however, it did not reach statistical significance. These results suggest that in patients with cryptogenic stroke, TC PFO closure may be beneficial in reducing the risk of recurrent vascular events when compared to medical treatment. The benefit of TC PFO closure may be greater in patients with a substantial shunt.

A pooled analysis of injection site-related adverse events in patients with schizophrenia treated with olanzapine long-acting injection.

PubMed

Atkins, Susan; Detke, Holland C; McDonnell, David P; Case, Michael G; Wang, Shufang

2014-01-14

Depot antipsychotic injections are an important tool for the management of patients with schizophrenia who have difficulty with adherence to oral medication. However, pain and discomfort at the injection site can be a potential impediment to the use of these long-acting formulations. We report here the results of a pooled analysis of injection site-related adverse events (AEs) collected during treatment with the olanzapine long-acting injection (olanzapine LAI). Unsolicited injection site-related AEs were pooled from 7 olanzapine LAI clinical trials conducted in patients between March 2001 and December 2010. All patients had a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) or Fourth Edition, Text Revision (DSM-IV-TR) diagnosis of schizophrenia or schizoaffective disorder and were between the ages of 18 and 75. Doses ranged from 45 to 405 mg olanzapine LAI, and injection intervals were 2, 3, or 4 weeks. Events were evaluated for severity, timing, possible risk factors, and outcome. A criterion of p < .05 for statistical significance was used for all tests. A total of 1752 patients received at least 1 olanzapine LAI injection. Of these, 92 patients (5.3%) reported at least 1 injection site-related AE, with "pain" being the most common type (2.9%). Most events were mild (81.4%) and the median duration was 3 days. Four patients (0.2%) discontinued due to injection site-related AEs. Dose volume and body mass index did not appear to affect the probability of injection site-related AEs. However, patients who experienced a post-injection delirium/sedation syndrome event (n = 37) were more likely to have or have had an injection site-related AE at some time during the study. Incidence of injection site-related AEs appeared to decrease over time. In 94.2% of the injection site-related AEs, no specific treatment or concomitant medication was reported; in 9 cases, patients received pharmacologic treatment for reaction, mass, abscess, rash, or pain. Injection site-related AEs with olanzapine LAI were generally mild. The incidence and nature of these injection site-related AEs were generally similar to those occurring during treatment with other injectable antipsychotics. ClinicalTrials.gov ID; URL: NCT00094640, NCT00088478, NCT00088491, NCT00088465, and NCT00320489.

The effect of replacing saturated fat with mostly n-6 polyunsaturated fat on coronary heart disease: a meta-analysis of randomised controlled trials.

PubMed

Hamley, Steven

2017-05-19

A cornerstone of conventional dietary advice is the recommendation to replace saturated fatty acids (SFA) with mostly n-6 polyunsaturated fatty acids (PUFA) to reduce the risk of coronary heart disease (CHD). Many clinical trials aimed to test this advice and have had their results pooled in several meta-analyses. However, earlier meta-analyses did not sufficiently account for major confounding variables that were present in some of those trials. Therefore, the aim of the study was to account for the major confounding variables in the diet heart trials, and emphasise the results from those trials that most accurately test the effect of replacing SFA with mostly n-6 PUFA. Clinical trials were identified from earlier meta-analyses. Relevant trials were categorised as 'adequately controlled' or 'inadequately controlled' depending on whether there were substantial dietary or non-dietary differences between the experimental and control groups that were not related to SFA or mostly n-6 PUFA intake, then were subject to different subgroup analyses. When pooling results from only the adequately controlled trials there was no effect for major CHD events (RR = 1.06, CI = 0.86-1.31), total CHD events (RR = 1.02, CI = 0.84-1.23), CHD mortality (RR = 1.13, CI = 0.91-1.40) and total mortality (RR = 1.07, CI = 0.90-1.26). Whereas, the pooled results from all trials, including the inadequately controlled trials, suggested that replacing SFA with mostly n-6 PUFA would significantly reduce the risk of total CHD events (RR = 0.80, CI = 0.65-0.98, P = 0.03), but not major CHD events (RR = 0.87, CI = 0.70-1.07), CHD mortality (RR = 0.90, CI = 0.70-1.17) and total mortality (RR = 1.00, CI = 0.90-1.10). Available evidence from adequately controlled randomised controlled trials suggest replacing SFA with mostly n-6 PUFA is unlikely to reduce CHD events, CHD mortality or total mortality. The suggestion of benefits reported in earlier meta-analyses is due to the inclusion of inadequately controlled trials. These findings have implications for current dietary recommendations.

Environmental forcing of terrestrial carbon isotope excursion amplification across five Eocene hyperthermals

NASA Astrophysics Data System (ADS)

Bowen, G. J.; Abels, H.

2015-12-01

Abrupt changes in the isotope composition of exogenic carbon pools accompany many major episodes of global change in the geologic record. The global expression of this change in substrates that reflect multiple carbon pools provides important evidence that many events reflect persistent, global redistribution of carbon between reduced and oxidized stocks. As the diversity of records documenting any event grows, however, discrepancies in the expression of carbon isotope change among substrates are almost always revealed. These differences in magnitude, pace, and pattern of change can complicate interpretations of global carbon redistribution, but under ideal circumstances can also provide additional information on changes in specific environmental and biogeochemical systems that accompanied the global events. Here we evaluate possible environmental influences on new terrestrial records of the negative carbon isotope excursions (CIEs) associated with multiple hyperthermals of the Early Eocene, which show a common pattern of amplified carbon isotope change in terrestrial paleosol carbonate records relative to that recorded in marine substrates. Scaling relationships between climate and carbon-cycle proxies suggest that that the climatic (temperature) impact of each event scaled proportionally with the magnitude of its marine CIE, likely implying that all events involved release of reduced carbon with a similar isotopic composition. Amplification of the terrestrial CIEs, however, does not scale with event magnitude, being proportionally less for the first, largest event (the PETM). We conduct a sensitivity test of a coupled plant-soil carbon isotope model to identify conditions that could account for the observed CIE scaling. At least two possibilities consistent with independent lines of evidence emerge: first, varying effects of pCO2 change on photosynthetic carbon isotope discrimination under changing background pCO2, and second, contrasting changes in regional hydroclimate during the PETM and subsequent hyperthermals. These mechanisms have very different implications for the reconstruction of environmental conditions, and resolving the correct interpretation will require new, complimentary records of plant and soil conditions associated with the Early Eocene hyperthermals.

Pooled efficacy and safety of eslicarbazepine acetate as add-on treatment in patients with focal-onset seizures: Data from four double-blind placebo-controlled pivotal phase III clinical studies.

PubMed

Elger, Christian; Koepp, Mathias; Trinka, Eugen; Villanueva, Vicente; Chaves, João; Ben-Menachen, Elinor; Kowacs, Pedro A; Gil-Nagel, António; Moreira, Joana; Gama, Helena; Rocha, José-Francisco; Soares-da-Silva, Patrício

2017-12-01

Pooled evaluation of the key efficacy and safety profile of eslicarbazepine acetate (ESL) added-on to stable antiepileptic therapy in adults with focal-onset seizures. Data from 1703 patients enrolled in four phase III double-blind, randomized, placebo-controlled studies were pooled and analyzed. Following a 2 week titration period, ESL was administered at 400 mg, 800 mg, and 1200 mg once-daily doses for 12 weeks (maintenance period). Pooled efficacy variable was standardized (/4 weeks) seizure frequency (SSF) analyzed over the maintenance period as reduction in absolute and relative SSF and proportion of responders (≥50% reduction in SSF). Pooled safety was analyzed by means of adverse events and clinical laboratory assessments. SSF was significantly reduced with ESL 800 mg (P < 0.0001) and 1200 mg (P < 0.0001) compared to placebo. Median relative reduction in SSF was 33.4% for ESL 800 mg and 37.8% for 1200 mg (placebo: 17.6%), and responder rate was 33.8% and 43.1% (placebo: 22.2%). ESL was more efficacious than placebo regardless of gender, geographical region, epilepsy duration, age at time of diagnosis, seizure type, and type of concomitant antiepileptic drugs (AED). Incidence of adverse events (AEs) and AEs leading to discontinuation was dose dependent. Most common AEs (>10% patients) were dizziness, somnolence, and nausea. The incidence of treatment-emergent AEs (dizziness, somnolence, ataxia, vomiting, and nausea) was lower in patients who began taking ESL 400 mg (followed by 400 mg increments to 800 or 1200 mg) than in those who began taking ESL 600 mg or 800 mg. Once-daily ESL 800 mg and 1200 mg showed consistent results across all efficacy and safety endpoints, independent of study population characteristics and type of concomitant AEDs. Treatment initiated with ESL 400 mg followed by 400 mg increments to 800 or 1200 mg provides optimal balance of efficacy and tolerability. © 2017 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.

Simulation of local convective rainfall over metropolitan area on 16 August 2015 using high resolution model

NASA Astrophysics Data System (ADS)

Lee, Y. H.; Min, K. H.

2017-12-01

We investigated the ability of high-resolution numerical weather prediction (NWP) model (nested grid spacing at 500 m) in simulating convective precipitation event over the Seoul metropolitan area on 16 August 2015. Intense rainfall occurred from 0930 UTC to 1030 UTC and subsequent trailing precipitation lasted until 1400 UTC. The synoptic condition for the convective event was characterized by a large value of convective available potential energy (CAPE) at the outer edge of a meso-high pressure system. Observational analysis showed that triggering mechanism for convective rainfall was provided by the convergence of northeasterly wind which was driven by a cold pool in the northeastern Kyonggi province. The cold pool formed after heavy rain occurred in northeastern Kyonggi province at 0500UTC. Several experiments were performed in order to evaluate the sensitivity of different initial conditions (IC12, IC18, IC00, IC06) and the impact of data assimilation (IC06A) on simulating the convective event. The quantitative precipitation forecasts (QPF) appeared to vary widely among the experiments, depending on the timing of ICs that were chosen. QPF amount was underestimated in all experiments when data assimilation was not performed. Among the four experiments, QPF amounts and locations were better simulated in the 1200 UTC 15 August (IC12) run due to large values of CAPE in late afternoon and the presence of low-level convergence zone in the metropolitan area. Although 0600 UTC 16 August (IC06) run simulated the largest CAPE in late afternoon, the location and amount of heavy rainfall were significantly different from observations. IC06 did not simulate the convergence of low-level wind associated with the mesoscale cold pool. However, when assimilation of surface observations and radar data at 0600 UTC was performed (IC06A), the simulation reproduced the location and amount of rainfall reasonably well, indicating that high-resolution NWP model with data assimilation can predict the local convective precipitation event with a short-life time (1 3 hours) effectively within 6 hours.

Measurements and Modeling of Turbulent Fluxes during Persistent Cold Air Pool Events in Salt Lake Valley, Utah

NASA Astrophysics Data System (ADS)

Ivey, C. E.; Sun, X.; Holmes, H.

2017-12-01

Land surface processes are important in meteorology and climate research since they control the partitioning of surface energy and water exchange at the earth's surface. The surface layer is coupled to the planetary boundary layer (PBL) by surface fluxes, which serve as sinks or sources of energy, moisture, momentum, and atmospheric pollutants. Quantifying the surface heat and momentum fluxes at the land-atmosphere interface, especially for different surface land cover types, is important because they can further influence the atmospheric dynamics, vertical mixing, and transport processes that impact local, regional, and global climate. A cold air pool (CAP) forms when a topographic depression (i.e., valley) fills with cold air, where the air in the stagnant layer is colder than the air aloft. Insufficient surface heating, which is not able to sufficiently erode the temperature inversion that forms during the nighttime stable boundary layer, can lead to the formation of persistent CAPs during wintertime. These persistent CAPs can last for days, or even weeks, and are associated with increased air pollution concentrations. Thus, realistic simulations of the land-atmosphere exchange are meaningful to achieve improved predictions of the accumulation, transport, and dispersion of air pollution concentrations. The focus of this presentation is on observations and modeling results using turbulence data collected in Salt Lake Valley, Utah during the 2010-2011 wintertime Persistent Cold Air Pool Study (PCAPS). Turbulent fluxes and the surface energy balance over seven land use types are quantified. The urban site has an energy balance ratio (EBR) larger than one (1.276). Negative Bowen ratio (-0.070) is found at the cropland site. In addition to turbulence observations, half-hourly WRF simulated net radiation, latent heat, sensible heat, ground heat fluxes during one persistent CAP event are evaluated using the PCAPS observations. The results show that sensible and latent heat fluxes during the CAP event are overestimated. The sensitivity of WRF results to large-scale forcing datasets, PBL schemes and land surface models (LSMs) are also investigated. The optimal WRF configuration for simulating surface turbulent fluxes and atmospheric mixing during CAP events is determined.

Hylan G-F 20 Versus Low Molecular Weight Hyaluronic Acids for Knee Osteoarthritis: A Meta-Analysis.

PubMed

Zhao, Hongmou; Liu, Hongliang; Liang, Xiaojun; Li, Yi; Wang, Junhu; Liu, Cheng

2016-10-01

Hyaluronic acid injection has been reported to decrease pain compared with baseline levels in knee joint osteoarthritis. Hylan G-F 20 is distinguished from the other products by its chemical structure and relatively higher molecular weight. Many trials have compared hylan G-F 20 and low molecular weight hyaluronic acids (LMWHAs); however, their relative efficacy and safety are still debated. The aim was to compare the effectiveness and safety of intra-articular injection of hylan G-F 20 and LMWHA in the treatment of knee joint osteoarthritis. A comprehensive search of the literature up to February 2016 was performed; multiple databases were searched with 'Synvisc' or 'hylan' or 'hyaluronan' as free word terms. The pain-related outcomes and treatment-related adverse events from intent-to-treat analyzed studies were pooled for meta-analysis; other functional outcomes were included in the qualitative analysis. Twenty trials with a total of 3034 patients and 3153 knees were included, with a pooled dropout rate of 7.2 %. The pooled pain-related outcomes at 2 to 3 months reached a statistically significant difference in favor of hylan G-F 20 (I 2  = 88 %; random effects; P = 0.02), and the significance still existed with exclusion (in order to eliminate heterogeneity) of the three studies that most favored hylan G-F 20 (I 2  = 51 %; fixed effect; P = 0.03). No significant difference was reached for other group and subgroup analyses. No significant difference was reached in comparing the patients with treatment-related adverse events (seven trials; 2025 patients; P = 0.13) or the treatment-related adverse events (six trials; 1633 patients; P = 0.14). According to the current results, limited evidence showed a superior effect favoring hylan G-F 20 over LMWHA in the period from 2 to 3 months post-injection for pain-related outcomes. There was no evidence of increased risk of treatment-related adverse events for hylan G-F 20 injections.

Cardiovascular Events Following Smoke-Free Legislations: An Updated Systematic Review and Meta-Analysis

PubMed Central

Jones, Miranda R.; Barnoya, Joaquin; Stranges, Saverio; Losonczy, Lia; Navas-Acien, Ana

2014-01-01

Background Legislations banning smoking in indoor public places and workplaces are being implemented worldwide to protect the population from secondhand smoke exposure. Several studies have reported reductions in hospitalizations for acute coronary events following the enactment of smoke-free laws. Objective We set out to conduct a systematic review and meta-analysis of epidemiologic studies examining how legislations that ban smoking in indoor public places impact the risk of acute coronary events. Methods We searched MEDLINE, EMBASE, and relevant bibliographies including previous systematic reviews for studies that evaluated changes in acute coronary events, following implementation of smoke-free legislations. Studies were identified through December 2013. We pooled relative risk (RR) estimates for acute coronary events comparing post- vs. pre-legislation using inverse-variance weighted random-effects models. Results Thirty-one studies providing estimates for 47 locations were included. The legislations were implemented between 1991 and 2010. Following the enactment of smoke-free legislations, there was a 12 % reduction in hospitalizations for acute coronary events (pooled RR: 0.88, 95 % CI: 0.85–0.90). Reductions were 14 % in locations that implemented comprehensive legislations compared to an 8 % reduction in locations that only had partial restrictions. In locations with reductions in smoking prevalence post-legislation above the mean (2.1 % reduction) there was a 14 % reduction in events compared to 10 % in locations below the mean. The RRs for acute coronary events associated with enacting smoke-free legislation were 0.87 vs. 0.89 in locations with smoking prevalence pre-legislation above and below the mean (23.1 %), and 0.87 vs. 0.89 in studies from the Americas vs. other regions. Conclusion The implementation of smoke-free legislations was related to reductions in acute coronary event hospitalizations in most populations evaluated. Benefits are greater in locations with comprehensive legislations and with greater reduction in smoking prevalence post-legislation. These cardiovascular benefits reinforce the urgent need to enact and enforce smoke-free legislations that protect all citizens around the world from exposure to tobacco smoke in public places. PMID:25328861

Organic horizon and mineral soil mercury along three clear-cut forest chronosequences across the northeastern USA.

PubMed

Richardson, Justin B; Petrenko, Chelsea L; Friedland, Andrew J

2017-12-01

Mercury (Hg) is a globally distributed pollutant trace metal that has been increasing in terrestrial environments due to rising anthropogenic emissions. Vegetation plays an important role in Hg sequestration in forested environments, but increasing tree removal for biofuels and wood products may affect this process. The long-term effect of clear-cutting on forest soil Hg remains uncertain, since most studies are limited to measuring changes for < 10 years following a single harvest event. The chronosequence approach, which substitutes space for time using forest stands of different ages since clear-cutting, allows for investigation of processes occurring over decades to centuries. Here, we utilized three clear-cut forest soil chronosequences across the northeastern USA to understand Hg accumulation and retention over several decades. Total Hg concentrations and pools were quantified for five soil depth increments along three chronosequences. Our results showed Hg concentrations and pools decreased in the initial 20 years following clear-cutting. Mineral soil Hg pools decreased 21-53% (7-14 mg m -2 ) between 1-5-year-old stands and 15-25-year-old stands but mineral soil Hg pools recovered in 55-140-year-old stands to similar values as measured in 1-5-year-old stands. Our study is one of the first to demonstrate a decrease and recovery in Hg pool size. These changes in Hg did not correspond with changes in bulk density, soil C, or pH. We utilized a simple two-box model to determine how different Hg fluxes affected organic and mineral soil horizon Hg pools. Our simple model suggests that changes in litterfall and volatilization rates could have caused the observed changes in organic horizon Hg pools. However, only increases in leaching could reproduce observed decreases to mineral soil Hg pools. Further studies are needed to determine the mechanism of Hg loss from forest soils following clear-cutting.

Safety of Tofacitinib in the Treatment of Rheumatoid Arthritis in Latin America Compared With the Rest of the World Population.

PubMed

Castañeda, Oswaldo M; Romero, Felix J; Salinas, Ariel; Citera, Gustavo; Mysler, Eduardo; Rillo, Oscar; Radominski, Sebastiao C; Cardiel, Mario H; Jaller, Juan J; Alvarez-Moreno, Carlos; Ponce de Leon, Dario; Castelli, Graciela; García, Erika G; Kwok, Kenneth; Rojo, Ricardo

2017-06-01

Rheumatoid arthritis (RA) is a chronic, autoimmune disease characterized by joint destruction. Tofacitinib is an oral Janus kinase inhibitor for the treatment of RA. This post hoc analysis assessed the safety of tofacitinib in Latin American (LA) patients with RA versus the Rest of World (RoW) population. Data were pooled from 14 clinical studies of tofacitinib: six Phase 2, six Phase 3 and two long-term extension studies. Incidence rates (IRs; patients with events/100 patient-years of treatment exposure) were calculated for safety events of special interest combined across tofacitinib doses. 95% confidence intervals (CI) for IRs were calculated using the maximum likelihood method. Descriptive comparisons were made between LA and RoW (excluding LA) populations. This analysis included data from 984 LA patients and 4687 RoW patients. IRs for safety events of special interest were generally similar between LA and RoW populations, with overlapping 95% CIs. IRs for discontinuation due to adverse events, serious infections, tuberculosis, all herpes zoster (HZ), serious HZ, malignancies (excluding non-melanoma skin cancer) and major adverse cardiovascular events were numerically lower for LA versus RoW patients; IR for mortality was numerically higher. No lymphoma was reported in the LA population versus eight cases in the RoW population. Exposure (extent and length) was lower in the LA population (2148.33 patient-years [mean = 2.18 years]) versus RoW (10515.68 patient-years [mean = 2.24 years]). This analysis of pooled data from clinical studies of tofacitinib in patients with RA demonstrates that tofacitinib has a consistent safety profile across LA and RoW patient populations.

Soft drinks and sweetened beverages and the risk of cardiovascular disease and mortality: a systematic review and meta-analysis.

PubMed

Narain, A; Kwok, C S; Mamas, M A

2016-10-01

Soft drink consumption is associated with adverse health behaviours that predispose to adverse cardiovascular risk factor profiles; however, it is unclear whether their intake independently leads to an increased risk of cardiovascular events and mortality. We conducted a systematic review and meta-analysis to evaluate this. Medline and EMBASE were searched in July 2015 for studies that considered soft drink intake and risk of mortality, myocardial infarction (MI) or stroke. Pooled risk ratios (RRs) for adverse outcomes were calculated using inverse variance with a random effects model, and heterogeneity was assessed using the I 2 statistic. A total of seven prospective cohort studies with 308,420 participants (age range 34-75 years) were included in the review. The pooled results suggest a greater risk of stroke (RR 1.13, 95% CI 1.02-1.24), and MI (RR 1.22, 95% CI 1.14-1.30), but not vascular events with incremental increase in sugar-sweetened beverage (SSB) consumption. With incremental increase in artificially sweetened beverage (ASB) consumption, there was a greater risk of stroke (RR 1.08, 95% CI 1.03-1.14), but not vascular events or MI. In the evaluation of high vs. low SSB, there was a greater risk of MI (RR 1.19, 95% CI 1.09-1.31) but not stroke, vascular events or mortality. For ASB, there was a significantly greater risk of stroke (RR 1.14, 95% CI 1.04-1.26) and vascular events (RR 1.44, 95% CI 1.02-2.03) but not MI or mortality. Our results suggest an association between consumption of sugar-sweetened and ASBs and cardiovascular risk, although consumption may be a surrogate for adverse health behaviours. © 2016 John Wiley & Sons Ltd.

Sitagliptin: review of preclinical and clinical data regarding incidence of pancreatitis

PubMed Central

Engel, S S; Williams-Herman, D E; Golm, G T; Clay, R J; Machotka, S V; Kaufman, K D; Goldstein, B J

2010-01-01

Recent case reports of acute pancreatitis in patients with type 2 diabetes (T2DM) treated with incretin-based therapies have triggered interest regarding the possibility of a mechanism-based association between pancreatitis and glucagon-like peptide-1 mimetics or dipeptidyl peptidase-4 (DPP-4) inhibitors. The objective of this review was to describe the controlled preclinical and clinical trial data regarding the incidence of pancreatitis with sitagliptin, the first DPP-4 inhibitor approved for use in patients with T2DM. Tissue samples from multiple animal species treated with sitagliptin for up to 2 years at plasma exposures substantially in excess of human exposure were evaluated to determine whether any potential gross or histomorphological changes suggestive of pancreatitis occurred. Sections were prepared by routine methods, stained with haematoxylin and eosin and examined microscopically. A pooled analysis of 19 controlled clinical trials, comprising 10,246 patients with T2DM treated for up to 2 years, was performed using patient-level data from each study for the evaluation of clinical and laboratory adverse events. Adverse events were encoded using the Medical Dictionary for Regulatory Activities (MedDRA) version 12.0 system. Incidences of adverse events were adjusted for patient exposure. Tissue samples from preclinical studies in multiple animal species did not reveal any evidence of treatment-related pancreatitis. The pooled analysis of controlled clinical trials revealed similar incidence rates of pancreatitis in patients treated with sitagliptin compared with those not treated with sitagliptin (0.08 events per 100 patient-years vs. 0.10 events per 100 patient-years, respectively). Preclinical and clinical trial data with sitagliptin to date do not indicate an increased risk of pancreatitis in patients with T2DM treated with sitagliptin. PMID:20412332

From the concept of ``Kaltlufttropfen'' (cold air pool) to the cut-off low. The case of September 1971 in Spain as an example of their role in heavy rainfalls

NASA Astrophysics Data System (ADS)

Llasat, M.-C.; Martín, F.; Barrera, A.

2007-04-01

Over the last 25 years the term “cold pool” has come to be used in many spheres as a synonym for floods. This has given rise to a major confusion that has even moved into international scientific and technical circles. In this paper we analyse how the concept of “cold air pool” has evolved from when it was defined at the beginning of the 20th century down to the present day, in which the Spanish term “DANA” (similar to a cut-off low) has been introduced in order to avoid existing confusions. In the course of the paper we take account of cold air pool genesis and their thermal and dynamic characteristics, and we discuss the factors that have led to them being identified (erroneously) with heavy rainfall events. The study takes as its basis a systematic analysis of all the cold air pools recorded in Europe, and particularly in the Iberian Peninsula, over the period 1974-1983, as well as in studies of the floods recorded in eastern Spain since 1950 until nowadays. The discussion done on the basis of this accurate analysis leads to the identification of a cold air pool as a type cut-off low (COL) and justifying the use of this more generic term when a structure like this is present in a heavy rainfall event. For a better illustration of the previous discussion and understanding of the role of COLs in intense rainfall events, we present the episode of September 1971 in Catalonia, in which over 400 mm were recorded. The analysis was carried out with the MM5 initialised with the ERA-40 re-analyses. The results show that the role of COLs in the heavy rainfall episodes recorded in Spain is mainly dynamic, both in terms of the circulation they create at low levels and the potential vorticity anomaly generated. This circulation draws in very warm, moist and potentially unstable air perpendicularly to the coast and the littoral mountain chains. The factor of thermal instability, owing to the presence of cold air at medium and higher levels, shows itself to be more important in zones where this warm moist advection at low levels is not as significant as in the Mediterranean zone.

Effect of paracetamol (acetaminophen) on body temperature in acute stroke: A meta-analysis.

PubMed

Fang, Junjie; Chen, Chensong; Cheng, Hongsen; Wang, Ren; Ma, Linhao

2017-10-01

The objective of this study was to assess the efficacy of paracetamol (acetaminophen) on body temperature in acute stroke. Medline, Cochrane Central Register of Controlled Trials, EMBASE, Chinese BioMedical Literature Database, China National Knowledge Infrastructure, and the World Health Organization (WHO) International Clinical Trials Registry Platform were searched electronically. Relevant journals and references of studies included were hand-searched for randomized controlled trials (RCT) and controlled clinical trials (CCT) regarding the efficacy of paracetamol (acetaminophen) on body temperature in acute stroke. Two reviewers independently performed data extraction and quality assessment. Data were analyzed using RevMan 5.3 software by the Cochrane Collaboration. Five studies were included. To compare the efficacy of paracetamol (acetaminophen) in acute stroke, the pooled RR (Risk Ratio) and its 95% CI of body temperature reduction at 24h from the start of treatment were -0.3 (95% CI: -0.52 to -0.08), with statistical significance (P=0.007). Consistently, the pooled RR (Risk Ratio) and its 95% CI of body temperature at 24h from the start of treatment were -0.22 (-0.29, -0.15), with statistical significance (P<0.00001). When analyzing the body temperature reduction after 5days from the start of treatment, the pooled RR (Risk Ratio) and its 95% CI were 0.04 (95% CI: -0.20 to 0.29), with no statistical significance (P=0.73). For functional outcome (mRS≤2) analysis, the pooled RR and its 95% CI were 1.08 (0.88, 1.32), with no statistical significance (P=0.45). In addition, the difference of serious adverse events between acetaminophen and placebo was 0.86 (95% CI: 0.62 to 1.2), with no statistical significance (P=0.27). Acetaminophen was revealed to have some favorable influence in body temperature reduction in acute stroke, but showed no important effect on improving functional outcome and reducing adverse events of patients. What is already known on this subject? Paracetamol (acetaminophen) is one of the most commonly used antipyretic drugs and has some capability to reduce body temperature through acting on central nervous system. Acetaminophen showed some capability to decrease body temperature for acute stroke. Acetaminophen could not improve functional outcome and reduce adverse events of patients with acute stroke. Copyright © 2017 Elsevier Inc. All rights reserved.

Developmental Reversals in False Memory: Effects of Emotional Valence and Arousal

ERIC Educational Resources Information Center

Brainerd, C. J.; Holliday, R. E.; Reyna, V. F.; Yang, Y.; Toglia, M. P.

2010-01-01

Do the emotional valence and arousal of events distort children's memories? Do valence and arousal modulate counterintuitive age increases in false memory? We investigated those questions in children, adolescents, and adults using the Cornell/Cortland Emotion Lists, a word list pool that induces false memories and in which valence and arousal can…

Eyeing New York's Newspaper Strike.

ERIC Educational Resources Information Center

Fishleder, Paul

The New York newspaper strike of 1978 was the direct result of a series of events that started in 1923 when the pressmen's union established a system that provided a minimum fixed number of pressmen per press unit and legitimized a loose labor pool. From that time, the number of pressmen increased through family-dominated union management that…

Cryptosporidiosis Outbreak Associated With a Single Hotel.

PubMed

Fill, Mary-Margaret A; Lloyd, Jennifer; Chakraverty, Tamal; Sweat, David; Manners, Judy; Garman, Katie; Hlavsa, Michele C; Roellig, Dawn M; Dunn, John R; Schaffner, William; Jones, Timothy F

2017-05-01

We investigated a gastrointestinal illness cluster among persons who attended a baseball tournament (>200 teams) during July 2015. We interviewed representatives of 19 teams; illness was reported among only the 9 (47%) teams that stayed at Hotel A (p < .01). We identified 55 primary cases. A case-control study demonstrated that pool exposure at Hotel A was significantly associated with illness (odds ratio: 7.3; 95% confidence interval: 3.6, 15.2). Eight out of nine (89%) stool specimens tested were positive for Cryptosporidium, with C. hominis IfA12G1 subtype identified in two specimens. The environmental health assessment detected a low free available chlorine level, and pool water tested positive for E. coli and total coliforms. A possible diarrheal contamination event, substantial hotel pool use, and use of cyanuric acid might have contributed to this outbreak and magnitude. Aquatic facilities practicing proper operation and maintenance (e.g., following the Centers for Disease Control and Prevention’s Model Aquatic Health Code) can protect the public’s health.

Mechanical characterization of atherosclerotic arteries using finite-element modeling: feasibility study on mock arteries.

PubMed

Pazos, Valérie; Mongrain, Rosaire; Tardif, Jean-Claude

2010-06-01

Clinical studies on lipid-lowering therapy have shown that changing the composition of lipid pools reduced significantly the risk of cardiac events associated with plaque rupture. It has been shown also that changing the composition of the lipid pool affects its mechanical properties. However, knowledge about the mechanical properties of human atherosclerotic lesions remains limited due to the difficulty of the experiments. This paper aims to assess the feasibility of characterizing a lipid pool embedded in the wall of a pressurized vessel using finite-element simulations and an optimization algorithm. Finite-element simulations of inflation experiments were used together with nonlinear least squares algorithm to estimate the material model parameters of the wall and of the inclusion. An optimal fit of the simulated experiment and the real experiment was sought with the parameter estimation algorithm. The method was first tested on a single-layer polyvinyl alcohol (PVA) cryogel stenotic vessel, and then, applied on a double-layered PVA cryogel stenotic vessel with a lipid inclusion.

Modeling evaporation from spent nuclear fuel storage pools: A diffusion approach

NASA Astrophysics Data System (ADS)

Hugo, Bruce Robert

Accurate prediction of evaporative losses from light water reactor nuclear power plant (NPP) spent fuel storage pools (SFPs) is important for activities ranging from sizing of water makeup systems during NPP design to predicting the time available to supply emergency makeup water following severe accidents. Existing correlations for predicting evaporation from water surfaces are only optimized for conditions typical of swimming pools. This new approach modeling evaporation as a diffusion process has yielded an evaporation rate model that provided a better fit of published high temperature evaporation data and measurements from two SFPs than other published evaporation correlations. Insights from treating evaporation as a diffusion process include correcting for the effects of air flow and solutes on evaporation rate. An accurate modeling of the effects of air flow on evaporation rate is required to explain the observed temperature data from the Fukushima Daiichi Unit 4 SFP during the 2011 loss of cooling event; the diffusion model of evaporation provides a significantly better fit to this data than existing evaporation models.

Loss of DHR sequences at Browns Ferry Unit One - accident-sequence analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cook, D.H.; Grene, S.R.; Harrington, R.M.

1983-05-01

This study describes the predicted response of Unit One at the Browns Ferry Nuclear Plant to a postulated loss of decay heat removal (DHR) capability following scram from full power with the power conversion system unavailable. In accident sequences without DHR capability, the residual heat removal (RHR) system functions of pressure suppression pool cooling and reactor vessel shutdown cooling are unavailable. Consequently, all decay heat energy is stored in the pressure suppression pool with a concomitant increase in pool temperature and primary containment pressure. With the assumption that DHR capability is not regained during the lengthy course of this accidentmore » sequence, the containment ultimately fails by overpressurization. Although unlikely, this catastrophic failure might lead to loss of the ability to inject cooling water into the reactor vessel, causing subsequent core uncovery and meltdown. The timing of these events and the effective mitigating actions that might be taken by the operator are discussed in this report.« less

Long-term antibiotics for prevention of recurrent urinary tract infection in older adults: systematic review and meta-analysis of randomised trials.

PubMed

Ahmed, Haroon; Davies, Freya; Francis, Nick; Farewell, Daniel; Butler, Christoper; Paranjothy, Shantini

2017-05-29

To address clinical uncertainties about the effectiveness and safety of long-term antibiotic therapy for preventing recurrent urinary tract infections (UTIs) in older adults. Systematic review andmeta-analysis of randomised trials. We searched Medline, Embase, The Cumulative Index to Nursing and Allied Health Literature( CINAHL), and the Cochrane Register of Controlled Trials from inception to August 2016. Eligible studies compared long-term antibiotic therapy with non-antibiotic therapy or placebo in men or women aged over 65, or in postmenopausal women, with recurrent UTIs. We did not identify any studies that included older men. Three randomised controlled trials compared long-term antibiotics with vaginal oestrogens (n=150), oral lactobacilli (n=238) and D-mannose powder (n=94) in postmenopausal women. Long-term antibiotics reduced the risk of UTI recurrence by 24% (three trials, n=482; pooled risk ratio (RR) 0.76; 95% CI 0.61 to 0.95, number needed to treat=8.5). There was no statistically significant increase in risk of adverse events (mild adverse events: pooled RR 1.52; 95% CI 0.76 to 3.03; serious adverse events: pooled RR 0.90, 95% CI 0.31 to 2.66). One trial showed 90% of urinary and faecal Escherichia coli isolates were resistant to trimethoprim-sulfamethoxazole after 1 month of prophylaxis. Findings from three small trials with relatively short follow-up periods suggest long-term antibiotic therapy reduces the risk of recurrence in postmenopausal women with recurrent UTI. We did not identify any evidence to inform several clinically important scenarios including, benefits and harms in older men or frail care home residents, optimal duration of prophylaxis, recurrence rates once prophylaxis stops and effects on urinary antibiotic resistance. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Systematic review with meta-analysis: the efficacy and safety of CT-P13, a biosimilar of anti-tumour necrosis factor-α agent (infliximab), in inflammatory bowel diseases.

PubMed

Komaki, Y; Yamada, A; Komaki, F; Micic, D; Ido, A; Sakuraba, A

2017-04-01

Biosimilars of anti-tumour necrosis factor (TNF)-α agents have now become clinically available for the treatment of inflammatory bowel diseases (IBD). To perform a systematic review and meta-analysis to evaluate the efficacy and safety of biosimilars of anti-TNF-α agents in patients with IBD. Electronic databases were searched. The outcomes were the pooled rates of clinical response or remission, sustained clinical response or remission, and adverse events in patients with IBD induced with or switched to biosimilars of anti-TNF-α agents. Eleven observational studies reporting outcomes in 829 patients treated with biosimilar of infliximab (CT-P13) were identified. The pooled rates of clinical response among Crohn's disease (CD) and ulcerative colitis (UC) at 8-14 weeks were 0.79 (95% confidence interval (CI) = 0.65-0.88) and 0.74 (95% CI = 0.65-0.82), respectively, and at 24-30 weeks were 0.77 (95% CI = 0.63-0.86) and 0.77 (95% CI = 0.67-0.85) respectively. Adverse events were rare (CD, 0.08 (95% CI = 0.02-0.26); UC, 0.08 (95% CI = 0.03-0.17)). The pooled rates of sustained clinical response among CD and UC after switching from infliximab to CT-P13 at 30-32 weeks were 0.85 (95% CI = 0.71-0.93) and 0.96 (95% CI = 0.58-1.00), respectively, and at 48-63 weeks were 0.75 (95% CI = 0.44-0.92) and 0.83 (95% CI = 0.19-0.99) respectively. Adverse events were rare (CD, 0.10, 95% CI = 0.02-0.31; UC, 0.22, 95% CI = 0.04-0.63). CT-P13 was associated with excellent clinical efficacy and safety profile, supporting its use in the treatment of IBD. © 2017 John Wiley & Sons Ltd.

Temporal Changes in Photochemically Labile DOM and Implications for Carbon Budgets in Peatland Aquatic Systems

NASA Astrophysics Data System (ADS)

Pickard, A.

2015-12-01

Aquatic systems in peatland catchments are subject to high loading of dissolved organic matter (DOM) from surrounding terrestrial environments. However the significance of photochemical transformation of DOM in peatland carbon budgets remains poorly constrained. In this study UV irradiation experiments were conducted on water samples collected over one year from two contrasting systems in Scotland: a stream draining a peatland with high levels of DOM and a reservoir draining a peat catchment with low levels of DOM. Further samples were collected from the high DOM system during two storm events. After experimental exposure, optical and chemical analyses were employed to determine photochemical lability of the DOM pool. At both sites irradiation-induced decreases in dissolved organic carbon (DOC) as a percentage of the total carbon pool were greatest in winter, suggesting that DOM was depleted in photo-reactive molecules in summer. Seasonal variability in DOC was high at the stream site and was positively correlated with CO₂ and CO photoproduction (r2 = 0.81 and 0.83, respectively; p<0.05). Lignin phenol analyses indicate considerable contribution of peat to the DOM pool at the stream site, particularly during summer. Whilst DOC concentrations did not vary greatly during storm events, UV-Vis absorbance indicators did, signifying changing DOM source material from activation of different hydrological pathways. The most photo-reactive DOM occurred 5-10 hours after peak discharge, suggesting that storms replenish photochemically labile DOM in headwater streams. Conservative estimates using data from this study suggest that up to 7% of the DOM pool of peatland streams can be lost (primarily as CO₂ and CO) upon exposure to 8 hours of environmentally representative UV irradiation. Further investigation in field campaigns under natural UV exposure are underway to assess the importance of photodegradation of DOM as a loss pathway of carbon based gases from aquatic systems.

Enzyme replacement therapy for Anderson-Fabry disease: A complementary overview of a Cochrane publication through a linear regression and a pooled analysis of proportions from cohort studies

PubMed Central

El Dib, Regina; Gomaa, Huda; Ortiz, Alberto; Politei, Juan; Kapoor, Anil; Barreto, Fellype

2017-01-01

Background Anderson-Fabry disease (AFD) is an X-linked recessive inborn error of glycosphingolipid metabolism caused by a deficiency of alpha-galactosidase A. Renal failure, heart and cerebrovascular involvement reduce survival. A Cochrane review provided little evidence on the use of enzyme replacement therapy (ERT). We now complement this review through a linear regression and a pooled analysis of proportions from cohort studies. Objectives To evaluate the efficacy and safety of ERT for AFD. Materials and methods For the systematic review, a literature search was performed, from inception to March 2016, using Medline, EMBASE and LILACS. Inclusion criteria were cohort studies, patients with AFD on ERT or natural history, and at least one patient-important outcome (all-cause mortality, renal, cardiovascular or cerebrovascular events, and adverse events) reported. The pooled proportion and the confidence interval (CI) are shown for each outcome. Simple linear regressions for composite endpoints were performed. Results 77 cohort studies involving 15,305 participants proved eligible. The pooled proportions were as follows: a) for renal complications, agalsidase alfa 15.3% [95% CI 0.048, 0.303; I2 = 77.2%, p = 0.0005]; agalsidase beta 6% [95% CI 0.04, 0.07; I2 = not applicable]; and untreated patients 21.4% [95% CI 0.1522, 0.2835; I2 = 89.6%, p<0.0001]. Effect differences favored agalsidase beta compared to untreated patients; b) for cardiovascular complications, agalsidase alfa 28% [95% CI 0.07, 0.55; I2 = 96.7%, p<0.0001]; agalsidase beta 7% [95% CI 0.05, 0.08; I2 = not applicable]; and untreated patients 26.2% [95% CI 0.149, 0.394; I2 = 98.8%, p<0.0001]. Effect differences favored agalsidase beta compared to untreated patients; and c) for cerebrovascular complications, agalsidase alfa 11.1% [95% CI 0.058, 0.179; I2 = 70.5%, p = 0.0024]; agalsidase beta 3.5% [95% CI 0.024, 0.046; I2 = 0%, p = 0.4209]; and untreated patients 18.3% [95% CI 0.129, 0.245; I2 = 95% p < 0.0001]. Effect differences favored agalsidase beta over agalsidase alfa or untreated patients. A linear regression showed that Fabry patients receiving agalsidase alfa are more likely to have higher rates of composite endpoints compared to those receiving agalsidase beta. Conclusions Agalsidase beta is associated to a significantly lower incidence of renal, cardiovascular and cerebrovascular events than no ERT, and to a significantly lower incidence of cerebrovascular events than agalsidase alfa. In view of these results, the use of agalsidase beta for preventing major organ complications related to AFD can be recommended. PMID:28296917

Enzyme replacement therapy for Anderson-Fabry disease: A complementary overview of a Cochrane publication through a linear regression and a pooled analysis of proportions from cohort studies.

PubMed

El Dib, Regina; Gomaa, Huda; Ortiz, Alberto; Politei, Juan; Kapoor, Anil; Barreto, Fellype

2017-01-01

Anderson-Fabry disease (AFD) is an X-linked recessive inborn error of glycosphingolipid metabolism caused by a deficiency of alpha-galactosidase A. Renal failure, heart and cerebrovascular involvement reduce survival. A Cochrane review provided little evidence on the use of enzyme replacement therapy (ERT). We now complement this review through a linear regression and a pooled analysis of proportions from cohort studies. To evaluate the efficacy and safety of ERT for AFD. For the systematic review, a literature search was performed, from inception to March 2016, using Medline, EMBASE and LILACS. Inclusion criteria were cohort studies, patients with AFD on ERT or natural history, and at least one patient-important outcome (all-cause mortality, renal, cardiovascular or cerebrovascular events, and adverse events) reported. The pooled proportion and the confidence interval (CI) are shown for each outcome. Simple linear regressions for composite endpoints were performed. 77 cohort studies involving 15,305 participants proved eligible. The pooled proportions were as follows: a) for renal complications, agalsidase alfa 15.3% [95% CI 0.048, 0.303; I2 = 77.2%, p = 0.0005]; agalsidase beta 6% [95% CI 0.04, 0.07; I2 = not applicable]; and untreated patients 21.4% [95% CI 0.1522, 0.2835; I2 = 89.6%, p<0.0001]. Effect differences favored agalsidase beta compared to untreated patients; b) for cardiovascular complications, agalsidase alfa 28% [95% CI 0.07, 0.55; I2 = 96.7%, p<0.0001]; agalsidase beta 7% [95% CI 0.05, 0.08; I2 = not applicable]; and untreated patients 26.2% [95% CI 0.149, 0.394; I2 = 98.8%, p<0.0001]. Effect differences favored agalsidase beta compared to untreated patients; and c) for cerebrovascular complications, agalsidase alfa 11.1% [95% CI 0.058, 0.179; I2 = 70.5%, p = 0.0024]; agalsidase beta 3.5% [95% CI 0.024, 0.046; I2 = 0%, p = 0.4209]; and untreated patients 18.3% [95% CI 0.129, 0.245; I2 = 95% p < 0.0001]. Effect differences favored agalsidase beta over agalsidase alfa or untreated patients. A linear regression showed that Fabry patients receiving agalsidase alfa are more likely to have higher rates of composite endpoints compared to those receiving agalsidase beta. Agalsidase beta is associated to a significantly lower incidence of renal, cardiovascular and cerebrovascular events than no ERT, and to a significantly lower incidence of cerebrovascular events than agalsidase alfa. In view of these results, the use of agalsidase beta for preventing major organ complications related to AFD can be recommended.

Interventions for non-metastatic squamous cell carcinoma of the skin: systematic review and pooled analysis of observational studies

PubMed Central

Bath-Hextall, Fiona; Perkins, William; Stanton, Wendy; Leonardi-Bee, Jo

2013-01-01

Objectives To assess the effects of treatments for non-metastatic invasive squamous cell carcinoma (SCC) of the skin using evidence from observational studies, given the paucity of evidence from randomised controlled trials. Design Systematic review of observational studies. Data sources Medline, Embase, to December 2012. Review methods Observational studies of interventions for primary, non-metastatic, invasive, SCC of the skin that reported recurrence during follow-up, quality of life, initial response to treatment, adverse events, cosmetic appearance, or death from disease. Studies were excluded if data for primary cutaneous SCC was not separable from other data. Data were extracted independently by two reviewers. Meta-analysis was performed where appropriate using a random effects model to estimate the pooled proportion of an event with 95% confidence intervals. Results 118 publications were included, covering seven treatment modalities. Pooled estimates of recurrence of SCCs were lowest after cryotherapy (0.8% (95% confidence interval 0.1% to 2%)) and curettage and electrodesiccation (1.7% (0.5% to 3.4%)), but most treated SCCs were small, low risk lesions. After Mohs micrographic surgery, the pooled estimate of local recurrence during variable follow-up periods from 10 studies was 3.0% (2.2% to 3.9%), which was non-significantly lower than the pooled average local recurrence of 5.4% (2.5% to 9.1%) after standard surgical excision (12 studies), and 6.4% (3.0% to 11.0%) after external radiotherapy (7 studies). After an apparently successful initial response of SCCs to photodynamic therapy, pooled average recurrence of 26.4% (12.3% to 43.7%; 8 studies) was significantly higher than other treatments. Evidence was limited for laser treatment (1 study) and for topical and systemic treatments (mostly single case reports or small non-comparative series with limited follow-up). Conclusions Many observational studies have looked at different treatment modalities for SCC, but the evidence base for the effectiveness of these interventions is poor. Comparison of outcomes after different treatments should be interpreted cautiously owing to biases inherent in the types of study included, and lack of direct comparisons to enable the estimation of relative treatment effect. Further evidence is needed to develop a prognostic model and stratify individuals at high risk of developing SCC, to improve the evidence base for this common cancer and to optimise clinical management. Protocol registration International Prospective Register of Systematic Reviews (PROSPERO) registration number CRD42011001450. PMID:24191270

Quantification of Interbasin Transfers into the Addicks Reservoir during Hurricane Harvey

NASA Astrophysics Data System (ADS)

Sebastian, A.; Juan, A.; Gori, A.; Maulsby, F.; Bedient, P. B.

2017-12-01

Between August 25 and 30, Hurricane Harvey dropped unprecedented rainfall over southeast Texas causing widespread flooding in the City of Houston. Water levels in the Addicks and Barker reservoirs, built in the 1940s to protect downtown Houston, exceeded previous records by approximately 2 meters. Concerns regarding structural integrity of the dams and damage to neighbourhoods in within the reservoir pool resulted in controlled releases into Buffalo Bayou, flooding an estimated 4,000 additional structures downstream of the dams. In 2016, during the Tax Day it became apparent that overflows from Cypress Creek in northern Harris County substantially contribute to water levels in Addicks. Prior to this event, little was known about the hydrodynamics of this overflow area or about the additional stress placed on Addicks and Barker reservoirs due to the volume of overflow. However, this information is critical for determining flood risk in Addicks Watershed, and ultimately Buffalo Bayou. In this study, we utilize the recently developed HEC-RAS 2D model the interbasin transfer that occurs between Cypress Creek Watershed and Addicks Reservoir to quantify the volume and rate at which water from Cypress enters the reservoir during extreme events. Ultimately, the results of this study will help inform the official hydrologic models used by HCFCD to determine reservoir operation during future storm events and better inform residents living in or above the reservoir pool about their potential flood risk.

Thromboembolism in adults with primary immune thrombocytopenia: a systematic literature review and meta-analysis.

PubMed

Doobaree, Indraraj Umesh; Nandigam, Raghava; Bennett, Dimitri; Newland, Adrian; Provan, Drew

2016-10-01

Adults with primary immune thrombocytopenia (ITP) may be susceptible to thromboembolism (TE). The objective of this systematic review was to evaluate studies that reported the prevalence and risk of developing TE in the ITP population from ITP diagnosis and splenectomy. We searched several bibliographic databases and included 29 studies. Using meta-analytical techniques, the pooled prevalence of TE before ITP diagnosis was 7.84% (arterial 6.25%; venous 1.95%). The pooled 'annualised' cumulative incidence (without prior TE) and cumulative risk (irrespective of prior TE) were 1.29%/yr and 3.00%/yr, respectively. Splenectomised patients had pooled cumulative risk of arterial TE (ATE) and venous TE (VTE) of 0.19%/yr and 1.10%/yr, respectively. In cohorts, regardless of a history of TE, the pooled relative risk (RR) of any TE was 1.60 (1.34, 1.86) for ITP vs. ITP-free individuals [arterial: 1.52 (1.25, 1.80); venous: 1.70 (0.96, 2.43)]. Splenectomised patients were at higher risk of venous events, pooled RR 2.39 (1.61, 3.17). To conclude, we found an increased risk of TE (mainly ATE) among ITP individuals and a higher risk of VTEs after splenectomy. How intrinsic (ITP pathophysiology, age, gender) and extrinsic factors (treatment) contribute to this risk could not be investigated here but is a task for future studies. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Assessing the general safety and tolerability of vildagliptin: value of pooled analyses from a large safety database versus evaluation of individual studies

PubMed Central

Schweizer, Anja; Dejager, Sylvie; Foley, James E; Kothny, Wolfgang

2011-01-01

Aim: Analyzing safety aspects of a drug from individual studies can lead to difficult-to-interpret results. The aim of this paper is therefore to assess the general safety and tolerability, including incidences of the most common adverse events (AEs), of vildagliptin based on a large pooled database of Phase II and III clinical trials. Methods: Safety data were pooled from 38 studies of ≥12 to ≥104 weeks’ duration. AE profiles of vildagliptin (50 mg bid; N = 6116) were evaluated relative to a pool of comparators (placebo and active comparators; N = 6210). Absolute incidence rates were calculated for all AEs, serious AEs (SAEs), discontinuations due to AEs, and deaths. Results: Overall AEs, SAEs, discontinuations due to AEs, and deaths were all reported with a similar frequency in patients receiving vildagliptin (69.1%, 8.9%, 5.7%, and 0.4%, respectively) and patients receiving comparators (69.0%, 9.0%, 6.4%, and 0.4%, respectively), whereas drug-related AEs were seen with a lower frequency in vildagliptin-treated patients (15.7% vs 21.7% with comparators). The incidences of the most commonly reported specific AEs were also similar between vildagliptin and comparators, except for increased incidences of hypoglycemia, tremor, and hyperhidrosis in the comparator group related to the use of sulfonylureas. Conclusions: The present pooled analysis shows that vildagliptin was overall well tolerated in clinical trials of up to >2 years in duration. The data further emphasize the value of a pooled analysis from a large safety database versus assessing safety and tolerability from individual studies. PMID:21415917

The pool of preactivated Lck in the initiation of T-cell signaling: a critical re-evaluation of the Lck standby model.

PubMed

Ballek, Ondřej; Valečka, Jan; Manning, Jasper; Filipp, Dominik

2015-04-01

The initiation of T-cell receptor (TCR) signaling, based on the cobinding of TCR and CD4-Lck heterodimer to a peptide-major histocompatibility complex II on antigen presenting cells, represents a classical model of T-cell signaling. What is less clear however, is the mechanism which translates TCR engagement to the phosphorylation of immunoreceptor tyrosine-based activation motifs on CD3 chains and how this event is coupled to the delivery of Lck function. Recently proposed 'standby model of Lck' posits that resting T-cells contain an abundant pool of constitutively active Lck (pY394(Lck)) required for TCR triggering, and this amount, upon TCR engagement, remains constant. Here, we show that although maintenance of the limited pool of pY394(Lck) is necessary for the generation of TCR proximal signals in a time-restricted fashion, the total amount of this pool, ~2%, is much smaller than previously reported (~40%). We provide evidence that this dramatic discrepancy in the content of pY394(Lck)is likely the consequence of spontaneous phosphorylation of Lck that occurred after cell solubilization. Additional discrepancies can be accounted for by the sensitivity of different pY394(Lck)-specific antibodies and the type of detergents used. These data suggest that reagents and conditions used for the quantification of signaling parameters must be carefully validated and interpreted. Thus, the limited size of pY394(Lck) pool in primary T-cells invites a discussion regarding the adjustment of the quantitative parameters of the standby model of Lck and reevaluation of the mechanism by which this pool contributes to the generation of proximal TCR signaling.

Non-equilbrium dynamics of ecosystem processes in a changing world

NASA Astrophysics Data System (ADS)

Reid, Joseph Pignatello

The relatively mild and stable climate of the last 10,000 years betrays a history of environmental variability and rapid changes. Humans have recently accelerated global environmental change, ushering in the Anthropocene. Meeting accelerating demands for food, energy, and goods and services has accelerated species extinctions, shows of reactive nitrogen and phosphorus, and warming of the atmosphere. I address the over- arching question of how ecosystems will respond to changing and variable environments through several focused studies. Each study examines an ecosystem response to ex- pected environmental changes in the future. To address how the changing environment affects the sizes and turnover rates of slowly and quickly cycling soil carbon pools, I analyzed the responses of grassland soils to simulated species diversity loss, increased deposition of nitrogen and increased atmospheric CO2. I used a soil respiration experiment to fit models of soil carbon pool turnover to respired carbon dioxide. Species diversity, nitrogen deposition and atmospheric CO2 had no effect on the total soil carbon after 8 years of treatments. Although total soil carbon did not change, the rates of cycling in the fast and slow pools changed in response to elevated CO2 and diversity loss treatments. Nitrogen treatments increased the size of the slowly cycling carbon pool. Precipitation variability has increased around most of the world since the industrial revolution. I used plant mesocosms in a greenhouse experiment to manipulate rainfall variability and mycorrhizal associations. I hypothesized that 1) rewetting events re- sult in higher nitrogen uxes from dry soils than moist soils, 2) a repeated pattern of events caused by low-frequency simulated rainfall results in higher nitrogen uxes and 3) the better ability of ectomycorrhizal fungi relative to arbuscular mycorrhizal fungi to decompose and assimilate organic nitrogen reduces leaching losses of nitrogen caused by both rewetting events and patterns of repeated events. In response to individual rewetting events, drier soils released more nitrate and total nitrogen than wetter soils. Ectomycorrhizal treatments slightly reduced the effect of antecedent soil moisture on total nitrogen and nitrate losses from rewetting events. This supports my hypotheses iii that drier soils release more nitrogen after rainfall events and that ectomycorrhizal asso- ciations can reduce nitrogen losses associated with soil rewetting events. However, only ammonium increased in proportion to the variance in rainfall quantity and mycorrhizal treatments had no effect, largely refuting my hypothesis that soils would release more nitrogen when exposed to higher variability patterns of rainfall. The current pressures that humans place on the environment are only expected to increase as populations and incomes continue to climb. The more than 9 billion peo- ple expected on the planet by 2050 require food, energy, shelter and other goods and services. Historically, producing those benefits has resulted in environmental damage, especially nitrogen pollution through agricultural fertilizers, atmospheric nitrogen de- position and human waste. I developed a model to test the effectiveness of various technologies and strategies to reduce the environmental harms associated with meeting the needs of human well-being. I tested the effects of increased crop yields through genetic gains, increased nutrient efficiency in agricultural systems, reduced meat con- sumption, reduced food waste and improved wastewater treatment on nitrogen yield. The tested levers were mildly effective at reducing nitrogen yield from the baseline busi- ness as usual (BAU) scenario, but still resulted in at least 15% greater nitrogen yield than the present. Applied in combination, in the 'Super Ag' scenario, the levers out performed the sum of their contributions when applied singly. Some levers were more effective in some places than others. Taken together, these results suggest that there is no one solution, and that solutions will be most effective when developed for local conditions and applied in combination.

Dynamics of nitrate and chloride during storm events in agricultural catchments with different subsurface drainage intensity (Indiana, USA)

USDA-ARS?s Scientific Manuscript database

Grids of perforated pipe buried beneath many poorly drained agricultural fields in the Midwestern U.S. are believed to “short circuit” pools of nitrate-laden soil water and shallow groundwater directly into streams that eventually discharge to the Mississippi River. Although much is known about the ...

A decade of belowground reorganization following multiple disturbances in a subtropical wet forest

Treesearch

Y.A. Teh; W.L. Silver; F.N. Scatena

2009-01-01

Humid tropical forests are dynamic ecosystems that experience multiple and overlapping disturbance events that vary in frequency, intensity, and spatial extent. Here we report the results of a 10-year study investigating the effects of forest clearing and multiple hurricanes on ecosystem carbon reservoirs, nutrient pools and vegetation. The aboveground plant community...

26 CFR 44.4401-2 - Person liable for tax.

Code of Federal Regulations, 2010 CFR

2010-04-01

... event or a contest is liable for the tax on any such wager accepted by him. Every person who operates a wagering pool or lottery conducted for profit is liable for the tax with respect to any wager or... profit, he shall, notwithstanding such lay-off, be liable for the tax on the wagers or contributions...

STS_135_Russia

NASA Image and Video Library

2011-03-30

JSC2011-E-040332 (30 March 2011) --- NASA astronauts Rex Walheim and Chris Ferguson visit Red Square in Moscow on March 30, 2011. The crew of the final shuttle mission traveled to Moscow for a suit fit check of their Russian Soyuz suits which would be required in the event of an emergency. Photo credit: NASA Photo/Houston Chronicle, Smiley N. Pool

STS_135_Russia

NASA Image and Video Library

2011-03-30

JSC2011-E-040330 (30 March 2011) --- NASA astronaut Chris Ferguson (foreground), STS-135 commander, visits Red Square in Moscow on March 30, 2011. The crew of the final shuttle mission traveled to Moscow for a suit fit check of their Russian Sokol suits which would be required in the event of an emergency. Photo credit: NASA Photo/Houston Chronicle, Smiley N. Pool

STS_135_Russia

NASA Image and Video Library

2011-03-29

NASA astronaut Chris Ferguson undergoes a fit check of his Sokol space suit at the Zvezda facility on Tuesday, March 29, 2011, in Moscow. The crew of the final shuttle mission traveled to Moscow for a suit fit check of their Russian Soyuz suits that will be required in the event of an emergency. ( NASA Photo / Houston Chronicle, Smiley N. Pool )

STS_135_Russia

NASA Image and Video Library

2011-03-28

NASA astronaut Rex Walheim undergoes a fit check of his Sokol space suit at the Zvezda facility on Monday, March 28, 2011, in Moscow. The crew of the final shuttle mission traveled to Moscow for a suit fit check of their Russian Soyuz suits that will be required in the event of an emergency. ( NASA Photo / Houston Chronicle, Smiley N. Pool )

Genetic relationships among American donkey populations: insights into the process of colonization.

PubMed

Jordana, J; Ferrando, A; Miró, J; Goyache, F; Loarca, A; Martínez López, O R; Canelón, J L; Stemmer, A; Aguirre, L; Lara, M A C; Álvarez, L A; Llambí, S; Gómez, N; Gama, L T; Nóvoa, M F; Martínez, R D; Pérez, E; Sierra, A; Contreras, M A; Guastella, A M; Marletta, D; Arsenos, G; Curik, I; Landi, V; Martínez, A; Delgado, J V

2016-04-01

This study presents the first insights into the genetic diversity and structure of the American donkey metapopulation. The primary objectives were to detect the main structural features underlying variability among American donkey populations, identify boundaries between differentiated gene pools, and draw the main colonization pathways since the introduction of donkeys into America in the 15th century. A panel of 14 microsatellite markers was applied for genotyping 350 American donkeys from 13 countries. The genetic structure of this metapopulation was analysed using descriptive statistics and Bayesian model-based methods. These populations were then compared to a database containing information on 476 individuals from 11 European breeds to identify the most likely ancestral donor populations. Results showed the presence of two distinct genetic pools, with confluence of the two in Colombia. The southern pool showed a unique genetic signature subsequent to an older founder event, but lacked any significant influence of modern gene flow from Europe. The northern pool, conversely, may have retained more ancestral polymorphisms and/or have experienced modern gene flow from Spanish breeds. The Andalusian and, to a lesser extent, the Catalan breeds have left a more pronounced footprint in some of the American donkey populations analysed. © 2015 Blackwell Verlag GmbH.

STS-60 Cosmonauts in Weightless Environment Training Facility (WETF) training

NASA Image and Video Library

1993-01-07

S93-26022 (Feb 1993) --- Russian cosmonaut Sergei Krikalev maneuvers a small life raft during bailout training at the Johnson Space Center's (JSC) Weightless Environment Training Facility (WET-F). Shuttle crew members frequently utilize the 25-ft. deep pool to learn proper procedures to follow in the event of emergency egress from their Space Shuttle via the escape pole system. Krikalev is one of two cosmonauts in training for the STS-60 mission. One of the two will serve as primary payload specialist with the other filling an alternate's role. This pool and the facility in which it is housed are titled the WET-F because they are also used by astronauts rehearsing both mission-specific and contingency extravehicular activities (EVA).

STS-65 Mission Specialist Chiao floats in a single person raft in JSC's WETF

NASA Technical Reports Server (NTRS)

1994-01-01

Having just deployed a small, single-person life raft, astronaut and STS-65 Mission Specialist Leroy Chiao, outfitted in a launch and entry suit (LES) and launch and entry helmet (LEH), floats in a 25-feet deep pool at the Johnson Space Center (JSC). The astronaut was in the Weightless Environment Training Facility (WETF) Bldg 29 pool for a training exercise, designed to familiarize crewmembers with procedures to call on in the event of an emergency egress situation with the Space Shuttle. Chiao will join five other NASA astronauts and a Japanese payload specialist for the second International Microgravity Laboratory 2 (IML-2) mission aboard the Space Shuttle Columbia, Orbiter Vehicle (OV) 102, later this year.

Imputing forest carbon stock estimates from inventory plots to a nationally continuous coverage

PubMed Central

2013-01-01

The U.S. has been providing national-scale estimates of forest carbon (C) stocks and stock change to meet United Nations Framework Convention on Climate Change (UNFCCC) reporting requirements for years. Although these currently are provided as national estimates by pool and year to meet greenhouse gas monitoring requirements, there is growing need to disaggregate these estimates to finer scales to enable strategic forest management and monitoring activities focused on various ecosystem services such as C storage enhancement. Through application of a nearest-neighbor imputation approach, spatially extant estimates of forest C density were developed for the conterminous U.S. using the U.S.’s annual forest inventory. Results suggest that an existing forest inventory plot imputation approach can be readily modified to provide raster maps of C density across a range of pools (e.g., live tree to soil organic carbon) and spatial scales (e.g., sub-county to biome). Comparisons among imputed maps indicate strong regional differences across C pools. The C density of pools closely related to detrital input (e.g., dead wood) is often highest in forests suffering from recent mortality events such as those in the northern Rocky Mountains (e.g., beetle infestations). In contrast, live tree carbon density is often highest on the highest quality forest sites such as those found in the Pacific Northwest. Validation results suggest strong agreement between the estimates produced from the forest inventory plots and those from the imputed maps, particularly when the C pool is closely associated with the imputation model (e.g., aboveground live biomass and live tree basal area), with weaker agreement for detrital pools (e.g., standing dead trees). Forest inventory imputed plot maps provide an efficient and flexible approach to monitoring diverse C pools at national (e.g., UNFCCC) and regional scales (e.g., Reducing Emissions from Deforestation and Forest Degradation projects) while allowing timely incorporation of empirical data (e.g., annual forest inventory). PMID:23305341

Gaining efficiency by centralising the corporate business resiliency process.

PubMed

Martinez, Robert

2017-06-01

Organisations have compiled many business continuity plans over the years in response to uncontrollable events and natural disasters. As the types of threats increase, even more plans are being created. Unfortunately, many corporations do not communicate the existence of these various plans outside of their centre of excellence. Creating a centralised oversight of your business resiliency process brings many benefits, including greater awareness, a bigger pool of expertise, common terminology and reducing the chances of redundant efforts. Having an overarching corporate response plan in place makes it possible to have high-level leadership trained and ready in case an extreme event occurs.

A billion years of metasomatic alteration of the Kaapvaal SCLM encapsulated in fibrous diamonds

NASA Astrophysics Data System (ADS)

Weiss, Yaakov; Goldstein, Steven; Class, Cornelia; Winckler, Gisela

2017-04-01

Constraining the nature and timing of metasomatic events by C-O-H fluids in the sub-continental lithospheric mantle (SCLM) is an ongoing challenge in our understanding of the SCLM history. 'Fibrous' diamonds, which rapidly grow during such fluid-rock interaction, commonly encapsulate the C-O-H fluid metasomatic agents, which are trapped and encapsulated as μm-scale high-density fluid (HDF) inclusions and can be directly sampled. They thus offer a unique opportunity to investigate metasomatic events involving C-O-H fluids in the SCLM. We analyzed major and trace elements and the helium content and isotopic composition of the HDFs included in a set of diamonds from the DeBeers-Pool and Finsch kimberlites in the Kaapvaal craton, South Africa. Saline HDF micro-inclusions in 3 of the DeBeers diamonds and in 2 from Finsch have very similar major and trace element compositions, suggesting they formed in related metasomatic events. They are characterized by high alkalis (K, Rb and Cs), Ba and LREEs compared to Th, U, Nb and Ta, and by Ti, Zr, Hf and Y negative anomalies relative to REEs of similar compatibility. Their 3He/4He ratios vary between 3-4 Ra. Plotting the 3 DeBeers-Pool diamonds on an 4He/3He vs 238U/3He diagram defines an 'isochron' with an age of 96±45 Ma. This result represents the first radiometric age reported for fibrous diamonds and the C-O-H mantle fluids they carry. In addition, 1 diamond from DeBeers-Pool has silicic microinclusion compositions while 2 diamonds from Finsch carry carbonatitic HDFs. These diamonds display more radiogenic 3He/4He ratios between 0.07-0.6 Ra, which suggests formation during earlier and different metasomatic events. Using the measured U, Th, 4He and 3He content of these diamonds, and the equation for 4He production by U and Th, we calculate 3He/4He ratios as a function of time. Assuming that the HDFs initial R/Ra values varied between 3-11, representing common values for MORB, the SCLM and subducted components, the silicic and carbonatitic HDFs signify two older metasomatic events that took place in the Kaapvaal lithosphere at 350 and 850 Ma, respectively. Thus, our new data reveal 3 episodes of chemical changes in the Kaapvaal craton SCLM during the last 1 Ga, each by a different metasomatic agent. The youngest episodes indicate direct relationships between highly-saline fluid metasomatism, fibrous diamond formation and late-Mesozoic kimberlite eruptions, while the older silicic and carbonatitic metasomatic events may be related to the regional Namaqua-Natal Orogeny and Damara Orogeny at 1 Ga and 500 Ma, respectively.

Amyloid-β protein precursor regulates phosphorylation and cellular compartmentalization of microtubule associated protein tau.

PubMed

Nizzari, Mario; Barbieri, Federica; Gentile, Maria Teresa; Passarella, Daniela; Caorsi, Calentina; Diaspro, Alberto; Taglialatela, Maurizio; Pagano, Aldo; Colucci-D'Amato, Luca; Florio, Tullio; Russo, Claudio

2012-01-01

Tau is a multifunctional protein detected in different cellular compartments in neuronal and non-neuronal cells. When hyperphosphorylated and aggregated in atrophic neurons, tau is considered the culprit for neuronal death in familial and sporadic tauopathies. With regards to Alzheimer's disease (AD) pathogenesis, it is not yet established whether entangled tau represents a cause or a consequence of neurodegeneration. In fact, it is unquestionably accepted that amyloid-β protein precursor (AβPP) plays a pivotal role in the genesis of the disease, and it is postulated that the formation of toxic amyloid-β peptides from AβPP is the primary event that subsequently induces abnormal tau phosphorylation. In this work, we show that in the brain of AD patients there is an imbalance between the nuclear and the cytoskeletal pools of phospho-tau. We observed that in non-AD subjects, there is a stable pool of phospho-tau which remains strictly confined to neuronal nuclei, while nuclear localization of phospho-tau is significantly underrepresented in neurons of AD patients bearing neurofibrillary tangles. A specific phosphorylation of tau is required during mitosis in vitro and in vivo, likely via a Grb2-ERK1/2 signaling cascade. In differentiated neuronal A1 cells, the overexpression of AβPP modulates tau phosphorylation, altering the ratio between cytoskeletal and nuclear pools, and correlates with cell death. Altogether our data provide evidence that AβPP, in addition to amyloid formation, modulates the phosphorylation of tau and its subcellular compartmentalization, an event that may lead to the formation of neurofibrillary tangles and to neurodegeneration when occurring in postmitotic neurons.

Traffic calming for the prevention of road traffic injuries: systematic review and meta-analysis.

PubMed

Bunn, F; Collier, T; Frost, C; Ker, K; Roberts, I; Wentz, R

2003-09-01

To assess whether area-wide traffic calming schemes can reduce road crash related deaths and injuries. Systematic review and meta-analysis. Cochrane Injuries Group Specialised Register, Cochrane Central Register of Controlled Trials, Medline, EMBASE, Sociological Abstracts Science (and social science) citation index, National Technical Information service, Psychlit, Transport Research Information Service, International Road Research Documentation, and Transdoc, and web sites of road safety organisation were searched; experts were contacted, conference proceedings were handsearched, and relevant reference lists were checked. Randomised controlled trials, and controlled before/after studies of area-wide traffic calming schemes designed to discourage and slow down through traffic on residential roads. Data were collected on road user deaths, injuries, and traffic crashes. For each study rate ratios were calculated, the ratio of event rates before and after intervention in the traffic calmed area divided by the corresponding ratio of event rates in the control area, which were pooled to give an overall estimate using a random effects model. Sixteen controlled before/after studies met our inclusion criteria. Eight studies reported the number of road user deaths: pooled rate ratio 0.63 (95% confidence interval (CI) 0.14 to 2.59). Sixteen studies reported the number of injuries (fatal and non-fatal): pooled rate ratio 0.89 (95% CI 0.80 to 1.00). All studies were in high income countries. Area-wide traffic calming in towns and cities has the potential to reduce road traffic injuries. However, further rigorous evaluations of this intervention are needed, especially in low and middle income countries.

Regional Frequency and Uncertainty Analysis of Extreme Precipitation in Bangladesh

NASA Astrophysics Data System (ADS)

Mortuza, M. R.; Demissie, Y.; Li, H. Y.

2014-12-01

Increased frequency of extreme precipitations, especially those with multiday durations, are responsible for recent urban floods and associated significant losses of lives and infrastructures in Bangladesh. Reliable and routinely updated estimation of the frequency of occurrence of such extreme precipitation events are thus important for developing up-to-date hydraulic structures and stormwater drainage system that can effectively minimize future risk from similar events. In this study, we have updated the intensity-duration-frequency (IDF) curves for Bangladesh using daily precipitation data from 1961 to 2010 and quantified associated uncertainties. Regional frequency analysis based on L-moments is applied on 1-day, 2-day and 5-day annual maximum precipitation series due to its advantages over at-site estimation. The regional frequency approach pools the information from climatologically similar sites to make reliable estimates of quantiles given that the pooling group is homogeneous and of reasonable size. We have used Region of influence (ROI) approach along with homogeneity measure based on L-moments to identify the homogenous pooling groups for each site. Five 3-parameter distributions (i.e., Generalized Logistic, Generalized Extreme value, Generalized Normal, Pearson Type Three, and Generalized Pareto) are used for a thorough selection of appropriate models that fit the sample data. Uncertainties related to the selection of the distributions and historical data are quantified using the Bayesian Model Averaging and Balanced Bootstrap approaches respectively. The results from this study can be used to update the current design and management of hydraulic structures as well as in exploring spatio-temporal variations of extreme precipitation and associated risk.

Variability in the combustion-derived fraction of urban humidity in Salt Lake City winter estimated from stable water vapor isotopes and its relationship to atmospheric stability and inversion structure

NASA Astrophysics Data System (ADS)

Fiorella, R.; Bares, R.; Lin, J. C.; Strong, C.; Bowen, G. J.

2017-12-01

Water released from the combustion of fossil fuels, while a negligible part of the global hydrological cycle, may be a significant contributor to urban humidity as fossil fuel emissions are strongly concentrated in space and time. The fraction of urban humidity comprised of combustion-derived vapor (CDV) cannot be observed through humidity measurements alone. However, the distinct stable isotopic composition of CDV, which arises from the reaction of 18O-enriched atmospheric O2 with 2H-depleted organic molecules, represents a promising method to apportion observed humidity between CDV and advected vapor. We apply stable water vapor isotopes to investigate variability in CDV amount and its relationship to atmospheric conditions in Salt Lake City, Utah. The Salt Lake Valley experiences several periods of atmospheric stratification during winter known as cold air pools, during which concentrations of CDV and pollutants can be markedly elevated due to reduced atmospheric mixing. Therefore, the SLV during winter is an ideal place to investigate variability in CDV fraction across a spectrum of boundary layer conditions, ranging from well-mixed to very stable. We present water vapor isotope data from four winters (2013-2017) from the top of a 30 m building on the University of Utah (U of U) Campus. Additionally, we present water vapor isotope data from the summit of Hidden Peak from the 2016-2017 winter, 25 km SE and 2000 m above the U of U site. The Hidden Peak site is consistently above the cold air pool emplaced in the SLV during stable events. We find the expression of the CDV signal in the valley is related to the atmospheric structure of the cold air pools in the SLV, and that the fraction of CDV inferred in the valley is likely related to the mixing height within the cold air pool. Furthermore, we find that patterns between the Hidden Peak and U of U sites during inversion events may record the large-scale atmospheric dynamics promoting emplacement of the cold air pool in the SLV. Further refinements of CDV estimation through stable isotope methods will bring improved mechanistic understanding of the role of CDV in the urban hydrological cycle and improve model simulations of urban environments.

Impact of including or excluding both-armed zero-event studies on using standard meta-analysis methods for rare event outcome: a simulation study

PubMed Central

Cheng, Ji; Pullenayegum, Eleanor; Marshall, John K; Thabane, Lehana

2016-01-01

Objectives There is no consensus on whether studies with no observed events in the treatment and control arms, the so-called both-armed zero-event studies, should be included in a meta-analysis of randomised controlled trials (RCTs). Current analytic approaches handled them differently depending on the choice of effect measures and authors' discretion. Our objective is to evaluate the impact of including or excluding both-armed zero-event (BA0E) studies in meta-analysis of RCTs with rare outcome events through a simulation study. Method We simulated 2500 data sets for different scenarios varying the parameters of baseline event rate, treatment effect and number of patients in each trial, and between-study variance. We evaluated the performance of commonly used pooling methods in classical meta-analysis—namely, Peto, Mantel-Haenszel with fixed-effects and random-effects models, and inverse variance method with fixed-effects and random-effects models—using bias, root mean square error, length of 95% CI and coverage. Results The overall performance of the approaches of including or excluding BA0E studies in meta-analysis varied according to the magnitude of true treatment effect. Including BA0E studies introduced very little bias, decreased mean square error, narrowed the 95% CI and increased the coverage when no true treatment effect existed. However, when a true treatment effect existed, the estimates from the approach of excluding BA0E studies led to smaller bias than including them. Among all evaluated methods, the Peto method excluding BA0E studies gave the least biased results when a true treatment effect existed. Conclusions We recommend including BA0E studies when treatment effects are unlikely, but excluding them when there is a decisive treatment effect. Providing results of including and excluding BA0E studies to assess the robustness of the pooled estimated effect is a sensible way to communicate the results of a meta-analysis when the treatment effects are unclear. PMID:27531725

Priming with a simplified intradermal HIV-1 DNA vaccine regimen followed by boosting with recombinant HIV-1 MVA vaccine is safe and immunogenic: a phase IIa randomized clinical trial.

PubMed

Munseri, Patricia J; Kroidl, Arne; Nilsson, Charlotta; Joachim, Agricola; Geldmacher, Christof; Mann, Philipp; Moshiro, Candida; Aboud, Said; Lyamuya, Eligius; Maboko, Leonard; Missanga, Marco; Kaluwa, Bahati; Mfinanga, Sayoki; Podola, Lilly; Bauer, Asli; Godoy-Ramirez, Karina; Marovich, Mary; Moss, Bernard; Hoelscher, Michael; Gotch, Frances; Stöhr, Wolfgang; Stout, Richard; McCormack, Sheena; Wahren, Britta; Mhalu, Fred; Robb, Merlin L; Biberfeld, Gunnel; Sandström, Eric; Bakari, Muhammad

2015-01-01

Intradermal priming with HIV-1 DNA plasmids followed by HIV-1MVA boosting induces strong and broad cellular and humoral immune responses. In our previous HIVIS-03 trial, we used 5 injections with 2 pools of HIV-DNA at separate sites for each priming immunization. The present study explores whether HIV-DNA priming can be simplified by reducing the number of DNA injections and administration of combined versus separated plasmid pools. In this phase IIa, randomized trial, priming was performed using 5 injections of HIV-DNA, 1000 μg total dose, (3 Env and 2 Gag encoding plasmids) compared to two "simplified" regimens of 2 injections of HIV-DNA, 600 μg total dose, of Env- and Gag-encoding plasmid pools with each pool either administered separately or combined. HIV-DNA immunizations were given intradermally at weeks 0, 4, and 12. Boosting was performed intramuscularly with 108 pfu HIV-MVA at weeks 30 and 46. 129 healthy Tanzanian participants were enrolled. There were no differences in adverse events between the groups. The proportion of IFN-γ ELISpot responders to Gag and/or Env peptides after the second HIV-MVA boost did not differ significantly between the groups primed with 2 injections of combined HIV-DNA pools, 2 injections with separated pools, and 5 injections with separated pools (90%, 97% and 97%). There were no significant differences in the magnitude of Gag and/or Env IFN-γ ELISpot responses, in CD4+ and CD8+ T cell responses measured as IFN-γ/IL-2 production by intracellular cytokine staining (ICS) or in response rates and median titers for binding antibodies to Env gp160 between study groups. A simplified intradermal vaccination regimen with 2 injections of a total of 600 μg with combined HIV-DNA plasmids primed cellular responses as efficiently as the standard regimen of 5 injections of a total of 1000 μg with separated plasmid pools after boosting twice with HIV-MVA. World Health Organization International Clinical Trials Registry Platform PACTR2010050002122368.

Large-scale pattern of genetic differentiation within African rainforest trees: insights on the roles of ecological gradients and past climate changes on the evolution of Erythrophleum spp (Fabaceae).

PubMed

Duminil, Jerome; Brown, Richard P; Ewédjè, Eben-Ezer B K; Mardulyn, Patrick; Doucet, Jean-Louis; Hardy, Olivier J

2013-09-12

The evolutionary events that have shaped biodiversity patterns in the African rainforests are still poorly documented. Past forest fragmentation and ecological gradients have been advocated as important drivers of genetic differentiation but their respective roles remain unclear. Using nuclear microsatellites (nSSRs) and chloroplast non-coding sequences (pDNA), we characterised the spatial genetic structure of Erythrophleum (Fabaceae) forest trees in West and Central Africa (Guinea Region, GR). This widespread genus displays a wide ecological amplitude and taxonomists recognize two forest tree species, E. ivorense and E. suaveolens, which are difficult to distinguish in the field and often confused. Bayesian-clustering applied on nSSRs of a blind sample of 648 specimens identified three major gene pools showing no or very limited introgression. They present parapatric distributions correlated to rainfall gradients and forest types. One gene pool is restricted to coastal evergreen forests and corresponds to E. ivorense; a second one is found in gallery forests from the dry forest zone of West Africa and North-West Cameroon and corresponds to West-African E. suaveolens; the third gene pool occurs in semi-evergreen forests and corresponds to Central African E. suaveolens. These gene pools have mostly unique pDNA haplotypes but they do not form reciprocally monophyletic clades. Nevertheless, pDNA molecular dating indicates that the divergence between E. ivorense and Central African E. suaveolens predates the Pleistocene. Further Bayesian-clustering applied within each major gene pool identified diffuse genetic discontinuities (minor gene pools displaying substantial introgression) at a latitude between 0 and 2°N in Central Africa for both species, and at a longitude between 5° and 8°E for E. ivorense. Moreover, we detected evidence of past population declines which are consistent with historical habitat fragmentation induced by Pleistocene climate changes. Overall, deep genetic differentiation (major gene pools) follows ecological gradients that may be at the origin of speciation, while diffuse differentiation (minor gene pools) are tentatively interpreted as the signature of past forest fragmentation induced by past climate changes.

Large-scale pattern of genetic differentiation within African rainforest trees: insights on the roles of ecological gradients and past climate changes on the evolution of Erythrophleum spp (Fabaceae)

PubMed Central

2013-01-01

Background The evolutionary events that have shaped biodiversity patterns in the African rainforests are still poorly documented. Past forest fragmentation and ecological gradients have been advocated as important drivers of genetic differentiation but their respective roles remain unclear. Using nuclear microsatellites (nSSRs) and chloroplast non-coding sequences (pDNA), we characterised the spatial genetic structure of Erythrophleum (Fabaceae) forest trees in West and Central Africa (Guinea Region, GR). This widespread genus displays a wide ecological amplitude and taxonomists recognize two forest tree species, E. ivorense and E. suaveolens, which are difficult to distinguish in the field and often confused. Results Bayesian-clustering applied on nSSRs of a blind sample of 648 specimens identified three major gene pools showing no or very limited introgression. They present parapatric distributions correlated to rainfall gradients and forest types. One gene pool is restricted to coastal evergreen forests and corresponds to E. ivorense; a second one is found in gallery forests from the dry forest zone of West Africa and North-West Cameroon and corresponds to West-African E. suaveolens; the third gene pool occurs in semi-evergreen forests and corresponds to Central African E. suaveolens. These gene pools have mostly unique pDNA haplotypes but they do not form reciprocally monophyletic clades. Nevertheless, pDNA molecular dating indicates that the divergence between E. ivorense and Central African E. suaveolens predates the Pleistocene. Further Bayesian-clustering applied within each major gene pool identified diffuse genetic discontinuities (minor gene pools displaying substantial introgression) at a latitude between 0 and 2°N in Central Africa for both species, and at a longitude between 5° and 8°E for E. ivorense. Moreover, we detected evidence of past population declines which are consistent with historical habitat fragmentation induced by Pleistocene climate changes. Conclusions Overall, deep genetic differentiation (major gene pools) follows ecological gradients that may be at the origin of speciation, while diffuse differentiation (minor gene pools) are tentatively interpreted as the signature of past forest fragmentation induced by past climate changes. PMID:24028582

The effectiveness of computerized order entry at reducing preventable adverse drug events and medication errors in hospital settings: a systematic review and meta-analysis

PubMed Central

2014-01-01

Background The Health Information Technology for Economic and Clinical Health (HITECH) Act subsidizes implementation by hospitals of electronic health records with computerized provider order entry (CPOE), which may reduce patient injuries caused by medication errors (preventable adverse drug events, pADEs). Effects on pADEs have not been rigorously quantified, and effects on medication errors have been variable. The objectives of this analysis were to assess the effectiveness of CPOE at reducing pADEs in hospital-related settings, and examine reasons for heterogeneous effects on medication errors. Methods Articles were identified using MEDLINE, Cochrane Library, Econlit, web-based databases, and bibliographies of previous systematic reviews (September 2013). Eligible studies compared CPOE with paper-order entry in acute care hospitals, and examined diverse pADEs or medication errors. Studies on children or with limited event-detection methods were excluded. Two investigators extracted data on events and factors potentially associated with effectiveness. We used random effects models to pool data. Results Sixteen studies addressing medication errors met pooling criteria; six also addressed pADEs. Thirteen studies used pre-post designs. Compared with paper-order entry, CPOE was associated with half as many pADEs (pooled risk ratio (RR) = 0.47, 95% CI 0.31 to 0.71) and medication errors (RR = 0.46, 95% CI 0.35 to 0.60). Regarding reasons for heterogeneous effects on medication errors, five intervention factors and two contextual factors were sufficiently reported to support subgroup analyses or meta-regression. Differences between commercial versus homegrown systems, presence and sophistication of clinical decision support, hospital-wide versus limited implementation, and US versus non-US studies were not significant, nor was timing of publication. Higher baseline rates of medication errors predicted greater reductions (P < 0.001). Other context and implementation variables were seldom reported. Conclusions In hospital-related settings, implementing CPOE is associated with a greater than 50% decline in pADEs, although the studies used weak designs. Decreases in medication errors are similar and robust to variations in important aspects of intervention design and context. This suggests that CPOE implementation, as subsidized under the HITECH Act, may benefit public health. More detailed reporting of the context and process of implementation could shed light on factors associated with greater effectiveness. PMID:24894078

A statistical power analysis of woody carbon flux from forest inventory data

Treesearch

James A. Westfall; Christopher W. Woodall; Mark A. Hatfield

2013-01-01

At a national scale, the carbon (C) balance of numerous forest ecosystem C pools can be monitored using a stock change approach based on national forest inventory data. Given the potential influence of disturbance events and/or climate change processes, the statistical detection of changes in forest C stocks is paramount to maintaining the net sequestration status of...

A rare Uroglena bloom in Beaver Lake, Arkansas, spring 2015

USGS Publications Warehouse

Green, William R.; Hufhines, Brad

2017-01-01

A combination of factors triggered a Uroglena volvox bloom and taste and odor event in Beaver Lake, a water-supply reservoir in northwest Arkansas, in late April 2015. Factors contributing to the bloom included increased rainfall and runoff containing increased concentrations of dissolved organic carbon, followed by a stable pool, low nutrient concentrations, and an expansion of lake surface area and littoral zone. This was the first time U. volvox was identified in Beaver Lake and the first time it was recognized as a source of taste and odor. Routine water quality samples happened to be collected by the US Geological Survey and the Beaver Water District throughout the reservoir during the bloom—. Higher than normal rainfall in March 2015 increased the pool elevation in Beaver Lake by 2.3 m (by early April), increased the surface area by 10%, and increased the littoral zone by 1214 ha; these conditions persisted for 38 days, resulting from flood water being retained behind the dam. Monitoring programs that cover a wide range of reservoir features, including dissolved organic carbon, zooplankton, and phytoplankton, are valuable in explaining unusual events such as this Uroglena bloom.

Tracing the origin of the east-west population admixture in the Altai region (Central Asia).

PubMed

González-Ruiz, Mercedes; Santos, Cristina; Jordana, Xavier; Simón, Marc; Lalueza-Fox, Carles; Gigli, Elena; Aluja, Maria Pilar; Malgosa, Assumpció

2012-01-01

A recent discovery of Iron Age burials (Pazyryk culture) in the Altai Mountains of Mongolia may shed light on the mode and tempo of the generation of the current genetic east-west population admixture in Central Asia. Studies on ancient mitochondrial DNA of this region suggest that the Altai Mountains played the role of a geographical barrier between West and East Eurasian lineages until the beginning of the Iron Age. After the 7th century BC, coinciding with Scythian expansion across the Eurasian steppes, a gradual influx of East Eurasian sequences in Western steppes is detected. However, the underlying events behind the genetic admixture in Altai during the Iron Age are still unresolved: 1) whether it was a result of migratory events (eastward firstly, westward secondly), or 2) whether it was a result of a local demographic expansion in a 'contact zone' between European and East Asian people. In the present work, we analyzed the mitochondrial DNA lineages in human remains from Bronze and Iron Age burials of Mongolian Altai. Here we present support to the hypothesis that the gene pool of Iron Age inhabitants of Mongolian Altai was similar to that of western Iron Age Altaians (Russia and Kazakhstan). Thus, this people not only shared the same culture (Pazyryk), but also shared the same genetic east-west population admixture. In turn, Pazyryks appear to have a similar gene pool that current Altaians. Our results further show that Iron Age Altaians displayed mitochondrial lineages already present around Altai region before the Iron Age. This would provide support for a demographic expansion of local people of Altai instead of westward or eastward migratory events, as the demographic event behind the high population genetic admixture and diversity in Central Asia.

Tracing the Origin of the East-West Population Admixture in the Altai Region (Central Asia)

PubMed Central

González-Ruiz, Mercedes; Santos, Cristina; Jordana, Xavier; Simón, Marc; Lalueza-Fox, Carles; Gigli, Elena; Aluja, Maria Pilar; Malgosa, Assumpció

2012-01-01

A recent discovery of Iron Age burials (Pazyryk culture) in the Altai Mountains of Mongolia may shed light on the mode and tempo of the generation of the current genetic east-west population admixture in Central Asia. Studies on ancient mitochondrial DNA of this region suggest that the Altai Mountains played the role of a geographical barrier between West and East Eurasian lineages until the beginning of the Iron Age. After the 7th century BC, coinciding with Scythian expansion across the Eurasian steppes, a gradual influx of East Eurasian sequences in Western steppes is detected. However, the underlying events behind the genetic admixture in Altai during the Iron Age are still unresolved: 1) whether it was a result of migratory events (eastward firstly, westward secondly), or 2) whether it was a result of a local demographic expansion in a ‘contact zone’ between European and East Asian people. In the present work, we analyzed the mitochondrial DNA lineages in human remains from Bronze and Iron Age burials of Mongolian Altai. Here we present support to the hypothesis that the gene pool of Iron Age inhabitants of Mongolian Altai was similar to that of western Iron Age Altaians (Russia and Kazakhstan). Thus, this people not only shared the same culture (Pazyryk), but also shared the same genetic east-west population admixture. In turn, Pazyryks appear to have a similar gene pool that current Altaians. Our results further show that Iron Age Altaians displayed mitochondrial lineages already present around Altai region before the Iron Age. This would provide support for a demographic expansion of local people of Altai instead of westward or eastward migratory events, as the demographic event behind the high population genetic admixture and diversity in Central Asia. PMID:23152818

Hitting rock bottom: morphological responses of bedrock-confined streams to a catastrophic flood

NASA Astrophysics Data System (ADS)

Baggs Sargood, M.; Cohen, T. J.; Thompson, C. J.; Croke, J.

2015-06-01

The role of extreme events in shaping the Earth's surface is one that has held the interests of Earth scientists for centuries. A catastrophic flood in a tectonically quiescent setting in eastern Australia in 2011 provides valuable insight into how semi-alluvial channels respond to such events. Field survey data (3 reaches) and desktop analyses (10 reaches) with catchment areas ranging from 0.5 to 168 km2 show that the predicted discharge for the 2011 event ranged from 415 to 933 m3 s-1, with unit stream power estimates of up to 1077 W m-2. Estimated entrainment relationships predict the mobility of the entire grain-size population, and field data suggest the localised mobility of boulders up to 4.8 m in diameter. Analysis of repeat lidar data demonstrates that all reaches (field and desktop) were areas of net degradation via extensive scouring of coarse-grained alluvium with a strong positive relationship between catchment area and normalised erosion (R2 = 0.72-0.74). The extensive scouring in the 2011 flood decreased thalweg variance significantly removing previous step pools and other coarse-grained in-channel units, forming lengths of plane-bed (cobble) reach morphology. This was also accompanied by the exposure of planar bedrock surfaces, marginal bedrock straths and bedrock steps. Post-flood field data indicate a slight increase in thalweg variance as a result of the smaller 2013 flood rebuilding the alluvial overprint with pool-riffle formation. However, the current form and distribution of channel morphological units does not conform to previous classifications of bedrock or headwater river systems. This variation in post-flood form indicates that in semi-alluvial systems extreme events are significant for re-setting the morphology of in-channel units and for exposing the underlying lithology to ongoing erosion.

Normal saline solution versus other viscous solutions for submucosal injection during endoscopic mucosal resection: a systematic review and meta-analysis.

PubMed

Yandrapu, Harathi; Desai, Madhav; Siddique, Sameer; Vennalganti, Prashanth; Vennalaganti, Sreekar; Parasa, Sravanthi; Rai, Tarun; Kanakadandi, Vijay; Bansal, Ajay; Titi, Mohammad; Repici, Alessandro; Bechtold, Matthew L; Sharma, Prateek; Choudhary, Abhishek

2017-04-01

EMR is being increasingly practiced for the removal of large colorectal polyps. A variety of solutions such as normal saline solution (NS) and other viscous and hypertonic solutions (VS) have been used as submucosal injections for EMR. A systematic review and meta-analysis is presented comparing the efficacy and adverse events of EMR performed using NS versus VS. Two independent reviewers conducted a search of all databases for human, randomized controlled trials that compared NS with VS for EMR of colorectal polyps. Data on complete en bloc resection, presence of residual lesions, and adverse events were extracted using a standardized protocol. Pooled odds ratio (OR) estimates along with 95% confidence intervals (CI) were calculated using fixed effect or random effects models. Five prospective, randomized controlled trials (504 patients) met the inclusion criteria. The mean polyp sizes were 20.84 mm with NS and 21.44 mm with VS. On pooled analysis, a significant increase in en bloc resection (OR, 1.91; 95% CI, 1.11-3.29; P = .02; I 2  = 0%) and decrease in residual lesions (OR, 0.54; 95% CI, 0.32-0.91; P = .02; I 2  = 0%) were noted in VS compared with NS. There was no significant difference in the rate of overall adverse events between the 2 groups. Use of VS during EMR leads to higher rates of en bloc resection and lower rates of residual lesions compared with NS, without any significant difference in adverse events. Endoscopists could consider using VS for EMR of large colorectal polyps and NS for smaller polyps because there is no significant difference in the outcomes with lesions <2 cm. Published by Elsevier Inc.

Thymic progenitor homing and lymphocyte homeostasis are linked via S1P-controlled expression of thymic P-selectin/CCL25.

PubMed

Gossens, Klaus; Naus, Silvia; Corbel, Stephane Y; Lin, Shujun; Rossi, Fabio M V; Kast, Jürgen; Ziltener, Hermann J

2009-04-13

Thymic T cell progenitor (TCP) importation is a periodic, gated event that is dependent on the expression of functional P-selectin ligands on TCPs. Occupancy of intrathymic TCP niches is believed to negatively regulate TCP importation, but the nature of this feedback mechanism is not yet resolved. We show that P-selectin and CCL25 are periodically expressed in the thymus and are essential parts of the thymic gate-keeping mechanism. Periodicity of thymic TCP receptivity and the size of the earliest intrathymic TCP pool were dependent on the presence of functional P-selectin ligand on TCPs. Furthermore, we show that the numbers of peripheral blood lymphocytes directly affected thymic P-selectin expression and TCP receptivity. We identified sphingosine-1-phosphate (S1P) as one feedback signal that could mediate influence of the peripheral lymphocyte pool on thymic TCP receptivity. Our findings suggest a model whereby thymic TCP importation is controlled by both early thymic niche occupancy and the peripheral lymphocyte pool via S1P.

Innate control of actin nucleation determines two distinct migration behaviours in dendritic cells

PubMed Central

Vargas, Pablo; Maiuri, Paolo; Bretou, Marine; Sáez, Pablo J.; Pierobon, Paolo; Maurin, Mathieu; Chabaud, Mélanie; Lankar, Danielle; Obino, Dorian; Terriac, Emmanuel; Raab, Matthew; Thiam, Hawa-Racine; Brocker, Thomas; Kitchen-Goosen, Susan M.; Alberts, Arthur S.; Sunareni, Praveen; Xia, Sheng; Li, Rong; Voituriez, Raphael; Piel, Matthieu; Lennon-Duménil, Ana-Maria

2018-01-01

Dendritic cell (DC) migration in peripheral tissues serves two main functions: antigen sampling by immature DCs, and chemokine-guided migration towards lymphatic vessels (LVs) on maturation. These migratory events determine the efficiency of the adaptive immune response. Their regulation by the core cell locomotion machinery has not been determined. Here, we show that the migration of immature DCs depends on two main actin pools: a RhoA–mDia1-dependent actin pool located at their rear, which facilitates forward locomotion; and a Cdc42–Arp2/3-dependent actin pool present at their front, which limits migration but promotes antigen capture. Following TLR4–MyD88-induced maturation, Arp2/3-dependent actin enrichment at the cell front is markedly reduced. Consequently, mature DCs switch to a faster and more persistent mDia1-dependent locomotion mode that facilitates chemotactic migration to LVs and lymph nodes. Thus, the differential use of actin-nucleating machineries optimizes the migration of immature and mature DCs according to their specific function. PMID:26641718

El Nino Southern Oscillation and Tuna in the Western Pacific

NASA Technical Reports Server (NTRS)

Lehodey, P.; Bertignac, M.; Hampton, J.; Lewis, A.; Picaut, J.

1997-01-01

Nearly 70% of the world's annual tuna harvest, currently 3.2 million tonnes, comes from the Pacific Ocean. Skipjack tuna (Katsuwonus pelamis) dominate the catch. Although skipjack are distributed in the surface mixed layer throughout the equatorial and subtropical Pacific, catches are highest in the western equatorial Pacific warm pool, a region characterized by low primary productivity rates that has the warmest surface waters of the world's oceans. Assessments of tuna stocks indicate that recent western Pacific skipjack catches approaching one million tonnes annually are sustainable. The warm pool, which is fundamental to the El Nino Southern Oscillation (ENSO) and the Earth's climate in general, must therefore also provide a habitat capable of supporting this highly productive tuna population. Here we show that apparent spatial shifts in the skipjack population are linked to large zonal displacements of the warm pool that occur during ENSO events. This relationship can be used to predict (several months in advance) the region of highest skipjack abundance, within a fishing ground extending over 6,000 km along the Equator.

Drop impact into a deep pool: vortex shedding and jet formation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Agbaglah, G.; Thoraval, M. -J.; Thoroddsen, S. T.

2015-02-01

One of the simplest splashing scenarios results from the impact of a single drop on a deep pool. The traditional understanding of this process is that the impact generates an axisymmetric sheet-like jet that later breaks up into secondary droplets. Recently it was shown that even this simplest of scenarios is more complicated than expected because multiple jets can be generated from a single impact event and there are transitions in the multiplicity of jets as the experimental parameters are varied. Here, we use experiments and numerical simulations of a single drop impacting on a deep pool to examine themore » transition from impacts that produce a single jet to those that produce two jets. Using high-speed X-ray imaging methods we show that vortex separation within the drop leads to the formation of a second jet long after the formation of the ejecta sheet. Using numerical simulations we develop a phase diagram for this transition and show that the capillary number is the most appropriate order parameter for the transition.« less

Real-time radiography of Titan 4 Solid Rocket Motor Upgrade (SRMU) static firing test QM-2

NASA Astrophysics Data System (ADS)

Dolan, K. W.; Curnow, G. M.; Perkins, D. E.; Schneberk, D. J.; Costerus, B. W.; Lachapell, M. J.; Turner, D. E.; Wallace, P. W.

1994-03-01

Real-time radiography was successfully applied to the Titan-4 Solid Rocket Motor Upgrade (SRMU) static firing test QM-2 conducted February 22, 1993 at Phillips Laboratory, Edwards AFB, CA. The real-time video data obtained in this test gave the first incontrovertible evidence that the molten slag pool is low (less than 5 to 6 inches in depth referenced to the bottom of the aft dome cavity) before T + 55 seconds, builds fairly linearly from this point in time reaching a quasi-equilibrium depth of 16 to 17 inches at about T + 97 seconds, which is well below the top of the vectored nozzle, and maintains that level until T + 125 near the end motor burn. From T + 125 seconds to motor burn-out at T + 140 seconds the slag pool builds to a maximum depth of about 20 to 21 inches, still well below the top of the nozzle. The molten slag pool was observed to interact with motions of the vectored nozzle, and exhibit slosh and wave mode oscillations. A few slag ejection events were also observed.

Operating Room Fires and Surgical Skin Preparation.

PubMed

Jones, Edward L; Overbey, Douglas M; Chapman, Brandon C; Jones, Teresa S; Hilton, Sarah A; Moore, John T; Robinson, Thomas N

2017-07-01

Operating room fires are "never events" that remain an under-reported source of devastating complications. One common set-up that promotes fires is the use of surgical skin preparations combined with electrosurgery and oxygen. Limited data exist examining the incidence of fires and surgical skin preparations. A standardized, ex vivo model was created with a 15 × 15 cm section of clipped porcine skin. An electrosurgical "Bovie" pencil was activated for 2 seconds on 30 Watts coagulation mode in 21% oxygen (room air), both immediately and 3 minutes after skin preparation application. Skin preparations with and without alcohol were tested, and were applied with and without pooling. Alcohol-based skin preparations included 70% isopropyl alcohol (IPA) with 2% chlorhexidine gluconate, 74% IPA with 0.7% iodine povacrylex, and plain 70% IPA. No fires occurred with nonalcohol-based preparations (p < 0.001 vs alcohol-based preparations). Alcohol-based preparations caused flash flames at 0 minutes in 22% (13 of 60) and at 3 minutes in 10% (6 of 60) of tests. When examining pooling of alcohol-based preparations, fires occurred in 38% (23 of 60) at 0 minutes and 27% (16 of 60) at 3 minutes. Alcohol-based skin preparations fuel operating room fires in common clinical scenarios. Following manufacturer guidelines and allowing 3 minutes for drying, surgical fires were still created in 1 in 10 cases without pooling and more than one-quarter of cases with pooling. Surgeons can decrease the risk of an operating room fire by using nonalcohol-based skin preparations or avoiding pooling of the preparation solution. Published by Elsevier Inc.

Differences in ecosystem carbon distribution and nutrient cycling linked to forest tree species composition in a mid-successional boreal forest

USGS Publications Warehouse

Melvin, April M.; Mack, Michelle C.; Johnstone, Jill F.; McGuire, A. David; Genet, Helene; Schuur, Edward A.G.

2015-01-01

In the boreal forest of Alaska, increased fire severity associated with climate change is expanding deciduous forest cover in areas previously dominated by black spruce (Picea mariana). Needle-leaf conifer and broad-leaf deciduous species are commonly associated with differences in tree growth, carbon (C) and nutrient cycling, and C accumulation in soils. Although this suggests that changes in tree species composition in Alaska could impact C and nutrient pools and fluxes, few studies have measured these linkages. We quantified C, nitrogen, phosphorus, and base cation pools and fluxes in three stands of black spruce and Alaska paper birch (Betula neoalaskana) that established following a single fire event in 1958. Paper birch consistently displayed characteristics of more rapid C and nutrient cycling, including greater aboveground net primary productivity, higher live foliage and litter nutrient concentrations, and larger ammonium and nitrate pools in the soil organic layer (SOL). Ecosystem C stocks (aboveground + SOL + 0–10 cm mineral soil) were similar for the two species; however, in black spruce, 78% of measured C was found in soil pools, primarily in the SOL, whereas aboveground biomass dominated ecosystem C pools in birch forest. Radiocarbon analysis indicated that approximately one-quarter of the black spruce SOL C accumulated prior to the 1958 fire, whereas no pre-fire C was observed in birch soils. Our findings suggest that tree species exert a strong influence over C and nutrient cycling in boreal forest and forest compositional shifts may have long-term implications for ecosystem C and nutrient dynamics.

Determination of the steam volume fraction in the event of loss of cooling of the spent fuel storage pool

NASA Astrophysics Data System (ADS)

Sledkov, R. M.; Galkin, I. Yu.; Stepanov, O. E.; Strebnev, N. A.

2017-01-01

When one solves engineering problems related to the cooling of fuel assemblies (FAs) in a spent fuel storage pool (SFSP) and the assessment of nuclear safety of FA storage in an SFSP in the initial event of loss of SFSP cooling, it is essential to determine the coolant density and, consequently, steam volume fractions φ in bundles of fuel elements at a pressure of 0.1-0.5 MPa. Such formulas for calculating φ that remain valid in a wide range of operating parameters and geometric shapes of channels and take the conditions of loss of SFSP cooling into account are currently almost lacking. The results of systematization and analysis of the available formulas for φ are reported in the present study. The calculated values were compared with the experimental data obtained in the process of simulating the conditions of FA cooling in an SFSP in the event of loss of its cooling. Six formulas for calculating the steam volume fraction, which were used in this comparison, were chosen from a total of 11 considered relations. As a result, the formulas producing the most accurate values of φ in the conditions of loss of SFSP cooling were selected. In addition, a relation that allows one to perform more accurate calculations of steam volume fractions in the conditions of loss of SFSP cooling was derived based on the Fedorov formula in the two-group approximation.

Efficacy and Safety of Zoledronic Acid for Treatment of Postmenopausal Osteoporosis: A Meta-Analysis of Randomized Controlled Trials.

PubMed

Wang, Chao

We conducted a meta-analysis based on eligible studies to assess the efficacy and safety of zoledronic acid treatment for postmenopausal women with osteoporosis. PubMed, Web of Science, and Embase were searched for eligible studies that assessed the efficacy of zoledronic acid in the prevention of fractures among postmenopausal women with osteoporosis. The primary outcomes were new vertebral fracture, nonvertebral fracture, and hip fracture. Secondary outcomes were bone mineral density (BMD) and safety outcomes. A fixed-effect or random-effect model was used to pool the estimates according to the heterogeneity among the included studies. Eight randomized controlled trials, involving 13,335 patients, were included in this meta-analysis. Pooled results showed that treatment with zoledronic acid significantly reduced the incidences of nonvertebral fractures, vertebral fractures, and hip fractures, as compared with placebo. Zoledronic acid was also associated with significant improvement in BMD at lumbar spine, total hip, femoral neck, and trochanter. However, the incidence of any adverse events was higher in the zoledronic acid group than that in the control group, and serious adverse events were comparable between the 2 groups. This meta-analysis indicated that zoledronic acid could significantly reduce the fracture risk and increase BMD in postmenopausal women with osteoporosis. Furthermore, it would not result in serious adverse events. Zoledronic acid could be used as an effective and well-tolerated treatment for postmenopausal women with osteoporosis.

The Age of Terrestrial Carbon Export and Rainfall Intensity in a Temperate River Headwater System

NASA Astrophysics Data System (ADS)

Tittel, J.; Büttner, O.; Freier, K.; Heiser, A.; Sudbrack, R.; Ollesch, G.

2013-12-01

Riverine dissolved organic carbon (DOC) supports the production of estuaries and coastal ecosystems, constituting one of the most actively recycled pools of the global carbon cycle. A substantial proportion of DOC entering oceans is highly aged, but its origins remain unclear. Significant fluxes of old DOC have never been observed in temperate headwaters where terrestrial imports take place. Here, we studied the radiocarbon age of DOC in three streams draining forested headwater catchments of the river Mulde (Ore Mountains, Germany). We found modern DOC at moderately dry and moderately wet conditions as well as at high discharges during snowmelt. Old groundwater carbon contributed to stream DOC during the summer drought, although the yield was negligible. However, in a four-week summer precipitation event DOC aged at between 160 and 270 years was delivered into the watershed. In one stream, the DOC was modern but depleted in radiocarbon compared to other hydrological conditions. The yield was substantial and corresponded to 20 to 52% of the annual DOC yields in wet and dry years, respectively. Time-integrating samples of a downstream reservoir also revealed modern DOC ages under moderate conditions and old DOC from the rainfall event. Earlier studies suggested that increasing precipitation escalates the contribution of modern DOC from topsoil layers to surface runoff. Our results demonstrate a step change occurring if rainfall intensities increase and become extreme; then the consequences lead to the mobilization of old carbon in exceptionally high concentrations. The runoff/precipitation ratios of rainfall events indicated that during extreme events upland areas of the catchments were hydrologically connected to the stream and upland DOC was activated. Furthermore, the analysis of long-term data suggested that the DOC export in extreme precipitation events added to the annual yield and was not compensated for by lower exports in remaining periods. We conclude that climate change, along with additional processes associated with human activities, channels old soil carbon into more rapidly cycled carbon pools of the hydrosphere.

Cardiovascular and heart failure safety profile of vildagliptin: a meta-analysis of 17 000 patients.

PubMed

McInnes, G; Evans, M; Del Prato, S; Stumvoll, M; Schweizer, A; Lukashevich, V; Shao, Q; Kothny, W

2015-11-01

To report the cardiovascular (CV) safety profile and heart failure (HF) risk of vildagliptin from a large pool of studies, including trials in high-risk patients with type 2 diabetes mellitus (T2DM), such as those with congestive HF and/or moderate/severe renal impairment. We conducted a retrospective meta-analysis of prospectively adjudicated CV events. Patient-level data were pooled from 40 double-blind, randomized controlled phase III and IV vildagliptin studies. The primary endpoint was occurrence of major adverse CV events (MACEs; myocardial infarction, stroke and CV death). Assessments of the individual MACE components and HF events (requiring hospitalization or new onset) were secondary endpoints. The risk ratio (RR) of vildagliptin (50 mg once- and twice-daily combined) versus comparators (placebo and all non-vildagliptin treatments) was calculated using the Mantel-Haenszel (M-H) method. Of the 17 446 patients, 9599 received vildagliptin (9251.4 subject-years of exposure) and 7847 received comparators (7317.0 subject-years of exposure). The mean age of the patients was 57 years, body mass index 30.5 kg/m(2) (nearly 50% obese), glycated haemoglobin concentration 8.1% and T2DM duration 5.5 years. A MACE occurred in 83 (0.86%) vildagliptin-treated patients and 85 (1.20%) comparator-treated patients, with an M-H RR of 0.82 [95% confidence interval (CI) 0.61-1.11]. Similar RRs were observed for the individual events. Confirmed HF events were reported in 41 (0.43%) vildagliptin-treated patients and 32 (0.45%) comparator-treated patients, with an M-H RR 1.08 (95% CI 0.68-1.70). This large meta-analysis indicates that vildagliptin is not associated with an increased risk of adjudicated MACEs relative to comparators. Moreover, this analysis did not find a significant increased risk of HF in vildagliptin-treated patients. © 2015 John Wiley & Sons Ltd.

Secondary stroke prevention with ximelagatran versus warfarin in patients with atrial fibrillation: pooled analysis of SPORTIF III and V clinical trials.

PubMed

Akins, Paul T; Feldman, Harvey A; Zoble, Robert G; Newman, David; Spitzer, Stefan G; Diener, Hans-Christoph; Albers, Gregory W

2007-03-01

Patients with nonvalvular atrial fibrillation and prior stroke or transient ischemic attack (TIA) are at high risk for recurrent stroke. We investigated whether ximelagatran was noninferior to warfarin in patients with prior stroke or TIA. We analyzed pooled data from the SPORTIF III and V trials in patients with prior stroke/TIA. The primary outcome was the composite annual rate of both ischemic and hemorrhagic strokes and systemic embolic events. Secondary analyses considered ischemic and hemorrhagic strokes separately, bleeding, and nonrandomized, concomitant therapy with aspirin < or =100 mg/d. Patients from SPORTIF III (n=3407) and SPORTIF V (n=3922) trials were categorized by prior stroke/TIA (21%) versus no prior stroke/TIA (79%) and by treatment group (ximelagatran vs warfarin). The primary event rate in patients with prior stroke/TIA was 2.83%/y with ximelagatran and 3.27%/y with warfarin (absolute difference, -0.44%; 95% CI, -1.88 to1.01; P=0.625). In those without prior stroke/TIA, the primary event rate was 1.31%/y with ximelagatran and 1.26%/y with warfarin (P=NS). Ischemic strokes outnumbered cerebral hemorrhages with both warfarin (31 of 36) and ximelagatran (30 of 32) treatment (difference between treatments was not significant). Combining aspirin with either anticoagulant was associated with higher rates of major bleeding (1.5%/y with warfarin and 4.95%/y with warfarin plus aspirin, P=0.004; 2.35%/y with ximelagatran and 5.09%/y with ximelagatran plus aspirin, P=0.046) but not lower rates of primary events. Ximelagatran was at least as effective as well-controlled warfarin for the secondary prevention of stroke. The nonrandomized, concomitant treatment with aspirin and anticoagulation was associated with increased bleeding without evidence of a reduction in primary outcome events.

Evaluation of the Pooled Cohort Equations for Prediction of Cardiovascular Risk in a Contemporary Prospective Cohort.

PubMed

Emdin, Connor A; Khera, Amit V; Natarajan, Pradeep; Klarin, Derek; Baber, Usman; Mehran, Roxana; Rader, Daniel J; Fuster, Valentin; Kathiresan, Sekar

2017-03-15

Most guidelines suggest a baseline risk assessment to guide atherosclerotic cardiovascular disease (ASCVD) prevention strategies. The American Heart Association/American College of Cardiology Pooled Cohort Equations (PCEs) is one tool to assess baseline risk; however, the accuracy of this tool has been called into question. We aimed to examine the calibration and discrimination of the PCEs in the BioImage study, a contemporary multiethnic cohort of asymptomatic adults enrolled from 2008 to 2009 in the Humana Health System in Chicago, Illinois, and Fort Lauderdale, Florida. Our primary end point was hard ASCVD, defined as cardiovascular death, myocardial infarction, and stroke. A total of 3,635 adults who were not on lipid-lowering therapy at baseline were followed for a maximum of 4.6 years. The mean age was 68.6 years; 2000 (55%) participants were women and 935 patients reported being of non-white race (26%). Although 74 ASCVD events were observed over a median follow-up of 2.7 years, 198 events were predicted by the PCEs. The observed event rate was 7.9 per 1,000 participant-years (95% confidence interval [CI] 6.1 to 9.8), whereas the predicted rate by the PCEs was 21 per 1,000 participant-years (95% CI 20.7 to 21.8). This represents an overestimation of 167% (Hosmer-Lemeshow chi-square = 173; p <0.001). With regard to discrimination, the C-statistic of the PCEs was 0.65 (CI 0.58 to 0.71). In an analysis restricted to 3,080 participants without diabetes mellitus and with low-density lipoprotein cholesterol between 70 and 189 mg/dl, the PCEs similarly overestimated risk by 181% (152 predicted events vs 54 observed events; p <0.001). The PCEs substantially overestimate ASCVD risk in this middle-aged adult insured population. Refinement of existing risk prediction functions may be warranted. Copyright © 2016 Elsevier Inc. All rights reserved.

STS-60 Cosmonauts in Weightless Environment Training Facility (WETF) training

NASA Image and Video Library

1993-01-07

S93-26021 (Feb 1993) --- Russian cosmonaut Sergei Krikalev maneuvers a small life raft during bailout training at the Johnson Space Center's (JSC) Weightless Environment Training Facility (WET-F). Two SCUBA-equipped divers assisted Krikalev in the STS-60 training exercise. Shuttle crew members frequently utilize the 25-ft. deep pool to learn proper procedures to follow in the event of emergency egress from their Space Shuttle via the escape pole system. Krikalev is one of two cosmonauts in training for the STS-60 mission. One of the two will serve as primary payload specialist with the other filling an alternate's role. This pool and the facility in which it is housed are titled the WET-F, because they are also used by astronauts rehearsing both mission-specific and contingency extravehicular activities (EVA).

A Parallel Saturation Algorithm on Shared Memory Architectures

NASA Technical Reports Server (NTRS)

Ezekiel, Jonathan; Siminiceanu

2007-01-01

Symbolic state-space generators are notoriously hard to parallelize. However, the Saturation algorithm implemented in the SMART verification tool differs from other sequential symbolic state-space generators in that it exploits the locality of ring events in asynchronous system models. This paper explores whether event locality can be utilized to efficiently parallelize Saturation on shared-memory architectures. Conceptually, we propose to parallelize the ring of events within a decision diagram node, which is technically realized via a thread pool. We discuss the challenges involved in our parallel design and conduct experimental studies on its prototypical implementation. On a dual-processor dual core PC, our studies show speed-ups for several example models, e.g., of up to 50% for a Kanban model, when compared to running our algorithm only on a single core.

Job optimization in ATLAS TAG-based distributed analysis

NASA Astrophysics Data System (ADS)

Mambelli, M.; Cranshaw, J.; Gardner, R.; Maeno, T.; Malon, D.; Novak, M.

2010-04-01

The ATLAS experiment is projected to collect over one billion events/year during the first few years of operation. The efficient selection of events for various physics analyses across all appropriate samples presents a significant technical challenge. ATLAS computing infrastructure leverages the Grid to tackle the analysis across large samples by organizing data into a hierarchical structure and exploiting distributed computing to churn through the computations. This includes events at different stages of processing: RAW, ESD (Event Summary Data), AOD (Analysis Object Data), DPD (Derived Physics Data). Event Level Metadata Tags (TAGs) contain information about each event stored using multiple technologies accessible by POOL and various web services. This allows users to apply selection cuts on quantities of interest across the entire sample to compile a subset of events that are appropriate for their analysis. This paper describes new methods for organizing jobs using the TAGs criteria to analyze ATLAS data. It further compares different access patterns to the event data and explores ways to partition the workload for event selection and analysis. Here analysis is defined as a broader set of event processing tasks including event selection and reduction operations ("skimming", "slimming" and "thinning") as well as DPD making. Specifically it compares analysis with direct access to the events (AOD and ESD data) to access mediated by different TAG-based event selections. We then compare different ways of splitting the processing to maximize performance.

Eastern Tropical Pacific Precipitation Response to Zonal SPCZ events

NASA Astrophysics Data System (ADS)

Durán-Quesada, A. M.; Lintner, B. R.

2014-12-01

Extreme El Niño events and warming conditions in the eastern tropical Pacific have been linked to pronounced spatial displacements of the South Pacific Convergence Zone known as "zonal SPCZ" events.. Using a global dataset of Lagrangian back trajectories computed with the FLEXPART model for the period 1980-2013, comprehensive analysis of the 3D circulation characteristics associated with the SPCZ is undertaken. Ten days history of along-trajectory specific humidity, potential vorticity and temperature are reconstructed for zonal SPCZ events as well as other states,, with differences related to El Niño intensity and development stage as well as the state of the Western Hemisphere Warm Pool. How zonal events influence precipitation over the Eastern Tropical Pacific is examined using back trajectories, reanalysis, TRMM precipitation, and additional satellite derived cloud information. It is found that SPCZ displacements are associated with enhanced convection over the Eastern Tropical Pacific in good agreement with prior work. The connection between intensification of precipitation over the eastern Tropical Pacific during zonal events and suppression of rainfall over the Maritime continent is also described.

Phylogeographic Differentiation of Mitochondrial DNA in Han Chinese

PubMed Central

Yao, Yong-Gang; Kong, Qing-Peng; Bandelt, Hans-Jürgen; Kivisild, Toomas; Zhang, Ya-Ping

2002-01-01

To characterize the mitochondrial DNA (mtDNA) variation in Han Chinese from several provinces of China, we have sequenced the two hypervariable segments of the control region and the segment spanning nucleotide positions 10171–10659 of the coding region, and we have identified a number of specific coding-region mutations by direct sequencing or restriction-fragment–length–polymorphism tests. This allows us to define new haplogroups (clades of the mtDNA phylogeny) and to dissect the Han mtDNA pool on a phylogenetic basis, which is a prerequisite for any fine-grained phylogeographic analysis, the interpretation of ancient mtDNA, or future complete mtDNA sequencing efforts. Some of the haplogroups under study differ considerably in frequencies across different provinces. The southernmost provinces show more pronounced contrasts in their regional Han mtDNA pools than the central and northern provinces. These and other features of the geographical distribution of the mtDNA haplogroups observed in the Han Chinese make an initial Paleolithic colonization from south to north plausible but would suggest subsequent migration events in China that mainly proceeded from north to south and east to west. Lumping together all regional Han mtDNA pools into one fictive general mtDNA pool or choosing one or two regional Han populations to represent all Han Chinese is inappropriate for prehistoric considerations as well as for forensic purposes or medical disease studies. PMID:11836649

Multiyear Downstream Response to Dam Removal on the White Salmon River, WA

NASA Astrophysics Data System (ADS)

Wilcox, A. C.; O'Connor, J. E.; Major, J. J.

2017-12-01

The 2011 removal of the 38 m tall Condit Dam on the White Salmon River, Washington was one of the largest dam removals to date, in terms of both dam height and sediment release. We examined the multiyear geomorphic response to this event, through 2015, including in a bedrock-confined canyon and in a less-confined, backwater-influenced pool reach near the river's mouth, to the large, rapid influx of fine reservoir sediment produced by the breach and to subsequent sediment transfer in the free-flowing White Salmon River. In the canyon reach, aggraded sediments were rapidly eroded from riffles, returning them toward pre-breach bed elevations within weeks, but pool aggradation persisted for longer. The downstream, less-confined reach transformed from a deep pool to a narrower pool-riffle channel with alternate bars; multiyear observations showed persistence of bars and of this new and distinct morphology. This downstream reach marks a rare case in post-dam removal channel response; in most dam removals, channels have rapidly reverted toward pre-removal morphology, as in the canyon reach here. Comparison of the multiyear geomorphic evolution of the White Salmon River to other recent large dam removals in the U.S. allows evaluation of the relative influences of antecedent channel morphology, post-breach hydrology, and dam removal style, as well as providing a basis for predicting responses to future dam removals.

Membrane cholesterol removal changes mechanical properties of cells and induces secretion of a specific pool of lysosomes.

PubMed

Hissa, Barbara; Pontes, Bruno; Roma, Paula Magda S; Alves, Ana Paula; Rocha, Carolina D; Valverde, Thalita M; Aguiar, Pedro Henrique N; Almeida, Fernando P; Guimarães, Allan J; Guatimosim, Cristina; Silva, Aristóbolo M; Fernandes, Maria C; Andrews, Norma W; Viana, Nathan B; Mesquita, Oscar N; Agero, Ubirajara; Andrade, Luciana O

2013-01-01

In a previous study we had shown that membrane cholesterol removal induced unregulated lysosomal exocytosis events leading to the depletion of lysosomes located at cell periphery. However, the mechanism by which cholesterol triggered these exocytic events had not been uncovered. In this study we investigated the importance of cholesterol in controlling mechanical properties of cells and its connection with lysosomal exocytosis. Tether extraction with optical tweezers and defocusing microscopy were used to assess cell dynamics in mouse fibroblasts. These assays showed that bending modulus and surface tension increased when cholesterol was extracted from fibroblasts plasma membrane upon incubation with MβCD, and that the membrane-cytoskeleton relaxation time increased at the beginning of MβCD treatment and decreased at the end. We also showed for the first time that the amplitude of membrane-cytoskeleton fluctuation decreased during cholesterol sequestration, showing that these cells become stiffer. These changes in membrane dynamics involved not only rearrangement of the actin cytoskeleton, but also de novo actin polymerization and stress fiber formation through Rho activation. We found that these mechanical changes observed after cholesterol sequestration were involved in triggering lysosomal exocytosis. Exocytosis occurred even in the absence of the lysosomal calcium sensor synaptotagmin VII, and was associated with actin polymerization induced by MβCD. Notably, exocytosis triggered by cholesterol removal led to the secretion of a unique population of lysosomes, different from the pool mobilized by actin depolymerizing drugs such as Latrunculin-A. These data support the existence of at least two different pools of lysosomes with different exocytosis dynamics, one of which is directly mobilized for plasma membrane fusion after cholesterol removal.

Membrane Cholesterol Removal Changes Mechanical Properties of Cells and Induces Secretion of a Specific Pool of Lysosomes

PubMed Central

Roma, Paula Magda S.; Alves, Ana Paula; Rocha, Carolina D.; Valverde, Thalita M.; Aguiar, Pedro Henrique N.; Almeida, Fernando P.; Guimarães, Allan J.; Guatimosim, Cristina; Silva, Aristóbolo M.; Fernandes, Maria C.; Andrews, Norma W.; Viana, Nathan B.; Mesquita, Oscar N.; Agero, Ubirajara; Andrade, Luciana O.

2013-01-01

In a previous study we had shown that membrane cholesterol removal induced unregulated lysosomal exocytosis events leading to the depletion of lysosomes located at cell periphery. However, the mechanism by which cholesterol triggered these exocytic events had not been uncovered. In this study we investigated the importance of cholesterol in controlling mechanical properties of cells and its connection with lysosomal exocytosis. Tether extraction with optical tweezers and defocusing microscopy were used to assess cell dynamics in mouse fibroblasts. These assays showed that bending modulus and surface tension increased when cholesterol was extracted from fibroblasts plasma membrane upon incubation with MβCD, and that the membrane-cytoskeleton relaxation time increased at the beginning of MβCD treatment and decreased at the end. We also showed for the first time that the amplitude of membrane-cytoskeleton fluctuation decreased during cholesterol sequestration, showing that these cells become stiffer. These changes in membrane dynamics involved not only rearrangement of the actin cytoskeleton, but also de novo actin polymerization and stress fiber formation through Rho activation. We found that these mechanical changes observed after cholesterol sequestration were involved in triggering lysosomal exocytosis. Exocytosis occurred even in the absence of the lysosomal calcium sensor synaptotagmin VII, and was associated with actin polymerization induced by MβCD. Notably, exocytosis triggered by cholesterol removal led to the secretion of a unique population of lysosomes, different from the pool mobilized by actin depolymerizing drugs such as Latrunculin-A. These data support the existence of at least two different pools of lysosomes with different exocytosis dynamics, one of which is directly mobilized for plasma membrane fusion after cholesterol removal. PMID:24376622

Efficacy and safety of rilpivirine (TMC278) versus efavirenz at 48 weeks in treatment-naive HIV-1-infected patients: pooled results from the phase 3 double-blind randomized ECHO and THRIVE Trials.

PubMed

Cohen, Calvin J; Molina, Jean-Michel; Cahn, Pedro; Clotet, Bonaventura; Fourie, Jan; Grinsztejn, Beatriz; Wu, Hao; Johnson, Margaret A; Saag, Michael; Supparatpinyo, Khuanchai; Crauwels, Herta; Lefebvre, Eric; Rimsky, Laurence T; Vanveggel, Simon; Williams, Peter; Boven, Katia

2012-05-01

Pooled analysis of phase 3, double-blind, double-dummy ECHO and THRIVE trials comparing rilpivirine (TMC278) and efavirenz. Treatment-naive HIV-1-infected adults were randomized 1:1 to rilpivirine 25 mg once daily or efavirenz 600 mg once daily, with background tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) (ECHO) or TDF/FTC, zidovudine/lamivudine, or abacavir/lamivudine (THRIVE). The primary endpoint was confirmed response [viral load <50 copies per milliliter; intent-to-treat time-to-loss-of-virologic-response (ITT-TLOVR) algorithm] at week 48. The pooled data set enabled analyses of subgroups and predictors of response/virologic failure. Confirmed responses were 84% (rilpivirine) and 82% (efavirenz). The difference in response rates (95% confidence interval) was 2.0% (-2.0% to 6.0%). The incidence of virologic failure was 9% (rilpivirine) versus 5% (efavirenz). Responses in ITT-TLOVR and ITT-snapshot analyses were consistent. Responses were similar for rilpivirine and efavirenz by background regimen, gender, race and clade. Suboptimal adherence and higher baseline viral load resulted in lower responses, higher virologic failure, and development of resistance in both groups; the effects on virologic failure were more apparent with rilpivirine. CD4 cell count increased over time in both groups. Rilpivirine compared with efavirenz gave smaller incidences of adverse events leading to discontinuation (3% vs. 8%, respectively), treatment-related grade 2-4 adverse events (16% vs. 31%), rash (3% vs. 14%), dizziness (8% vs. 26%), abnormal dreams/nightmares (8% vs. 13%), and grade 2-4 lipid abnormalities. At week 48, rilpivirine 25 mg once daily and efavirenz 600 mg once daily had comparable response rates. Rilpivirine had more virologic failures and improved tolerability versus efavirenz.

Heavy rainfall and risk of infectious intestinal diseases in the most populous city in Vietnam.

PubMed

Phung, Dung; Chu, Cordia; Rutherford, Shannon; Nguyen, Huong Lien Thi; Luong, Mai Anh; Do, Cuong Manh; Huang, Cunrui

2017-02-15

The association between heavy rainfall and infectious intestinal diseases (IID) has not been well described and little research has been conducted in developing countries. This study examines the association between heavy rainfall and hospital admissions for IID in Ho Chi Minh City, the most populous city in Vietnam. An interrupted time-series method was used to examine the effect of each individual heavy rainfall event (HRE) on IID. The percentage changes in post-HRE level and trends of IID were estimated for 30days following each HRE. Then a random-effect meta-analysis was used to quantify the pooled estimate of effect sizes of all HREs on IID. The pooled estimates were calculated over a 21day lag period. The effects of a HRE on IID varied across individual HREs. The pooled estimates indicate that the levels of IID following a HRE increased from 7.3% to 13.5% for lags from 0 to 21days, however statistically significant increases were only observed for lags from 4 to 6days (13.5%, 95%CI: 1.4-25.4; 13.3%, 95%CI: 1.5-25.0; and 12.9%, 95%CI: 1.6-24.1 respectively). An average decrease of 0.11% (95%CI: -0.55-0.33) per day was observed for the post-HRE trend. This finding has important implications for the projected impacts on residents living in this city which is highly vulnerable to increased heavy rainfall associated with climate change. Adaptation and intervention programs should be developed to prevent this additional burden of disease and to protect residents from the adverse impacts of extreme weather events. Copyright © 2016 Elsevier B.V. All rights reserved.

Effect of regional anesthesia on the success rate of external cephalic version: a systematic review and meta-analysis.

PubMed

Goetzinger, Katherine R; Harper, Lorie M; Tuuli, Methodius G; Macones, George A; Colditz, Graham A

2011-11-01

To estimate whether the use of regional anesthesia is associated with increased success of external cephalic version. We searched MEDLINE, EMBASE, the Cochrane Library, and clinical trial registries. Electronic databases were searched from 1966 through April 2011 for published, randomized controlled trials in the English language comparing regional anesthesia with no regional anesthesia for external cephalic version. The primary outcome was external cephalic version success. Secondary outcomes included cesarean delivery, maternal discomfort, and adverse events. Pooled risk ratios (relative risk) were calculated using a random-effects model. Heterogeneity was assessed using the Cochran's Q statistic and quantified using the I Z method. Six randomized controlled trials met criteria for study inclusion. Regional anesthesia was associated with a higher external cephalic version success rate compared with intravenous or no analgesia (59.7% compared with 37.6%; pooled relative risk 1.58; 95% confidence interval [CI] 1.29-1.93). This significant association persisted when the data were stratified by type of regional anesthesia (spinal compared with epidural). The number needed to treat with regional anesthesia to achieve one additional successful external cephalic version was five. There was no evidence of statistical heterogeneity (P=.32, I Z=14.9%) or publication bias (Harbord test P=.78). There was no statistically significant difference in the risk of cesarean delivery comparing regional anesthesia with intravenous or no analgesia (48.4% compared with 59.3%; pooled relative risk 0.80; 95% CI 0.55-1.17). Adverse events were rare and not significantly different between the two groups. Regional anesthesia is associated with a higher success rate of external cephalic version.

Traffic calming for the prevention of road traffic injuries: systematic review and meta-analysis

PubMed Central

Bunn, F; Collier, T; Frost, C; Ker, K; Roberts, I; Wentz, R

2003-01-01

Objective: To assess whether area-wide traffic calming schemes can reduce road crash related deaths and injuries. Design: Systematic review and meta-analysis. Data sources: Cochrane Injuries Group Specialised Register, Cochrane Central Register of Controlled Trials, Medline, EMBASE, Sociological Abstracts Science (and social science) citation index, National Technical Information service, Psychlit, Transport Research Information Service, International Road Research Documentation, and Transdoc, and web sites of road safety organisation were searched; experts were contacted, conference proceedings were handsearched, and relevant reference lists were checked. Inclusion criteria: Randomised controlled trials, and controlled before/after studies of area-wide traffic calming schemes designed to discourage and slow down through traffic on residential roads. Methods: Data were collected on road user deaths, injuries, and traffic crashes. For each study rate ratios were calculated, the ratio of event rates before and after intervention in the traffic calmed area divided by the corresponding ratio of event rates in the control area, which were pooled to give an overall estimate using a random effects model. Findings: Sixteen controlled before/after studies met our inclusion criteria. Eight studies reported the number of road user deaths: pooled rate ratio 0.63 (95% confidence interval (CI) 0.14 to 2.59). Sixteen studies reported the number of injuries (fatal and non-fatal): pooled rate ratio 0.89 (95% CI 0.80 to 1.00). All studies were in high income countries. Conclusion: Area-wide traffic calming in towns and cities has the potential to reduce road traffic injuries. However, further rigorous evaluations of this intervention are needed, especially in low and middle income countries. PMID:12966005

Return to Play in Elite Contact Athletes After Anterior Cervical Discectomy and Fusion: A Meta-Analysis

PubMed Central

McAnany, Steven J.; Overley, Samuel; Andelman, Steven; Patterson, Diana C.; Cho, Samuel K.; Qureshi, Sheeraz; Hsu, Wellington K.

2017-01-01

Study Design: Systematic literature review and meta-analysis of studies published in English language. Objective: Return to play after anterior cervical discectomy and fusion (ACDF) in contact athletes remains a controversial topic with no consensus opinion in the literature. Additional information is needed to properly advise and treat this population of patients. This study is a meta-analysis assessing return to competitive contact sports after undergoing an ACDF. Methods: A literature search of Medline, Embase, and Cochrane Reviews was performed to identify investigations reporting return to play following ACDF in professional contact athletes. The pooled results were performed by calculating the effect size based on the logic event rate. Studies were weighted by the inverse of the variance, which included both within and between-study error. Confidence intervals (CIs) were reported at 95%. Heterogeneity was assessed using the Q statistic and I 2. Sensitivity analysis and publication bias calculations were performed. Results: The initial literature search resulted in 166 articles, of which 5 were determined relevant. Overall, return to play data was provided for 48 patients. The pooled clinical success rate for return to play was 73.5% (CI = 56.7%, 85.8%). The logit event rate was calculated to be 1.036 (CI = 0.270, 1.802), which was statistically significant (P = .008). The studies included in this meta-analysis demonstrated minimal heterogeneity with Q value of 4.038 and I 2 value of 0.956. Conclusions: Elite contact athletes return to competition 73.5% of the time after undergoing ACDF. As this is the first study to pool results from existing studies, it provides strong evidence to guide decision making and expectations in this patient population. PMID:28894685

Protective effects of methotrexate against ischemic cardiovascular disorders in patients treated for rheumatoid arthritis or psoriasis: novel therapeutic insights coming from a meta-analysis of the literature data

PubMed Central

Vecchis, Renato De; Baldi, Cesare; Palmisani, Leonardo

2016-01-01

Objective: The association between chronic use of methotrexate and decreased risk of ischemic cardiovascular events (CVE) among patients with psoriatic or rheumatoid arthritis (RA) was investigated using a systematic review and meta-analysis. Methods: The studies should have recruited adults receiving methotrexate, followed up for at least one year. Moreover, studies should have reported “hard” cardiovascular endpoints, by evaluating the cardiovascular outcomes of the habitual users of the drug or of new users compared with patients with the same disease who had never used methotrexate. The outcome of interest was the overall pooled odds ratio (OR) of major adverse cardiovascular events, i.e., a composite of new- onset angina, acute coronary syndrome, need for percutaneous or surgical coronary revascularization, stroke, and cardiovascular death. The study was performed according to the PRISMA statement. Results: Seven observational studies, mostly engaging patients with RA, were included in the meta-analysis. The pooled odds ratio (OR) was 0.73 (95% CI=0.70- 0.77 p<0.001). When stratified meta-analysis models were assessed, the pooled OR was 0.80 (95% CI=0.66-0.97; p=0.022) for studies adjusting for clinical severity of RA. Furthermore, the OR was even more significant after adjustment for concomitant use of other drugs specific for RA (OR=0.71, 95% CI=0.67-0.75, p<0.001). Conclusion: Methotrexate at low doses, such those used for maintenance therapy of RA, predicted a decreased risk of CVE. Since methotrexate doesn’t interfere with blood lipids, platelet aggregation or insulin resistance, the protective association may originate from mechanisms other than those exerted by antiplatelet drugs or statins. PMID:26467356

Effects of recent logging on the main channel of North Fork Caspar Creek

Treesearch

Thomas E. Lisle; Michael Napolitano

1998-01-01

The response of the mainstem channel of North Fork Caspar Creek to recent logging is examined by time trends in bed load yield, scour and fill at resurveyed cross sections, and the volume and fine-sediment content of pools. Companion papers report that recent logging has increased streamflow during the summer and moderate winter rainfall events, and blowdowns from...

Effects of simulated drought on the carbon balance of Everglades short-hydroperiod marsh

Treesearch

Sparkle L Malone; Gregory Starr; Christina L. Staudhammer; Michael G. Ryan

2013-01-01

Hydrology drives the carbon balance of wetlands by controlling the uptake and release of CO2 and CH4. Longer dry periods in between heavier precipitation events predicted for the Everglades region, may alter the stability of large carbon pools in this wetland's ecosystems. To determine the effects of drought on CO2 fluxes and CH4 emissions, we simulated changes in...

STS_135_Russia

NASA Image and Video Library

2011-03-28

Space suit designer Oleg Gerasimenko shares some tips on the Sokol suit with NASA astronaut Rex Walheim during a fit check at the Zvezda facility on Monday, March 28, 2011, in Moscow. The crew of the final shuttle mission traveled to Moscow for a suit fit check of their Russian Soyuz suits that will be required in the event of an emergency. ( NASA Photo / Houston Chronicle, Smiley N. Pool )

STS_135_Russia

NASA Image and Video Library

2011-03-28

JSC2011-E-040298 (28 March 2011) --- NASA astronaut Rex Walheim, STS-135 mission specialist, undergoes a fit check of his Sokol spacesuit at the Zvezda facility in Moscow on March 28, 2011. The crew of the final shuttle mission traveled to Moscow for a suit fit check of their Russian suits would be required in the event of an emergency. Photo credit: NASA Photo/Houston Chronicle, Smiley N. Pool

STS_135_Russia

NASA Image and Video Library

2011-03-29

JSC2011-E-040322 (29 March 2011) --- NASA astronaut Sandy Magnus, STS-135 mission specialist, undergoes a fit check of her Sokol spacesuit March 29, 2011, at the Zvezda facility in Moscow. The crew of the final shuttle mission traveled to Moscow for a suit fit check of their Russian Soyuz suits that will be required in the event of an emergency. Photo credit: NASA Photo / Houston Chronicle, Smiley N. Pool

Effect of supersaturated oxygen delivery on infarct size after percutaneous coronary intervention in acute myocardial infarction.

PubMed

Stone, Gregg W; Martin, Jack L; de Boer, Menko-Jan; Margheri, Massimo; Bramucci, Ezio; Blankenship, James C; Metzger, D Christopher; Gibbons, Raymond J; Lindsay, Barbara S; Weiner, Bonnie H; Lansky, Alexandra J; Krucoff, Mitchell W; Fahy, Martin; Boscardin, W John

2009-10-01

Myocardial salvage is often suboptimal after percutaneous coronary intervention in ST-segment elevation myocardial infarction. Posthoc subgroup analysis from a previous trial (AMIHOT I) suggested that intracoronary delivery of supersaturated oxygen (SSO(2)) may reduce infarct size in patients with large ST-segment elevation myocardial infarction treated early. A prospective, multicenter trial was performed in which 301 patients with anterior ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention within 6 hours of symptom onset were randomized to a 90-minute intracoronary SSO(2) infusion in the left anterior descending artery infarct territory (n=222) or control (n=79). The primary efficacy measure was infarct size in the intention-to-treat population (powered for superiority), and the primary safety measure was composite major adverse cardiovascular events at 30 days in the intention-to-treat and per-protocol populations (powered for noninferiority), with Bayesian hierarchical modeling used to allow partial pooling of evidence from AMIHOT I. Among 281 randomized patients with tc-99m-sestamibi single-photon emission computed tomography data in AMIHOT II, median (interquartile range) infarct size was 26.5% (8.5%, 44%) with control compared with 20% (6%, 37%) after SSO(2). The pooled adjusted infarct size was 25% (7%, 42%) with control compared with 18.5% (3.5%, 34.5%) after SSO(2) (P(Wilcoxon)=0.02; Bayesian posterior probability of superiority, 96.9%). The Bayesian pooled 30-day mean (+/-SE) rates of major adverse cardiovascular events were 5.0+/-1.4% for control and 5.9+/-1.4% for SSO(2) by intention-to-treat, and 5.1+/-1.5% for control and 4.7+/-1.5% for SSO(2) by per-protocol analysis (posterior probability of noninferiority, 99.5% and 99.9%, respectively). Among patients with anterior ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention within 6 hours of symptom onset, infusion of SSO(2) into the left anterior descending artery infarct territory results in a significant reduction in infarct size with noninferior rates of major adverse cardiovascular events at 30 days. Clinical Trial Registration- clinicaltrials.gov Identifier: NCT00175058.

Role of upper-level wind shear on the structure and maintenance of derecho-producing convective systems

NASA Astrophysics Data System (ADS)

Coniglio, Michael Charles

Common large-scale environments associated with the development of derecho-producing convective systems from a large number of events are identified using statistical clustering of the 500-mb geopotential heights as guidance. The majority of the events (72%) fall into three main patterns that include a well-defined upstream trough (40%), a ridge (20%), and a zonal, low-amplitude flow (12%), which is defined as an additional warm-season pattern that is not identified in past studies of derecho environments. Through an analysis of proximity soundings, discrepancies are found in both low-level and deep-tropospheric shear parameters between observations and the shear profiles considered favorable for strong, long-lived convective systems in idealized simulations. To explore the role of upper-level shear in derecho environments, a set of two-dimensional simulations of density currents within a dry, neutrally stable environment are used to examine the ability of a cold pool to lift environmental air within a vertically sheared flow. The results confirm that the addition of upper-level shear to a wind profile with weak to moderate low-level shear increases the vertical displacement of low-level parcels despite a decrease in the vertical velocity along the cold pool interface, as suggested by previous studies. Parcels that are elevated above the surface (1-2 km) overturn and are responsible for the deep lifting in the deep-shear environments. This deep overturning caused by the upper-level shear helps to maintain the tilt of the convective systems in more complex two-dimensional and three dimensional simulations. The overturning also is shown to greatly increase the size of the convective systems in the three-dimensional simulations by facilitating the initiation and maintenance of convective cells along the cold pool. When combined with estimates of the cold pool motion and the storm-relative hodograph, these results may best be used for the prediction of the demise of strong, linear mesoscale convective systems (MCSs) and may provide a conceptual model for the persistence of strong MCSs above a surface nocturnal inversion in situations that are not forced by a low-level jet.

Safety of the 2D/3D direct-acting antiviral regimen in HCV-induced Child-Pugh A cirrhosis - A pooled analysis.

PubMed

Poordad, Fred; Nelson, David R; Feld, Jordan J; Fried, Michael W; Wedemeyer, Heiner; Larsen, Lois; Cohen, Daniel E; Cohen, Eric; Mobashery, Niloufar; Tatsch, Fernando; Foster, Graham R

2017-10-01

Chronic hepatitis C virus (HCV)-infected patients with cirrhosis are a high-priority population for treatment. To help inform the benefit-risk profile of the all-oral direct-acting antiviral (DAA) combination regimen of ombitasvir, paritaprevir, and ritonavir, with or without dasabuvir (OBV/PTV/r±DSV) in patients with Child-Pugh A cirrhosis, we undertook a comprehensive review of AbbVie-sponsored clinical trials enrolling patients with Child-Pugh A cirrhosis. Twelve phase II or III clinical trials of the 2-DAA regimen of OBV/PTV/r±ribavirin (RBV) or the 3-DAA regimen of OBV/PTV/r+DSV±RBV that included patients with Child-Pugh A cirrhosis were reviewed; patients who completed treatment by November 16, 2015 were included in a pooled, post hoc safety assessment. The number and percentage of patients with treatment-emergent adverse events (TEAEs), serious TEAEs, and TEAEs consistent with hepatic decompensation were reported. In 1,066 patients with Child-Pugh A cirrhosis, rates of serious TEAEs and TEAEs leading to study drug discontinuation were 5.3% (95% confidence interval [CI]: 4.1-6.8) and 2.2% (95% CI: 1.4-3.2), respectively. Thirteen patients (1.2%; 95% CI: 0.7-2.1) had a TEAE that was consistent with hepatic decompensation. The most frequent TEAEs consistent with hepatic decompensation were ascites (n=8), esophageal variceal hemorrhage (n=4), and hepatic encephalopathy (n=2). This pooled analysis in 1,066 HCV-infected patients with Child-Pugh A cirrhosis confirms the safety of OBV/PTV/r±DSV±RBV in this population. These results support the use of OBV/PTV/r±DSV±RBV in this high-priority population. Lay summary: This pooled safety analysis in 1,066 HCV-infected patients with compensated cirrhosis, receiving treatment with ombitasvir, paritaprevir, and ritonavir with or without dasabuvir, with or without ribavirin, shows that the rate of hepatic decompensation events was similar to previously reported rates in untreated patients. Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Risk of pneumonia with budesonide-containing treatments in COPD: an individual patient-level pooled analysis of interventional studies

PubMed Central

Hollis, Sally; Jorup, Carin; Lythgoe, Dan; Martensson, Gunnar; Regnell, Pontus; Eckerwall, Göran

2017-01-01

Background Concerns have been raised that treatment of COPD with inhaled corticosteroids may increase pneumonia risk. Responding to a request from the European Medicines Agency Pharmacovigilance Risk Assessment Committee, a pooled analysis of interventional studies compared pneumonia risk with inhaled budesonide-containing versus non-budesonide-containing treatments and the impact of other clinically relevant factors. Methods AstraZeneca-sponsored, parallel-group, double-blind, randomized controlled trials meeting the following criteria were included: >8 weeks’ duration; ≥60 patients with COPD; inhaled budesonide treatment arm (budesonide/formoterol or budesonide); and non-budesonide-containing comparator arm (formoterol or placebo). Primary and secondary outcomes were time to first pneumonia treatment-emergent serious adverse event (TESAE) and treatment-emergent adverse event (TEAEs), respectively, analyzed using Cox regression models stratified by study. Results Eleven studies were identified; 10,570 out of 10,574 randomized patients receiving ≥1 dose of study treatment were included for safety analysis (budesonide-containing, n=5,750; non-budesonide-containing, n=4,820). Maximum exposure to treatment was 48 months. The overall pooled hazard ratio (HR), comparing budesonide versus non-budesonide-containing treatments, was 1.15 for pneumonia TESAEs (95% confidence interval [CI]: 0.83, 1.57) and 1.13 for pneumonia TEAEs (95% CI: 0.94, 1.36). The annual incidence of pneumonia TESAEs was 1.9% and 1.5% for budesonide-containing and non-budesonide-containing treatments, respectively. Comparing budesonide/formoterol with non-budesonide-containing treatment, the HRs for pneumonia TESAEs and TEAEs were 1.00 (95% CI: 0.69, 1.44) and 1.21 (95% CI: 0.93, 1.57), respectively. For budesonide versus placebo, HRs were 1.57 for pneumonia TESAEs (95% CI: 0.90, 2.74) and 1.07 for pneumonia TEAEs (95% CI: 0.83, 1.38). Conclusion This pooled analysis found no statistically significant increase in overall risk for pneumonia TESAEs or TEAEs with budesonide-containing versus non-budesonide-containing treatments. However, a small increase in risk with budesonide-containing treatment cannot be ruled out; there is considerable heterogeneity in study designs and patient characteristics, particularly in the early budesonide studies, and each study contributes <40 pneumonia TESAEs. PMID:28435240

Risk of pneumonia with budesonide-containing treatments in COPD: an individual patient-level pooled analysis of interventional studies.

PubMed

Hollis, Sally; Jorup, Carin; Lythgoe, Dan; Martensson, Gunnar; Regnell, Pontus; Eckerwall, Göran

2017-01-01

Concerns have been raised that treatment of COPD with inhaled corticosteroids may increase pneumonia risk. Responding to a request from the European Medicines Agency Pharmacovigilance Risk Assessment Committee, a pooled analysis of interventional studies compared pneumonia risk with inhaled budesonide-containing versus non-budesonide-containing treatments and the impact of other clinically relevant factors. AstraZeneca-sponsored, parallel-group, double-blind, randomized controlled trials meeting the following criteria were included: >8 weeks' duration; ≥60 patients with COPD; inhaled budesonide treatment arm (budesonide/formoterol or budesonide); and non-budesonide-containing comparator arm (formoterol or placebo). Primary and secondary outcomes were time to first pneumonia treatment-emergent serious adverse event (TESAE) and treatment-emergent adverse event (TEAEs), respectively, analyzed using Cox regression models stratified by study. Eleven studies were identified; 10,570 out of 10,574 randomized patients receiving ≥1 dose of study treatment were included for safety analysis (budesonide-containing, n=5,750; non-budesonide-containing, n=4,820). Maximum exposure to treatment was 48 months. The overall pooled hazard ratio (HR), comparing budesonide versus non-budesonide-containing treatments, was 1.15 for pneumonia TESAEs (95% confidence interval [CI]: 0.83, 1.57) and 1.13 for pneumonia TEAEs (95% CI: 0.94, 1.36). The annual incidence of pneumonia TESAEs was 1.9% and 1.5% for budesonide-containing and non-budesonide-containing treatments, respectively. Comparing budesonide/formoterol with non-budesonide-containing treatment, the HRs for pneumonia TESAEs and TEAEs were 1.00 (95% CI: 0.69, 1.44) and 1.21 (95% CI: 0.93, 1.57), respectively. For budesonide versus placebo, HRs were 1.57 for pneumonia TESAEs (95% CI: 0.90, 2.74) and 1.07 for pneumonia TEAEs (95% CI: 0.83, 1.38). This pooled analysis found no statistically significant increase in overall risk for pneumonia TESAEs or TEAEs with budesonide-containing versus non-budesonide-containing treatments. However, a small increase in risk with budesonide-containing treatment cannot be ruled out; there is considerable heterogeneity in study designs and patient characteristics, particularly in the early budesonide studies, and each study contributes <40 pneumonia TESAEs.

Pooled Systemic Efficacy and Safety Data from the Pivotal Phase II Studies (NP28673 and NP28761) of Alectinib in ALK-positive Non-Small Cell Lung Cancer.

PubMed

Yang, James Chih-Hsin; Ou, Sai-Hong Ignatius; De Petris, Luigi; Gadgeel, Shirish; Gandhi, Leena; Kim, Dong-Wan; Barlesi, Fabrice; Govindan, Ramaswamy; Dingemans, Anne-Marie C; Crino, Lucio; Lena, Herve; Popat, Sanjay; Ahn, Jin Seok; Dansin, Eric; Golding, Sophie; Bordogna, Walter; Balas, Bogdana; Morcos, Peter N; Zeaiter, Ali; Shaw, Alice T

2017-10-01

Alectinib demonstrated clinical efficacy and an acceptable safety profile in two phase II studies (NP28761 and NP28673). Here we report the pooled efficacy and safety data after 15 and 18 months more follow-up than in the respective primary analyses. Enrolled patients had ALK receptor tyrosine kinase gene (ALK)-positive NSCLC and had progressed while taking, or could not tolerate, crizotinib. Patients received oral alectinib, 600 mg twice daily. The primary end point in both studies was objective response rate assessed by an independent review committee (IRC) using the Response Evaluation Criteria in Solid Tumors, version 1.1. Secondary end points included disease control rate, duration of response, progression-free survival, overall survival, and safety. The pooled data set included 225 patients (n = 138 in NP28673 and n = 87 in NP28761). The response-evaluable population included 189 patients (84% [n = 122 in NP28673 and n = 67 in NP28761]). In the response-evaluable population, objective response rate as assessed by the IRC was 51.3% (95% confidence interval [CI]: 44.0-58.6 [all PRs]), the disease control rate was 78.8% (95% CI: 72.3-84.4), and the median duration of response was 14.9 months (95% CI: 11.1-20.4) after 58% of events. Median progression-free survival as assessed by the IRC was 8.3 months (95% CI: 7.0-11.3) and median overall survival was 26.0 months (95% CI: 21.4-not estimable). Grade 3 or higher adverse events (AEs) occurred in 40% of patients, 6% of patients had treatment withdrawn on account of AEs, and 33% had AEs leading to dose interruptions/modification. This pooled data analysis confirmed the robust systemic efficacy of alectinib in ALK-positive NSCLC with a durable response rate. Alectinib also had an acceptable safety profile with a longer duration of follow-up. Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Regional sub-cratonic mantle heterogeneities under the Kaapvaal craton recorded by sulfide inclusions in diamond.

NASA Astrophysics Data System (ADS)

Thomassot, E.; Lorand, J. P.

2016-12-01

Sulfide inclusions in diamonds (SID) have been trapped by their host at depth greater than 150 km and then protected from alteration or reequilibration processes. Subsequently, depending on their initial composition, there have experienced multiple exsolution events at temperatures between 650°C and 200°C. Mineralogical and isotopic composition of SID thus directly reflects their sources whereas their texture give information on the exhumation history of their diamond host. Our samples originating from Koffiefontein, De Beers Pool and Jwaneng kimberlites, include both peridotitic (P-type, n=6) and eclogitic (E-type, n=151) sulfides. P-type sulfides are monosulfide solid solutions (exsolved from a nickeliferous monosulfide solid solution, mss, stable at T>300°C). Their Ni and Cr content indicate that the sublithospheric mantle under Koffiefontein (Ni=26wt%; Cr=0.36 wt%) is more refractory than De Beers Pool (Ni=24wt%; Cr=0.28wt%) and Jwaneng (Ni=17wt%; Cr=0.22wt%). Sulfides from De Beers Pool have S/Se (3900±100) greater than the chondritic values ( 2540) pointing to a metasomatic overprint predating the formation of diamonds. S-isotopic composition (d34S=-0.9 ± 0.5‰, Δ33S=0‰) are homogeneous, and consistent with the composition of MORB. E-type sulfides are unmixed assemblage of chalcopyrite (crystallized from an intermediate solid solution formed at T 650°C) pentlandite (T° from 260 to >200°C) and pyrrhotite. Comparing the chemical composition of the unmixed phases with experimental data, we determined a blocking T° for E-type assemblages ranging from 540°C at Koffiefontein, to less than 200°C at Jwaneng and DeBeersPool. E-type sulfides thus confirm the chemical heterogeneity from one mine to the other, with d34S extended to fractionated values (-9 to +11‰). Our study indicates that SID are robust probes to explore regional scale mantle heterogeneities likely associated to discrete depletion events and possible recycling of ancient sediment, predating the formation of diamonds. Major, trace element and isotopes data will be presented at the conference in order to support this conclusion.

Adverse events with bismuth salts for Helicobacter pylori eradication: Systematic review and meta-analysis

PubMed Central

Ford, Alexander C; Malfertheiner, Peter; Giguère, Monique; Santana, José; Khan, Mostafizur; Moayyedi, Paul

2008-01-01

AIM: To assess the safety of bismuth used in Helicobacter pylori (H pylori) eradication therapy regimens. METHODS: We conducted a systematic review and meta-analysis. MEDLINE and EMBASE were searched (up to October 2007) to identify randomised controlled trials comparing bismuth with placebo or no treatment, or bismuth salts in combination with antibiotics as part of eradication therapy with the same dose and duration of antibiotics alone or, in combination, with acid suppression. Total numbers of adverse events were recorded. Data were pooled and expressed as relative risks with 95% confidence intervals (CI). RESULTS: We identified 35 randomised controlled trials containing 4763 patients. There were no serious adverse events occurring with bismuth therapy. There was no statistically significant difference detected in total adverse events with bismuth [relative risk (RR) = 1.01; 95% CI: 0.87-1.16], specific individual adverse events, with the exception of dark stools (RR = 5.06; 95% CI: 1.59-16.12), or adverse events leading to withdrawal of therapy (RR = 0.86; 95% CI: 0.54-1.37). CONCLUSION: Bismuth for the treatment of H pylori is safe and well-tolerated. The only adverse event occurring significantly more commonly was dark stools. PMID:19109870

Teasing Apart the Effects of Atmospheric Nitrogen Deposition from Grazing and Drought in Vernal Pool Wetlands and Adjacent Grassland

NASA Astrophysics Data System (ADS)

Fogel, M. L.; Araiza, D. N.; Nakamoto, B. J.; Vega, M. C.; Bradley, C. J.; Swarth, C. W.

2014-12-01

The remaining vernal pools flanking California's Central Valley may be protected from development, but they are not pristine environments. At UC Merced's Vernal Pools and Grassland Reserve, dairy cattle grazing is a fact of life, needed to keep non-native grasses from encroaching on and dominating these low lying, ephemeral pools. In addition to grazing, atmospheric deposition of nitrogen from adjacent agricultural farms and dairies has affected the biogeochemical cycling here, in particular because the area has never been ploughed and is essentially a terminal, interior catchment with almost no outputs. For the past two years, the region has been subjected to extreme drought resulting in altered patterns in vernal pool development and nutrient exchange. We are using stable nitrogen, carbon, and hydrogen isotopes in organic and inorganic reservoirs to understand which of the three stressors (e.g. N loading, grazing, or drought) affects the ecosystem functioning the most. Simple measurements of residual dry matter (the rancher's standard) coupled with soil analyses and plant distribution, isotopic composition, and productivity will be presented at a landscape scale. Atmospheric deposition, as rain in winter and early spring and as dust in summer and fall, delivers substantial ammonium and nitrate to the Reserve and could be traced back to nearby hotspots, as well as from major storm systems. Concentrations and compositions of N in precipitation were highly variable depending on when the last storm event had occurred. Ammonia/ammonium in rainwater ranged from δ15N= -24 to +7‰, probably explaining the large range in the δ15N of plant tissues collected in winter/spring (-4.3 to +10.9‰,) and that of extractable ammonium from surface soils (δ15N = -7 to +13‰). Interior grassland and vernal pool ecosystems, with substantial inputs and little to no outputs, host biogeochemical processes that amplify heterogeneity on relative small scales.

Experiments on Pool-riffle Sequences with Multi-fractional Sediment Bed During Floods

NASA Astrophysics Data System (ADS)

Rodriguez, J. F.; Vahidi, E.; Bayat, E.; de Almeida, G. A. M.; Saco, P. M.

2017-12-01

The morphodynamics of pools and riffles has been the subject of research for over a century and has more recently attracted intense attention for their central role in providing habitat diversity conditions, both in terms of flow and substrate. Initial efforts to explain the long-term stability of the pool-riffle (PR) sequences (often referred to as self-maintenance) focused almost exclusively on cross sectional flow characteristics (either average or near bed velocity or shear stress), using episodic shifts in higher shear stress or velocities from riffles to pools during floods (i.e. reversal conditions) as an indication of the long-term self-maintenance of the structures.. However, less attention has been paid to the interactions of flow unsteadiness, sediment supply and sedimentological contrasts as the drivers for maintaining PR sequences. Here we investigate these effects through laboratory experiments on a scaled-down PR sequence of an existing gravel bed river. Froude similitude and equality of Shields' number were applied to scale one- to four-year recurrence flood events and sediment size distributions, respectively. We conducted experiments with different hydrographs and different sedimentological conditions. In each experiment we continuously measured velocities and shear stresses (using acoustic velocity profilers) bed levels (using a bed profiler) and bed grain size distribution (using an automatic digital technique on the painted bed sediments) during the hydrographs. Our results show that the most important factors for self-maintenance were the sediment bed composition, the level of infilling of the pool and the sediment supply grainsize distribution. These results highlight the need to consider the time varying sedimentological characteristics of a PR sequence to assess its capacity for self-maintenance.

Safety Profile of Eslicarbazepine Acetate as Add-On Therapy in Adults with Refractory Focal-Onset Seizures: From Clinical Studies to 6 Years of Post-Marketing Experience.

PubMed

Gama, Helena; Vieira, Mariana; Costa, Raquel; Graça, Joana; Magalhães, Luís M; Soares-da-Silva, Patrício

2017-12-01

Eslicarbazepine acetate was first approved in the European Union in 2009 as adjunctive therapy in adults with partial-onset seizures with or without secondary generalization. The objective of this study was to review the safety profile of eslicarbazepine acetate analyzing the data from several clinical studies to 6 years of post-marketing surveillance. We used a post-hoc pooled safety analysis of four phase III, double-blind, randomized, placebo-controlled studies (BIA-2093-301, -302, -303, -304) of eslicarbazepine acetate as add-on therapy in adults. Safety data of eslicarbazepine acetate in special populations of patients aged ≥65 years with partial-onset seizures (BIA-2093-401) and subjects with moderate hepatic impairment (BIA-2093-111) and renal impairment (BIA-2093-112) are also considered. The incidences of treatment-emergent adverse events, treatment-emergent adverse events leading to discontinuation, and serious adverse events were analyzed. The global safety database of eslicarbazepine acetate was analyzed for all cases from post-marketing surveillance from 1 October, 2009 to 21 October, 2015. From a pooled analysis of four phase III studies, it was concluded that the incidence of treatment-emergent adverse events, treatment-emergent adverse events leading to discontinuation, and adverse drug reactions were dose dependent. Dizziness, somnolence, headache, and nausea were the most common treatment-emergent adverse events (≥10% of patients) and the majority were of mild-to-moderate intensity. No dose-dependent trend was observed for serious adverse events and individual serious adverse events were reported in less than 1% of patients. Hyponatremia was classified as a possibly related treatment-emergent adverse event in phase III studies (1.2%); however, after 6 years of post-marketing surveillance it represents the most frequently (10.2%) reported adverse drug reaction, with more than half of these cases occurring with eslicarbazepine acetate at daily doses of 1200 mg. Other adverse drug reactions reported in post-marketing surveillance are seizure (5.8%), dizziness (4.1%), rash (2.6%), and fatigue (2.1%). The safety profile of eslicarbazepine acetate in renal and hepatic impairment subjects (phase I studies) and in elderly patients (phase III study) did not raise any specific concern. After 6 years of post-marketing surveillance, eslicarbazepine acetate maintains a similar safety profile to that observed in pivotal clinical studies.

Tropical Intraseasonal Air-Sea Exchanges during the 1997 Pacific Warming

NASA Technical Reports Server (NTRS)

Sui, C.-H.; Lau, K.-M.; Chou, S.-H.; Wang, Zihou

1999-01-01

The Madden Julian Oscillations (MJO) and associated westerly wind (WW) events account for much of the tropical intraseasonal variability (TISV). The TISV has been suggested as an important stochastic forcing that may be one of the underlying causes for the observed irregularities of the El Nino-Southern Oscillation (ENSO). Recent observational studies and theories of interannual to interdecadal-scale variability suggest that ENSO may arise from different mechanisms depending on the basic states. The Pacific warming event of 1997, being associated with a period of strong MJO and WW events, serves as a natural experiment for studying the possible role of TISV in triggering an ENSO event. We have performed a combined statistical and composite analysis of surface WW events based on the assimilated surface wind and sea level pressure for the period of 1980-1993, the SSM/I wind for the period of 1988-1997, and OLR. Results indicates that extratropical forcing contribute significantly to the evolution of MJO and establishment of WW events over the Pacific warm pool. Following the major WW events, there appeared an eastward extension of equatorial warm SST anomalies from the western Pacific warm pool. Such tropical-extratropical interaction is particularly clear in the winter of 96-97 that leads to the recent warming event in 1997/98. From the above discussion, our current study on this subject is based on the hypothesis that 1) there is an enhanced air-sea interaction associated with TISV and the northerly surges from the extratropics in the initial phase of the 97/98 warming event, and 2) the relevant mechanisms are functions of the basic state of the coupled system (in terms of SST distribution and atmospheric mean circulation) that varies at the interannual and interdecadal time scale. We are analyzing the space-time structure of the northerly surges, their association with air-sea fluxes and upper ocean responses during the period of September 1996 to June 1997. The estimate of daily values of latent heat fluxes is based on NSCAT wind, SST, and ECMWF surface air temperature and SSM/I water vapor data (Chou et al. 1997). To understand the relevant mechanisms, we will analyze the origin of the northerly surges in terms of atmospheric instability associated with the extratropical circulation, and the mutual influence between the tropical heating and the extratropical circulation. In this meeting, we will report the analysis addressing the first part of the above hypothesis.

Development of a Culture Specific Critical Thinking Ability Test and Using It as a Supportive Diagnostic Test for Giftedness

ERIC Educational Resources Information Center

Köksal, Mustafa Serdar

2016-01-01

The purposes of this study were to develop a culture specific critical thinking ability test for 6, 7, and 8. grade students in Turkey and to use it as an assessment instrument for giftedness. For these purposes, item pool involving 22 items was formed by writing items focusing on the current and common events presented in (Turkish) media from…

STS_135_Russia

NASA Image and Video Library

2011-03-30

JSC2011-E-040325 (30 March 2011) --- NASA astronaut Doug Hurley, STS-135 pilot, waits in a pressure chamber before a test of his Sokol spacesuit at the Zvezda facility in Moscow March 30, 2011. The crew of the final shuttle mission traveled to Moscow for a suit fit check of their Russian spacesuits which would be required in the event of an emergency. Photo credit: NASA Photo/Houston Chronicle, Smiley N. Pool

Using discrete-event simulation in strategic capacity planning for an outpatient physical therapy service.

PubMed

Rau, Chi-Lun; Tsai, Pei-Fang Jennifer; Liang, Sheau-Farn Max; Tan, Jhih-Cian; Syu, Hong-Cheng; Jheng, Yue-Ling; Ciou, Ting-Syuan; Jaw, Fu-Shan

2013-12-01

This study uses a simulation model as a tool for strategic capacity planning for an outpatient physical therapy clinic in Taipei, Taiwan. The clinic provides a wide range of physical treatments, with 6 full-time therapists in each session. We constructed a discrete-event simulation model to study the dynamics of patient mixes with realistic treatment plans, and to estimate the practical capacity of the physical therapy room. The changes in time-related and space-related performance measurements were used to evaluate the impact of various strategies on the capacity of the clinic. The simulation results confirmed that the clinic is extremely patient-oriented, with a bottleneck occurring at the traction units for Intermittent Pelvic Traction (IPT), with usage at 58.9 %. Sensitivity analysis showed that attending to more patients would significantly increase the number of patients staying for overtime sessions. We found that pooling the therapists produced beneficial results. The average waiting time per patient could be reduced by 45 % when we pooled 2 therapists. We found that treating up to 12 new patients per session had no significantly negative impact on returning patients. Moreover, we found that the average waiting time for new patients decreased if they were given priority over returning patients when called by the therapists.

Systematic review of prognostic importance of extramural venous invasion in rectal cancer

PubMed Central

Chand, Manish; Siddiqui, Muhammed RS; Swift, Ian; Brown, Gina

2016-01-01

AIM: To systematically review the survival outcomes relating to extramural venous invasion in rectal cancer. METHODS: A systematic review was conducted using PRISMA guidelines. An electronic search was carried out using MEDLINE, EMBASE, CINAHL, Cochrane library databases, Google scholar and PubMed until October 2014. Search terms were used in combination to yield articles on extramural venous invasion in rectal cancer. Outcome measures included prevalence and 5-year survival rates. These were graphically displayed using Forest plots. Statistical analysis of the data was carried out. RESULTS: Fourteen studies reported the prevalence of extramural venous invasion (EMVI) positive patients. Prevalence ranged from 9%-61%. The pooled prevalence of EMVI positivity was 26% [Random effects: Event rate 0.26 (0.18, 0.36)]. Most studies showed that EMVI related to worse oncological outcomes. The pooled overall survival was 39.5% [Random effects: Event rate 0.395 (0.29, 0.51)]. CONCLUSION: Historically, there has been huge variation in the prevalence of EMVI through inconsistent reporting. However the presence of EMVI clearly leads to worse survival outcomes. As detection rates become more consistent, EMVI may be considered as part of risk-stratification in rectal cancer. Standardised histopathological definitions and the use of magnetic resonance imaging to identify EMVI will improve detection rates in the future. PMID:26819536

Unraveling the non-senescence phenomenon in Hydra.

PubMed

Dańko, Maciej J; Kozłowski, Jan; Schaible, Ralf

2015-10-07

Unlike other metazoans, Hydra does not experience the distinctive rise in mortality with age known as senescence, which results from an increasing imbalance between cell damage and cell repair. We propose that the Hydra controls damage accumulation mainly through damage-dependent cell selection and cell sloughing. We examine our hypothesis with a model that combines cellular damage with stem cell renewal, differentiation, and elimination. The Hydra individual can be seen as a large single pool of three types of stem cells with some features of differentiated cells. This large stem cell community prevents "cellular damage drift," which is inevitable in complex conglomerate (differentiated) metazoans with numerous and generally isolated pools of stem cells. The process of cellular damage drift is based on changes in the distribution of damage among cells due to random events, and is thus similar to Muller's ratchet in asexual populations. Events in the model that are sources of randomness include budding, cellular death, and cellular damage and repair. Our results suggest that non-senescence is possible only in simple Hydra-like organisms which have a high proportion and number of stem cells, continuous cell divisions, an effective cell selection mechanism, and stem cells with the ability to undertake some roles of differentiated cells. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Effects of vilazodone on suicidal ideation and behavior in adults with major depressive disorder or generalized anxiety disorder: post-hoc analysis of randomized, double-blind, placebo-controlled trials.

PubMed

Thase, Michael E; Edwards, John; Durgam, Suresh; Chen, Changzheng; Chang, Cheng-Tao; Mathews, Maju; Gommoll, Carl P

2017-09-01

Treatment-emergent suicidal ideation and behavior are ongoing concerns with antidepressants. Vilazodone, currently approved for the treatment of major depressive disorder (MDD) in adults, has also been evaluated in generalized anxiety disorder (GAD). Post-hoc analyses of vilazodone trials were carried out to examine its effects on suicidal ideation and behavior in adults with MDD or GAD. Data were pooled from vilazodone trials in MDD (four studies) and GAD (three studies). The incidence of suicide-related events was analyzed on the basis of treatment-emergent adverse event reporting and Columbia-Suicide Severity Rating Scale (C-SSRS) monitoring. Treatment-emergent suicidal ideation was analyzed on the basis of a C-SSRS category shift from no suicidal ideation/behavior (C-SSRS=0) at baseline to suicide ideation (C-SSRS=1-5) during treatment. In pooled safety populations (MDD, n=2233; GAD, n=1475), suicide-related treatment-emergent adverse events occurred in less than 1% of vilazodone-treated and placebo-treated patients. Incidences of C-SSRS suicidal ideation were as follows: MDD (vilazodone=19.9%, placebo=24.7%); GAD (vilazodone=7.7%, placebo=9.4%). Shifts from no suicidal ideation/behavior at baseline to suicidal ideation during treatment were as follows: MDD (vilazodone=9.4%, placebo=10.3%); GAD (vilazodone=4.4%, placebo=6.1%). Data from placebo-controlled studies indicate little or no risk of treatment-emergent suicidal ideation or behavior with vilazodone in adults with MDD or GAD. Nevertheless, all patients should be monitored for suicidal thoughts and behaviors during antidepressant treatment.

Budesonide Foam Has a Favorable Safety Profile for Inducing Remission in Mild-to-Moderate Ulcerative Proctitis or Proctosigmoiditis.

PubMed

Rubin, David T; Sandborn, William J; Bosworth, Brian; Zakko, Salam; Gordon, Glenn L; Sale, Mark E; Rolleri, Robert L; Golden, Pamela L; Barrett, Andrew C; Bortey, Enoch; Forbes, William P

2015-11-01

Budesonide foam, a rectally administered, second-generation corticosteroid with extensive hepatic first-pass metabolism, is efficacious for the treatment of mild-to-moderate ulcerative proctitis and ulcerative proctosigmoiditis. The aim of this study was to comprehensively assess the safety and pharmacokinetic profile of budesonide foam. Data from five phase III studies were pooled to further evaluate safety, including an open-label study (once-daily treatment for 8 weeks), an active-comparator study (once-daily treatment for 4 weeks), and two placebo-controlled studies and an open-label extension study (twice-daily treatment for 2 weeks, then once daily for 4 weeks). Data from the placebo-controlled studies and two phase I studies (i.e., patients with mild-to-moderate ulcerative colitis and healthy volunteers) were pooled to evaluate the pharmacokinetics of budesonide foam. A similar percentage of patients reported adverse events in the budesonide foam and placebo groups, with the majority of adverse events being mild or moderate in intensity (93.3 vs 96.0%, respectively). Adverse events occurred in 41.4 and 36.3% of patients receiving budesonide foam and placebo, respectively. Mean morning cortisol concentrations remained within the normal range for up to 8 weeks of treatment; there were no clinically relevant effects of budesonide foam on the hypothalamic-pituitary-adrenal axis. Population pharmacokinetic analysis demonstrated low systemic exposure after budesonide foam administration. This integrated analysis demonstrated that budesonide foam for the induction of remission of distal ulcerative colitis is safe overall, with no clinically relevant effects on the hypothalamic-pituitary-adrenal axis.

The efficacy and short-term effects of electronic cigarettes as a method for smoking cessation: a systematic review and a meta-analysis.

PubMed

Khoudigian, S; Devji, T; Lytvyn, L; Campbell, K; Hopkins, R; O'Reilly, D

2016-03-01

E-cigarettes are increasingly popular as smoking cessation aids. This review assessed the efficacy of e-cigarettes for smoking cessation as well as desire to smoke, withdrawal symptoms, and adverse events in adult smokers. A systematic review was conducted. Studies comparing e-cigarettes to other nicotine replacement therapies or placebo were included. Data were pooled using meta-analysis. Of 569 articles, 5 were eligible. Study participants were more likely to stop smoking when using nicotine e-cigarettes (43/489, 9 %) versus placebo e-cigarettes (8/173, 5 %); however, this difference was not statistically significant (RR 2.02; 95 % CI 0.97, 4.22). The pooled effect estimates for the desire to smoke (RR -0.22; 95 % CI -0.80, 0.36), irritability (RR -0.03; 95% CI -0.38, 0.31), restlessness (RR -0.03; 95 % CI -0.42, 0.35), poor concentration (RR -0.01; 95 % CI -0.35, 0.32), depression (RR -0.01; 95 % CI -0.22, 0.20), hunger (RR -0.01; 95 % CI -0.32, 0.30), and average number of non-serious adverse events (RR -0.09; 95 % CI -0.28, 0.46) were not statistically significantly different. Only one study reported serious adverse events with no apparent association with e-cigarette use. Limited low-quality evidence of a non-statistically significant trend toward smoking cessation in adults using nicotine e-cigarettes exists compared with other therapies or placebo. Larger, high-quality studies are needed to inform policy decisions.

An Assessment of Fission Product Scrubbing in Sodium Pools Following a Core Damage Event in a Sodium Cooled Fast Reactor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bucknor, M.; Farmer, M.; Grabaskas, D.

The U.S. Nuclear Regulatory Commission has stated that mechanistic source term (MST) calculations are expected to be required as part of the advanced reactor licensing process. A recent study by Argonne National Laboratory has concluded that fission product scrubbing in sodium pools is an important aspect of an MST calculation for a sodium-cooled fast reactor (SFR). To model the phenomena associated with sodium pool scrubbing, a computational tool, developed as part of the Integral Fast Reactor (IFR) program, was utilized in an MST trial calculation. This tool was developed by applying classical theories of aerosol scrubbing to the decontamination ofmore » gases produced as a result of postulated fuel pin failures during an SFR accident scenario. The model currently considers aerosol capture by Brownian diffusion, inertial deposition, and gravitational sedimentation. The effects of sodium vapour condensation on aerosol scrubbing are also treated. This paper provides details of the individual scrubbing mechanisms utilized in the IFR code as well as results from a trial mechanistic source term assessment led by Argonne National Laboratory in 2016.« less

Measurement of the temporal progression of scour in a pool-riffle sequence in a gravel bed stream using an electronic scour monitor

NASA Astrophysics Data System (ADS)

Devries, Paul; Burges, Stephen J.; Daigneau, Julie; Stearns, Daniel

2001-11-01

A relatively inexpensive prototype monitor was designed and developed to record temporal variation in scour depth and was field-tested in a gravel bed stream. The device consists of plastic practice golf balls that are fitted internally with ring magnets and strung on a two-conductor cable enclosing a small reed switch. The balls are installed and oriented near-vertically in the streambed. As each ball is disturbed and released, it slides along the cable past the reed switch, and the time of circuit closure caused by passage of the magnet is recorded by a data logger. The device can be applied in arrays that span large areas of the streambed, including in wide channels that are inaccessible during a flood. Data obtained from 19 devices installed in an aggrading site described scouring processes in a pool-riffle interface during a bed load transport event. Substantial bed excavation occurred in the region of the pool edge during the rising stage, indicating existence of a local, temporally varying imbalance in bed load transport rate. Bed disturbance in the rest of the site prior to aggradation was limited to the surface and immediate subpavement layer.

A Flight/Ground/Test Event Logging Facility

NASA Technical Reports Server (NTRS)

Dvorak, Daniel

1999-01-01

The onboard control software for spacecraft such as Mars Pathfinder and Cassini is composed of many subsystems including executive control, navigation, attitude control, imaging, data management, and telecommunications. The software in all of these subsystems needs to be instrumented for several purposes: to report required telemetry data, to report warning and error events, to verify internal behavior during system testing, and to provide ground operators with detailed data when investigating in-flight anomalies. Events can range in importance from purely informational events to major errors. It is desirable to provide a uniform mechanism for reporting such events and controlling their subsequent processing. Since radiation-hardened flight processors are several years behind the speed and memory of their commercial cousins, and since most subsystems require real-time control, and since downlink rates to earth can be very low from deep space, there are limits to how much of the data can be saved and transmitted. Some kinds of events are more important than others and should therefore be preferentially retained when memory is low. Some faults can cause an event to recur at a high rate, but this must not be allowed to consume the memory pool. Some event occurrences may be of low importance when reported but suddenly become more important when a subsequent error event gets reported. Some events may be so low-level that they need not be saved and reported unless specifically requested by ground operators.

Enhanced Pacific Ocean Sea Surface Temperature and Its Relation to Typhoon Haiyan

NASA Technical Reports Server (NTRS)

Comiso, Josefino C.; Perez, Gay Jane P.; Stock, Larry V.

2015-01-01

Typhoon Haiyan, which devastated the Visayan Islands in the Philippines on November 8, 2013 was recorded as the strongest typhoon ever-observed using satellite data. Typhoons in the region usually originate from the mid-Pacific region that includes the Warm Pool, which is regarded as the warmest ocean surface region globally. Two study areas were considered: one in the Warm Pool Region and the other in the West Pacific Region near the Philippines. Among the most important factors that affect the strength of a typhoon are sea surface temperature (SST) and water vapor. It is remarkable that in November 2013 the average SST in the Warm Pool Region was the highest observed during the 1981 to 2014 period while that of the West Pacific Region was among the highest as well. Moreover, the increasing trend in SST was around 0.20C per decade in the warm pool region and even higher at 0.23C per decade in the West Pacific region. The yearly minimum SST has also been increasing suggesting that the temperature of the ocean mixed layer is also increasing. Further analysis indicated that water vapor, clouds, winds and sea level pressure for the same period did not reveal strong signals associated with the 2013 event. The SST is shown to be well-correlated with wind strength of historically strong typhoons in the country and the observed trends in SST suggest that extremely destructive typhoons like Haiyan are likely to occur in the future.

Cerebrovascular accidents in patients treated for choroidal neovascularization with ranibizumab in randomized controlled trials.

PubMed

Bressler, Neil M; Boyer, David S; Williams, David F; Butler, Steven; Francom, Steven F; Brown, Benton; Di Nucci, Flavia; Cramm, Timothy; Tuomi, Lisa L; Ianchulev, Tsontcho; Rubio, Roman G

2012-10-01

To analyze cerebrovascular accidents (CVAs) pooled from large, randomized, controlled clinical trials of ranibizumab treatment for neovascular age-related macular degeneration. Events in five trials (FOCUS, MARINA, ANCHOR, PIER, and SAILOR) were analyzed using a standard safety monitoring process. Exact methods, stratified by study, were used to test for treatment differences based on odds ratios. A stepwise logistic regression model was fit to classify subjects' risk for CVA based on medical history. Treatment differences in CVA rates at 1 year or 2 years were evaluated within risk groups using stratified exact methods. Pooled 2-year CVA rates were <3%; odds ratios (95% confidence intervals) for CVA risk were 1.2 (0.4-4.4) for ranibizumab 0.3-mg versus control, 2.2 (0.8-7.1) for 0.5 mg versus control, and 1.5 (0.8-3.0) for 0.5-mg versus 0.3-mg ranibizumab. No substantial increased risk of CVA for 0.5 mg versus 0.3 mg was identified in pooled analyses or any of the individual trials. In pooled analyses, the difference between 0.5-mg ranibizumab and control was larger (7.7 [1.2-177]) among high-risk CVA patients. This analysis provided some evidence, although not definitive, of a potential increased risk of CVA with ranibizumab versus control or with 0.5-mg versus 0.3-mg ranibizumab. Continued monitoring for CVA within clinical trials seems warrented.

Origin of year-long bean (Phaseolus dumosus Macfady, Fabaceae) from reticulated hybridization events between multiple Phaseolus species.

PubMed

Mina-Vargas, Angela M; McKeown, Peter C; Flanagan, Nicola S; Debouck, Daniel G; Kilian, Andrzej; Hodkinson, Trevor R; Spillane, Charles

2016-08-06

Improved understanding of the secondary gene pools of crops is essential for advancing genetic gain in breeding programmes. Common bean, Phaseolus vulgaris, is a staple crop with several wild relatives in its secondary gene pool. The year-long bean, P. dumosus, an important crop in Guatemala, is considered particularly closely related to P. vulgaris and a potential source of novel variation. However, the genetic diversity and relationship to other Phaseolus species of P. dumosus remain unclear. We conducted the first comprehensive investigation of P. dumosus genetic diversity using both nuclear and chloroplast genome markers. Our nuclear marker set included over 700 markers present within the Phaseolus DArT (Diversity Arrays Technology) array, which we applied to P. dumosus and other relatives of P. vulgaris (including every secondary gene pool species: P. acutifolius, P. albescens, P. coccineus and P. costaricensis). Phaseolus dumosus arose from hybridization of P. vulgaris and P. coccineus, followed by at least two later hybridizations with sympatric congener populations. Existing P. dumosus collections have low genetic diversity. The under-utilized crop P. dumosus has a complex hybrid origin. Further sampling in the region in which it arose may uncover additional germplasm for introgressing favourable traits into crops within the P. vulgaris gene pool. © The Author 2016. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Meta-analysis of serum lactate dehydrogenase and prognosis for osteosarcoma.

PubMed

Fu, Yucheng; Lan, Tao; Cai, Hongliu; Lu, Anwei; Yu, Wei

2018-05-01

A large number of studies have reported the relationships between serum lactate dehydrogenase (LDH) and prognosis of osteosarcoma. However, the result is still controversial and no consensus has been reached. Therefore, we performed a meta-analysis to evaluate the prognostic role of serum LDH in osteosarcoma patients. We performed the systematic computerized search for eligible articles from PubMed, Embase, and Cochrane databases until December 21, 2017. The pooled hazard ratio (HR) and 95% confidence intervals (CIs) of overall survival (OS) and event-free survival (EFS) were obtained to assess the prognostic value of serum LDH. A total of 18 studies with 2543 osteosarcoma patients were included. Overall, 15 studies assessed the elevated serum LDH level on OS and the pooled HR was 1.87 (95% CI = 1.58-2.20). Meanwhile, the pooled HR to evaluate the relationship between serum LDH and EFS in 9 studies was 1.78 (95% CI = 1.51-2.10). The same results were acquired when these studies were stratified by Enneking stage, geographic region, and sample size. No heterogeneity existed between these subgroups (P > .05). Begg's funnel plot and Egger's test (OS: P = .04; EFS: P = .34) showed that possible publication bias might exist in OS studies. Sensitivity analysis suggested the pooled HR was robust. This meta-analysis demonstrates that elevated serum LDH level is apparently associated with lower EFS rate and serum LDH could be a prognostic biomarker for osteosarcoma patients.

The Coast Artillery Journal. Volume 61, Number 5, November 1924

DTIC Science & Technology

1924-11-01

34 put into their work. Every afternoon and evening the tennis courts, bowling alleys, handball courts and the baseball diamond were cluttered up with...pushball, handball , bowling, track and field events and several informal games thrown in. The individuals starred in tennis, bowling, pool and in the War...and C. M. T. C. candidates were trans- ported to various beach resorts in the neighborhood of Pensacola. Several churches in Pensacola invited the

STS-39 MS Hieb prepares for emergency egress exercises in JSC's WETF Bldg 29

NASA Technical Reports Server (NTRS)

1990-01-01

STS-39 Mission Specialist (MS) Richard J. Hieb, wearing launch and entry suit (LES), parachute pack, and communications carrier assembly (CCA), listens to instructions prior to emergency egress bailout exercises in JSC's Weightless Environment Training Facility (WETF) Bldg 29. The WETF's 25 ft deep pool will simulate the ocean. Crewmembers will practice procedures necessary in the event of an emergency onboard the Space Shuttle requiring a water landing.

ASCAN Precourt floats on life raft during Elgin AFB water survival training

NASA Technical Reports Server (NTRS)

1990-01-01

1990 Group 13 Astronaut Candidate (ASCAN) Charles J. Precourt, wearing helmet and flight suit, floats in pool using an underarm flotation device and a single person life raft at Elgin Air Force Base (AFB) in Pensacola, Florida, during water survival exercises. The training familiarized the candidates with survival techniques necessary in the event of a water landing. ASCANs participated in the exercises from 08-14-90 through 08-17-90.

STS_135_Russia

NASA Image and Video Library

2011-03-28

JSC2011-E-040302 (28 March 2011) --- NASA astronaut Rex Walheim's name is seen in both English and Russian on a "Penguin" suit during a suit fit check at the Zvezda facility in Moscow on March 28, 2011. The crew of the final shuttle mission traveled to Moscow for a suit fit check of their Russian Sokol suits which would be required in the event of an emergency. Photo credit: NASA Photo/Houston Chronicle, Smiley N. Pool

Regulation of Pituitary Stem Cells by Epithelial to Mesenchymal Transition Events and Signaling Pathways

PubMed Central

Cheung, Leonard Y. M.; Davis, Shannon W.; Brinkmeier, Michelle L.; Camper, Sally A.; Pérez-Millán, María Inés

2017-01-01

The anterior pituitary gland is comprised of specialized cell-types that produce and secrete polypeptide hormones in response to hypothalamic input and feedback from target organs. These specialized cells arise from stem cells that express SOX2 and the pituitary transcription factor PROP1, which is necessary to establish the stem cell pool and promote an epithelial to mesenchymal-like transition, releasing progenitors from the niche. The adult anterior pituitary responds to physiological challenge by mobilizing the SOX2-expressing progenitor pool and producing additional hormone-producing cells. Knowledge of the role of signaling pathways and extracellular matrix components in these processes may lead to improvements in the efficiency of differentiation of embryonic stem cells or induced pluripotent stem cells into hormone producing cells in vitro. Advances in our basic understanding of pituitary stem cell regulation and differentiation may lead to improved diagnosis and treatment for patients with hypopituitarism. PMID:27650955

Ultrastructural and functional fate of recycled vesicles in hippocampal synapses

PubMed Central

Rey, Stephanie A.; Smith, Catherine A.; Fowler, Milena W.; Crawford, Freya; Burden, Jemima J.; Staras, Kevin

2015-01-01

Efficient recycling of synaptic vesicles is thought to be critical for sustained information transfer at central terminals. However, the specific contribution that retrieved vesicles make to future transmission events remains unclear. Here we exploit fluorescence and time-stamped electron microscopy to track the functional and positional fate of vesicles endocytosed after readily releasable pool (RRP) stimulation in rat hippocampal synapses. We show that most vesicles are recovered near the active zone but subsequently take up random positions in the cluster, without preferential bias for future use. These vesicles non-selectively queue, advancing towards the release site with further stimulation in an actin-dependent manner. Nonetheless, the small subset of vesicles retrieved recently in the stimulus train persist nearer the active zone and exhibit more privileged use in the next RRP. Our findings reveal heterogeneity in vesicle fate based on nanoscale position and timing rules, providing new insights into the origins of future pool constitution. PMID:26292808

Placebo effects in trials evaluating 12 selected minimally invasive interventions: a systematic review and meta-analysis

PubMed Central

Holtedahl, Robin; Brox, Jens Ivar; Tjomsland, Ole

2015-01-01

Objectives To analyse the impact of placebo effects on outcome in trials of selected minimally invasive procedures and to assess reported adverse events in both trial arms. Design A systematic review and meta-analysis. Data sources and study selection We searched MEDLINE and Cochrane library to identify systematic reviews of musculoskeletal, neurological and cardiac conditions published between January 2009 and January 2014 comparing selected minimally invasive with placebo (sham) procedures. We searched MEDLINE for additional randomised controlled trials published between January 2000 and January 2014. Data synthesis Effect sizes (ES) in the active and placebo arms in the trials’ primary and pooled secondary end points were calculated. Linear regression was used to analyse the association between end points in the active and sham groups. Reported adverse events in both trial arms were registered. Results We included 21 trials involving 2519 adult participants. For primary end points, there was a large clinical effect (ES≥0.8) after active treatment in 12 trials and after sham procedures in 11 trials. For secondary end points, 7 and 5 trials showed a large clinical effect. Three trials showed a moderate difference in ES between active treatment and sham on primary end points (ES ≥0.5) but no trials reported a large difference. No trials showed large or moderate differences in ES on pooled secondary end points. Regression analysis of end points in active treatment and sham arms estimated an R2 of 0.78 for primary and 0.84 for secondary end points. Adverse events after sham were in most cases minor and of short duration. Conclusions The generally small differences in ES between active treatment and sham suggest that non-specific mechanisms, including placebo, are major predictors of the observed effects. Adverse events related to sham procedures were mainly minor and short-lived. Ethical arguments frequently raised against sham-controlled trials were generally not substantiated. PMID:25636794

Safety of inhaled glycopyrronium in patients with COPD: a comprehensive analysis of clinical studies and post-marketing data.

PubMed

D'Urzo, Anthony D; Kerwin, Edward M; Chapman, Kenneth R; Decramer, Marc; DiGiovanni, Robert; D'Andrea, Peter; Hu, Huilin; Goyal, Pankaj; Altman, Pablo

2015-01-01

Chronic use of inhaled anticholinergics by patients with chronic obstructive pulmonary disease (COPD) has raised long-term safety concerns, particularly cardiovascular. Glycopyrronium is a once-daily anticholinergic with greater receptor selectivity than previously available agents. We assessed the safety of inhaled glycopyrronium using data pooled from two analysis sets, involving six clinical studies and over 4,000 patients with COPD who received one of the following treatments: glycopyrronium 50 μg, placebo (both delivered via the Breezhaler device), or tiotropium 18 μg (delivered via the HandiHaler device). Data were pooled from studies that varied in their duration and severity of COPD of the patients (ie, ≤12 weeks duration with patients having moderate or severe COPD; and >1 year duration with patients having severe and very severe COPD). Safety comparisons were made for glycopyrronium vs tiotropium or placebo. Poisson regression was used to assess the relative risk for either active drug or placebo (and between drugs where placebo was not available) for assessing the incidence of safety events. During post-marketing surveillance (PMS), safety was assessed by obtaining reports from various sources, and disproportionality scores were computed using EMPIRICA. In particular, the cardiac safety of glycopyrronium during the post-marketing phase was evaluated. The overall incidence of adverse events and deaths was similar across groups, while the incidence of serious adverse events was numerically higher in placebo. Furthermore, glycopyrronium did not result in an increased risk of cerebro-cardiovascular events vs placebo. There were no new safety reports during the PMS phase that suggested an increased risk compared to results from the clinical studies. Moreover, the cardiac safety of glycopyrronium during the PMS phase was also consistent with the clinical data. The overall safety profile of glycopyrronium was similar to its comparators indicating no increase in the overall risk for any of the investigated safety end points.

Simeprevir plus sofosbuvir, with or without ribavirin, to treat chronic infection with hepatitis C virus genotype 1 in non-responders to pegylated interferon and ribavirin and treatment-naive patients: the COSMOS randomised study.

PubMed

Lawitz, Eric; Sulkowski, Mark S; Ghalib, Reem; Rodriguez-Torres, Maribel; Younossi, Zobair M; Corregidor, Ana; DeJesus, Edwin; Pearlman, Brian; Rabinovitz, Mordechai; Gitlin, Norman; Lim, Joseph K; Pockros, Paul J; Scott, John D; Fevery, Bart; Lambrecht, Tom; Ouwerkerk-Mahadevan, Sivi; Callewaert, Katleen; Symonds, William T; Picchio, Gaston; Lindsay, Karen L; Beumont, Maria; Jacobson, Ira M

2014-11-15

Interferon-free regimens are needed to treat hepatitis C virus (HCV) infections. We investigated the efficacy of combined simeprevir and sofosbuvir. We enrolled patients with chronic HCV genotype 1 infections who had previously not responded to pegylated interferon (peginterferon) and ribavirin or were treatment naive. Patients were randomly assigned in a 2:1:2:1 ratio to receive 150 mg simeprevir and 400 mg sofosbuvir daily for 24 weeks with (group 1) or without (group 2) ribavirin or for 12 weeks with (group 3) or without (group 4) ribavirin, in two cohorts: previous non-responders with METAVIR scores F0-F2 (cohort 1) and previous non-responders and treatment-naive patients with METAVIR scores F3-F4 (cohort 2). The primary endpoint was sustained virological response 12 weeks after stopping treatment (SVR12). Analysis was done by intention to treat. Safety data from cohorts 1 and 2 were pooled for analysis. This study is registered with ClinicalTrials.gov, number NCT01466790. 168 patients were enrolled and randomised, and 167 started treatment (n=80 in cohort 1 and n=87 in cohort 2). SVR12 was achieved in 154 (92%) patients (n=72 [90%, 95% CI 81-96] in cohort 1 and n=82 [94%, 87-98] in cohort 2). The most common adverse events in the pooled groups were fatigue (n=52 [31%]), headache (n=33 [20%]), and nausea (n=26 [16%]). Grade 4 adverse events were seen in one (2%) of 54 patients in each of groups 1 and 3 and in three (10%) of 31 patients in group 2, whereas grade 3-4 events were reported in less than 5% of all patients, except increased blood amylase concentration. Serious adverse events were seen in four (2%) patients, all in groups 1 and 2. Four (2%) patients discontinued all study treatment because of adverse events, three before week 12. Combined simeprevir and sofosbuvir was efficacious and well tolerated. Janssen. Copyright © 2014 Elsevier Ltd. All rights reserved.

The effectiveness of smoking cessation, physical activity/diet and alcohol reduction interventions delivered by mobile phones for the prevention of non-communicable diseases: A systematic review of randomised controlled trials

PubMed Central

Sutherland, Jennifer; Barnard, Sharmani; Wynne, Aileen; Rezel, Emma; Doel, Andrew; Grigsby-Duffy, Lily; Edwards, Suzanne; Russell, Sophie; Hotopf, Ellie; Perel, Pablo; Free, Caroline

2018-01-01

Background We conducted a systematic review to assess the effectiveness of smoking cessation, physical activity (PA), diet, and alcohol reduction interventions delivered by mobile technology to prevent non-communicable diseases (NCDs). Methods We searched for randomised controlled trials (RCTs) of mobile-based NCD prevention interventions using MEDLINE, EMBASE, Global Health, CINAHL (Jan 1990–Jan 2016). Two authors extracted data. Findings 71 trials were included: smoking cessation (n = 18); PA (n = 15), diet (n = 3), PA and diet (n = 25); PA, diet, and smoking cessation (n = 2); and harmful alcohol consumption (n = 8). 4 trials had low risk of bias. The effect of SMS-based smoking cessation support on biochemically verified continuous abstinence was pooled relative risk [RR] 2.19 [95% CI 1.80–2.68], I2 = 0%) and on verified 7 day point prevalence of smoking cessation was pooled RR 1.51 [95% CI 1.06–2.15], I2 = 0%, with no reported adverse events. There was no difference in peak oxygen intake at 3 months in a trial of an SMS-based PA intervention. The effect of SMS-based diet and PA interventions on: incidence of diabetes was pooled RR 0.67 [95% CI 0.49, 0.90], I2 = 0.0%; end-point weight was pooled MD -0.99Kg [95% CI -3.63, 1.64] I2 = 29.4%; % change in weight was pooled MD -3.1 [95%CI -4.86- -1.3] I2 0.3%; and on triglyceride levels was pooled MD -0.19 mmol/L [95% CI -0.29, -0.08], I2 = 0.0%. The results of other pooled analyses of the effect of SMS-based diet and PA interventions were heterogenous (I2 59–90%). The effects of alcohol reduction interventions were inconclusive. Conclusions Smoking cessation support delivered by SMS increases quitting rates. Trials of PA interventions reporting outcomes ≥3 months showed no benefits. There were at best modest benefits of diet and PA interventions. The effects of the most promising SMS-based smoking, diet and PA interventions on morbidity and mortality in high-risk groups should be established in adequately powered RCTs. PMID:29304148

The effectiveness of smoking cessation, physical activity/diet and alcohol reduction interventions delivered by mobile phones for the prevention of non-communicable diseases: A systematic review of randomised controlled trials.

PubMed

Palmer, Melissa; Sutherland, Jennifer; Barnard, Sharmani; Wynne, Aileen; Rezel, Emma; Doel, Andrew; Grigsby-Duffy, Lily; Edwards, Suzanne; Russell, Sophie; Hotopf, Ellie; Perel, Pablo; Free, Caroline

2018-01-01

We conducted a systematic review to assess the effectiveness of smoking cessation, physical activity (PA), diet, and alcohol reduction interventions delivered by mobile technology to prevent non-communicable diseases (NCDs). We searched for randomised controlled trials (RCTs) of mobile-based NCD prevention interventions using MEDLINE, EMBASE, Global Health, CINAHL (Jan 1990-Jan 2016). Two authors extracted data. 71 trials were included: smoking cessation (n = 18); PA (n = 15), diet (n = 3), PA and diet (n = 25); PA, diet, and smoking cessation (n = 2); and harmful alcohol consumption (n = 8). 4 trials had low risk of bias. The effect of SMS-based smoking cessation support on biochemically verified continuous abstinence was pooled relative risk [RR] 2.19 [95% CI 1.80-2.68], I2 = 0%) and on verified 7 day point prevalence of smoking cessation was pooled RR 1.51 [95% CI 1.06-2.15], I2 = 0%, with no reported adverse events. There was no difference in peak oxygen intake at 3 months in a trial of an SMS-based PA intervention. The effect of SMS-based diet and PA interventions on: incidence of diabetes was pooled RR 0.67 [95% CI 0.49, 0.90], I2 = 0.0%; end-point weight was pooled MD -0.99Kg [95% CI -3.63, 1.64] I2 = 29.4%; % change in weight was pooled MD -3.1 [95%CI -4.86- -1.3] I2 0.3%; and on triglyceride levels was pooled MD -0.19 mmol/L [95% CI -0.29, -0.08], I2 = 0.0%. The results of other pooled analyses of the effect of SMS-based diet and PA interventions were heterogenous (I2 59-90%). The effects of alcohol reduction interventions were inconclusive. Smoking cessation support delivered by SMS increases quitting rates. Trials of PA interventions reporting outcomes ≥3 months showed no benefits. There were at best modest benefits of diet and PA interventions. The effects of the most promising SMS-based smoking, diet and PA interventions on morbidity and mortality in high-risk groups should be established in adequately powered RCTs.

Habitual chocolate consumption and risk of cardiovascular disease among healthy men and women.

PubMed

Kwok, Chun Shing; Boekholdt, S Matthijs; Lentjes, Marleen A H; Loke, Yoon K; Luben, Robert N; Yeong, Jessica K; Wareham, Nicholas J; Myint, Phyo K; Khaw, Kay-Tee

2015-08-01

To examine the association between chocolate intake and the risk of future cardiovascular events. We conducted a prospective study using data from the European Prospective Investigation into Cancer (EPIC)-Norfolk cohort. Habitual chocolate intake was quantified using the baseline food frequency questionnaire (1993-1997) and cardiovascular end points were ascertained up to March 2008. A systematic review was performed to evaluate chocolate consumption and cardiovascular outcomes. A total of 20,951 men and women were included in EPIC-Norfolk analysis (mean follow-up 11.3±2.8 years, median 11.9 years). The percentage of participants with coronary heart disease (CHD) in the highest and lowest quintile of chocolate consumption was 9.7% and 13.8%, and the respective rates for stroke were 3.1% and 5.4%. The multivariate-adjusted HR for CHD was 0.88 (95% CI 0.77 to 1.01) for those in the top quintile of chocolate consumption (16-99 g/day) versus non-consumers of chocolate intake. The corresponding HR for stroke and cardiovascular disease (cardiovascular disease defined by the sum of CHD and stroke) were 0.77 (95% CI 0.62 to 0.97) and 0.86 (95% CI 0.76 to 0.97). The propensity score matched estimates showed a similar trend. A total of nine studies with 157,809 participants were included in the meta-analysis. Higher compared to lower chocolate consumption was associated with significantly lower CHD risk (five studies; pooled RR 0.71, 95% CI 0.56 to 0.92), stroke (five studies; pooled RR 0.79, 95% CI 0.70 to 0.87), composite cardiovascular adverse outcome (two studies; pooled RR 0.75, 95% CI 0.54 to 1.05), and cardiovascular mortality (three studies; pooled RR 0.55, 95% CI 0.36 to 0.83). Cumulative evidence suggests that higher chocolate intake is associated with a lower risk of future cardiovascular events, although residual confounding cannot be excluded. There does not appear to be any evidence to say that chocolate should be avoided in those who are concerned about cardiovascular risk. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Homocysteine lowering interventions for preventing cardiovascular events

PubMed Central

Martí-Carvajal, Arturo J; Solà, Ivan; Lathyris, Dimitrios; Salanti, Georgia

2014-01-01

Background Cardiovascular disease such as coronary artery disease, stroke and congestive heart failure, is a leading cause of death worldwide. A postulated risk factor is elevated circulating total homocysteine (tHcy) levels which is influenced mainly by blood levels of cyanocobalamin (vitamin B12), folic acid (vitamin B9) and pyridoxine (vitamin B6). There is uncertainty regarding the strength of association between tHcy and the risk of cardiovascular disease. Objectives To assess the clinical effectiveness of homocysteine-lowering interventions (HLI) in people with or without pre-existing cardiovascular disease. Search methods We searched The Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library (issue 3 2008), MEDLINE (1950 to August 2008), EMBASE (1988 to August 2008), and LILACS (1982 to September 2, 2008). We also searched in Allied and Complementary Medicine (AMED; 1985 to August 2008), ISI Web of Science (1993 to August 2008), and the Cochrane Stroke Group Specialised Register (April 2007). We hand searched pertinent journals and the reference lists of included papers. We also contacted researchers in the field. There was no language restriction in the search. Selection criteria We included randomised clinical trials (RCTs) assessing the effects of HLI for preventing cardiovascular events with a follow-up period of 1 year or longer. We considered myocardial infarction and stroke as the primary outcomes. We excluded studies in patients with end-stage renal disease. Data collection and analysis We independently performed study selection, risk of bias assessment and data extraction. We estimated relative risks (RR) for dichotomous outcomes. We measured statistical heterogeneity using I2. We used a random-effects model to synthesise the findings. Main results We included eight RCTs involving 24,210 participants with a low risk of bias in general terms. HLI did not reduce the risk of non-fatal or fatal myocardial infarction, stroke, or death by any cause (pooled RR 1.03, 95% CI 0.94 to 1.13, I2 = 0%; pooled RR 0.89, 95% CI 0.73 to 1.08, I2 = 15%); and pooled RR 1.00 (95% CI 0.92 to 1.09, I2: 0%), respectively. Authors’ conclusions Results from available published trials suggest that there is no evidence to support the use of HLI to prevent cardiovascular events. PMID:19821378

Accuracy of the Atherosclerotic Cardiovascular Risk Equation in a Large Contemporary, Multiethnic Population.

PubMed

Rana, Jamal S; Tabada, Grace H; Solomon, Matthew D; Lo, Joan C; Jaffe, Marc G; Sung, Sue Hee; Ballantyne, Christie M; Go, Alan S

2016-05-10

The accuracy of the 2013 American College of Cardiology/American Heart Association (ACC/AHA) Pooled Cohort Risk Equation for atherosclerotic cardiovascular disease (ASCVD) events in contemporary and ethnically diverse populations is not well understood. The goal of this study was to evaluate the accuracy of the 2013 ACC/AHA Pooled Cohort Risk Equation within a large, multiethnic population in clinical care. The target population for consideration of cholesterol-lowering therapy in a large, integrated health care delivery system population was identified in 2008 and followed up through 2013. The main analyses excluded those with known ASCVD, diabetes mellitus, low-density lipoprotein cholesterol levels <70 or ≥190 mg/dl, prior lipid-lowering therapy use, or incomplete 5-year follow-up. Patient characteristics were obtained from electronic medical records, and ASCVD events were ascertained by using validated algorithms for hospitalization databases and death certificates. We compared predicted versus observed 5-year ASCVD risk, overall and according to sex and race/ethnicity. We additionally examined predicted versus observed risk in patients with diabetes mellitus. Among 307,591 eligible adults without diabetes between 40 and 75 years of age, 22,283 were black, 52,917 were Asian/Pacific Islander, and 18,745 were Hispanic. We observed 2,061 ASCVD events during 1,515,142 person-years. In each 5-year predicted ASCVD risk category, observed 5-year ASCVD risk was substantially lower: 0.20% for predicted risk <2.50%; 0.65% for predicted risk 2.50% to <3.75%; 0.90% for predicted risk 3.75% to <5.00%; and 1.85% for predicted risk ≥5.00% (C statistic: 0.74). Similar ASCVD risk overestimation and poor calibration with moderate discrimination (C statistic: 0.68 to 0.74) were observed in sex, racial/ethnic, and socioeconomic status subgroups, and in sensitivity analyses among patients receiving statins for primary prevention. Calibration among 4,242 eligible adults with diabetes was improved, but discrimination was worse (C statistic: 0.64). In a large, contemporary "real-world" population, the ACC/AHA Pooled Cohort Risk Equation substantially overestimated actual 5-year risk in adults without diabetes, overall and across sociodemographic subgroups. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Net clinical benefit of dabigatran vs. warfarin in venous thromboembolism: analyses from RE-COVER®, RE-COVER™ II, and RE-MEDY™.

PubMed

Feuring, Martin; Schulman, Sam; Eriksson, Henry; Kakkar, Ajay J; Schellong, Sebastian; Hantel, Stefan; Schueler, Elke; Kreuzer, Jörg; Goldhaber, Samuel Z

2017-05-01

The direct oral anticoagulants, e.g., dabigatran etexilate (DE), are effective and well tolerated treatments for venous thromboembolism (VTE). Net clinical benefit (NCB) is a useful concept in weighing potential benefits against potential harm of comparator drugs. The NCB of DE vs. warfarin in VTE treatment was compared. Post-hoc analyses were performed on pooled data from the 6-month RE-COVER® and RE-COVER™ II trials, and data from the RE-MEDY™ trial (up to 36 months), to compare the NCB of DE (150 mg twice daily) and warfarin [target international normalized ratio (INR) 2.0-3.0]. Patients (≥18 years old) had symptomatic proximal deep vein thrombosis and/or pulmonary embolism. NCB was the composite of cardiovascular endpoints (non-fatal events of recurrent VTE, myocardial infarction, stroke or systemic embolism), all-cause death, and bleeding outcomes, all weighted equally. A broad definition of NCB included major bleeding events (MBE) and clinically relevant non-major bleeding events as bleeding outcomes, while a narrow definition included just MBE. The pooled dataset totalled 5107 patients from RE-COVER/RE-COVER II and 2856 patients from RE-MEDY. When NCB was narrowly defined, NCB was similar between DE and warfarin. When broadly defined, NCB was superior with DE vs. warfarin [RE-COVER/RE-COVER II, hazard ratio (HR) 0.80; 95% confidence interval (CI), 0.68-0.95 and RE-MEDY, HR 0.73; 95% CI 0.59-0.91]. These findings were unaffected by warfarin time in therapeutic range. The NCB of DE was similar or superior to warfarin, depending on the NCB definition used, regardless of the quality of INR control.

Utility and safety of draining pleural effusions in mechanically ventilated patients: a systematic review and meta-analysis

PubMed Central

2011-01-01

Introduction Pleural effusions are frequently drained in mechanically ventilated patients but the benefits and risks of this procedure are not well established. Methods We performed a literature search of multiple databases (MEDLINE, EMBASE, HEALTHSTAR, CINAHL) up to April 2010 to identify studies reporting clinical or physiological outcomes of mechanically ventilated critically ill patients who underwent drainage of pleural effusions. Studies were adjudicated for inclusion independently and in duplicate. Data on duration of ventilation and other clinical outcomes, oxygenation and lung mechanics, and adverse events were abstracted in duplicate independently. Results Nineteen observational studies (N = 1,124) met selection criteria. The mean PaO2:FiO2 ratio improved by 18% (95% confidence interval (CI) 5% to 33%, I2 = 53.7%, five studies including 118 patients) after effusion drainage. Reported complication rates were low for pneumothorax (20 events in 14 studies including 965 patients; pooled mean 3.4%, 95% CI 1.7 to 6.5%, I2 = 52.5%) and hemothorax (4 events in 10 studies including 721 patients; pooled mean 1.6%, 95% CI 0.8 to 3.3%, I2 = 0%). The use of ultrasound guidance (either real-time or for site marking) was not associated with a statistically significant reduction in the risk of pneumothorax (OR = 0.32; 95% CI 0.08 to 1.19). Studies did not report duration of ventilation, length of stay in the intensive care unit or hospital, or mortality. Conclusions Drainage of pleural effusions in mechanically ventilated patients appears to improve oxygenation and is safe. We found no data to either support or refute claims of beneficial effects on clinically important outcomes such as duration of ventilation or length of stay. PMID:21288334

Effects of vilazodone on suicidal ideation and behavior in adults with major depressive disorder or generalized anxiety disorder: post-hoc analysis of randomized, double-blind, placebo-controlled trials

PubMed Central

Edwards, John; Durgam, Suresh; Chen, Changzheng; Chang, Cheng-Tao; Mathews, Maju; Gommoll, Carl P.

2017-01-01

Treatment-emergent suicidal ideation and behavior are ongoing concerns with antidepressants. Vilazodone, currently approved for the treatment of major depressive disorder (MDD) in adults, has also been evaluated in generalized anxiety disorder (GAD). Post-hoc analyses of vilazodone trials were carried out to examine its effects on suicidal ideation and behavior in adults with MDD or GAD. Data were pooled from vilazodone trials in MDD (four studies) and GAD (three studies). The incidence of suicide-related events was analyzed on the basis of treatment-emergent adverse event reporting and Columbia-Suicide Severity Rating Scale (C-SSRS) monitoring. Treatment-emergent suicidal ideation was analyzed on the basis of a C-SSRS category shift from no suicidal ideation/behavior (C-SSRS=0) at baseline to suicide ideation (C-SSRS=1–5) during treatment. In pooled safety populations (MDD, n=2233; GAD, n=1475), suicide-related treatment-emergent adverse events occurred in less than 1% of vilazodone-treated and placebo-treated patients. Incidences of C-SSRS suicidal ideation were as follows: MDD (vilazodone=19.9%, placebo=24.7%); GAD (vilazodone=7.7%, placebo=9.4%). Shifts from no suicidal ideation/behavior at baseline to suicidal ideation during treatment were as follows: MDD (vilazodone=9.4%, placebo=10.3%); GAD (vilazodone=4.4%, placebo=6.1%). Data from placebo-controlled studies indicate little or no risk of treatment-emergent suicidal ideation or behavior with vilazodone in adults with MDD or GAD. Nevertheless, all patients should be monitored for suicidal thoughts and behaviors during antidepressant treatment. PMID:28538024

Safety and efficacy of ocrelizumab in rheumatoid arthritis patients with an inadequate response to methotrexate or tumor necrosis factor inhibitors: a systematic review and meta-analysis.

PubMed

Abushouk, Abdelrahman Ibrahim; Ahmed, Hussien; Ismail, Ammar; Elmaraezy, Ahmed; Badr, Ahmed Said; Gadelkarim, Mohamed; Elnenny, Mohammed

2017-07-01

We conducted this systematic reviews and meta-analysis to investigate the safety and efficacy of ocrelizumab in patients with active rheumatoid arthritis (RA) who exhibited resistance or intolerance to methotrexate or biological therapy. We performed a web-based literature search of PubMed, Google Scholar, EBSCO, Scopus, Embase, and Web of science for studies that compared ocrelizumab plus methotrexate versus methotrexate plus placebo in RA patients. Data were extracted from eligible studies and pooled as risk ratios (RR), using RevMan software. Pooling data from four RCTs (2230 patients) showed that ocrelizumab plus methotrexate were superior to methotrexate plus placebo at 24 weeks in terms of improvement on the American college of rheumatology (ACR20, ACR50, and ACR70) criteria (p < 0.00001), disease activity score 28-ESR (RR = 3.77, 95% CI [2.47, 5.74], p < 0.00001), and Sharp/van der Heijde radiological score (RR = 1.63, 95% CI [1.43, 1.85], p < 0.00001). These effects were consistent among all ocrelizumab doses. The rates of serious adverse events were comparable between the ocrelizumab and placebo containing groups (RR = 1, 95% CI [0.78, 1.28], p = 0.98). However, infusion related reactions were significantly higher in ocrelizumab group (RR = 2.13, 95% CI [1.69, 2.68], p < 0.00001), compared to placebo group. The combination of ocrelizumab plus methotrexate was superior to methotrexate plus placebo on all clinical and radiographic improvement scales. The incidence of adverse events, including serious adverse events, was comparable between both groups. Future trials should investigate the efficacy of ocrelizumab alone and develop strategies to alleviate its related infusion reactions.

Occurrence of Anti-Drug Antibodies against Interferon-Beta and Natalizumab in Multiple Sclerosis: A Collaborative Cohort Analysis

PubMed Central

Mbogning, Cyprien; Link, Jenny; Ryner, Malin; Ramanujam, Ryan; Auer, Michael; Hyldgaard Jensen, Poul Erik; Koch-Henriksen, Nils; Warnke, Clemens; Ingenhoven, Kathleen; Buck, Dorothea; Grummel, Verena; Lawton, Andy; Donnellan, Naoimh; Hincelin-Mery, Agnès; Sikkema, Dan; Pallardy, Marc; Kieseier, Bernd; Hemmer, Bernard; Hartung, Hans Peter; Soelberg Sorensen, Per; Deisenhammer, Florian; Dönnes, Pierre; Davidson, Julie; Fogdell-Hahn, Anna; Broët, Philippe

2016-01-01

Immunogenicity of biopharmaceutical products in multiple sclerosis is a frequent side effect which has a multifactorial etiology. Here we study associations between anti-drug antibody (ADA) occurrence and demographic and clinical factors. Retrospective data from routine ADA test laboratories in Sweden, Denmark, Austria and Germany (Dusseldorf group) and from one research study in Germany (Munich group) were gathered to build a collaborative multi-cohort dataset within the framework of the ABIRISK project. A subset of 5638 interferon-beta (IFNβ)-treated and 3440 natalizumab-treated patients having data on at least the first two years of treatment were eligible for interval-censored time-to-event analysis. In multivariate Cox regression, IFNβ-1a subcutaneous and IFNβ-1b subcutaneous treated patients were at higher risk of ADA occurrence compared to IFNβ-1a intramuscular-treated patients (pooled HR = 6.4, 95% CI 4.9–8.4 and pooled HR = 8.7, 95% CI 6.6–11.4 respectively). Patients older than 50 years at start of IFNβ therapy developed ADA more frequently than adult patients younger than 30 (pooled HR = 1.8, 95% CI 1.4–2.3). Men developed ADA more frequently than women (pooled HR = 1.3, 95% CI 1.1–1.6). Interestingly we observed that in Sweden and Germany, patients who started IFNβ in April were at higher risk of developing ADA (HR = 1.6, 95% CI 1.1–2.4 and HR = 2.4, 95% CI 1.5–3.9 respectively). This result is not confirmed in the other cohorts and warrants further investigations. Concerning natalizumab, patients older than 45 years had a higher ADA rate (pooled HR = 1.4, 95% CI 1.0–1.8) and women developed ADA more frequently than men (pooled HR = 1.4, 95% CI 1.0–2.0). We confirmed previously reported differences in immunogenicity of the different types of IFNβ. Differences in ADA occurrence by sex and age are reported here for the first time. These findings should be further investigated taking into account other exposures and biomarkers. PMID:27806057

Topical versus oral antibiotics, with or without corticosteroids, in the treatment of tympanostomy tube otorrhea.

PubMed

Chee, Jeremy; Pang, Khang Wen; Yong, Jui May; Ho, Roger Chun-Man; Ngo, Raymond

2016-07-01

Antibiotic treatment is the standard of care for tympanostomy tube otorrhea. This meta-analysis aims to evaluate the efficacy of topical antibiotics with or without corticosteroids versus oral antibiotics in the treatment of tube otorrhea in children. MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and ProQuest. The above databases were searched using a search strategy for randomized controlled trials for optimal treatment of tube otorrhea in the pediatric population. PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines were followed. Primary outcome was cure (i.e. clearance of otorrhea) at 2-3 weeks. Secondary outcomes were microbiological eradication and complications such as dermatitis and diarrhea. The incidence of these events was defined as dichotomous variables and expressed as a risk ratio (RR) and number needed to benefit (NNTB) in a random-effects model. We identified 1491 articles and selected 4 randomized controlled trials which met our inclusion criteria. Topical treatment had better cure (NNTB = 4.7, pooled RR = 1.35, p < 0.001) and microbiological eradication (NNTB = 3.5, pooled RR = 1.47, p < 0.001 among 3 of the studies) than oral antibiotics. Oral antibiotics had higher risk of diarrhea (pooled RR = 21.5, 95% CI 8.00-58.0, p < 0.001, Number needed to harm (NNTH) = 5.4) and dermatitis (pooled RR = 3.14, 95% CI 1.20-8.20, p = 0.019, NNTH = 32). The use of topical steroids in addition to topical antibiotics was associated with a higher cure rate (pooled RR = 1.59, p < 0.001 vs pooled RR = 1.57, p = 0.293). Topical antibiotics should be the recommended treatment for management of tympanostomy tube otorrhea in view of its significantly improved clinical and microbiological efficacy with lower risk of systemic toxicity as compared to oral antibiotics. Further research is necessary to confirm the benefits of topical corticosteroids as an adjunct to topical antibiotics. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A Phase Ib study of ruxolitinib + gemcitabine ± nab-paclitaxel in patients with advanced solid tumors.

PubMed

Bauer, Todd M; Patel, Manish R; Forero-Torres, Andres; George, Thomas J; Assad, Albert; Du, Yining; Hurwitz, Herbert

2018-01-01

Aberrant activation of the Janus-associated kinase (JAK)/signal transducer and activator of transcription (STAT) pathway is associated with increased malignant cell proliferation and survival. This Phase Ib study evaluated ruxolitinib, a potent JAK1/2 inhibitor, in combination with gemcitabine with or without nab-paclitaxel in patients with advanced solid tumors. Patients received ruxolitinib + gemcitabine (regimen A) or ruxolitinib + gemcitabine + nab-paclitaxel (regimen B). The objective of the dose-finding phase was to identify the maximum tolerated doses (MTDs) of ruxolitinib plus gemcitabine with or without nab-paclitaxel. Among 42 patients enrolled, the median age was 62.5 years, 81.0% had pancreatic cancer, and almost 62% had received prior systemic therapy. Regimen A was tolerated with standard doses of gemcitabine; regimen B was tolerated with reduced doses of gemcitabine/nab-paclitaxel or concomitant granulocyte colony-stimulating factor. The sponsor decided to terminate the study early due to the interim analysis results of the Phase III JANUS 1 study. Discontinuations were mainly due to radiologic or clinical disease progression (81.0% of patients). Median treatment durations were 55.5 days (cohort A0) and 150.5 days (pooled B cohorts). Four patients (pooled B cohorts) had dose-limiting toxicities: grade 3 pneumonia (n=1), grade 4 neutropenia (n=1), and grade 4 thrombocytopenia (n=2). The most common grade 3/4 hematologic adverse events (AEs) were anemia, thrombocytopenia, and neutropenia. Serious AEs occurring in ≥2 patients in cohort A0 or pooled B cohorts were abdominal pain, sepsis (cohort A0), dehydration, anemia, and asthenia (pooled B cohorts). Overall response rates (ORRs) were 12.5% in cohort A0 and 38.5% in pooled B cohorts. Among patients with pancreatic cancer, ORR was 23.5% (14.0% cohort A0 30.0% pooled B cohorts). The study was terminated early prior to reaching MTDs per sponsor decision; although ruxolitinib plus gemcitabine with or without nab-paclitaxel was generally safe and well tolerated in patients with advanced solid tumors, this combination will not be pursued further.

Development and evaluation of a reservoir model for the Chain of Lakes in Illinois

USGS Publications Warehouse

Domanski, Marian M.

2017-01-27

Forecasts of flows entering and leaving the Chain of Lakes reservoir on the Fox River in northeastern Illinois are critical information to water-resource managers who determine the optimal operation of the dam at McHenry, Illinois, to help minimize damages to property and loss of life because of flooding on the Fox River. In 2014, the U.S. Geological Survey; the Illinois Department of Natural Resources, Office of Water Resources; and National Weather Service, North Central River Forecast Center began a cooperative study to develop a system to enable engineers and planners to simulate and communicate flows and to prepare proactively for precipitation events in near real time in the upper Fox River watershed. The purpose of this report is to document the development and evaluation of the Chain of Lakes reservoir model developed in this study.The reservoir model for the Chain of Lakes was developed using the Hydrologic Engineering Center–Reservoir System Simulation program. Because of the complex relation between the dam headwater and reservoir pool elevations, the reservoir model uses a linear regression model that relates dam headwater elevation to reservoir pool elevation. The linear regression model was developed using 17 U.S. Geological Survey streamflow measurements, along with the gage height in the reservoir pool and the gage height at the dam headwater. The Nash-Sutcliffe model efficiency coefficients for all three linear regression model variables ranged from 0.90 to 0.98.The reservoir model performance was evaluated by graphically comparing simulated and observed reservoir pool elevation time series during nine periods of high pool elevation. In addition, the peak elevations during these time periods were graphically compared to the closest-in-time observed pool elevation peak. The mean difference in the simulated and observed peak elevations was -0.03 feet, with a standard deviation of 0.19 feet. The Nash-Sutcliffe coefficient for peak prediction was calculated as 0.94. Evaluation of the model based on accuracy of peak prediction and the ability to simulate an elevation time series showed the performance of the model was satisfactory.

Perioperative Aspirin for Prevention of Venous Thromboembolism: The PeriOperative ISchemia Evaluation-2 Trial and a Pooled Analysis of the Randomized Trials.

PubMed

Eikelboom, John W; Kearon, Clive; Guyatt, Gordon; Sessler, Daniel I; Yusuf, Salim; Cook, Deborah; Douketis, James; Patel, Ameen; Kurz, Andrea; Allard, Rene; Jones, Philip M; Dennis, Rodolfo J; Painter, Thomas W; Bergese, Sergio D; Leslie, Kate; Wijeysundera, Duminda N; Balasubramanian, Kumar; Duceppe, Emmanuelle; Miller, Scott; Diedericks, Johan; Devereaux, P J

2016-12-01

The PeriOperative ISchemia Evaluation-2 (POISE-2) trial compared aspirin with placebo after noncardiac surgery. The authors randomly assigned 10,010 patients undergoing noncardiac surgery to receive 200 mg aspirin or placebo 2 to 4 h before surgery and then 100 mg aspirin daily or placebo daily for up to 30 days after surgery. Herein, the authors report the effect of aspirin on venous thromboembolism (VTE), including deep vein thrombosis and pulmonary embolism, as well as an updated pooled analysis of randomized trials of antiplatelet therapy for VTE prevention in noncardiac surgery patients. Six thousand five hundred forty-eight patients (65.4%) received anticoagulant prophylaxis. VTE occurred in 53 patients (1.1%) allocated to aspirin and in 60 patients (1.2%) allocated to placebo (hazard ratio, 0.89; 95% CI, 0.61 to 1.28). Major or life-threatening bleeding occurred in 312 patients (6.3%) allocated to aspirin and in 256 patients (5.1%) allocated to placebo (hazard ratio, 1.22; 95% CI, 1.04 to 1.44). Concomitant use of anticoagulant prophylaxis did not modify the effect of aspirin on VTE or bleeding. Pooled analysis of the POISE-2 and Pulmonary Embolism Prevention trials demonstrated that symptomatic VTE occurred in 173 (1.3%) of 13,724 patients allocated to aspirin and in 246 (1.8%) of 13,730 patients allocated to placebo (odds ratio, 0.71; 95% CI, 0.56 to 0.89; heterogeneity P = 0.27; I = 17%); the impact of aspirin was very similar in those who did and did not receive pharmacologic prophylaxis. Pooled estimates for symptomatic VTE were similar to the pooled estimates for any deep vein thrombosis and pulmonary embolism from the POISE-2 trial, Pulmonary Embolism Prevention trial, and the Antiplatelet Trialists' Collaboration meta-analysis. Aspirin in the POISE-2 trial did not reduce VTE, but two thirds of patients received anticoagulant prophylaxis, there were few VTE events, and results were consistent with a wide range of aspirin effects. A pooled analysis of the randomized trials demonstrates evidence for the efficacy of aspirin for VTE prevention in hospitalized surgical patients.

Occurrence of Anti-Drug Antibodies against Interferon-Beta and Natalizumab in Multiple Sclerosis: A Collaborative Cohort Analysis.

PubMed

Bachelet, Delphine; Hässler, Signe; Mbogning, Cyprien; Link, Jenny; Ryner, Malin; Ramanujam, Ryan; Auer, Michael; Hyldgaard Jensen, Poul Erik; Koch-Henriksen, Nils; Warnke, Clemens; Ingenhoven, Kathleen; Buck, Dorothea; Grummel, Verena; Lawton, Andy; Donnellan, Naoimh; Hincelin-Mery, Agnès; Sikkema, Dan; Pallardy, Marc; Kieseier, Bernd; Hemmer, Bernard; Hartung, Hans Peter; Soelberg Sorensen, Per; Deisenhammer, Florian; Dönnes, Pierre; Davidson, Julie; Fogdell-Hahn, Anna; Broët, Philippe

2016-01-01

Immunogenicity of biopharmaceutical products in multiple sclerosis is a frequent side effect which has a multifactorial etiology. Here we study associations between anti-drug antibody (ADA) occurrence and demographic and clinical factors. Retrospective data from routine ADA test laboratories in Sweden, Denmark, Austria and Germany (Dusseldorf group) and from one research study in Germany (Munich group) were gathered to build a collaborative multi-cohort dataset within the framework of the ABIRISK project. A subset of 5638 interferon-beta (IFNβ)-treated and 3440 natalizumab-treated patients having data on at least the first two years of treatment were eligible for interval-censored time-to-event analysis. In multivariate Cox regression, IFNβ-1a subcutaneous and IFNβ-1b subcutaneous treated patients were at higher risk of ADA occurrence compared to IFNβ-1a intramuscular-treated patients (pooled HR = 6.4, 95% CI 4.9-8.4 and pooled HR = 8.7, 95% CI 6.6-11.4 respectively). Patients older than 50 years at start of IFNβ therapy developed ADA more frequently than adult patients younger than 30 (pooled HR = 1.8, 95% CI 1.4-2.3). Men developed ADA more frequently than women (pooled HR = 1.3, 95% CI 1.1-1.6). Interestingly we observed that in Sweden and Germany, patients who started IFNβ in April were at higher risk of developing ADA (HR = 1.6, 95% CI 1.1-2.4 and HR = 2.4, 95% CI 1.5-3.9 respectively). This result is not confirmed in the other cohorts and warrants further investigations. Concerning natalizumab, patients older than 45 years had a higher ADA rate (pooled HR = 1.4, 95% CI 1.0-1.8) and women developed ADA more frequently than men (pooled HR = 1.4, 95% CI 1.0-2.0). We confirmed previously reported differences in immunogenicity of the different types of IFNβ. Differences in ADA occurrence by sex and age are reported here for the first time. These findings should be further investigated taking into account other exposures and biomarkers.

Financing development stage biotechnology companies: RMs vs. IPOs.

PubMed

Ahn, Mark J; Couch, Robert B; Wu, Wei

2011-01-01

We examine reverse mergers (RMs) in the biotechnology industry and find that, when compared to initial public offerings (IPOs), RMs are smaller, have significantly lower market valuations relative to size, and generally invest less. We also find that RMs exhibit positive abnormal returns on the announcement date and throughout the first year after the RM event. In looking at liquidity measures, we find that RMs tend to be less liquid than IPOs and that illiquidity is greater during the six-month lock-up period following the RM event. Thus, RMs may be an appropriate alternative financing vehicle in capital intensive, high-risk biotechnology companies which require accessing deeper and larger pools of investors in public capital markets across multiple milestone periods in a "pay for progress" environment.

Seismicity of the Pahute Mesa area, Nevada Test Site: 8 October 1975 to 30 June 1976

USGS Publications Warehouse

Rogers, A.M.; Wuollet, Geraldine M.; Covington, P.A.

1977-01-01

A total of 1,075 earthquakes occurred in the Pahute Mesa area with 2.5≤ML≤4.9 during the period October 28, 1975, to June 28, 1976. The majority of these earthquakes are aftershocks of the nuclear events, Kasseri, Inlet, Muenster, Fontina, Cheshire, Estuary, Colby, and Pool (5.8≤ML≤6.3). Smaller nuclear events (ML≤5.5) on Rainier Mesa and Yucca Flat detonated in the same time period did not trigger aftershock sequences. The aftershock series were displaced laterally from ground zero and occurred deeper (at 4–6 km) than the nuclear even depth of burial (~1 km). The aftershocks appear to occur on vertical faults with approximately north-south strike.

ABO blood group and vascular disease: an update.

PubMed

Dentali, Francesco; Sironi, Anna Paola; Ageno, Walter; Crestani, Silvia; Franchini, Massimo

2014-02-01

It has been well known for many years that the ABO blood group has a major influence on hemostasis, through its influence on von Willebrand factor and, consequently, factor VIII plasma levels. Although the relationship between non-O blood type and the risk of venous thromboembolism is nowadays also well established, the association with arterial thrombotic events (i.e., myocardial infarction [MI] and ischemic stroke) is less well characterized. To elucidate the latter issue, we have conducted a systematic review and meta-analysis of the existing literature. After an electronic search strategy using MEDLINE and EMBASE and a manual review of abstract books of the International Society on Thrombosis and Haemostasis and of reference lists of all retrieved articles, 28 studies were finally included in our systematic review. The prevalence of non-O blood group was significantly higher in patients with MI (pooled odds ratio [OR]: 1.28, 95% confidence interval [CI]: 1.17-1.40; p < 0.001) and ischemic stroke (pooled OR: 1.17, 95% CI: 1.01-1.35; p = 0.03) than in controls. The restriction of the analysis to high quality studies only confirmed the association with MI (pooled OR: 1.17, 95% CI: 1.03-1.32) but not with ischemic stroke (pooled OR: 1.28, 95% CI: 0.94-1.74). In conclusion, the results of our meta-analysis confirm the existing literature evidence of a weak association between non-O blood group and vascular arterial thrombosis, in particular myocardial ischemia. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Association between switching antiepileptic drug products and healthcare utilization: A systematic review.

PubMed

Kwan, Patrick; Palmini, André

2017-08-01

There is ongoing concern whether switching between different antiepileptic drug (AED) products may compromise patient care. We systematically reviewed changes in healthcare utilization following AED switch. We searched MEDLINE and EMBASE databases (1980-October 2016) for studies that assessed the effect of AED switching in patients with epilepsy on outpatient visits, emergency room visits, hospitalization and hospital stay duration. A total of 14 articles met the inclusion criteria. All were retrospective studies. Four provided findings for specific AEDs only (lamotrigine, topiramate, phenytoin and divalproex), 9 presented pooled findings from multiple AEDs, and 1 study provided both specific (lamotrigine, topiramate, oxcarbazepine, and levetiracetam) and pooled findings. Three studies found an association between a switch of topiramate and an increase in healthcare utilization. Another three studies found that a brand-to-generic lamotrigine switch was not associated with an increased risk of emergently treated events (ambulance use, ER visits or hospitalization). The outcomes of the pooled AED switch studies were inconsistent; 5 studies reported an increased healthcare utilization while 5 studies did not. Studies that have examined the association between an AED switch and a change in healthcare utilization report conflicting findings. Factors that may explain these inconsistent outcomes include inter-study differences in the type of analysis undertaken (pooled vs individual AED data), the covariates used for data adjustment, and the type of switch examined. Future medical claim database studies employing a prospective design are encouraged to address these and other factors in order to enhance inter-study comparability and extrapolation of findings. Copyright © 2017 Elsevier Inc. All rights reserved.

Kinship and mate choice in a historic eastern Blue Ridge community, Madison County, Virginia.

PubMed

Frankenberg, S R

1990-12-01

Potential mates analysis is difficult to apply to small historic populations that lack clear boundaries or regular vital event registration. Here I analyze the actual mate pool as an alternative way to identify causes of nonrandom mating when unmarried members are unknown. Factors influencing mate choice within a historic eastern Blue Ridge community in Madison County, Virginia, are examined for four marriage cohorts: 1850-1879, 1880-1899, 1900-1919, and 1920-1939. These factors include nuclear kin avoidance, preferred age differences between mates, and preferences for more distant kin. A simulation is used to recombine members of the cohort-specific pools of married individuals to generate the probabilities of various types of kin marriages. The pedigree and vital statistics data are derived from first-time marriage licenses filled by community members in Madison County from 1794 to 1939. The numbers of marriages examined for each cohort are 88, 120, 132, and 132, respectively; the mate pools constructed from the samples are viewed from the female perspective. The results generated by simulation on the actual mate pools consist of mean kinship coefficients, numbers of marriages between "allowed" kin types, and probabilities of these values when marriage is random with respect to kinship. The results indicate significantly high levels of inbreeding in all four marriage cohorts, primarily because of high levels of first-cousin marriages in the first three cohorts and of first-cousin once-removed marriages in the 1920 cohort. The observed mating patterns are discussed in terms of the social history of the Blue Ridge community and restrictions of the data.

Quantifying wintertime boundary layer ozone production from frequent profile measurements in the Uinta Basin, UT, oil and gas region

NASA Astrophysics Data System (ADS)

Schnell, Russell C.; Johnson, Bryan J.; Oltmans, Samuel J.; Cullis, Patrick; Sterling, Chance; Hall, Emrys; Jordan, Allen; Helmig, Detlev; Petron, Gabrielle; Ahmadov, Ravan; Wendell, James; Albee, Robert; Boylan, Patrick; Thompson, Chelsea R.; Evans, Jason; Hueber, Jacques; Curtis, Abigale J.; Park, Jeong-Hoo

2016-09-01

As part of the Uinta Basin Winter Ozone Study, January-February 2013, we conducted 937 tethered balloon-borne ozone vertical and temperature profiles from three sites in the Uinta Basin, Utah (UB). Emissions from oil and gas operations combined with snow cover were favorable for producing high ozone-mixing ratios in the surface layer during stagnant and cold-pool episodes. The highly resolved profiles documented the development of approximately week-long ozone production episodes building from regional backgrounds of 40 ppbv to >165 ppbv within a shallow cold pool up to 200 m in depth. Beginning in midmorning, ozone-mixing ratios increased uniformly through the cold pool layer at rates of 5-12 ppbv/h. During ozone events, there was a strong diurnal cycle with each succeeding day accumulating 4-8 ppbv greater than the previous day. The top of the elevated ozone production layer was nearly uniform in altitude across the UB independent of topography. Above the ozone production layer, mixing ratios decreased with height to 400 m above ground level where they approached regional background levels. Rapid clean-out of ozone-rich air occurred within a day when frontal systems brought in fresh air. Solar heating and basin topography led to a diurnal flow pattern in which daytime upslope winds distributed ozone precursors and ozone in the Basin. NOx-rich plumes from a coal-fired power plant in the eastern sector of the Basin did not appear to mix down into the cold pool during this field study.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jaech, J.L.

The use of a pooling technique in leak testing Plutonium Recycle Test Reactor fuel elements to reduce the number of tests is discussed. Since the proportion of defectives in this case is small, application of the method would suggest that the group size be large. It was suggested that additional savings might be introduced by subgrouping the originally grouped items in the event of a positive result, rather than testing them individually. An investigation was made to determine optimum subgrouping sizes. (M.C.G.)

Effects of exenatide twice daily, exenatide once weekly or insulin in patients with type 2 diabetes and baseline HbA1c ≥10.0%: Two pooled analyses including 20 randomised controlled trials.

PubMed

Busch, Robert S; Ruggles, James; Han, Jenny; Hardy, Elise

2017-12-01

Patients with advanced type 2 diabetes (T2D) and high glycated haemoglobin (HbA1c) values can be difficult to treat because of their severe metabolic disease. This pooled analysis examined the treatment effects of exenatide twice daily (BID), exenatide once weekly (QW) and insulin in patients with high baseline HbA1c (≥10.0%). This post hoc analysis used pooled data from 12 and 8 randomised controlled trials of exenatide BID and exenatide QW, respectively. Patients with T2D who completed at least 24 weeks of treatment with exenatide BID, exenatide QW or insulin (insulin glargine, insulin detemir or insulin aspart) were categorised by baseline HbA1c. Patients with HbA1c ≥10.0% were included in the analysis. Both exenatide and insulin reduced HbA1c (mean ± SE reduction: -2.0% ± 0.2% [exenatide] and -2.1% ± 0.2% [insulin] in the exenatide BID studies, and -2.6% ± 0.1% [exenatide] and -2.1% ± 0.2% [insulin] in the exenatide QW studies; all P < .001). Body weight decreased with exenatide and increased with insulin. Systolic blood pressure decreased with exenatide QW. Insulin dose increased over the course of treatment. The most common adverse events with exenatide were gastrointestinal. Insulin was associated with some hypoglycaemia risk. Hypoglycaemia events occurred infrequently with exenatide when given without sulphonylureas. For patients with high HbA1c, treatment with exenatide or insulin both improved glycaemic control. Given the associated weight loss and low risk of hypoglycaemia, exenatide may be a suitable alternative to treatment with insulin in certain patients with T2D and high HbA1c. © 2017 John Wiley & Sons Ltd.

Efficacy of preoperative biliary drainage in malignant obstructive jaundice: a meta-analysis and systematic review.

PubMed

Moole, Harsha; Bechtold, Matthew; Puli, Srinivas R

2016-07-11

In patients requiring surgical resection for malignant biliary jaundice, it is unclear if preoperative biliary drainage (PBD) would improve mortality and morbidity by restoration of biliary flow prior to operation. This is a meta-analysis to pool the evidence and assess the utility of PBD in patients with malignant obstructive jaundice. The primary outcome is comparing mortality outcomes in patients with malignant obstructive jaundice undergoing direct surgery (DS) versus PBD. The secondary outcomes include major adverse events and length of hospital stay in both the groups. Studies using PBD in patients with malignant obstructive jaundice were included in this study. For the data collection and extraction, articles were searched in MEDLINE, PubMed, Embase, Cochrane Central Register of Controlled Trials & Database of Systematic Reviews, etc. Pooled proportions were calculated using both Mantel-Haenszel method (fixed effects model) and DerSimonian-Laird method (random effects model). Initial search identified 2230 reference articles, of which 204 were selected and reviewed. Twenty-six studies (N = 3532) for PBD in malignant obstructive jaundice which met the inclusion criteria were included in this analysis. The odds ratio for mortality in PBD group versus DS group was 0.96 (95 % CI = 0.71 to 1.29). Pooled number of major adverse effects was lower in the PBD group at 10.40 (95 % CI = 9.96 to 10.83) compared to 15.56 (95 % CI = 15.06 to 16.05) in the DS group. Subgroup analysis comparing internal PBD to DS group showed lower odds for major adverse events (odds ratio, 0.48 with 95 % CI = 0.32 to 0.74). In patients with malignant biliary jaundice requiring surgery, PBD group had significantly less major adverse effects than DS group. Length of hospital stay and mortality rate were comparable in both the groups.

A secure distributed logistic regression protocol for the detection of rare adverse drug events

PubMed Central

El Emam, Khaled; Samet, Saeed; Arbuckle, Luk; Tamblyn, Robyn; Earle, Craig; Kantarcioglu, Murat

2013-01-01

Background There is limited capacity to assess the comparative risks of medications after they enter the market. For rare adverse events, the pooling of data from multiple sources is necessary to have the power and sufficient population heterogeneity to detect differences in safety and effectiveness in genetic, ethnic and clinically defined subpopulations. However, combining datasets from different data custodians or jurisdictions to perform an analysis on the pooled data creates significant privacy concerns that would need to be addressed. Existing protocols for addressing these concerns can result in reduced analysis accuracy and can allow sensitive information to leak. Objective To develop a secure distributed multi-party computation protocol for logistic regression that provides strong privacy guarantees. Methods We developed a secure distributed logistic regression protocol using a single analysis center with multiple sites providing data. A theoretical security analysis demonstrates that the protocol is robust to plausible collusion attacks and does not allow the parties to gain new information from the data that are exchanged among them. The computational performance and accuracy of the protocol were evaluated on simulated datasets. Results The computational performance scales linearly as the dataset sizes increase. The addition of sites results in an exponential growth in computation time. However, for up to five sites, the time is still short and would not affect practical applications. The model parameters are the same as the results on pooled raw data analyzed in SAS, demonstrating high model accuracy. Conclusion The proposed protocol and prototype system would allow the development of logistic regression models in a secure manner without requiring the sharing of personal health information. This can alleviate one of the key barriers to the establishment of large-scale post-marketing surveillance programs. We extended the secure protocol to account for correlations among patients within sites through generalized estimating equations, and to accommodate other link functions by extending it to generalized linear models. PMID:22871397

Blonanserin for schizophrenia: systematic review and meta-analysis of double-blind, randomized, controlled trials.

PubMed

Kishi, Taro; Matsuda, Yuki; Nakamura, Hiroshi; Iwata, Nakao

2013-02-01

There is uncertainty about the efficacy and tolerability of blonanserin in schizophrenia. PubMed, the Cochrane Library databases, PsycINFO, and Google Scholar were searched up to September 2012. A systematic review and meta-analysis of individual patient data from randomized, controlled trials comparing blonanserin with other antipsychotics were conducted. The risk ratio (RR), 95% confidence intervals (CI), numbers-needed-to-harm (NNH), and weighted mean difference (WMD) were calculated. Four studies (total n = 1080) were identified (vs. risperidone studies [n = 508], vs. haloperidol studies [n = 572]). Comparing blonanserin with other pooled antipsychotics, there were no significant differences in the Positive and Negative Syndrome Scale (PANSS) total score (p = 0.75), PANSS positive (p = 0.41), PANSS negative (p = 0.09), and PANSS general psychopathology subscale scores (p = 0.96), and response rate (p = 0.72). However, blonanserin showed greater efficacy in PANSS negative subscale scores compared with haloperidol (WMD = -1.29, CI = -2.29 to -0.30, p = 0.01, I(2) = 0%). No significant differences were found in discontinuation rates between blonanserin and other pooled antipsychotics (due to any cause: p = 0.29, inefficacy: p = 0.32, adverse events: p = 0.56). Blonanserin had a 0.31 lower risk of hyperprolactinemia than the other pooled antipsychotics (CI = 0.20-0.49, NNH = not significant). While dizziness (RR = 0.47, CI = 0.23-0.93, NNH = not significant) and akathisia (RR = 0.54, CI = 0.32-0.90, NNH = 7) occurred significantly less often with blonanserin than with haloperidol, blonanserin had a 1.62 higher risk of akathisia than risperidone (CI = 1.18-2.22, NNH = 8) [corrected]. Our results suggest that although blonanserin has a more beneficial effect on negative symptoms than haloperidol, there was a significant difference in the adverse events profile between blonanserin and other antipsychotics. Copyright © 2012 Elsevier Ltd. All rights reserved.

The Ahmed shunt versus the Baerveldt shunt for refractory glaucoma: a meta-analysis.

PubMed

Wang, Shiming; Gao, Xiaoming; Qian, Nana

2016-06-08

The purpose of this study was to compare the efficacy and tolerability of the Ahmed glaucoma valve (AGV) implant and the Baerveldt implant for the treatment of refractory glaucoma. We comprehensively searched four databases, including PubMed, EMBASE, Web of Science, and the Cochrane Library databases, selecting the relevant studies. The continuous variables, namely, intraocular pressure reduction (IOPR) and a reduction in glaucoma medication, were pooled by the weighted mean differences (WMDs), and the dichotomous outcomes, including success rates and tolerability estimates, were pooled by the odds ratio (ORs). A total of 929 patients from six studies were included. The WMDs of the IOPR between the AGV implant and the Baerveldt implant were 1.58 [95 % confidence interval (CI): -2.99 to 6.15] at 6 months, -1.01 (95 % CI: -3.40 to 1.98) at 12 months, -0.54 (95 % CI: -4.89 to 3.82) at 24 months, and -0.47 (95 % CI: -3.29 to 2.35) at 36 months. No significant difference was detected between the two groups at any point in time. The pooled ORs comparing the AGV implant with the Baerveldt implant were 0.51 (95 % CI: 0.33 to 0.80) for the complete success rate and 0.67 (95 % CI: 0.50 to 0.91) for qualified success rate. The Baerveldt implant was associated with a reduction in glaucoma medication at -0.51 (95 % CI: -0.90 to -0.12). There were no significant differences between the AGV implant and the Baerveldt implant on the rates of adverse events. The Baerveldt implant is more effective in both its surgical success rate and reducing glaucoma medication, but it is comparable to the AGV implant in lowering IOP. Both implants may have comparable incidences of adverse events.

Evaluation of forest management practices through application of a biogeochemical model, PnET-BGC

NASA Astrophysics Data System (ADS)

Valipour, M.; Driscoll, C. T.; Johnson, C. E.; Campbell, J. L.; Fahey, T.; Zeng, T.

2017-12-01

Forest ecosystem response to logging disturbance varies significantly, depending on site conditions, species composition, land use history, and the method and frequency of harvesting. The long-term effects of forest cuttings are less clear due to limited information on land use history and long-term time series observations. The hydrochemical model, PnET-BGC was modified and verified using field data from multiple experimentally harvested northern hardwood watersheds at the Hubbard Brook Experimental Forest (HBEF), New Hampshire, USA, including a commercial whole-tree harvest (Watershed 5), a devegetation experiment (Watershed 2; devegetation and herbicide treatment), a commercial strip-cut (Watershed 4) to simulate the hydrology, biomass accumulation, and soil solution and stream water chemistry responses to clear-cutting. The confirmed model was used to investigate temporal changes in aboveground biomass accumulation and nutrient dynamics under three different harvesting intensities (40%, 60%, 80%) over four varied rotation lengths (20, 40, 60, 80 years) with results compared with a scenario of no forest harvesting. The total ecosystem carbon pool (biomass, soil and litter) was reduced over harvesting events. The greatest decline occurred in litter by 40%-70%, while the pool of carbon stored in aboveground biomass decreased by 30%-60% for 80% cutting levels at 40 and 20 year rotation lengths, respectively. The large pool of soil organic carbon remained relatively stable, with only minor declines over logging regimes. Stream water simulations demonstrated increased loss of major elements over cutting events. Ca+2 and NO3- were the most sensitive elements to leaching over frequent intensive logging. Accumulated leaching of Ca+2 and NO3- varied between 90-520 t Ca/ha and 40-420 t N/ha from conservative (80-year period and 40% cutting) to aggressive (20-year period and 80% cutting) cutting regimes, respectively. Moreover, a reduction in nutrient plant uptake over logging scenarios was estimated. Model simulations indicated nutrient losses were more sensitive to harvesting rotation length than intensity.

The effect of early in-hospital medication review on health outcomes: a systematic review.

PubMed

Hohl, Corinne M; Wickham, Maeve E; Sobolev, Boris; Perry, Jeff J; Sivilotti, Marco L A; Garrison, Scott; Lang, Eddy; Brasher, Penny; Doyle-Waters, Mary M; Brar, Baljeet; Rowe, Brian H; Lexchin, Joel; Holland, Richard

2015-07-01

Adverse drug events are an important cause of emergency department visits, unplanned admissions and prolonged hospital stays. Our objective was to synthesize the evidence on the effect of early in-hospital pharmacist-led medication review on patient-oriented outcomes based on observed data. We systematically searched eight bibliographic reference databases, electronic grey literature, medical journals, conference proceedings, trial registries and bibliographies of relevant papers. We included studies that employed random or quasi-random methods to allocate subjects to pharmacist-led medication review or control. Medication review had to include, at a minimum, obtaining a best possible medication history and reviewing medications for appropriateness and adverse drug events. The intervention had to be initiated within 24 h of emergency department presentation or 72 h of admission. We extracted data in duplicate and pooled outcomes from clinically homogeneous studies of the same design using random effects meta-analysis. We retrieved 4549 titles of which seven were included, reporting the outcomes of 3292 patients. We pooled data from studies of the same design, and found no significant differences in length of hospital admission (weighted mean difference [WMD] -0.04 days, 95% confidence interval [CI] -1.63, 1.55), mortality (odds ratio [OR] 1.09, 95% CI 0.69, 1.72), readmissions (OR 1.15, 95% CI 0.81, 1.63) or emergency department revisits at 3 months (OR 0.60, 95% CI 0.27, 1.32). Two large studies reporting reductions in readmissions could not be included in our pooled estimates due to differences in study design. Wide confidence intervals suggest that additional research is likely to influence the effect size estimates and clarify the effect of medication review on patient-oriented outcomes. This systematic review failed to identify an effect of pharmacist-led medication review on health outcomes. © 2015 The British Pharmacological Society.

A secure distributed logistic regression protocol for the detection of rare adverse drug events.

PubMed

El Emam, Khaled; Samet, Saeed; Arbuckle, Luk; Tamblyn, Robyn; Earle, Craig; Kantarcioglu, Murat

2013-05-01

There is limited capacity to assess the comparative risks of medications after they enter the market. For rare adverse events, the pooling of data from multiple sources is necessary to have the power and sufficient population heterogeneity to detect differences in safety and effectiveness in genetic, ethnic and clinically defined subpopulations. However, combining datasets from different data custodians or jurisdictions to perform an analysis on the pooled data creates significant privacy concerns that would need to be addressed. Existing protocols for addressing these concerns can result in reduced analysis accuracy and can allow sensitive information to leak. To develop a secure distributed multi-party computation protocol for logistic regression that provides strong privacy guarantees. We developed a secure distributed logistic regression protocol using a single analysis center with multiple sites providing data. A theoretical security analysis demonstrates that the protocol is robust to plausible collusion attacks and does not allow the parties to gain new information from the data that are exchanged among them. The computational performance and accuracy of the protocol were evaluated on simulated datasets. The computational performance scales linearly as the dataset sizes increase. The addition of sites results in an exponential growth in computation time. However, for up to five sites, the time is still short and would not affect practical applications. The model parameters are the same as the results on pooled raw data analyzed in SAS, demonstrating high model accuracy. The proposed protocol and prototype system would allow the development of logistic regression models in a secure manner without requiring the sharing of personal health information. This can alleviate one of the key barriers to the establishment of large-scale post-marketing surveillance programs. We extended the secure protocol to account for correlations among patients within sites through generalized estimating equations, and to accommodate other link functions by extending it to generalized linear models.

Cardiovascular Profile of Valbenazine: Analysis of Pooled Data from Three Randomized, Double-Blind, Placebo-Controlled Trials.

PubMed

Thai-Cuarto, Dao; O'Brien, Christopher F; Jimenez, Roland; Liang, Grace S; Burke, Joshua

2018-04-01

Valbenazine is a novel vesicular monoamine transporter 2 inhibitor approved for the treatment of tardive dyskinesia in adults. Using data from double-blind, placebo-controlled trials, analyses were conducted to evaluate the cardiovascular effects of once-daily valbenazine in patients with a psychiatric disorder who developed tardive dyskinesia after exposure to a dopamine-blocking medication. Data were pooled from three 6-week, double-blind, placebo-controlled trials: KINECT (NCT01688037), KINECT 2 (NCT01733121), and KINECT 3 (NCT02274558). Data from the 42-week valbenazine extension period of KINECT 3 were also analyzed. Outcomes of interest included cardiovascular-related treatment-emergent adverse events, vital sign measurements, and electrocardiogram parameters. The pooled safety population included 400 participants (placebo, n = 178; valbenazine 40 mg/day, n = 110; valbenazine 80 mg/day, n = 112). A history of cardiac disorders was present in 11.8% of participants, and 74.3% were taking a concomitant medication with known potential for QT prolongation. Mean changes from baseline to week 6 in supine vital signs and QTcF (Fridericia correction) were as follows for placebo, valbenazine 40 mg/day, and valbenazine 80 mg/day, respectively: systolic blood pressure (0.2, - 2.1, - 1.8 mmHg), diastolic blood pressure (- 0.1, - 1.6, - 1.2 mmHg), heart rate (- 1.7, - 2.2, - 1.7 bpm), QTcF interval (1.2, 1.1, 2.1 ms); all p > 0.05 for valbenazine vs. placebo. No statistically significant differences were observed between placebo and valbenazine in cardiovascular-related, treatment-emergent adverse events. No notable additional effects on cardiovascular outcomes were found with up to 48 weeks of valbenazine treatment. Results from double-blind, placebo-controlled trials showed no apparent difference between valbenazine and placebo on cardiovascular outcomes. No additional cardiovascular risk was detected during a longer extension study with valbenazine.

Cyclic spattering, seismic tremor, and surface fluctuation within a perched lava channel, Kīlauea Volcano

NASA Astrophysics Data System (ADS)

Patrick, Matthew R.; Orr, Tim; Wilson, David; Dow, David; Freeman, Richard

2011-08-01

In late 2007, a perched lava channel, built up to 45 m above the preexisting surface, developed during the ongoing eruption near Pu`u `Ō`ō cone on Kīlauea Volcano's east rift zone. The lava channel was segmented into four pools extending over a total of 1.4 km. From late October to mid-December, a cyclic behavior, consisting of steady lava level rise terminated by vigorous spattering and an abrupt drop in lava level, was commonly observed in pool 1. We use geologic observations, video, time-lapse camera images, and seismicity to characterize and understand this cyclic behavior. Spattering episodes occurred at intervals of 40-100 min during peak activity and involved small (5-10-m-high) fountains limited to the margins of the pool. Most spattering episodes had fountains which migrated downchannel. Each spattering episode was associated with a rapid lava level drop of about 1 m, which was concurrent with a conspicuous cigar-shaped tremor burst with peak frequencies of 4-5 Hz. We interpret this cyclic behavior to be gas pistoning, and this is the first documented instance of gas pistoning in lava well away from the deeper conduit. Our observations and data indicate that the gas pistoning was driven by gas accumulation beneath the visco-elastic component of the surface crust, contrary to other studies which attribute similar behavior to the periodic rise of gas slugs. The gas piston events typically had a gas mass of about 2,500 kg (similar to the explosions at Stromboli), with gas accumulation and release rates of about 1.1 and 5.7 kg s-1, respectively. The time-averaged gas output rate of the gas pistoning events accounted for about 1-2% of the total gas output rate of the east rift zone eruption.

Cyclic spattering, seismic tremor, and surface fluctuation within a perched lava channel, Kīlauea Volcano

USGS Publications Warehouse

Patrick, M.R.; Orr, T.; Wilson, D.; Dow, D.; Freeman, R.

2011-01-01

In late 2007, a perched lava channel, built up to 45 m above the preexisting surface, developed during the ongoing eruption near Pu‘u ‘Ō‘ō cone on Kīlauea Volcano’s east rift zone. The lava channel was segmented into four pools extending over a total of 1.4 km. From late October to mid-December, a cyclic behavior, consisting of steady lava level rise terminated by vigorous spattering and an abrupt drop in lava level, was commonly observed in pool 1. We use geologic observations, video, time-lapse camera images, and seismicity to characterize and understand this cyclic behavior. Spattering episodes occurred at intervals of 40–100 min during peak activity and involved small (5–10-m-high) fountains limited to the margins of the pool. Most spattering episodes had fountains which migrated downchannel. Each spattering episode was associated with a rapid lava level drop of about 1 m, which was concurrent with a conspicuous cigar-shaped tremor burst with peak frequencies of 4–5 Hz. We interpret this cyclic behavior to be gas pistoning, and this is the first documented instance of gas pistoning in lava well away from the deeper conduit. Our observations and data indicate that the gas pistoning was driven by gas accumulation beneath the visco-elastic component of the surface crust, contrary to other studies which attribute similar behavior to the periodic rise of gas slugs. The gas piston events typically had a gas mass of about 2,500 kg (similar to the explosions at Stromboli), with gas accumulation and release rates of about 1.1 and 5.7 kg s−1, respectively. The time-averaged gas output rate of the gas pistoning events accounted for about 1–2% of the total gas output rate of the east rift zone eruption.

Western Pacific Warm Pool expansion event during 2.0-1.5 Ma and its implications to global climate dynamics

NASA Astrophysics Data System (ADS)

Lo, L.; Chuang, C. K.; Wei, K. Y.; Shen, C. C.; Mii, H. S.; Chang, Y. P.

2017-12-01

In this study, we reconstruct surface and upper thermocline seawater temperatures by using planktonic foraminifera Globigerinoides sacculifer and Neogloboquadrina deutertrei in the southern Western Pacific Warm Pool (S-WPWP, ODP Site 1115B, 9o11'S, 151o34'E, water depth 1149 m) during past 2.2-1.1 million years (Ma). Significant S-WPWP surface warming in both glacial and interglacial periods during 1.86-1.55 Ma is accompanied with gradual upper thermocline cooling. S-WPWP sea surface temperature dropped 2.1oC from 1.50-1.21 Ma but upper thermocline temperature further decreased 1.1oC at this time period. WPWP expansion event is also supported by vertical foraminiferal Mg/Ca-derived temperature profile records in the central WPWP (ODP Site 806, Ford et al. 2015). Although foraminiferal Mg/Ca-derived temperature records from Eastern Equatorial Pacific suggests long-term cooling trend (Wara et al. 2005), alkenone undersaturation index (UK'37)-inferred surface temperature records suggest 1oC warming during 2.0-1.5 Ma (Fedorov et al. 2013). We argue that seasonal expansion of WPWP may be attributable to the meridional thermocline gradient increasing (Martinez-Garcia et al. 2010) during 2.0-1.5 Ma. Long-term extent variability of WPWP could have impact on cross-equatorial energy transportation and meridional precipitation belt movements (Lo et al., 2014).

Ontogeny of the stress response in chinook salmon, Oncorhynchus tshawytscha

USGS Publications Warehouse

Feist, G.; Schreck, C.B.

2001-01-01

Whole body concentrations of cortisol were determined via radioimmunoassay in chinook salmon, Onchorynchus tshawytscha, during early development in both stressed and non-stressed fish to determine when the corticosteroidogenic stress response first appeared. Progeny from both pooled and individual females were examined to determine if differences existed in offspring from different females. Levels of cortisol were low in eyed eggs, increased at hatch, decreased 2 weeks later and then remained constant thereafter. Differences in cortisol between stressed and control fish were found 1 week after hatch and persisted for the remainder of the study. The magnitude of the stress response, or relative amount of cortisol produced, generally increased from the time when it was first detected, but a decrease in the ability to elicit cortisol was seen 4 weeks after hatching. Cortisol content of separate progeny from two individual females showed a similar pattern to that seen in pooled eggs. Our results indicate that chinook salmon are capable of producing cortisol following a stressful event approximately 1 week after the time of hatching. The decrease in endogenous cortisol content seen 2 weeks after hatching, and the decrease in the magnitude of the stress response seen 4 weeks after hatching may be comparable to developmental events documented in mammals where corticosteroid synthesis is inhibited to neutralize possible detrimental effects of these hormones during critical periods of development.

Molecular control of brain size: Regulators of neural stem cell life, death and beyond

DOE Office of Scientific and Technical Information (OSTI.GOV)

Joseph, Bertrand; Hermanson, Ola, E-mail: ola.hermanson@ki.se

2010-05-01

The proper development of the brain and other organs depends on multiple parameters, including strictly controlled expansion of specific progenitor pools. The regulation of such expansion events includes enzymatic activities that govern the correct number of specific cells to be generated via an orchestrated control of cell proliferation, cell cycle exit, differentiation, cell death etc. Certain proteins in turn exert direct control of these enzymatic activities and thus progenitor pool expansion and organ size. The members of the Cip/Kip family (p21Cip1/p27Kip1/p57Kip2) are well-known regulators of cell cycle exit that interact with and inhibit the activity of cyclin-CDK complexes, whereas membersmore » of the p53/p63/p73 family are traditionally associated with regulation of cell death. It has however become clear that the roles for these proteins are not as clear-cut as initially thought. In this review, we discuss the roles for proteins of the Cip/Kip and p53/p63/p73 families in the regulation of cell cycle control, differentiation, and death of neural stem cells. We suggest that these proteins act as molecular interfaces, or 'pilots', to assure the correct assembly of protein complexes with enzymatic activities at the right place at the right time, thereby regulating essential decisions in multiple cellular events.« less

Linkage disequilibrium and population structure in wild and domesticated populations of Phaseolus vulgaris L.

PubMed Central

Rossi, Monica; Bitocchi, Elena; Bellucci, Elisa; Nanni, Laura; Rau, Domenico; Attene, Giovanna; Papa, Roberto

2009-01-01

Together with the knowledge of the population structure, a critical aspect for the planning of association and/or population genomics studies is the level of linkage disequilibrium (LD) that characterizes the species and the population used for such an analysis. We have analyzed the population structure and LD in wild and domesticated populations of Phaseolus vulgaris L. using amplified fragment length polymorphism markers, most of which were genetically mapped in two recombinant inbred populations. Our results reflect the previous knowledge of the occurrence of two major wild gene pools of P. vulgaris, from which two independent domestication events originated, one in the Andes and one in Mesoamerica. The high level of LD in the whole sample was mostly due to the gene pool structure, with a much higher LD in domesticated compared to wild populations. In relation to association studies, our results also suggest that whole-genome-scan approaches are feasible in the common bean. Interestingly, an excess of inter-chromosomal LD was found in the domesticated populations, which suggests an important role for epistatic selection during domestication. Moreover, our results indicate the occurrence of a strong bottleneck in the Andean wild population before domestication, suggesting a Mesoamerican origin of P. vulgaris. Finally, our data support the occurrence of a single domestication event in Mesoamerica, and the same scenario in the Andes. PMID:25567895

Fecal Microbiota Transplantation for Ulcerative Colitis: A Systematic Review and Meta-Analysis.

PubMed

Shi, Yanqiang; Dong, Yiwei; Huang, Wenhui; Zhu, Decong; Mao, Hua; Su, Peizhu

2016-01-01

Fecal microbiota transplantation (FMT) has been recognized as a novel treatment for ulcerative colitis (UC). However, its efficacy and safety remain unclear. We conducted this systematic review to assess the efficacy and safety of FMT in UC. PubMed, EMBASE, Cochrane Central, Web of Science Core Collection, and three other Chinese databases were searched for reports of FMT in UC with clear outcomes. We estimated pooled rates [with 95% confidence interval (CI)] of clinical remission among 15 cohort studies and clinical response among 16 cohort studies. Twenty five studies (2 randomized controlled trials, 15 cohort studies, and 8 case studies) with 234 UC patients were included. Overall, 41.58% (84/202) patients achieved clinical remission (CR) and 65.28% (126/193) achieved clinical response. Among the cohort studies, the pooled estimate of patients who achieved CR and clinical response were 40.5% (95% CI 24.7%-58.7%), and 66.1% (95% CI 43.7%-83.0%). Most adverse events were slight and self-resolving. The analyses of gut microbiota in 7 studies showed that FMT could increase microbiota diversity and richness, similarity, and certain change of bacterial composition. FMT provides a promising effect for UC with few adverse events. Successful FMT may be associated with an increase in microbiota diversity and richness, similarity, and certain change of bacterial composition.

Fecal Microbiota Transplantation for Ulcerative Colitis: A Systematic Review and Meta-Analysis

PubMed Central

Shi, Yanqiang; Dong, Yiwei; Huang, Wenhui; Zhu, Decong; Mao, Hua; Su, Peizhu

2016-01-01

Background Fecal microbiota transplantation (FMT) has been recognized as a novel treatment for ulcerative colitis (UC). However, its efficacy and safety remain unclear. Objective We conducted this systematic review to assess the efficacy and safety of FMT in UC. Data Sources PubMed, EMBASE, Cochrane Central, Web of Science Core Collection, and three other Chinese databases were searched for reports of FMT in UC with clear outcomes. Data Extraction and Synthesis We estimated pooled rates [with 95% confidence interval (CI)] of clinical remission among 15 cohort studies and clinical response among 16 cohort studies. Results Twenty five studies (2 randomized controlled trials, 15 cohort studies, and 8 case studies) with 234 UC patients were included. Overall, 41.58% (84/202) patients achieved clinical remission (CR) and 65.28% (126/193) achieved clinical response. Among the cohort studies, the pooled estimate of patients who achieved CR and clinical response were 40.5% (95% CI 24.7%-58.7%), and 66.1% (95% CI 43.7%-83.0%). Most adverse events were slight and self-resolving. The analyses of gut microbiota in 7 studies showed that FMT could increase microbiota diversity and richness, similarity, and certain change of bacterial composition. Conclusion FMT provides a promising effect for UC with few adverse events. Successful FMT may be associated with an increase in microbiota diversity and richness, similarity, and certain change of bacterial composition. PMID:27295210

Sequential parallel comparison design with binary and time-to-event outcomes.

PubMed

Silverman, Rachel Kloss; Ivanova, Anastasia; Fine, Jason

2018-04-30

Sequential parallel comparison design (SPCD) has been proposed to increase the likelihood of success of clinical trials especially trials with possibly high placebo effect. Sequential parallel comparison design is conducted with 2 stages. Participants are randomized between active therapy and placebo in stage 1. Then, stage 1 placebo nonresponders are rerandomized between active therapy and placebo. Data from the 2 stages are pooled to yield a single P value. We consider SPCD with binary and with time-to-event outcomes. For time-to-event outcomes, response is defined as a favorable event prior to the end of follow-up for a given stage of SPCD. We show that for these cases, the usual test statistics from stages 1 and 2 are asymptotically normal and uncorrelated under the null hypothesis, leading to a straightforward combined testing procedure. In addition, we show that the estimators of the treatment effects from the 2 stages are asymptotically normal and uncorrelated under the null and alternative hypothesis, yielding confidence interval procedures with correct coverage. Simulations and real data analysis demonstrate the utility of the binary and time-to-event SPCD. Copyright © 2018 John Wiley & Sons, Ltd.

How Safe Are Common Analgesics for the Treatment of Acute Pain for Children? A Systematic Review.

PubMed

Hartling, Lisa; Ali, Samina; Dryden, Donna M; Chordiya, Pritam; Johnson, David W; Plint, Amy C; Stang, Antonia; McGrath, Patrick J; Drendel, Amy L

2016-01-01

Background . Fear of adverse events and occurrence of side effects are commonly cited by families and physicians as obstructive to appropriate use of pain medication in children. We examined evidence comparing the safety profiles of three groups of oral medications, acetaminophen, nonsteroidal anti-inflammatory drugs, and opioids, to manage acute nonsurgical pain in children (<18 years) treated in ambulatory settings. Methods . A comprehensive search was performed to July 2015, including review of national data registries. Two reviewers screened articles for inclusion, assessed methodological quality, and extracted data. Risks (incidence rates) were pooled using a random effects model. Results . Forty-four studies were included; 23 reported on adverse events. Based on limited current evidence, acetaminophen, ibuprofen, and opioids have similar nausea and vomiting profiles. Opioids have the greatest risk of central nervous system adverse events. Dual therapy with a nonopioid/opioid combination resulted in a lower risk of adverse events than opioids alone. Conclusions . Ibuprofen and acetaminophen have similar reported adverse effects and notably less adverse events than opioids. Dual therapy with a nonopioid/opioid combination confers a protective effect for adverse events over opioids alone. This research highlights challenges in assessing medication safety, including lack of more detailed information in registry data, and inconsistent reporting in trials.

Current Warm-Up Practices and Contemporary Issues Faced by Elite Swimming Coaches.

PubMed

McGowan, Courtney J; Pyne, David B; Raglin, John S; Thompson, Kevin G; Rattray, Ben

2016-12-01

McGowan, CJ, Pyne, DB, Raglin, JS, Thompson, KG, and Rattray, B. Current warm-up practices and contemporary issues faced by elite swimming coaches. J Strength Cond Res 30(12): 3471-3480, 2016-A better understanding of current swimming warm-up strategies is needed to improve their effectiveness. The purpose of this study was to describe current precompetition warm-up practices and identify contemporary issues faced by elite swimming coaches during competition. Forty-six state-international level swimming coaches provided information through a questionnaire on their prescription of volume, intensity, and recovery within their pool and dryland-based competition warm-ups, and challenges faced during the final stages of event preparation. Coaches identified four key objectives of the precompetition warm-up: physiological (elevate body temperature and increase muscle activation), kinesthetic (tactile preparation, increase "feel" of the water), tactical (race-pace rehearsal), and mental (improve focus, reduce anxiety). Pool warm-up volume ranged from ∼1300 to 2100 m, beginning with 400-1000 m of continuous, low-intensity (∼50-70% of perceived maximal exertion) swimming, followed by 200-600 m of stroke drills and 1-2 sets (100-400 m in length) of increasing intensity (∼60-90%) swimming, concluding with 3-4 race or near race-pace efforts (25-100 m; ∼90-100%) and 100-400 m easy swimming. Dryland-based warm-up exercises, involving stretch cords and skipping, were also commonly prescribed. Coaches preferred swimmers complete their warm-up 20-30 minutes before race start. Lengthy marshalling periods (15-20+ minutes) and the time required to don racing suits (>10 minutes) were identified as complicating issues. Coaches believed that the pool warm-up affords athletes the opportunity to gain a tactile feel for the water and surrounding pool environment. The combination of dryland-based activation exercises followed by pool-based warm-up routines seems to be the preferred approach taken by elite swimming coaches preparing their athletes for competition.

Mixing effects on nitrogen and oxygen concentrations and the relationship to mean residence time in a hyporheic zone of a riffle-pool sequence

USGS Publications Warehouse

Naranjo, Ramon C.; Niswonger, Richard G.; Clinton Davis,

2015-01-01

Flow paths and residence times in the hyporheic zone are known to influence biogeochemical processes such as nitrification and denitrification. The exchange across the sediment-water interface may involve mixing of surface water and groundwater through complex hyporheic flow paths that contribute to highly variable biogeochemically active zones. Despite the recognition of these patterns in the literature, conceptualization and analysis of flow paths and nitrogen transformations beneath riffle-pool sequences often neglect to consider bed form driven exchange along the entire reach. In this study, the spatial and temporal distribution of dissolved oxygen (DO), nitrate (NO3-) and ammonium (NH4+) were monitored in the hyporheic zone beneath a riffle-pool sequence on a losing section of the Truckee River, NV. Spatially-varying hyporheic exchange and the occurrence of multi-scale hyporheic mixing cells are shown to influence concentrations of DO and NO3- and the mean residence time (MRT) of riffle and pool areas. Distinct patterns observed in piezometers are shown to be influenced by the first large flow event following a steady 8 month period of low flow conditions. Increases in surface water discharge resulted in reversed hydraulic gradients and production of nitrate through nitrification at small vertical spatial scales (0.10 to 0.25 m) beneath the sediment-water interface. In areas with high downward flow rates and low MRT, denitrification may be limited. The use of a longitudinal two-dimensional flow model helped identify important mechanisms such as multi-scale hyporheic mixing cells and spatially varying MRT, an important driver for nitrogen transformation in the riverbed. Our observations of DO and NO3- concentrations and model simulations highlight the role of multi-scale hyporheic mixing cells on MRT and nitrogen transformations in the hyporheic zone of riffle-pool sequences. This article is protected by copyright. All rights reserved.

Ocean-state dependency of the equatorial Pacific response to Westerly Wind Events

NASA Astrophysics Data System (ADS)

Puy, martin; Lengaigne, matthieu; Madec, gurvan; Vialard, jerome; Guilyardi, eric

2015-04-01

Short-lived wind events in the equatorial Pacific strongly influence the El Niño/Southern Oscillation (ENSO) evolution. In the first part of this study, we found in observations that both westerly wind events (WWEs) and their easterly wind events (EWEs) counterpart are unambiguously associated with increased Madden Julian oscillation and atmospheric equatorial Rossby waves activity, i.e. that the atmospheric state influences the occurrence probability of WWEs. In the second part, we investigate how the oceanic state modulates the response to these WWEs by applying the same WWE forcing over a interannually-varying ocean state in an OGCM simulation. We find that the amplitude of the SST response, both at the warm pool eastern edge and in the eastern Pacific, can vary by a factor of up to two depending on the ocean state. The sea level and current response are also clearly modulated, with varying contributions of the second and third baroclinic modes depending on the oceanic stratification. We will discuss the mechanisms by which the oceanic state modulates the response to the WWE, and how this could contribute to their impact on ENSO

Investigation of 2‐stage meta‐analysis methods for joint longitudinal and time‐to‐event data through simulation and real data application

PubMed Central

Tudur Smith, Catrin; Gueyffier, François; Kolamunnage‐Dona, Ruwanthi

2017-01-01

Background Joint modelling of longitudinal and time‐to‐event data is often preferred over separate longitudinal or time‐to‐event analyses as it can account for study dropout, error in longitudinally measured covariates, and correlation between longitudinal and time‐to‐event outcomes. The joint modelling literature focuses mainly on the analysis of single studies with no methods currently available for the meta‐analysis of joint model estimates from multiple studies. Methods We propose a 2‐stage method for meta‐analysis of joint model estimates. These methods are applied to the INDANA dataset to combine joint model estimates of systolic blood pressure with time to death, time to myocardial infarction, and time to stroke. Results are compared to meta‐analyses of separate longitudinal or time‐to‐event models. A simulation study is conducted to contrast separate versus joint analyses over a range of scenarios. Results Using the real dataset, similar results were obtained by using the separate and joint analyses. However, the simulation study indicated a benefit of use of joint rather than separate methods in a meta‐analytic setting where association exists between the longitudinal and time‐to‐event outcomes. Conclusions Where evidence of association between longitudinal and time‐to‐event outcomes exists, results from joint models over standalone analyses should be pooled in 2‐stage meta‐analyses. PMID:29250814

Astronaut Joseph Tanner is assisted into his EMU during training

NASA Technical Reports Server (NTRS)

1994-01-01

Astronaut Joseph R. Tanner, STS-66 mission specialist, is assisted by Boeing suit expert Steve Voyles in donning the gloves for his extravehicular mobility unit (EMU) as he prepares to be submerged in a 25-feet deep pool at JSC's Weightless Environment Training Facility (WETF). Though no extravehicular activity (EVA) is planned for the mission, at least two astronauts are trained to perform tasks that would require a space walk in the event of failure of remote systems.

United States Air Force Summer Faculty Research Program (1984). Program Management Report. Volume 3

DTIC Science & Technology

1984-12-01

Database Design 蕄 Raman Spectroscopy of Dr. Boake L. Plessy Glycosaminoglycans from -* Bovine Cornea 117 Study of Control Mixer Concept Dr. Kuldip S...simultaneously in polarized and non -polarized controls were repeated three times at 260-64, 368-70, 604-8-13, 735-7-40, 1277-80, 1760, 1775, and 1820 or four...times at S240-2-4, 1020 and 1874-8-90. Pooling replicates from the non -polarized components, six controls and two cAMP treatments, events repeating

STS-32 MS Dunbar wearing LES prepares for WETF water egress training

NASA Technical Reports Server (NTRS)

1989-01-01

STS-32 Mission Specialist (MS) Bonnie J. Dunbar, wearing a launch and entry suit (LES), orange parachute harness and life vest, is briefed on emergency egress procedures in JSC's Weightless Environment Training Facility (WETF) Bldg 29. During the exercises the crew practiced the procedures to follow in the event of an emergency aboard the Space Shuttle and familiarized themselves with post-Challenger pole system of emergency egress. The crewmembers will simulate parachuting into water by using the WETF's nearby 25 ft deep pool.

Clinical endpoint adjudication in a contemporary all-comers coronary stent investigation: methodology and external validation.

PubMed

Vranckx, Pascal; McFadden, Eugene; Cutlip, Donald E; Mehran, Roxana; Swart, Michael; Kint, P P; Zijlstra, Felix; Silber, Sigmund; Windecker, Stephan; Serruys, Patrick W C J

2013-01-01

Globalisation in coronary stent research calls for harmonization of clinical endpoint definitions and event adjudication. Little has been published about the various processes used for event adjudication or their impact on outcome reporting. We performed a validation of the clinical event committee (CEC) adjudication process on 100 suspected events in the RESOLUTE All-comers trial (Resolute-AC). Two experienced Clinical Research Organisations (CRO) that had already extensive internal validation processes in place, participated in the study. After initial adjudication by the primary-CEC, events were cross-adjudicated by an external-CEC using the same definitions. Major discrepancies affecting the primary end point of target-lesion failure (TLF), a composite of cardiac death, target vessel myocardial infarction (TV-MI), or clinically-indicated target-lesion revascularization (CI-TLR), were analysed by an independent oversight committee who provided recommendations for harmonization. Discordant adjudications were reconsidered by the primary CEC. Subsequently, the RAC database was interrogated for cases that based on these recommendations merited re-adjudication and these cases were also re-adjudicated by the primary CEC. Final discrepancies in adjudication of individual components of TLF occurred in 7 out of 100 events in 5 patients. Discrepancies for the (hierarchical) primary endpoint occurred in 5 events (2 cardiac deaths and 3 TV-MI). After application of harmonization recommendations to the overall RAC population (n=2292), the primary CEC adjudicated 3 additional clinical-TLRs and considered 1 TV-MI as no event. A harmonization process provided a high level of concordance for event adjudication and improved accuracy for final event reporting. These findings suggest it is feasible to pool clinical event outcome data across clinical trials even when different CECs are responsible for event adjudication. Copyright © 2012 Elsevier Inc. All rights reserved.

Alert Triage v 0.1 beta

DOE Office of Scientific and Technical Information (OSTI.GOV)

Doak, Justin E.; Ingram, Joe; Johnson, Josh

2016-01-06

In the cyber security operations of a typical organization, data from multiple sources are monitored, and when certain conditions in the data are met, an alert is generated in an alert management system. Analysts inspect these alerts to decide if any deserve promotion to an event requiring further scrutiny. This triage process is manual, time-consuming, and detracts from the in-depth investigation of events. We have created a software system that uses supervised machine learning to automatically prioritize these alerts. In particular we utilize active learning to make efficient use of the pool of unlabeled alerts, thereby improving the performance ofmore » our ranking models over passive learning. We have demonstrated the effectiveness of our system on a large, real-world dataset of cyber security alerts.« less

Biogeochemical processes in an urban, restored wetland of San Francisco Bay, California, 2007-2009; methods and data for plant, sediment and water parameters

USGS Publications Warehouse

Windham-Myers, Lisamarie; Marvin-DiPasquale, Mark C.; Agee, Jennifer L.; Kieu, Le H.; Kakouros, Evangelos; Erikson, Li H.; Ward, Kristen

2010-01-01

The restoration of 18 acres of historic tidal marsh at Crissy Field has had great success in terms of public outreach and visibility, but less success in terms of revegetated marsh sustainability. Native cordgrass (Spartina foliosa) has experienced dieback and has failed to recolonize following extended flooding events during unintended periodic closures of its inlet channel, which inhibits daily tidal flushing. We examined the biogeochemical impacts of these impoundment events on plant physiology and on sulfur and mercury chemistry to help the National Park Service land managers determine the relative influence of these inlet closures on marsh function. In this comparative study, we examined key pools of sulfur, mercury, and carbon compounds both during and between closure events. Further, we estimated the net hydrodynamic flux of methylmercury and total mercury to and from the marsh during a 24-hour diurnal cycle. This report documents the methods used and the data generated during the study.

Development and validation of a 48-target analytical method for high-throughput monitoring of genetically modified organisms.

PubMed

Li, Xiaofei; Wu, Yuhua; Li, Jun; Li, Yunjing; Long, Likun; Li, Feiwu; Wu, Gang

2015-01-05

The rapid increase in the number of genetically modified (GM) varieties has led to a demand for high-throughput methods to detect genetically modified organisms (GMOs). We describe a new dynamic array-based high throughput method to simultaneously detect 48 targets in 48 samples on a Fludigm system. The test targets included species-specific genes, common screening elements, most of the Chinese-approved GM events, and several unapproved events. The 48 TaqMan assays successfully amplified products from both single-event samples and complex samples with a GMO DNA amount of 0.05 ng, and displayed high specificity. To improve the sensitivity of detection, a preamplification step for 48 pooled targets was added to enrich the amount of template before performing dynamic chip assays. This dynamic chip-based method allowed the synchronous high-throughput detection of multiple targets in multiple samples. Thus, it represents an efficient, qualitative method for GMO multi-detection.

Development and Validation of A 48-Target Analytical Method for High-throughput Monitoring of Genetically Modified Organisms

PubMed Central

Li, Xiaofei; Wu, Yuhua; Li, Jun; Li, Yunjing; Long, Likun; Li, Feiwu; Wu, Gang

2015-01-01

The rapid increase in the number of genetically modified (GM) varieties has led to a demand for high-throughput methods to detect genetically modified organisms (GMOs). We describe a new dynamic array-based high throughput method to simultaneously detect 48 targets in 48 samples on a Fludigm system. The test targets included species-specific genes, common screening elements, most of the Chinese-approved GM events, and several unapproved events. The 48 TaqMan assays successfully amplified products from both single-event samples and complex samples with a GMO DNA amount of 0.05 ng, and displayed high specificity. To improve the sensitivity of detection, a preamplification step for 48 pooled targets was added to enrich the amount of template before performing dynamic chip assays. This dynamic chip-based method allowed the synchronous high-throughput detection of multiple targets in multiple samples. Thus, it represents an efficient, qualitative method for GMO multi-detection. PMID:25556930

Thiazolidinedione therapy and breast cancer risk in diabetic women: A systematic review and meta-analysis.

PubMed

Du, Rui; Lin, Lin; Cheng, Di; Xu, Yu; Xu, Min; Chen, Yuhong; Wang, Weiqing; Bi, Yufang; Li, Donghui; Lu, Jieli

2018-02-01

Rising experimental evidence suggests that thiazolidinediones (TZDs) exert a protective effect on breast cancer. However, studies concerning this issue were inconsistent and limited. Hence, we performed a meta-analysis with data from currently available studies to evaluate the effect of TZDs on breast cancer risk among diabetic women. We comprehensively searched for all pertinent studies addressing TZDs use and breast cancer risk published before January 1, 2016, in PubMed, Clinical Trials, and Cochrane Library. Data synthesis was performed in a random-effects model using Stata version 12.0 (Stata Corp, College Station, Texas). Fourteen independent studies were eventually selected in this meta-analysis, including 5 randomized controlled clinical trials (RCTs), 7 cohort studies, and 2 case-control studies. No significant associations of TZD use and risk of breast cancer were observed in the RCTs (pooled risk ratio [RR]: 0.77, 95% confidence interval (CI), 0.39-1.53, I 2  = 26%) or case-control studies (pooled odds ratio, 0.99, 95% CI, 0.76-1.28, I 2  = 31%). A 19% reduction in breast cancer risk (pooled RR: 0.81, 95% CI, 0.66-0.99, I 2  = 72%) was found in the cohort studies. However, after removing the study with the smallest event number and the greatest effect size, the association became nonsignificant with greatly decreased heterogeneity (pooled RR: 0.94, 95% CI, 0.86-1.03, I 2  = 16%). This meta-analysis did not find any significant association between TZDs use and risk of breast cancer among diabetic women. Copyright © 2017 John Wiley & Sons, Ltd.

Uniparental genetic heritage of belarusians: encounter of rare middle eastern matrilineages with a central European mitochondrial DNA pool.

PubMed

Kushniarevich, Alena; Sivitskaya, Larysa; Danilenko, Nina; Novogrodskii, Tadeush; Tsybovsky, Iosif; Kiseleva, Anna; Kotova, Svetlana; Chaubey, Gyaneshwer; Metspalu, Ene; Sahakyan, Hovhannes; Bahmanimehr, Ardeshir; Reidla, Maere; Rootsi, Siiri; Parik, Jüri; Reisberg, Tuuli; Achilli, Alessandro; Hooshiar Kashani, Baharak; Gandini, Francesca; Olivieri, Anna; Behar, Doron M; Torroni, Antonio; Davydenko, Oleg; Villems, Richard

2013-01-01

Ethnic Belarusians make up more than 80% of the nine and half million people inhabiting the Republic of Belarus. Belarusians together with Ukrainians and Russians represent the East Slavic linguistic group, largest both in numbers and territory, inhabiting East Europe alongside Baltic-, Finno-Permic- and Turkic-speaking people. Till date, only a limited number of low resolution genetic studies have been performed on this population. Therefore, with the phylogeographic analysis of 565 Y-chromosomes and 267 mitochondrial DNAs from six well covered geographic sub-regions of Belarus we strove to complement the existing genetic profile of eastern Europeans. Our results reveal that around 80% of the paternal Belarusian gene pool is composed of R1a, I2a and N1c Y-chromosome haplogroups - a profile which is very similar to the two other eastern European populations - Ukrainians and Russians. The maternal Belarusian gene pool encompasses a full range of West Eurasian haplogroups and agrees well with the genetic structure of central-east European populations. Our data attest that latitudinal gradients characterize the variation of the uniparentally transmitted gene pools of modern Belarusians. In particular, the Y-chromosome reflects movements of people in central-east Europe, starting probably as early as the beginning of the Holocene. Furthermore, the matrilineal legacy of Belarusians retains two rare mitochondrial DNA haplogroups, N1a3 and N3, whose phylogeographies were explored in detail after de novo sequencing of 20 and 13 complete mitogenomes, respectively, from all over Eurasia. Our phylogeographic analyses reveal that two mitochondrial DNA lineages, N3 and N1a3, both of Middle Eastern origin, might mark distinct events of matrilineal gene flow to Europe: during the mid-Holocene period and around the Pleistocene-Holocene transition, respectively.

Ezetimibe Increases Endogenous Cholesterol Excretion in Humans

PubMed Central

Lin, Xiaobo; Racette, Susan B; Ma, Lina; Wallendorf, Michael; Ostlund, Richard E

2017-01-01

Objective Ezetimibe improves cardiovascular outcomes when added to optimum statin treatment. It lowers LDL cholesterol and percent intestinal cholesterol absorption, but the exact cardioprotective mechanism is unknown. We tested the hypothesis that the dominant effect of ezetimibe is to increase the reverse transport of cholesterol from rapidly-mixing endogenous cholesterol pool into the stool. Approach and Results In a randomized, placebo-controlled, double-blind parallel trial in 24 healthy subjects with LDL cholesterol 100–200 mg/dL, we measured cholesterol metabolism before and after a 6-week treatment period with ezetimibe 10 mg/day or placebo. Plasma cholesterol was labeled by intravenous infusion of cholesterol-d7 in a lipid emulsion and dietary cholesterol with cholesterol-d5 and sitostanol-d4 solubilized in oil. Plasma and stool samples collected during a cholesterol- and phytosterol-controlled metabolic kitchen diet were analyzed by mass spectrometry. Ezetimibe reduced intestinal cholesterol absorption efficiency 30 ± 4.3% (SE, P < 0.0001) and LDL cholesterol 19.8 ± 1.9% (P = 0.0001). Body cholesterol pool size was unchanged, but fecal endogenous cholesterol excretion increased 66.6 ± 12.2% (P < 0.0001) and percent cholesterol excretion from body pools into the stool increased 74.7 ± 14.3% (P < 0.0001) while plasma cholesterol turnover rose 26.2 ± 3.6% (P = 0.0096). Fecal bile acids were unchanged. Conclusions Ezetimibe increased the efficiency of reverse cholesterol transport from rapidly-mixing plasma and tissue pools into the stool. Further work is needed to examine the potential relation of reverse cholesterol transport and whole body cholesterol metabolism to coronary events and the treatment of atherosclerosis. PMID:28279967

Ezetimibe Increases Endogenous Cholesterol Excretion in Humans.

PubMed

Lin, Xiaobo; Racette, Susan B; Ma, Lina; Wallendorf, Michael; Ostlund, Richard E

2017-05-01

Ezetimibe improves cardiovascular outcomes when added to optimum statin treatment. It lowers low-density lipoprotein cholesterol and percent intestinal cholesterol absorption, but the exact cardioprotective mechanism is unknown. We tested the hypothesis that the dominant effect of ezetimibe is to increase the reverse transport of cholesterol from rapidly mixing endogenous cholesterol pool into the stool. In a randomized, placebo-controlled, double-blind parallel trial in 24 healthy subjects with low-density lipoprotein cholesterol 100 to 200 mg/dL, we measured cholesterol metabolism before and after a 6-week treatment period with ezetimibe 10 mg/d or placebo. Plasma cholesterol was labeled by intravenous infusion of cholesterol-d 7 in a lipid emulsion and dietary cholesterol with cholesterol-d 5 and sitostanol-d 4 solubilized in oil. Plasma and stool samples collected during a cholesterol- and phytosterol-controlled metabolic kitchen diet were analyzed by mass spectrometry. Ezetimibe reduced intestinal cholesterol absorption efficiency 30±4.3% (SE, P <0.0001) and low-density lipoprotein cholesterol 19.8±1.9% ( P =0.0001). Body cholesterol pool size was unchanged, but fecal endogenous cholesterol excretion increased 66.6±12.2% ( P <0.0001) and percent cholesterol excretion from body pools into the stool increased 74.7±14.3% ( P <0.0001), whereas plasma cholesterol turnover rose 26.2±3.6% ( P =0.0096). Fecal bile acids were unchanged. Ezetimibe increased the efficiency of reverse cholesterol transport from rapidly mixing plasma and tissue pools into the stool. Further work is needed to examine the potential relation of reverse cholesterol transport and whole body cholesterol metabolism to coronary events and the treatment of atherosclerosis. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01603758. © 2017 American Heart Association, Inc.

Optimized DNA extraction methods for encysted embryos of the endangered fairy shrimp, Branchinecta sandiegonensis

USGS Publications Warehouse

Steele, A.N.; Simovich, M.A.; Pepino, D.; Schroeder, K.M.; Vandergast, A.G.; Bohonak, A.J.

2009-01-01

The San Diego fairy shrimp Branchinecta sandiegonensis is a federally endangered species endemic to vernal pools in southern California, USA. Filling events in these habitats are highly variable, with some pools failing to hold water long enough for reproduction over many successive years. Studies of this species are thus hindered by the relatively rare appearance of aquatically active life history phases. Because diapausing cysts are abundant and present at all times, they provide an underutilized opportunity for both species identification and genetic studies. However, methods for extracting DNA from cysts are technically challenging because of their structure and size. Here we present a protocol for extracting DNA from B. sandiegonensis cysts in sufficient quantities for "DNA Barcoding", microsatellite analysis and other genotyping and sequencing applications. The technique will aid in population genetic studies and species identification (since taxonomic keys only distinguish among adults), and will be applicable to other crustaceans with similar diapausing cysts. ?? Springer Science+Business Media B.V. 2008.

Two-stage opening of the Dover Strait and the origin of island Britain

PubMed Central

Gupta, Sanjeev; Collier, Jenny S.; Garcia-Moreno, David; Oggioni, Francesca; Trentesaux, Alain; Vanneste, Kris; De Batist, Marc; Camelbeeck, Thierry; Potter, Graeme; Van Vliet-Lanoë, Brigitte; Arthur, John C. R.

2017-01-01

Late Quaternary separation of Britain from mainland Europe is considered to be a consequence of spillover of a large proglacial lake in the Southern North Sea basin. Lake spillover is inferred to have caused breaching of a rock ridge at the Dover Strait, although this hypothesis remains untested. Here we show that opening of the Strait involved at least two major episodes of erosion. Sub-bottom records reveal a remarkable set of sediment-infilled depressions that are deeply incised into bedrock that we interpret as giant plunge pools. These support a model of initial erosion of the Dover Strait by lake overspill, plunge pool erosion by waterfalls and subsequent dam breaching. Cross-cutting of these landforms by a prominent bedrock-eroded valley that is characterized by features associated with catastrophic flooding indicates final breaching of the Strait by high-magnitude flows. These events set-up conditions for island Britain during sea-level highstands and caused large-scale re-routing of NW European drainage. PMID:28375202

Two-stage opening of the Dover Strait and the origin of island Britain

NASA Astrophysics Data System (ADS)

Gupta, Sanjeev; Collier, Jenny S.; Garcia-Moreno, David; Oggioni, Francesca; Trentesaux, Alain; Vanneste, Kris; de Batist, Marc; Camelbeeck, Thierry; Potter, Graeme; van Vliet-Lanoë, Brigitte; Arthur, John C. R.

2017-04-01

Late Quaternary separation of Britain from mainland Europe is considered to be a consequence of spillover of a large proglacial lake in the Southern North Sea basin. Lake spillover is inferred to have caused breaching of a rock ridge at the Dover Strait, although this hypothesis remains untested. Here we show that opening of the Strait involved at least two major episodes of erosion. Sub-bottom records reveal a remarkable set of sediment-infilled depressions that are deeply incised into bedrock that we interpret as giant plunge pools. These support a model of initial erosion of the Dover Strait by lake overspill, plunge pool erosion by waterfalls and subsequent dam breaching. Cross-cutting of these landforms by a prominent bedrock-eroded valley that is characterized by features associated with catastrophic flooding indicates final breaching of the Strait by high-magnitude flows. These events set-up conditions for island Britain during sea-level highstands and caused large-scale re-routing of NW European drainage.

Notch3-Jagged signaling controls the pool of undifferentiated airway progenitors

PubMed Central

Mori, Munemasa; Mahoney, John E.; Stupnikov, Maria R.; Paez-Cortez, Jesus R.; Szymaniak, Aleksander D.; Varelas, Xaralabos; Herrick, Dan B.; Schwob, James; Zhang, Hong; Cardoso, Wellington V.

2015-01-01

Basal cells are multipotent airway progenitors that generate distinct epithelial cell phenotypes crucial for homeostasis and repair of the conducting airways. Little is known about how these progenitor cells expand and transition to differentiation to form the pseudostratified airway epithelium in the developing and adult lung. Here, we show by genetic and pharmacological approaches that endogenous activation of Notch3 signaling selectively controls the pool of undifferentiated progenitors of upper airways available for differentiation. This mechanism depends on the availability of Jag1 and Jag2, and is key to generating a population of parabasal cells that later activates Notch1 and Notch2 for secretory-multiciliated cell fate selection. Disruption of this mechanism resulted in aberrant expansion of basal cells and altered pseudostratification. Analysis of human lungs showing similar abnormalities and decreased NOTCH3 expression in subjects with chronic obstructive pulmonary disease suggests an involvement of NOTCH3-dependent events in the pathogenesis of this condition. PMID:25564622

Droxidopa for orthostatic hypotension: a systematic review and meta-analysis.

PubMed

Strassheim, Victoria; Newton, Julia L; Tan, Maw Pin; Frith, James

2016-10-01

The systematic review and meta-analysis aims to determine the efficacy and safety of droxidopa in the treatment of orthostatic hypotension, following its recent approvals in the United States. MEDLINE, EMBASE, PubMed, Cochrane Controlled Trials Register, Web of Science, ProQuest, and the WHO Clinical Trials Registry were searched. Studies were included if they randomized adults with orthostatic hypotension to droxidopa or to control, and outcomes related to symptoms, daily activity, blood pressure, or adverse events. Data were extracted independently by two reviewers. Risk of bias was judged against the Cochrane risk of bias tool and quality of evidence measured using Grading of Recommendations Assessment, Development and Evaluation criteria. A fixed-effects model was used for pooled analysis. Of 224 identified records, four studies met eligibility, with a pooled sample size of 494. Study duration was between 1 and 8 weeks. Droxidopa was effective at reducing dizziness [mean difference -0.97 (95% confidence interval -1.51, -0.42)], overall symptoms [-0.52 (-0.98, -0.06)] and difficulty with activity [-0.86 (-1.34, -0.38)]. Droxidopa was also effective at improving standing SBP [3.9 (0.1, 7.69)]. Rates of adverse events were similar between droxidopa and control groups, including supine hypertension [odds ratio 1.93 (0.87, 4.25)]. Droxidopa is well tolerated and effective at reducing the symptoms associated with neurogenic orthostatic hypotension without increasing the risk of supine hypertension. PROSPERO ID CRD42015024612.

Autotransplantation of teeth in humans: a systematic review and meta-analysis.

PubMed

Almpani, Konstantinia; Papageorgiou, Spyridon N; Papadopoulos, Moschos A

2015-07-01

The aim of this investigation was to assess the currently available evidence concerning the complications and risk factors influencing the outcome of autotransplantation of teeth in humans. Electronic searches were conducted to identify randomized controlled and prospective clinical trials. Risk of bias within studies was assessed with the Downs and Black tool. Random-effects meta-analyses were conducted to pool the adverse event rates and relative risks with their 95% confidence intervals. Risk of bias across studies was assessed with the GRADE framework followed by sensitivity analyses. Thirty-eight studies were included in the analysis. Reported complications included the need for extraction, failure, hypermobility, pulp necrosis, pulp obliteration, and root resorption. Pooled complication event rates varied considerably, with small studies (<100 teeth) reporting greater complication rates. The analysis of risk factors was associated with both the primary outcome (extraction need) and secondary outcomes (failure, hypermobility, pulp necrosis, pulp obliteration, root resorption). The stage of root development seems to influence both the future survival, as well as the success of the transplanted teeth. Teeth with open apex were less likely to be extracted in comparison to teeth with closed apex (3 studies; 413 teeth; relative risk 0.3; 95% confidence interval 0.2-0.6). Due to the small number of the contributing studies, their methodological limitations, and the heterogeneous results reported, no firm conclusions can be drawn. Root development of the donor teeth has been established as one the most important factor related to the success of tooth autotransplantation.

Assessment of cardiovascular risk and vascular age in overweight/obese adults with primary hypertension: the EXERDIET-HTA study.

PubMed

Gorostegi-Anduaga, Ilargi; Pérez-Asenjo, Javier; Aispuru, Gualberto Rodrigo; Fryer, Simon M; Alonso-Colmenero, Ainara; Romaratezabala, Estíbaliz; Maldonado-Martín, Sara

2017-06-01

Hypertension (HTN), obesity and low cardiorespiratory fitness (CRF) are associated with an increased risk for a cardiovascular event. Enrolling overweight/obese individuals with HTN, the current study aimed to estimate cardiovascular risk (CVR) and vascular age (VA) profiles analyzing potential sex differences, determine whether VA is higher than chronological age, and whether CVR is associated with a low level of CRF. Overweight/obese non-Hispanic White participants (n=209; 141 men and 68 women) with primary HTN had their CVR and VA determined using the New Pooled Cohort Risk Equations and The Framingham method, respectively. Considering values of peak oxygen uptake, participants were divided into tertiles for each sex. The CVR, but not VA (P=0.339), was higher (P<0.001) in men compared with women irrespective of age. Irrespective of sex, VA was higher than chronological age (P<0.001). Age and BMI were higher (P<0.05) in the low CRF group compared with that in other groups. There were no differences in CVR (P=0.907) and VA (P=1.643) when values were separated into CRF groups. Pooled Cohort Equations could underestimate the risk of suffering a cardiovascular event in the following 10 years in overweight/obese non-Hispanic White women with HTN compared with men. The VA appears to be a useful tool in communicating CVR in this population irrespective of sex. The CRF alone may not be enough to moderate the CVR.

How Much Water Trees Access and How It Determines Forest Response to Drought

NASA Astrophysics Data System (ADS)

Berdanier, A. B.; Clark, J. S.

2015-12-01

Forests are transformed by drought as water availability drops below levels where trees of different sizes and species can maintain productivity and survive. Physiological studies have provided detailed understanding of how species differences affect drought vulnerability but they offer almost no insights about the amount of water different trees can access beyond general statements about rooting depth. While canopy architecture provides strong evidence for light availability aboveground, belowground moisture availability remains essentially unknown. For example, do larger trees always have greater access to soil moisture? In temperate mixed forests, the ability to access a large soil moisture pool could minimize damage during drought events and facilitate post-drought recovery, potentially at the expense of neighboring trees. We show that the pool of accessible soil moisture can be estimated for trees with data on whole-plant transpiration and that this data can be used to predict water availability for forest stands. We estimate soil water availability with a Bayesian state-space model based on a simple water balance, where cumulative depressions in water use below potential transpiration indicate soil resource depletion. We compare trees of different sizes and species, extend these findings to the entire stand, and connect them to our recent research showing that tree survival after drought depends on post-drought growth recovery and local moisture availability. These results can be used to predict competitive abilities for soil water, understand ecohydrological variation within stands, and identify trees that are at risk of damage from future drought events.

Kaplan-Meier survival analysis overestimates cumulative incidence of health-related events in competing risk settings: a meta-analysis.

PubMed

Lacny, Sarah; Wilson, Todd; Clement, Fiona; Roberts, Derek J; Faris, Peter; Ghali, William A; Marshall, Deborah A

2018-01-01

Kaplan-Meier survival analysis overestimates cumulative incidence in competing risks (CRs) settings. The extent of overestimation (or its clinical significance) has been questioned, and CRs methods are infrequently used. This meta-analysis compares the Kaplan-Meier method to the cumulative incidence function (CIF), a CRs method. We searched MEDLINE, EMBASE, BIOSIS Previews, Web of Science (1992-2016), and article bibliographies for studies estimating cumulative incidence using the Kaplan-Meier method and CIF. For studies with sufficient data, we calculated pooled risk ratios (RRs) comparing Kaplan-Meier and CIF estimates using DerSimonian and Laird random effects models. We performed stratified meta-analyses by clinical area, rate of CRs (CRs/events of interest), and follow-up time. Of 2,192 identified abstracts, we included 77 studies in the systematic review and meta-analyzed 55. The pooled RR demonstrated the Kaplan-Meier estimate was 1.41 [95% confidence interval (CI): 1.36, 1.47] times higher than the CIF. Overestimation was highest among studies with high rates of CRs [RR = 2.36 (95% CI: 1.79, 3.12)], studies related to hepatology [RR = 2.60 (95% CI: 2.12, 3.19)], and obstetrics and gynecology [RR = 1.84 (95% CI: 1.52, 2.23)]. The Kaplan-Meier method overestimated the cumulative incidence across 10 clinical areas. Using CRs methods will ensure accurate results inform clinical and policy decisions. Copyright © 2017 Elsevier Inc. All rights reserved.

Adverse event management in patients with relapsed and refractory multiple myeloma taking pomalidomide plus low-dose dexamethasone: A pooled analysis.

PubMed

Moreau, Philippe; Dimopoulos, Meletios A; Richardson, Paul G; Siegel, David S; Cavo, Michele; Corradini, Paolo; Weisel, Katja; Delforge, Michel; O'Gorman, Peter; Song, Kevin; Chen, Christine; Bahlis, Nizar; Oriol, Albert; Hansson, Markus; Kaiser, Martin; Anttila, Pekka; Raymakers, Reinier; Joao, Cristina; Cook, Gordon; Sternas, Lars; Biyukov, Tsvetan; Slaughter, Ana; Hong, Kevin; Herring, Jennifer; Yu, Xin; Zaki, Mohamed; San-Miguel, Jesus

2017-09-01

Heavily pretreated patients with relapsed and refractory multiple myeloma are susceptible to treatment-related adverse events (AEs). Managing AEs are important to ensure patients continue therapy long enough to receive the best clinical benefit. Data from the MM-002, MM-003, and MM-010 trials were pooled to further characterize the safety profile of pomalidomide plus low-dose dexamethasone and AE management. This analysis included 1088 patients who received ≥ 2 prior therapies, including lenalidomide and bortezomib, and progressed ≤ 60 days of last therapy. Patients received 28-day cycles of pomalidomide 4 mg/day on days 1-21 and low-dose dexamethasone 40 mg (20 mg if aged > 75 years) weekly until disease progression or unacceptable toxicity. Thromboprophylaxis was required. The most common grade 3/4 AEs were neutropenia (56.2%), anemia (32.3%), and thrombocytopenia (25.8%), which occurred within the first few cycles of treatment. Grade 3/4 infections occurred in 33.7% patients, of whom 13.9% had pneumonia, and 40.3% had neutropenia. Pomalidomide dose reductions or interruptions were reported in 24.2% and 66.0% of patients, respectively. AEs were managed by dose modifications and/or supportive care. Pomalidomide plus low-dose dexamethasone showed an acceptable safety profile, and AEs were well managed according to study protocols and established guidelines. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Activity screening of carrier domains within nonribosomal peptide synthetases using complex substrate mixtures and large molecule mass spectrometry.

PubMed

Dorrestein, Pieter C; Blackhall, Jonathan; Straight, Paul D; Fischbach, Michael A; Garneau-Tsodikova, Sylvie; Edwards, Daniel J; McLaughlin, Shaun; Lin, Myat; Gerwick, William H; Kolter, Roberto; Walsh, Christopher T; Kelleher, Neil L

2006-02-14

For screening a pool of potential substrates that load carrier domains found in nonribosomal peptide synthetases, large molecule mass spectrometry is shown to be a new, unbiased assay. Combining the high resolving power of Fourier transform mass spectrometry with the ability of adenylation domains to select their own substrates, the mass change that takes place upon formation of a covalent intermediate thus identifies the substrate. This assay has an advantage over traditional radiochemical assays in that many substrates, the substrate pool, can be screened simultaneously. Using proteins on the nikkomycin, clorobiocin, coumermycin A1, yersiniabactin, pyochelin, and enterobactin biosynthetic pathways as proof of principle, preferred substrates are readily identified from substrate pools. Furthermore, this assay can be used to provide insight into the timing of tailoring events of biosynthetic pathways as demonstrated using the bromination reaction found on the jamaicamide biosynthetic pathway. Finally, this assay can provide insight into the role and function of orphan gene clusters for which the encoded natural product is unknown. This is demonstrated by identifying the substrates for two NRPS modules from the pksN and pksJ genes that are found on an orphan NRPS/PKS hybrid cluster from Bacillus subtilis. This new assay format is especially timely for activity screening in an era when new types of thiotemplate assembly lines that defy classification are being discovered at an accelerating rate.

Pirfenidone for idiopathic pulmonary fibrosis: analysis of pooled data from three multinational phase 3 trials.

PubMed

Noble, Paul W; Albera, Carlo; Bradford, Williamson Z; Costabel, Ulrich; du Bois, Roland M; Fagan, Elizabeth A; Fishman, Robert S; Glaspole, Ian; Glassberg, Marilyn K; Lancaster, Lisa; Lederer, David J; Leff, Jonathan A; Nathan, Steven D; Pereira, Carlos A; Swigris, Jeffrey J; Valeyre, Dominique; King, Talmadge E

2016-01-01

Pirfenidone is an antifibrotic agent that has been evaluated in three multinational phase 3 trials in patients with idiopathic pulmonary fibrosis (IPF). We analysed pooled data from the multinational trials to obtain the most precise estimates of the magnitude of treatment effect on measures of disease progression.All patients randomised to pirfenidone 2403 mg·day(-1) or placebo in the CAPACITY or ASCEND studies were included in the analysis. Pooled analyses of outcomes at 1 year were based on the pre-specified end-points and analytic methods described in the ASCEND study protocol.A total of 1247 patients were included in the analysis. At 1 year, pirfenidone reduced the proportion of patients with a ≥10% decline in per cent predicted forced vital capacity or death by 43.8% (95% CI 29.3-55.4%) and increased the proportion of patients with no decline by 59.3% (95% CI 29.0-96.8%). A treatment benefit was also observed for progression-free survival, 6-min walk distance and dyspnoea. Gastrointestinal and skin-related adverse events were more common in the pirfenidone group, but rarely led to discontinuation.Analysis of data from three phase 3 trials demonstrated that treatment with pirfenidone for 1 year resulted in clinically meaningful reductions in disease progression in patients with IPF. Copyright ©ERS 2016.

The Selenocysteine-Specific Elongation Factor Contains Unique Sequences That Are Required for Both Nuclear Export and Selenocysteine Incorporation.

PubMed

Dubey, Aditi; Copeland, Paul R

2016-01-01

Selenocysteine (Sec) is a critical residue in at least 25 human proteins that are essential for antioxidant defense and redox signaling in cells. Sec is inserted into proteins cotranslationally by the recoding of an in-frame UGA termination codon to a Sec codon. In eukaryotes, this recoding event requires several specialized factors, including a dedicated, Sec-specific elongation factor called eEFSec, which binds Sec-tRNASec with high specificity and delivers it to the ribosome for selenoprotein production. Unlike most translation factors, including the canonical elongation factor eEF1A, eEFSec readily localizes to the nucleus of mammalian cells and shuttles between the cytoplasmic and nuclear compartments. The functional significance of eEFSec's nuclear localization has remained unclear. In this study, we have examined the subcellular localization of eEFSec in the context of altered Sec incorporation to demonstrate that reduced selenoprotein production does not correlate with changes in the nuclear localization of eEFSec. In addition, we identify several novel sequences of the protein that are essential for localization as well as Sec insertion activity, and show that eEFSec utilizes CRM1-mediated nuclear export pathway. Our findings argue for two distinct pools of eEFSec in the cell, where the cytoplasmic pool participates in Sec incorporation and the nuclear pool may be involved in an as yet unknown function.

Coupling between Chemical and Meteorological Processes under Persistent Cold-Air Pool Conditions: Evolution of Wintertime PM2.5 Pollution Events and N2O5 Observations in Utah's Salt Lake Valley.

PubMed

Baasandorj, Munkhbayar; Hoch, Sebastian W; Bares, Ryan; Lin, John C; Brown, Steven S; Millet, Dylan B; Martin, Randal; Kelly, Kerry; Zarzana, Kyle J; Whiteman, C David; Dube, William P; Tonnesen, Gail; Jaramillo, Isabel Cristina; Sohl, John

2017-06-06

The Salt Lake Valley experiences severe fine particulate matter pollution episodes in winter during persistent cold-air pools (PCAPs). We employ measurements throughout an entire winter from different elevations to examine the chemical and dynamical processes driving these episodes. Whereas primary pollutants such as NO x and CO were enhanced twofold during PCAPs, O 3 concentrations were approximately threefold lower. Atmospheric composition varies strongly with altitude within a PCAP at night with lower NO x and higher oxidants (O 3 ) and oxidized reactive nitrogen (N 2 O 5 ) aloft. We present observations of N 2 O 5 during PCAPs that provide evidence for its role in cold-pool nitrate formation. Our observations suggest that nighttime and early morning chemistry in the upper levels of a PCAP plays an important role in aerosol nitrate formation. Subsequent daytime mixing enhances surface PM 2.5 by dispersing the aerosol throughout the PCAP. As pollutants accumulate and deplete oxidants, nitrate chemistry becomes less active during the later stages of the pollution episodes. This leads to distinct stages of PM 2.5 pollution episodes, starting with a period of PM 2.5 buildup and followed by a period with plateauing concentrations. We discuss the implications of these findings for mitigation strategies.

Pirfenidone for idiopathic pulmonary fibrosis: analysis of pooled data from three multinational phase 3 trials

PubMed Central

Albera, Carlo; Bradford, Williamson Z.; Costabel, Ulrich; du Bois, Roland M.; Fagan, Elizabeth A.; Fishman, Robert S.; Glaspole, Ian; Glassberg, Marilyn K.; Lancaster, Lisa; Lederer, David J.; Leff, Jonathan A.; Nathan, Steven D.; Pereira, Carlos A.; Swigris, Jeffrey J.; Valeyre, Dominique; King, Talmadge E.

2016-01-01

Pirfenidone is an antifibrotic agent that has been evaluated in three multinational phase 3 trials in patients with idiopathic pulmonary fibrosis (IPF). We analysed pooled data from the multinational trials to obtain the most precise estimates of the magnitude of treatment effect on measures of disease progression. All patients randomised to pirfenidone 2403 mg·day−1 or placebo in the CAPACITY or ASCEND studies were included in the analysis. Pooled analyses of outcomes at 1 year were based on the pre-specified end-points and analytic methods described in the ASCEND study protocol. A total of 1247 patients were included in the analysis. At 1 year, pirfenidone reduced the proportion of patients with a ≥10% decline in per cent predicted forced vital capacity or death by 43.8% (95% CI 29.3–55.4%) and increased the proportion of patients with no decline by 59.3% (95% CI 29.0–96.8%). A treatment benefit was also observed for progression-free survival, 6-min walk distance and dyspnoea. Gastrointestinal and skin-related adverse events were more common in the pirfenidone group, but rarely led to discontinuation. Analysis of data from three phase 3 trials demonstrated that treatment with pirfenidone for 1 year resulted in clinically meaningful reductions in disease progression in patients with IPF. PMID:26647432

Once-daily mesalamine granules for maintaining remission of ulcerative colitis: pooled analysis of efficacy, safety, and prognostic factors.

PubMed

Zakko, Salam F; Gordon, Glenn L; Murthy, Uma; Sedghi, Shahriar; Pruitt, Ronald; Barrett, Andrew C; Bortey, Enoch; Paterson, Craig; Forbes, William P; Lichtenstein, Gary R

2016-01-01

A capsule formulation of mesalamine granules (MG) was developed for once-daily dosing and better compliance. The study aim was to evaluate MG efficacy and tolerability in maintaining ulcerative colitis (UC) remission. Pooled analysis of 2 identical phase 3, randomized, double-blind trials of once-daily MG 1.5 g or placebo for up to 6 months. The primary endpoint was percentage of patients remaining relapse-free at month 6 versus placebo. Relapse was defined as revised Sutherland Disease Activity Index (SDAI) rectal bleeding score ≥1 and mucosal appearance score ≥2, UC flare, or UC-related adverse event (AE). Data were pooled for patients receiving MG (n = 373) and placebo (n = 189). Significantly more patients were relapse-free at 6 months with MG (79.4%) than placebo (62.4%; P < 0.001) and across subgroups based on select demographic and baseline characteristics (P < 0.05). Secondary outcome measures including rectal bleeding, physician rating of disease activity, stool frequency, total SDAI score, and relapse-free duration favored MG (P < 0.01). Common AEs with MG and placebo, respectively, were headache (10.9% and 7.6%), diarrhea (7.9% and 7.0%), and abdominal pain (6.3% and 6.5%). Once-daily MG was more efficacious than and as well tolerated as placebo in maintaining UC remission. ClinicalTrials.gov identifiers: NCT00744016 and NCT00767728.

Efficacy and safety of memantine in patients with moderate-to-severe Alzheimer's disease: results of a pooled analysis of two randomized, double-blind, placebo-controlled trials in Japan

PubMed Central

Nakamura, Yu; Kitamura, Shin; Homma, Akira; Shiosakai, Kazuhito; Matsui, Daiju

2014-01-01

Background: With the increase in the aging population, there is a pressing need to provide effective treatment options for individuals with Alzheimer's disease (AD). Memantine is an N-methyl-D-aspartate receptor antagonist used to treat AD in > 80 countries worldwide, and studies in the USA and Europe have shown it to be effective in improving language deficits; however, there are currently no data on language improvements in Japanese patients treated with memantine. Objectives: To clarify the efficacy and safety of memantine in Japanese outpatients with moderate to severe AD, using a pooled analysis of two multicenter randomized placebo-controlled trials, a phase 2 dose-finding study and a phase 3 study. Results: The final analysis comprised 633 patients (318 receiving memantine and 315 placebo). Memantine produced better outcomes in terms of Severe Impairment Battery-Japanese version, Clinician's Interview-Based Impression of Change plus-Japanese version, Behavioral Pathology in AD Rating Scale, and language scores, versus placebo. The overall incidence of adverse events and adverse reactions was similar between groups. Conclusion: In this pooled analysis of Japanese patients, memantine achieved better outcomes than placebo in terms of cognition, including attention, praxis, visuospatial ability and language, and behavioral and psychological symptoms, including activity disturbances and aggressiveness. PMID:24673497

Bleeding Risk with Long-Term Low-Dose Aspirin: A Systematic Review of Observational Studies

PubMed Central

García Rodríguez, Luis A.; Martín-Pérez, Mar; Hennekens, Charles H.; Rothwell, Peter M.; Lanas, Angel

2016-01-01

Background Low-dose aspirin has proven effectiveness in secondary and primary prevention of cardiovascular events, but is also associated with an increased risk of major bleeding events. For primary prevention, this absolute risk must be carefully weighed against the benefits of aspirin; such assessments are currently limited by a lack of data from general populations. Methods Systematic searches of Medline and Embase were conducted to identify observational studies published between 1946 and 4 March 2015 that reported the risks of gastrointestinal (GI) bleeding or intracranial hemorrhage (ICH) with long-term, low-dose aspirin (75–325 mg/day). Pooled estimates of the relative risk (RR) for bleeding events with aspirin versus non-use were calculated using random-effects models, based on reported estimates of RR (including odds ratios, hazard ratios, incidence rate ratios and standardized incidence ratios) in 39 articles. Findings The incidence of GI bleeding with low-dose aspirin was 0.48–3.64 cases per 1000 person-years, and the overall pooled estimate of the RR with low-dose aspirin was 1.4 (95% confidence interval [CI]: 1.2–1.7). For upper and lower GI bleeding, the RRs with low-dose aspirin were 2.3 (2.0–2.6) and 1.8 (1.1–3.0), respectively. Neither aspirin dose nor duration of use had consistent effects on RRs for upper GI bleeding. The estimated RR for ICH with low-dose aspirin was 1.4 (1.2–1.7) overall. Aspirin was associated with increased bleeding risks when combined with non-steroidal anti-inflammatory drugs, clopidogrel and selective serotonin reuptake inhibitors compared with monotherapy. By contrast, concomitant use of proton pump inhibitors decreased upper GI bleeding risks relative to aspirin monotherapy. Conclusions The risks of major bleeding with low-dose aspirin in real-world settings are of a similar magnitude to those reported in randomized trials. These data will help inform clinical judgements regarding the use of low-dose aspirin in prevention of cardiovascular events. PMID:27490468

Document Set Differentiability Analyzer v. 0.1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Osborn, Thor D.

Software is a JMP Scripting Language (JSL) script designed to evaluate the differentiability of a set of documents that exhibit some conceptual commonalities but are expected to describe substantially different – thus differentiable – categories. The script imports the document set, a subset of which may be partitioned into an additions pool. The bulk of the documents form a basis pool. Text analysis is applied to the basis pool to extract a mathematical representation of its conceptual content, referred to as the document concept space. A bootstrapping approach is applied to that mathematical representation in order to generate a representationmore » of a large population of randomly designed documents that could be written within the concept space, notably without actually writing the text of those documents.The Kolmogorov-Smirnov test is applied to determine whether the basis pool document set exhibits superior differentiation relative to the randomly designed virtual documents produced by bootstrapping. If an additions pool exists, the documents are incrementally added to the basis pool, choosing the best differentiated remaining document at each step. In this manner the impact of additional categories to overall document set differentiability may be assessed.The software was developed to assess the differentiability of job description document sets. Differentiability is key to meaningful categorization. Poor job differentiation may have economic, ethical, and/or legal implications for an organization. Job categories are used in the assignment of market-based salaries; consequently, poor differentiation of job duties may set the stage for legal challenges if very similar jobs pay differently depending on title, a circumstance that also invites economic waste.The software can be applied to ensure job description set differentiability, reducing legal, economic, and ethical risks to an organization and its people. The extraction of the conceptual space to a mathematical representation enables identification of exceedingly similar documents. In the event of redundancy, two jobs may be collapsed into one. If in the judgment of the subject matter experts the jobs are truly different, the conceptual similarities are highlighted, inviting inclusion of appropriate descriptive content to explicitly characterize those differences. When additional job categories may be needed as the organization changes, the software enables evaluation of proposed additions to ensure that the resulting document set remains adequately differentiated.« less

Salinity anomaly as a trigger for ENSO events

PubMed Central

Zhu, Jieshun; Huang, Bohua; Zhang, Rong-Hua; Hu, Zeng-Zhen; Kumar, Arun; Balmaseda, Magdalena A.; Marx, Lawrence; Kinter III, James L.

2014-01-01

According to the classical theories of ENSO, subsurface anomalies in ocean thermal structure are precursors for ENSO events and their initial specification is essential for skillful ENSO forecast. Although ocean salinity in the tropical Pacific (particularly in the western Pacific warm pool) can vary in response to El Niño events, its effect on ENSO evolution and forecasts of ENSO has been less explored. Here we present evidence that, in addition to the passive response, salinity variability may also play an active role in ENSO evolution, and thus important in forecasting El Niño events. By comparing two forecast experiments in which the interannually variability of salinity in the ocean initial states is either included or excluded, the salinity variability is shown to be essential to correctly forecast the 2007/08 La Niña starting from April 2007. With realistic salinity initial states, the tendency to decay of the subsurface cold condition during the spring and early summer 2007 was interrupted by positive salinity anomalies in the upper central Pacific, which working together with the Bjerknes positive feedback, contributed to the development of the La Niña event. Our study suggests that ENSO forecasts will benefit from more accurate salinity observations with large-scale spatial coverage. PMID:25352285

Salinity anomaly as a trigger for ENSO events.

PubMed

Zhu, Jieshun; Huang, Bohua; Zhang, Rong-Hua; Hu, Zeng-Zhen; Kumar, Arun; Balmaseda, Magdalena A; Marx, Lawrence; Kinter, James L

2014-10-29

According to the classical theories of ENSO, subsurface anomalies in ocean thermal structure are precursors for ENSO events and their initial specification is essential for skillful ENSO forecast. Although ocean salinity in the tropical Pacific (particularly in the western Pacific warm pool) can vary in response to El Niño events, its effect on ENSO evolution and forecasts of ENSO has been less explored. Here we present evidence that, in addition to the passive response, salinity variability may also play an active role in ENSO evolution, and thus important in forecasting El Niño events. By comparing two forecast experiments in which the interannually variability of salinity in the ocean initial states is either included or excluded, the salinity variability is shown to be essential to correctly forecast the 2007/08 La Niña starting from April 2007. With realistic salinity initial states, the tendency to decay of the subsurface cold condition during the spring and early summer 2007 was interrupted by positive salinity anomalies in the upper central Pacific, which working together with the Bjerknes positive feedback, contributed to the development of the La Niña event. Our study suggests that ENSO forecasts will benefit from more accurate salinity observations with large-scale spatial coverage.

Transcriptome and metabolome of synthetic Solanum autotetraploids reveal key genomic stress events following polyploidization.

PubMed

Fasano, Carlo; Diretto, Gianfranco; Aversano, Riccardo; D'Agostino, Nunzio; Di Matteo, Antonio; Frusciante, Luigi; Giuliano, Giovanni; Carputo, Domenico

2016-06-01

Polyploids are generally classified as autopolyploids, derived from a single species, and allopolyploids, arising from interspecific hybridization. The former represent ideal materials with which to study the consequences of genome doubling and ascertain whether there are molecular and functional rules operating following polyploidization events. To investigate whether the effects of autopolyploidization are common to different species, or if species-specific or stochastic events are prevalent, we performed a comprehensive transcriptomic and metabolomic characterization of diploids and autotetraploids of Solanum commersonii and Solanum bulbocastanum. Autopolyploidization remodelled the transcriptome and the metabolome of both species. In S. commersonii, differentially expressed genes (DEGs) were highly enriched in pericentromeric regions. Most changes were stochastic, suggesting a strong genotypic response. However, a set of robustly regulated transcripts and metabolites was also detected, including purine bases and nucleosides, which are likely to underlie a common response to polyploidization. We hypothesize that autopolyploidization results in nucleotide pool imbalance, which in turn triggers a genomic shock responsible for the stochastic events observed. The more extensive genomic stress and the higher number of stochastic events observed in S. commersonii with respect to S. bulbocastanum could be the result of the higher nucleoside depletion observed in this species. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

Explosion Monitoring with Machine Learning: A LSTM Approach to Seismic Event Discrimination

NASA Astrophysics Data System (ADS)

Magana-Zook, S. A.; Ruppert, S. D.

2017-12-01

The streams of seismic data that analysts look at to discriminate natural from man- made events will soon grow from gigabytes of data per day to exponentially larger rates. This is an interesting problem as the requirement for real-time answers to questions of non-proliferation will remain the same, and the analyst pool cannot grow as fast as the data volume and velocity will. Machine learning is a tool that can solve the problem of seismic explosion monitoring at scale. Using machine learning, and Long Short-term Memory (LSTM) models in particular, analysts can become more efficient by focusing their attention on signals of interest. From a global dataset of earthquake and explosion events, a model was trained to recognize the different classes of events, given their spectrograms. Optimal recurrent node count and training iterations were found, and cross validation was performed to evaluate model performance. A 10-fold mean accuracy of 96.92% was achieved on a balanced dataset of 30,002 instances. Given that the model is 446.52 MB it can be used to simultaneously characterize all incoming signals by researchers looking at events in isolation on desktop machines, as well as at scale on all of the nodes of a real-time streaming platform. LLNL-ABS-735911

Economic Evaluations of the Health Impacts of Weather-Related Extreme Events: A Scoping Review

PubMed Central

Schmitt, Laetitia H. M.; Graham, Hilary M.; White, Piran C. L.

2016-01-01

The frequency and severity of extreme events is expected to increase under climate change. There is a need to understand the economic consequences of human exposure to these extreme events, to underpin decisions on risk reduction. We undertook a scoping review of economic evaluations of the adverse health effects from exposure to weather-related extreme events. We searched PubMed, Embase and Web of Science databases with no restrictions to the type of evaluations. Twenty studies were included, most of which were recently published. Most studies have been undertaken in the U.S. (nine studies) or Asia (seven studies), whereas we found no studies in Africa, Central and Latin America nor the Middle East. Extreme temperatures accounted for more than a third of the pool of studies (seven studies), closely followed by flooding (six studies). No economic study was found on drought. Whilst studies were heterogeneous in terms of objectives and methodology, they clearly indicate that extreme events will become a pressing public health issue with strong welfare and distributional implications. The current body of evidence, however, provides little information to support decisions on the allocation of scarce resources between risk reduction options. In particular, the review highlights a significant lack of research attention to the potential cost-effectiveness of interventions that exploit the capacity of natural ecosystems to reduce our exposure to, or ameliorate the consequences of, extreme events. PMID:27834843

Peginesatide in patients with anemia undergoing hemodialysis.

PubMed

Fishbane, Steven; Schiller, Brigitte; Locatelli, Francesco; Covic, Adrian C; Provenzano, Robert; Wiecek, Andrzej; Levin, Nathan W; Kaplan, Mark; Macdougall, Iain C; Francisco, Carol; Mayo, Martha R; Polu, Krishna R; Duliege, Anne-Marie; Besarab, Anatole

2013-01-24

Peginesatide, a synthetic peptide-based erythropoiesis-stimulating agent (ESA), is a potential therapy for anemia in patients with advanced chronic kidney disease. We conducted two randomized, controlled, open-label studies (EMERALD 1 and EMERALD 2) involving patients undergoing hemodialysis. Cardiovascular safety was evaluated by analysis of an adjudicated composite safety end point--death from any cause, stroke, myocardial infarction, or serious adverse events of congestive heart failure, unstable angina, or arrhythmia--with the use of pooled data from the two EMERALD studies and two studies involving patients not undergoing dialysis. In the EMERALD studies, 1608 patients received peginesatide once monthly or continued to receive epoetin one to three times a week, with the doses adjusted as necessary to maintain a hemoglobin level between 10.0 and 12.0 g per deciliter for 52 weeks or more. The primary efficacy end point was the mean change from the baseline hemoglobin level to the mean level during the evaluation period; noninferiority was established if the lower limit of the two-sided 95% confidence interval was -1.0 g per deciliter or higher in the comparison of peginesatide with epoetin. The aim of evaluating the composite safety end point in the pooled cohort was to exclude a hazard ratio with peginesatide relative to the comparator ESA of more than 1.3. In an analysis involving 693 patients from EMERALD 1 and 725 from EMERALD 2, peginesatide was noninferior to epoetin in maintaining hemoglobin levels (mean between-group difference, -0.15 g per deciliter; 95% confidence interval [CI], -0.30 to -0.01 in EMERALD 1; and 0.10 g per deciliter; 95% CI, -0.05 to 0.26 in EMERALD 2). The hazard ratio for the composite safety end point was 1.06 (95% CI, 0.89 to 1.26) with peginesatide relative to the comparator ESA in the four pooled studies (2591 patients) and 0.95 (95% CI, 0.77 to 1.17) in the EMERALD studies. The proportions of patients with adverse and serious adverse events were similar in the treatment groups in the EMERALD studies. The cardiovascular safety of peginesatide was similar to that of the comparator ESA in the pooled cohort. Peginesatide, administered monthly, was as effective as epoetin, administered one to three times per week, in maintaining hemoglobin levels in patients undergoing hemodialysis. (Funded by Affymax and Takeda Pharmaceutical; ClinicalTrials.gov numbers, NCT00597753 [EMERALD 1], NCT00597584 [EMERALD 2], NCT00598273 [PEARL 1], and NCT00598442 [PEARL 2].).

The hepatic safety and tolerability of the cyclooxygenase-2 selective NSAID celecoxib: pooled analysis of 41 randomized controlled trials.

PubMed

Soni, Paresh; Shell, Briton; Cawkwell, Gail; Li, Chunming; Ma, Hong

2009-08-01

To assess the hepatic safety and tolerability of celecoxib versus placebo and three commonly prescribed nonselective nonsteroidal anti-inflammatory drugs (NSAIDs). This was a retrospective, pooled analysis of a 41-study dataset involving patients with osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, chronic low back pain, and Alzheimer's disease. Criteria for selection of studies were: (1) Randomized, parallel-group design and planned treatment duration of > or =2 weeks (2) > or =1 placebo or NSAID comparator (3) > or =1 arm with celecoxib at total daily dose of > or =200 mg (4) Data available as of October 31, 2004 Data were pooled by treatment and subject from the safety analysis population of included studies. Treatment-emergent hepatobiliary adverse events (AEs) were compared for celecoxib <200 mg/day (943 patients), 200 mg/day (12 008 patients), 400 mg/day (7380 patients), and 800 mg/day (4602 patients); placebo (4057 patients); diclofenac 100-150 mg/day (7639 patients); naproxen 1000 mg/day (2953 patients); and ibuprofen 2400 mg/day (2484 patients). Hepatobiliary laboratory abnormalities were also analyzed. There were no cases of liver failure, treatment-related liver transplant, or treatment-related hepatobiliary death. Incidence of serious hepatic AEs was low, with 13 (0.05%) serious hepatic AEs among 24 933 celecoxib-treated patients, and 16 (0.21%) among 7639 diclofenac-treated patients. No patients receiving celecoxib or any nonselective NSAID met criteria for Hy's rule (alanine aminotransferase [ALT] > or =3 x upper limit of normal [ULN] with bilirubin > or =2 x ULN). The incidence of notable (> or =5 x ULN) and severe (> or =10 x ULN) ALT elevations was similar for all treatment groups except diclofenac. Significantly fewer hepatobiliary AEs were reported for celecoxib (any dose; 1.11%) than for diclofenac (vs. 4.24%, p < 0.0001); for ibuprofen (vs. 1.53%, p = 0.06) and placebo (vs. 0.89%, p = 0.21) the incidence of AEs was comparable to celecoxib. A number of limitations should be considered when evaluating the results: findings were limited by the quality and reporting of the studies selected; difficulty in estimating the incidence of AEs due to the low frequency of events; acetaminophen not included as an active comparator. In this pooled analysis, the incidence of hepatic AEs in patients treated with celecoxib was similar to that for both placebo-treated patients and patients treated with ibuprofen or naproxen, but lower than for diclofenac.

Investigation of 2-stage meta-analysis methods for joint longitudinal and time-to-event data through simulation and real data application.

PubMed

Sudell, Maria; Tudur Smith, Catrin; Gueyffier, François; Kolamunnage-Dona, Ruwanthi

2018-04-15

Joint modelling of longitudinal and time-to-event data is often preferred over separate longitudinal or time-to-event analyses as it can account for study dropout, error in longitudinally measured covariates, and correlation between longitudinal and time-to-event outcomes. The joint modelling literature focuses mainly on the analysis of single studies with no methods currently available for the meta-analysis of joint model estimates from multiple studies. We propose a 2-stage method for meta-analysis of joint model estimates. These methods are applied to the INDANA dataset to combine joint model estimates of systolic blood pressure with time to death, time to myocardial infarction, and time to stroke. Results are compared to meta-analyses of separate longitudinal or time-to-event models. A simulation study is conducted to contrast separate versus joint analyses over a range of scenarios. Using the real dataset, similar results were obtained by using the separate and joint analyses. However, the simulation study indicated a benefit of use of joint rather than separate methods in a meta-analytic setting where association exists between the longitudinal and time-to-event outcomes. Where evidence of association between longitudinal and time-to-event outcomes exists, results from joint models over standalone analyses should be pooled in 2-stage meta-analyses. © 2017 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.

Volcanic Tephra ejected in south eastern Asia is the sole cause of all historic ENSO events. This natural aerosol plume has been intensified by an anthropogenic plume in the same region in recent decades which has intensified some ENSO events and altered the Southern Oscillation Index characteristics

NASA Astrophysics Data System (ADS)

Potts, K. A.

2017-12-01

ENSO events are the most significant perturbation of the climate system. Previous attempts to link ENSO with volcanic eruptions typically failed because only large eruptions across the globe which eject tephra into the stratosphere were considered. I analyse all volcanic eruptions in South Eastern (SE) Asia (10ºS to 10ºN and from 90ºE to 160ºE) the most volcanically active area in the world with over 23% of all eruptions in the Global Volcanism Program database occurring here and with 5 volcanoes stated to have erupted nearly continuously for 30 years. SE Asia is also the region where the convective arm of the thermally direct Walker Circulation occurs driven by the intense equatorial solar radiation which creates the high surface temperature. The volcanic tephra plume intercepts some of the solar radiation by absorption/reflection which cools the surface and heats the atmosphere creating a temperature inversion compared to periods without the plume. This reduces convection and causes the Walker Cell and Trade Winds to weaken. This reduced wind speed causes the central Pacific Ocean to warm which creates convection there which further weakens the Walker Cell. With the reduced wind stress the western Pacific warm pool migrates east. This creates an ENSO event which continues until the tephra plume reduces, typically when the SE Asian monsoon commences, and convection is re-established over SE Asia and the Pacific warm pool migrates back to the west. Correlations of SE Asian tephra and the ENSO indices are typically over 0.80 at p < 0.01 In recent decades the anthropogenic SE Asian aerosol Plume (SEAP) has intensified the volcanic plume in some years from August to November. Using NASA satellite data from 1978 and the NASA MERRA 2 reanalysis dataset I show correlation coefficients typically over 0.70 and up to 0.97 at p < 0.01 between the aerosol optical depth or index and the ENSO indices. If two events A and B correlate 5 options are available: 1. A causes B; 2. B causes A; 3. C, another event, causes A &B simultaneously; 4. It's a coincidence; and 5. The relationship is complex with feedback. The volcanic correlations only allow options 1 or 4 as ENSO cannot cause volcanoes to erupt and are backed up by several independent satellite datasets. I conclude volcanic and anthropogenic aerosols over SE Asia are the sole cause of all ENSO events.

Impact Detection for Characterization of Complex Multiphase Flows

NASA Astrophysics Data System (ADS)

Chan, Wai Hong Ronald; Urzay, Javier; Mani, Ali; Moin, Parviz

2016-11-01

Multiphase flows often involve a wide range of impact events, such as liquid droplets impinging on a liquid pool or gas bubbles coalescing in a liquid medium. These events contribute to a myriad of large-scale phenomena, including breaking waves on ocean surfaces. As impacts between surfaces necessarily occur at isolated points, numerical simulations of impact events will require the resolution of molecular scales near the impact points for accurate modeling. This can be prohibitively expensive unless subgrid impact and breakup models are formulated to capture the effects of the interactions. The first step in a large-eddy simulation (LES) based computational methodology for complex multiphase flows like air-sea interactions requires effective detection of these impact events. The starting point of this work is a collision detection algorithm for structured grids on a coupled level set / volume of fluid (CLSVOF) solver adapted from an earlier algorithm for cloth animations that triangulates the interface with the marching cubes method. We explore the extension of collision detection to a geometric VOF solver and to unstructured grids. Supported by ONR/A*STAR. Agency of Science, Technology and Research, Singapore; Office of Naval Research, USA.

Developing a nationwide K-12 outreach model: Physiology Understanding (PhUn) Week 10 years later.

PubMed

Stieben, Margaret; Halpin, Patricia A; Matyas, Marsha Lakes

2017-09-01

Since 2005, nearly 600 Physiology Understanding Week (PhUn Week) events have taken place across the U.S., involving American Physiological Society (APS) members in K-12 outreach. The program seeks to build student understanding of physiology and physiology careers, assist teachers in recognizing physiology in their standards-based curriculum, and involve more physiologists in K-12 outreach. Formative goals included program growth (sites, participants, and leaders), diversification of program models, and development of a community of practice of physiologists and trainees involved in outreach. Eleven years of member-provided data indicate that the formative goals are being met. Nearly 100,000 K-12 students have been reached during the last decade as an increasing pool of physiologists took part in a growing number of events, including a number of international events. The number and types of PhUn Week events have steadily increased as a community of practice has formed to support the program. Future program goals include targeting regional areas for PhUn Week participation, establishing research collaboratives to further explore program impacts, and providing on-demand training for physiologists. Copyright © 2017 the American Physiological Society.

Modulation of equatorial Pacific westerly/easterly wind events by the Madden-Julian oscillation and convectively-coupled Rossby waves

NASA Astrophysics Data System (ADS)

Puy, Martin; Vialard, J.; Lengaigne, M.; Guilyardi, E.

2016-04-01

Synoptic wind events in the equatorial Pacific strongly influence the El Niño/Southern Oscillation (ENSO) evolution. This paper characterizes the spatio-temporal distribution of Easterly (EWEs) and Westerly Wind Events (WWEs) and quantifies their relationship with intraseasonal and interannual large-scale climate variability. We unambiguously demonstrate that the Madden-Julian Oscillation (MJO) and Convectively-coupled Rossby Waves (CRW) modulate both WWEs and EWEs occurrence probability. 86 % of WWEs occur within convective MJO and/or CRW phases and 83 % of EWEs occur within the suppressed phase of MJO and/or CRW. 41 % of WWEs and 26 % of EWEs are in particular associated with the combined occurrence of a CRW/MJO, far more than what would be expected from a random distribution (3 %). Wind events embedded within MJO phases also have a stronger impact on the ocean, due to a tendency to have a larger amplitude, zonal extent and longer duration. These findings are robust irrespective of the wind events and MJO/CRW detection methods. While WWEs and EWEs behave rather symmetrically with respect to MJO/CRW activity, the impact of ENSO on wind events is asymmetrical. The WWEs occurrence probability indeed increases when the warm pool is displaced eastward during El Niño events, an increase that can partly be related to interannual modulation of the MJO/CRW activity in the western Pacific. On the other hand, the EWEs modulation by ENSO is less robust, and strongly depends on the wind event detection method. The consequences of these results for ENSO predictability are discussed.

On the analysis of an extreme Bora wind event over the northern Adriatic Sea

NASA Astrophysics Data System (ADS)

Colucci, R. R.; Pucillo, A.

2010-09-01

On 10th March 2010 a severe Bora wind event affected the Friuli Venezia Giulia region, northeastern Italy, in particular the gulf of Trieste area (northern Adriatic Sea). Such event has been driven by a widespread westward moving cold pool aloft, coming from the Western Asia, that brought an intense potential vorticity anomaly over the western Mediterranean Sea. It determined a deep cyclogenesis involving all the troposphere. The pressure gradient force in the lowest layers forced a northeastern wind to blow with noticeable strength over the gulf of Trieste area and the Karstic region. The mean ground wind velocity has reached values above 27 m/s (about 100 km/h) for several hours, and maximum gusts exceeded 42 m/s (about 150 km/h) over Trieste town. The northeastern sector of the Adriatic Sea is frequently affected by strong Bora events in particular during the winter semester. This is a characteristic local wind mostly influenced by the orography of the Karstic relieves to the east of Trieste town. The target of this work is to assess the climatological relevance of such an event by comparing it with the most representative events of the past. It has been possible thanks to the long term archive of meteorological observations in Trieste site (I.R. Accademia di Commercio e Nautica, Regio Comitato Talassografico Italiano, Ministero dell'Agricoltura e Foreste, Consiglio Nazionale delle Ricerche): we have found out that this is one of the ten strongest Bora event along the 1871-2010 period. Considerations about the trend and frequency of severe Bora events have been proposed.

Cohort Profile: The International Childhood Cardiovascular Cohort (i3C) Consortium

PubMed Central

Dwyer, Terence; Sun, Cong; Magnussen, Costan G; Raitakari, Olli T; Schork, Nicholas J; Venn, Alison; Burns, Trudy L; Juonala, Markus; Steinberger, Julia; Sinaiko, Alan R; Prineas, Ronald J; Davis, Patricia H; Woo, Jessica G; Morrison, John A; Daniels, Stephen R; Chen, Wei; Srinivasan, Sathanur R; Viikari, Jorma SA; Berenson, Gerald S

2013-01-01

This is a consortium of large children's cohorts that contain measurements of major cardiovascular disease (CVD) risk factors in childhood and had the ability to follow those cohorts into adulthood. The purpose of this consortium is to enable the pooling of data to increase power, most importantly for the follow-up of CVD events in adulthood. Within the consortium, we hope to be able to obtain data on the independent effects of childhood and early adult levels of CVD risk factors on subsequent CVD occurrence. PMID:22434861

Astronaut Mario Runco in EMU during training in WETF

NASA Image and Video Library

1995-07-26

S95-15847 (26 July 1995) --- Wearing a training version of the Extravehicular Mobility Unit (EMU) space suit, astronaut Mario Runco Jr., mission specialist, prepares to participate in an underwater rehearsal of a contingency Extravehicular Activity (EVA). This type of training routinely takes place in the 25-feet deep pool of the Johnson Space Center's (JSC) Weightless Environment Training Center (WET-F). The training prepares at least two crew members on each flight for procedures to follow outside the spacecraft in event of failure of remote methods to perform various chores.

Effect of a Recently Completed Habitat Rehabilitation and Enhancement Project on Fish Abundance in La Grange Pool of the Illinois River Using Long Term Resource Monitoring Program Data

DTIC Science & Technology

2008-03-01

access from the Illinois River to Lake Chautauqua is provided by flood events that top the levee and water -control structure. Therefore, the south...cell of Lake Chautauqua may be considered a semi-natural backwater lake that mimics the hydrologic regime of the Illinois River during some years and...minimum water -level management, but the lake generally was connected to the Illinois River (Irons et. al. 1997). Lake Chautauqua is between RMs 124 and

STS_135_ M113

NASA Image and Video Library

2011-06-21

JSC2011-E-059628 (21 June 2011) --- NASA astronaut Chris Ferguson, STS-135 commander, laughs with his crew members before safety training in the M113 personnel carrier during the Terminal Countdown Demonstration Test (TCDT) at NASA?s Kennedy Space Center on June 21, 2011. TCDT serves as the prelaunch countdown rehearsal for the final space shuttle mission, which is scheduled for launch on July 8. The M113 would be used in the event of an emergency at the pad forcing the crew to evacuate. Photo credit: NASA Photo/Houston Chronicle, Smiley N. Pool

Canadian astronaut Marc Garneau during emergency bailout training

NASA Image and Video Library

1993-10-07

S93-45723 (7 October 1993) --- Canadian astronaut candidate Marc Garneau, later named as a mission specialist for NASA's STS-77 mission-representing the Canadian Space Agency (CSA), participates in emergency bailout training at the Johnson Space Center (JSC). Garneau was in the 1992 class of Astronaut Candidates (ASCAN). Wearing full parachute gear, Garneau is suspended above a 25-feet deep pool in JSC's Weightless Environment Training Facility (WET-F). This portion of an astronaut's training is to prepare them for proper measures to take in the event of bailout over water.

Wearing a training version of the Extravehicular Mobility Unit (EMU) space suit, astronaut Mario

NASA Technical Reports Server (NTRS)

1995-01-01

STS-77 TRAINING VIEW --- Wearing a training version of the Extravehicular Mobility Unit (EMU) space suit, astronaut Mario Runco, mission specialist, prepares to participate in an underwater rehearsal of a contingency Extravehicular Activity (EVA). This type of training routinely takes place in the 25-feet deep pool of the Johnson Space Centers (JSC) Weightless Environment Training Center (WET-F). The training prepares at least two crew members on each flight for procedures to follow outside the spacecraft in event of failure of remote methods to perform various chores.

STS-32 MS Dunbar wearing LES floats in life raft during water egress training

NASA Image and Video Library

1989-11-15

STS-32 Mission Specialist (MS) Bonnie J. Dunbar, wearing a launch and entry suit (LES) and lauch and entry helmet (LEH), in a single-occupant (one man) lift raft enlists the aid of two SCUBA-equipped divers as she floats in 25 ft deep pool located in JSC's Weightless Environment Training Facility (WETF) Bldg 29. During the exercises the crew practiced the procedures to follow in the event of an emergency aboard the Space Shuttle and familiarized themselves with post-Challenger pole system of emergency egress.

STS-32 MS Dunbar wearing LES floats in life raft during water egress training

NASA Technical Reports Server (NTRS)

1989-01-01

STS-32 Mission Specialist (MS) Bonnie J. Dunbar, wearing a launch and entry suit (LES) and lauch and entry helmet (LEH), in a single-occupant (one man) lift raft enlists the aid of two SCUBA-equipped divers as she floats in 25 ft deep pool located in JSC's Weightless Environment Training Facility (WETF) Bldg 29. During the exercises the crew practiced the procedures to follow in the event of an emergency aboard the Space Shuttle and familiarized themselves with post-Challenger pole system of emergency egress.

Vulvovaginitis and balanitis in patients with diabetes treated with dapagliflozin.

PubMed

Johnsson, Kristina M; Ptaszynska, Agata; Schmitz, Bridget; Sugg, Jennifer; Parikh, Shamik J; List, James F

2013-01-01

Vulvovaginitis, balanitis, and related genital infections are common in patients with type 2 diabetes. Glucosuria, which is an outcome of treatment with sodium glucose cotransporter 2 (SGLT2) inhibitors, is among the possible causes. Dapagliflozin, an SGLT2 inhibitor with demonstrated glycemic benefits in patients with diabetes, has been studied across a broad spectrum of patients. Analysis of multi-trial safety data may better define the relationship between glucosuria and genital infection. Safety data were pooled from 12 randomized, placebo-controlled Phase 2b/3 trials to analyze the association of glucosuria with genital infection in patients with suboptimally controlled diabetes (HbA1c >6.5%-12%). Patients were randomized to receive dapagliflozin (2.5mg, 5mg, or 10mg) or placebo once daily, either as monotherapy or add-on to metformin, insulin, sulfonylurea, or thiazolidinedione for 12-24weeks. The incidence of clinical diagnoses and of events suggestive of genital infection was evaluated. The pooled safety data included 4545 patients: 3152 who received once-daily dapagliflozin (2.5mg [n=814], 5mg [n=1145], or 10mg [n=1193]) as monotherapy or add-on treatment, and 1393 placebo-treated patients. For dapagliflozin 2.5mg, 5mg, 10mg, and placebo, diagnosed infections were reported in 4.1%, 5.7%, 4.8%, and 0.9%, respectively. Most infections were mild or moderate and responded to standard antimicrobial treatment. Discontinuation due to these events was rare. No clear dose-response relationship between dapagliflozin and genital infection was demonstrated. Treatment with dapagliflozin 2.5mg, 5mg, or 10mg once daily is accompanied by an increased risk of vulvovaginitis or balanitis, related to the induction of glucosuria. Events were generally mild to moderate, clinically manageable, and rarely led to discontinuation of treatment. Copyright © 2013 Elsevier Inc. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Andrew, S.E.; Goldberg, Y.P.; Squitieri, F.

Huntington disease (HD) is one of 7 disorders now known to be caused by expansion of a trinucleotide repeat. The HD mutation is a polymorphic trinucleotide (CAG) repeat in the 5{prime} region of a novel gene that expands beyond the normal range of 10-35 repeats in persons destined to develop the disease. Haplotype analysis of other dynamic mutation disorders such as myotonic dystrophy and Fragil X have suggested that a rare ancestral expansion event on a normal chromosome is followed by subsequent expansion events, resulting in a pool of chromosomes in the premutation range, which is inherently unstable and pronemore » to further multiple expansion events leading to disease range chromosomes. Haplotype analysis of 67 HD and 84 control chromosomes using 5 polymorphic markers, both intragenic and 5{prime} to the disease mutation, demonstrate that multiple haplotypes underlie HD. However, 94% of the chromosomes can be grouped under two major haplotypes. These two haplotypes are also present in the normal population. A third major haplotype is seen on 38% of normal chromosomes but rarely on HD chromosomes (6%). CAG lengths on the normal chromosomes with the two haplotypes seen in the HD population are higher than those seen on the normal chromosomes with the haplotype rarely seen on HD chromosomes. Furthermore, in populations with a diminished frequency of HD, CAG length on normal chromosomes is significantly less than other populations with higher prevalence rates for HD. These data suggest that CAG length on normal chromosomes may be a significant factor contributing to repeat instability that eventually leads to chromosomes with CAG repeat lengths in the HD range. Haplotypes on the HD chromosomes are identical to those normal chromosomes which have CAG lengths in the high range of normal, suggesting that further expansions of this pool of chromosomes leads to chromosomes with CAG repeat sizes within the disease range, consistent with a multistep model.« less

Risk-Stratified Imputation in Survival Analysis

PubMed Central

Kennedy, Richard E.; Adragni, Kofi P.; Tiwari, Hemant K.; Voeks, Jenifer H.; Brott, Thomas G.; Howard, George

2013-01-01

Background Censoring that is dependent on covariates associated with survival can arise in randomized trials due to changes in recruitment and eligibility criteria to minimize withdrawals, potentially leading to biased treatment effect estimates. Imputation approaches have been proposed to address censoring in survival analysis; and while these approaches may provide unbiased estimates of treatment effects, imputation of a large number of outcomes may over- or underestimate the associated variance based on the imputation pool selected. Purpose We propose an improved method, risk-stratified imputation, as an alternative to address withdrawal related to the risk of events in the context of time-to-event analyses. Methods Our algorithm performs imputation from a pool of replacement subjects with similar values of both treatment and covariate(s) of interest, that is, from a risk-stratified sample. This stratification prior to imputation addresses the requirement of time-to-event analysis that censored observations are representative of all other observations in the risk group with similar exposure variables. We compared our risk-stratified imputation to case deletion and bootstrap imputation in a simulated dataset in which the covariate of interest (study withdrawal) was related to treatment. A motivating example from a recent clinical trial is also presented to demonstrate the utility of our method. Results In our simulations, risk-stratified imputation gives estimates of treatment effect comparable to bootstrap and auxiliary variable imputation while avoiding inaccuracies of the latter two in estimating the associated variance. Similar results were obtained in analysis of clinical trial data. Limitations Risk-stratified imputation has little advantage over other imputation methods when covariates of interest are not related to treatment, although its performance is superior when covariates are related to treatment. Risk-stratified imputation is intended for categorical covariates, and may be sensitive to the width of the matching window if continuous covariates are used. Conclusions The use of the risk-stratified imputation should facilitate the analysis of many clinical trials, in which one group has a higher withdrawal rate that is related to treatment. PMID:23818434

Concentration-Discharge Behavior of Contaminants in a Stream Impacted by Acid Mine Drainage

NASA Astrophysics Data System (ADS)

Shaw, M. E.; Klein, M.; Herndon, E.

2017-12-01

Acid mine drainage (AMD) has severely degraded streams throughout the Appalachian coal region of the United States. AMD occurs when pyrite contained in coal is exposed to water and air during mining activities and oxidized to release high concentrations of sulfate, metals, and acidity into water bodies. Little is known about the concentration-discharge (CQ) relationships of solutes in AMD-impacted streams due to the complicated nature of acid mine drainage systems. For example, streams may receive inputs from multiple sources that include runoff, constructed treatment systems, and abandoned mines that bypass these systems to continue to contaminate the streams. It is important to understand the CQ relationships of contaminants in AMD-impacted streams in order to elucidate contaminant sources and to predict effects on aquatic ecosystems. Here, we study the CQ behaviors of acid and metals in a contaminated watershed in northeastern Ohio where limestone channels have been installed to remediate water draining from a mine pool into the stream. Stream chemistry was measured in samples collected once per day or once per hour during storm events, and stream flow was measured continuously at the watershed outlet. Increases in stream velocity during storm events resulted in an increase in pH (from 3 to 6) that subsequently decreased back to 3 as flow decreased. Additionally, Fe and Mn concentrations in the stream were high during baseflow (7 and 15 mg/L, respectively) and decreased with increasing discharge during storm events. These results indicate that the treatment system is only effective at neutralizing stream acidity and removing metals when water flow through the limestone channel is continuous. We infer that the acidic and metal-rich baseflow derives from upwelling of contaminated groundwater or subsurface flow from a mine pool. Ongoing studies aim to isolate the source of this baseflow contamination and evaluate the geochemical transformations that occur as it flows into the stream.

Risk and timing of clinical events according to diabetic status of patients treated with everolimus-eluting bioresorbable vascular scaffolds versus everolimus-eluting stent: 2-year results from a propensity score matched comparison of ABSORB EXTEND and SPIRIT trials.

PubMed

Campos, Carlos M; Caixeta, Adriano; Franken, Marcelo; Bartorelli, Antonio L; Whitbourn, Robert J; Wu, Chiung-Jen; Li Paul Kao, Hsien; Rosli, Mohd Ali; Carrie, Didier; De Bruyne, Bernard; Stone, Gregg W; Serruys, Patrick W; Abizaid, Alexandre

2018-02-15

to compare the occurrence of clinical events in diabetics treated with the Absorb bioresorbable vascular scaffold (Absorb BVS; Abbott Vascular, Santa Clara, CA) versus everolimus-eluting metal stents (EES; XIENCE V; Abbott Vascular, Santa Clara, CA) BACKGROUND: There are limited data dedicated to clinical outcomes of diabetic patients treated with bioresorbable scaffolds (BRS) at 2-year horizon. The present study included 812 patients in the ABSORB EXTEND study in which a total of 215 diabetic patients were treated with Absorb BVS. In addition, 882 diabetic patients treated with EES in pooled data from the SPIRIT clinical program (SPIRIT II, SPIRIT III and SPIRIT IV trials) were used for comparison by applying propensity score matching using 29 different variables. The primary endpoint was ischemia driven major adverse cardiac events (ID-MACE), including cardiac death, myocardial infarction (MI), and ischemia driven target lesion revascularization (ID-TLR). After 2 years, the ID-MACE rate was 6.5% in the Absorb BVS vs. 8.9% in the Xience group (P = 0.40). There was no difference for MACE components or definite/probable device thrombosis (HR: 1.43 [0.24,8.58]; P = 0.69). The occurrence of MACE was not different for both diabetic status (insulin- and non-insulin-requiring diabetes) in all time points up to the 2-year follow-up for the Absorb and Xience groups. In this largest ever patient-level pooled comparison on the treatment of diabetic patients with BRS out to two years, individuals with diabetes treated with the Absorb BVS had a similar rate of MACE as compared with diabetics treated with the Xience EES. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Incidence of hypersensitivity and anaphylaxis with sugammadex.

PubMed

Min, K Chris; Woo, Tiffany; Assaid, Christopher; McCrea, Jacqueline; Gurner, Deborah M; Sisk, Christine McCrary; Adkinson, Franklin; Herring, W Joseph

2018-06-01

To evaluate the incidence of hypersensitivity and anaphylaxis after administration of sugammadex. Retrospective analysis. Sugammadex clinical development program and post-marketing experience. Surgical patients and healthy volunteers who received sugammadex or placebo/comparator with anesthesia and/or neuromuscular blockade (NMB). Sugammadex administered as 2.0 mg/kg at reappearance of the second twitch, 4.0 mg/kg at 1-2 post-tetanic count, or 16.0 mg/kg at 3 min after rocuronium 1.2 mg/kg. Three analytical methods were used: 1) automated MedDRA queries; 2) searches of adverse events (AEs) consistent with treatment-related hypersensitivity reactions as diagnosed by the investigator; and 3) a retrospective adjudication of AEs suggestive of hypersensitivity by a blinded, independent adjudication committee (AC). In addition, a search of all post-marketing reports of events of hypersensitivity was performed, and events were retrospectively adjudicated by an independent AC. Anaphylaxis was determined according to Sampson Criterion 1. The pooled dataset included 3519 unique subjects who received sugammadex and 544 who received placebo. The automated MedDRA query method showed no apparent increase in hypersensitivity or anaphylaxis with sugammadex as compared to placebo or neostigmine. Similarly, there was a low overall incidence of AEs of treatment-related hypersensitivity (<1%), with no differences between sugammadex and placebo or neostigmine. Finally, the retrospective adjudication of AEs suggestive of hypersensitivity showed a low incidence of hypersensitivity (0.56% and 0.21% for sugammadex 2 mg/kg and 4 mg/kg, respectively), with an incidence similar to subjects who received placebo (0.55%). There were no confirmed cases of anaphylaxis in the pooled studies. During post-marketing use, spontaneous reports of anaphylaxis occurred with approximately 0.01% of sugammadex doses. Subjects who received sugammadex with general anesthesia and/or NMB had a low overall incidence of hypersensitivity, with no apparent increase in hypersensitivity or anaphylaxis with sugammadex as compared to placebo or neostigmine. Copyright © 2018 Elsevier Inc. All rights reserved.

Risankizumab versus Ustekinumab for Moderate-to-Severe Plaque Psoriasis.

PubMed

Papp, Kim A; Blauvelt, Andrew; Bukhalo, Michael; Gooderham, Melinda; Krueger, James G; Lacour, Jean-Philippe; Menter, Alan; Philipp, Sandra; Sofen, Howard; Tyring, Stephen; Berner, Beate R; Visvanathan, Sudha; Pamulapati, Chandrasena; Bennett, Nathan; Flack, Mary; Scholl, Paul; Padula, Steven J

2017-04-20

Interleukin-23 is thought to be critical to the pathogenesis of psoriasis. We compared risankizumab (BI 655066), a humanized IgG1 monoclonal antibody that inhibits interleukin-23 by specifically targeting the p19 subunit and thus prevents interleukin-23 signaling, and ustekinumab, an interleukin-12 and interleukin-23 inhibitor, in patients with moderate-to-severe plaque psoriasis. We randomly assigned a total of 166 patients to receive subcutaneous injections of risankizumab (a single 18-mg dose at week 0 or 90-mg or 180-mg doses at weeks 0, 4, and 16) or ustekinumab (45 or 90 mg, according to body weight, at weeks 0, 4, and 16). The primary end point was a 90% or greater reduction from baseline in the Psoriasis Area and Severity Index (PASI) score at week 12. At week 12, the percentage of patients with a 90% or greater reduction in the PASI score was 77% (64 of 83 patients) for risankizumab (90-mg and 180-mg groups, pooled), as compared with 40% (16 of 40 patients) for ustekinumab (P<0.001); the percentage of patients with a 100% reduction in the PASI score was 45% in the pooled 90-mg and 180-mg risankizumab groups, as compared with 18% in the ustekinumab group. Efficacy was generally maintained up to 20 weeks after the final dose of 90 or 180 mg of risankizumab. In the 18-mg and 90-mg risankizumab groups and the ustekinumab group, 5 patients (12%), 6 patients (15%), and 3 patients (8%), respectively, had serious adverse events, including two basal-cell carcinomas and one major cardiovascular adverse event; there were no serious adverse events in the 180-mg risankizumab group. In this phase 2 trial, selective blockade of interleukin-23 with risankizumab was associated with clinical responses superior to those associated with ustekinumab. This trial was not large enough or of long enough duration to draw conclusions about safety. (Funded by Boehringer Ingelheim; ClinicalTrials.gov number, NCT02054481 ).

Safety and efficacy of low molecular weight heparins in children: a systematic review of the literature and meta-analysis of single-arm studies.

PubMed

Bidlingmaier, Christoph; Kenet, Gili; Kurnik, Karin; Mathew, Prasad; Manner, Daniela; Mitchell, Lesley; Krümpel, Anne; Nowak-Göttl, Ulrike

2011-10-01

Within the last two decades low molecular weight heparins (LMWH) have gained increasing widespread use as anticoagulants in children. The use of LMWH has been implemented into clinical care even though there is a lack of firm evidence on the efficacy and safety of LMWH in this population due to the absence of sufficiently powered randomized controlled trials. In the absence of clinical trials, we performed a meta-analysis of available single-arm studies using LMWH in children. A systematic search of electronic databases (Medline, EMBASE, OVID, Web of Science, The Cochrane Library) for studies published from 1980 to 2010 was conducted using keywords in combination both as MeSH terms and text words. Two authors independently screened citations and those meeting a priori defined inclusion criteria were retained. Data on year of publication, study design, country of origin, number of patients, ethnicity, venous thromboembolic events type, and frequency of recurrence and major bleedings were abstracted. Pooled incidence rates (IR) including 95% confidence intervals (95% CIs) on efficacy and safety data of LMWH administration on primary prophylaxis, as well as on secondary prophylaxis in children following symptomatic thromboembolism (TE) were shown. We included 2251 pediatric patients derived from 35 single-arm studies from 12 study countries who were eligible for analysis in the present systematic review. Pooled incidence rates (95% CI) to develop first TE on primary prophylaxis, further TE event on LMWH secondary prophylaxis, or a major bleeding event on LMWH were 0.047 (0.023 to 0.091), 0.052 (0.037 to 0.073) for efficacy, and 0.054 (0.039 to 0.074) for safety (treatment data only), respectively. Efficacy and safety data are comparable with adult data. The present systematic review suggests that use of LMWH in children as primary prophylaxis and in treatment of symptomatic thrombosis is effective and safe. However, properly designed randomized controlled trials are needed. © Thieme Medical Publishers.

Lacosamide adjunctive therapy for partial-onset seizures: a meta-analysis

PubMed Central

Newman, Jennifer J.; Deshpande, Santosh; Jones, Philip M.

2013-01-01

Background. The relative efficacy and safety of lacosamide as adjunctive therapy compared to other antiepileptic drugs has not been well established. Objective. To determine if lacosamide provides improved efficacy and safety, reduced length of hospital stay and improved quality of life compared with other anti-epileptic therapies for adults with partial-onset seizures. Data Sources. A systematic review of the medical literature using Medline (1946–Week 4, 2012), EMBASE (1980–Week 3, 2012), Cochrane Central Register of Controlled Trials (Issue 1 of 12, January 2012). Additional studies were identified (through to February 7, 2012) by searching bibliographies, the FDA drug approval files, clinical trial registries and major national and international neurology meeting abstracts. No restrictions on publication status or language were applied. Study Selection. Randomized controlled trials of lacosamide in adults with partial-onset seizures were included. Data Extraction. Study selection, extraction and risk of bias assessment were performed independently by two authors. Authors of studies were contacted for missing data. Data Synthesis. All pooled analyses used the random effects model. Results. Three trials (1311 patients) met inclusion criteria. Lacosamide increased the 50% responder rate compared to placebo (RR 1.68 [95% CI 1.36 to 2.08]; I2 = 0%). Discontinuation due to adverse events was statistically significantly higher in the lacosamide arm (RR3.13 [95% CI 1.94 to 5.06]; I2 = 0%). Individual adverse events (ataxia, dizziness, fatigue, and nausea) were also significantly higher in the lacosamide group. Limitations. All dosage arms from the included studies were pooled to make a single pair-wise comparison to placebo. Selective reporting of outcomes was found in all of the included RCTs. Conclusions. Lacosamide as adjunctive therapy in patients with partial-onset seizures increases the 50% responder rate but with significantly more adverse events compared to the placebo. PMID:23940830

Nitrate isotopes illuminate the black box of paddy soil biogeochemistry: water and carbon management control nitrogen sources and sinks

NASA Astrophysics Data System (ADS)

Wells, N. S.; Clough, T. J.; Johnson-Beebout, S. E.; Buresh, R. J.

2010-12-01

Accurate prediction of the available nitrogen (N) pool in submerged paddy soils is needed in order to produce rice, one of the world’s most essential crops, in an economically and environmentally sustainable manner. By applying emerging nitrate dual-isotope (δ15N- δ18O- NO3-) techniques to paddy systems, we were able to obtain a unique process-level quantification of the synergistic impacts of carbon (C) and water management on N availability. Soil and water samples were collected from fallow experimental plots, with or without organic C amendments, that were maintained under 1 of 3 different hydrologic regimens: continuously submerged, water excluded, or alternate wetting and drying. In continuously submerged soils the δ15N-NO3- : δ18O-NO3- signal of denitrification was not present, indicating that there was no N attenuation. Biological nitrogen fixation (BNF) was the dominant factor in defining the available N pool under these conditions, with δ15N-NO3- approaching atmospheric levels as size of the pool increased. Using an isotope-based pool-mixing model, it was calculated that 10±2 µg N g-1 soil were contributed by BNF during the fallow. A lack of BNF combined with removal via denitrification (δ15N-NO3- : δ18O-NO3- = 1) caused relatively lower available N levels in dried and alternate wetting-drying soils during this period. Magnitude and net impact of denitrification was defined by the extent of drying and C availability, with rice straw C additions driving tighter coupling of nitrification and denitrification (δ15N:δ18O <1). However, despite high rates of attenuation during wetting events, soils that had been completely dried and received straw amendments ultimately retained a significantly larger available N pool due to enhanced input from soil organic matter. These findings underline the necessity of, and validate a new means for, accurate quantification micro-scale biogeochemical interactions for developing farm-scale management practices that can maximize N storage and minimize environmentally undesirable losses.

The role of particle jamming on the formation and stability of step-pool morphology: insight from a reduced-complexity model

NASA Astrophysics Data System (ADS)

Saletti, M.; Molnar, P.; Hassan, M. A.

2017-12-01

Granular processes have been recognized as key drivers in earth surface dynamics, especially in steep landscapes because of the large size of sediment found in channels. In this work we focus on step-pool morphologies, studying the effect of particle jamming on step formation. Starting from the jammed-state hypothesis, we assume that grains generate steps because of particle jamming and those steps are inherently more stable because of additional force chains in the transversal direction. We test this hypothesis with a particle-based reduced-complexity model, CAST2, where sediment is organized in patches and entrainment, transport and deposition of grains depend on flow stage and local topography through simplified phenomenological rules. The model operates with 2 grain sizes: fine grains, that can be mobilized both my large and moderate flows, and coarse grains, mobile only during large floods. First, we identify the minimum set of processes necessary to generate and maintain steps in a numerical channel: (a) occurrence of floods, (b) particle jamming, (c) low sediment supply, and (d) presence of sediment with different entrainment probabilities. Numerical results are compared with field observations collected in different step-pool channels in terms of step density, a variable that captures the proportion of the channel occupied by steps. Not only the longitudinal profiles of numerical channels display step sequences similar to those observed in real step-pool streams, but also the values of step density are very similar when all the processes mentioned before are considered. Moreover, with CAST2 it is possible to run long simulations with repeated flood events, to test the effect of flood frequency on step formation. Numerical results indicate that larger step densities belong to system more frequently perturbed by floods, compared to system having a lower flood frequency. Our results highlight the important interactions between external hydrological forcing and internal geomorphic adjustment (e.g. jamming) on the response of step-pool streams, showing the potential of reduced-complexity models in fluvial geomorphology.

Incidence of seizure exacerbation and seizures reported as adverse events during adjunctive treatment with eslicarbazepine acetate: A pooled analysis of three Phase III controlled trials.

PubMed

Carreño, Mar; Benbadis, Selim; Rocha, Francisco; Blum, David; Cheng, Hailong

2017-12-01

To investigate whether adjunctive eslicarbazepine acetate (ESL) could lead to exacerbation of seizures in some patients. Post-hoc analysis of data pooled from three Phase III trials of adjunctive ESL (studies 301, 302, and 304) for refractory partial-onset seizures (POS). Following an 8-week baseline period, patients were randomized to receive placebo or ESL 400, 800, or 1,200 mg once daily (2-week titration, 12-week maintenance, 2-4 week tapering-off periods). Patient seizure diary data and seizure treatment-emergent adverse event (TEAE) reports were pooled for analysis. The modified intent-to-treat and safety populations comprised 1,410 patients and 1,447 patients, respectively. Titration period : Compared with placebo (32/21%), significantly smaller proportions of patients taking ESL 800 mg (20/15%) and 1,200 mg (22/12%) had a ≥25/≥50% increase in standardized seizure frequency (SSF) from baseline; there was no significant difference between placebo and ESL 400 mg. Maintenance period : Compared with placebo (20%), significantly smaller proportions of patients taking ESL (400 mg, 12%; 800 mg, 12%; 1,200 mg, 14%) had an increase in SSF ≥25%. When evaluating ≥50% increases in SSF, only ESL 800 mg (7%) was significantly different from placebo (12%). Some patients had no secondarily generalized tonic-clonic (sGTC) seizures during baseline but had ≥1 sGTC seizure during maintenance treatment (placebo, 11%; ESL 400 mg, 5%; 800 mg, 10%; 1,200 mg, 5%). Fewer patients had a ≥25% increase in sGTC seizure frequency with ESL (400 mg, 11%; 800 mg, 9%; 1,200 mg, 14%) versus placebo (19%). The incidence of seizures reported as TEAEs was low in all treatment groups; incidences were generally lower with ESL versus placebo. Tapering-off period : Similar proportions of patients taking ESL and placebo had a ≥25/≥50% increase in SSF. Seizure TEAE incidence was numerically higher with ESL versus placebo. Treatment with adjunctive ESL does not appear to aggravate POS or sGTC seizures.

Age modifies the relative risk of stenting versus endarterectomy for symptomatic carotid stenosis--a pooled analysis of EVA-3S, SPACE and ICSS.

PubMed

Bonati, L H; Fraedrich, G

2011-02-01

Recent randomised controlled trials comparing carotid artery stenting (CAS) with endarterectomy (CEA) for the treatment of symptomatic carotid stenosis were not powered to investigate differences in risks in specific patient subgroups. We therefore performed a pooled analysis of individual patient data from the Symptomatic Severe Carotid Stenosis trial (EVA-3S), the Stent-Protected Angioplasty versus Carotid Endarterectomy trial (SPACE), and the International Carotid Stenting Study (ICSS). Individual data from all 3433 patients randomised and analysed in these trials were pooled and analysed with fixed-effect binomial regression models adjusted for source trial. The primary outcome event was any stroke or death. In the first 120 days after randomisation (ITT analysis), the primary outcome event occurred in 153/1725 patients in the CAS group (8.9%) compared with 99/1708 patients in the CEA group (5.8%, risk ratio [RR] 1.53, 95% confidence interval [CI] 1.20-1.95, p = 0.0006; absolute risk difference 3.2, 95% CI 1.4-4.9). Age was the only subgroup variable which significantly modified the treatment effect: in patients <70 years old (the median age), the 120-day stroke or death risk was 5.8% in CAS and 5.7% in CEA (RR 1.00, 0.68-1.47); in patients 70 years or older, there was an estimated two-fold increase in risk with CAS over CEA (12.0% vs. 5.9%, RR 2.04, 1.48-2.82, interaction p = 0.0053). Endarterectomy was safer in the short-term than stenting, because of an increased risk of stroke associated with stenting in patients over the age of 70 years. Stenting should be avoided in older patients, but may be as safe as endarterectomy in younger patients. Determination of the efficacy and ultimate balance between the two procedures requires further data on long-term stroke recurrence. Copyright © 2011 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Life-stress and reactivity by gender in a longitudinal birth cohort at 30 and 35 years.

PubMed

McLeod, Geraldine F H; Horwood, L J; Fergusson, D M; Boden, J M

2016-10-01

Previous literature has shown gender differences in reactivity to stressful life events. However, it is unclear whether gender differences in stress reactivity are consistent across a series of life event domains among longitudinal adult sample populations. Data were gathered from the Christchurch Health and Development Study (CHDS). The CHDS is a longitudinal birth cohort of 1265 children born in 1977 in Christchurch, New Zealand. Cohort members were questioned on their experience of, and distress from, a series of life event domains (interpersonal problems; victimization; illness/death; pregnancy/parenthood; employment/finance problems) spanning two age-periods 25-30 years (data collected in 2007) and 30-35 years (data collected in 2012). The data were pooled across observations and analyzed using population-averaged repeated-measures regression methods. Overall, men and women reported experiencing similar numbers of life events for each domain. However, men reported more victimization and more employment/financial problems; women reported more illness/death events. Women reported experiencing more distress per life event for the domains of interpersonal problems, illness/death and pregnancy/parenthood. Men and women reported similar distress per life event for the victimization and employment/finance domains. The results were robust to control for: child and adolescent factors (childhood abuse exposure; adolescent personality; mental health) and adult factors (mental health; self-esteem). These findings are consistent with a growing body of evidence indicating that some life events including interpersonal problems, illness/death and pregnancy/parenthood may be intrinsically more distressing for women. Detection of life event distress is important to aid in the prevention of mental/physical health problems.

Extension of volcanic forcing data back to 100 BC using the Analog method

NASA Astrophysics Data System (ADS)

Wagner, Sebastian; Zorita, Eduardo

2013-04-01

Present reconstructions of volcanic forcing to be used for climate simulations so far extend back until 500 AD for stratospheric aerosol sulphate injection (Gao et al., 2008), and back until 800 AD for aerosol optical depth and effective radius (Crowley et al. 2012; ICI5 data set). Here, we aim to extent the volcanic data set of Crowley et al. (2012) back to 100 BC. This data sets originally starts in 800 AD, for aerosol optical depth and effective radius. The method we apply is the Analog method, using information in the already existing reconstruction and extending it back in time by using information of long volcanic sulphate contained in Greenland and Antarctic Ice cores published in previous studies. The reconstruction of the volcanic forcing in first millennium is based on the search of analogs in the second millennium. The pool of analogs includes the ICI5 data set for the period 800-2000 AD. The basic philosophy is to find volcanic events with the same or similar magnitude in terms of volcanic sulphate deposition in Greenland and Antarctic ice cores. For the Northern Hemisphere the estimated maximum total stratospheric sulphate loading from Zielinski (1995) is used. For the Southern Hemisphere the Plummer et al. (2012) data set and the Ferris et al. (2011) data set are used in terms of sulphate deposition. To ensure that the volcanic event was large enough in magnitude, a certain threshold is applied to the analog selection. The extension, i.e. the analog search, is carried out separately for the four different latitudinal bands of the ICI5 data set. The method can be applied when better records than the Zielinski et al. (1995), record for the Northern Hemisphere become available. The analogs are selected based on the comparison between the information contained in the ice cores in the pre-800 AD period and post-800 AD period. For each event in the pre-800 AD period (the target), the most similar event (the analog) in the post-800 AD pool in terms of ice-core sulphate is identified. The forcing data (effective radius and aerosol optical depth) of the ICI5 data set for that analog event is then used as a surrogate for the target event. In the case that the analog does not exactly match the amplitude of the pre-800 AD event a scaling correction factor is applied, taking into account the relative difference of ice-core sulphate between the analog and the target. Although the method does not take into account the specific structure of each volcanic event, the basic patterns are reproduced reasonably well for a validation period in the second millennium AD. The largest uncertainties relate to the dating of each volcanic event, including the season of the eruption, the synchronization of hemispheric versus global eruptions and the translation of the ice core volcanic sulphate concentrations into stratospheric aerosol loadings. However, these uncertainties will essentially remain using different methods based on the sulphate information contained in Antarctic and Greenland ice cores.

On the role of tropopause folds in summertime tropospheric ozone over the eastern Mediterranean and the Middle East

NASA Astrophysics Data System (ADS)

Akritidis, Dimitris; Pozzer, Andrea; Zanis, Prodromos; Tyrlis, Evangelos; Škerlak, Bojan; Sprenger, Michael; Lelieveld, Jos

2016-11-01

We study the contribution of tropopause folds in the summertime pool of tropospheric ozone over the eastern Mediterranean and the Middle East (EMME) with the aid of the ECHAM5/MESSy Atmospheric Chemistry (EMAC) model. Tropopause fold events in EMAC simulations were identified with a 3-D labeling algorithm that detects folds at grid points where multiple crossings of the dynamical tropopause are computed. Subsequently the events featuring the largest horizontal and vertical extent were selected for further study. For the selection of these events we identified a significant contribution of the stratospheric ozone reservoir to the high concentrations of ozone in the middle and lower free troposphere over the EMME. A distinct increase of ozone is found over the EMME in the middle troposphere during summer as a result of the fold activity, shifting towards the southeast and decreasing altitude. We find that the interannual variability of near-surface ozone over the eastern Mediterranean (EM) during summer is related to that of both tropopause folds and ozone in the free troposphere.

Bremelanotide for Female Sexual Dysfunctions in Premenopausal Women: A Randomized, Placebo-Controlled Dose-Finding Trial

PubMed Central

Clayton, Anita H; Althof, Stanley E; Kingsberg, Sheryl; DeRogatis, Leonard R; Kroll, Robin; Goldstein, Irwin; Kaminetsky, Jed; Spana, Carl; Lucas, Johna; Jordan, Robert; Portman, David J

2016-01-01

Aim: Evaluate efficacy/safety of bremelanotide (BMT), a melanocortin-receptor-4 agonist, to treat female sexual dysfunctions in premenopausal women. Methods: Patients randomized to receive placebo or BMT 0.75, 1.25 or 1.75 mg self-administered subcutaneously, as desired, over 12 weeks. Primary end point was change in satisfying sexual events/month. Secondary end points included total score changes on female sexual function index and female sexual distress scale-desire/arousal/orgasm. Results: Efficacy data, n = 327. For 1.25/1.75-mg pooled versus placebo, mean changes from baseline to study end were +0.7 versus +0.2 satisfying sexual events/month (p = 0.0180), +3.6 versus +1.9 female sexual function index total score (p = 0.0017), −11.1 versus −6.8 female sexual distress scale-desire/arousal/orgasm total score (p = 0.0014). Adverse events: nausea, flushing, headache. Conclusion: In premenopausal women with female sexual dysfunctions, self-administered, as desired, subcutaneous BMT was safe, effective, and well tolerated (NCT01382719). PMID:27181790

A time-varying subjective quality model for mobile streaming videos with stalling events

NASA Astrophysics Data System (ADS)

Ghadiyaram, Deepti; Pan, Janice; Bovik, Alan C.

2015-09-01

Over-the-top mobile video streaming is invariably influenced by volatile network conditions which cause playback interruptions (stalling events), thereby impairing users' quality of experience (QoE). Developing models that can accurately predict users' QoE could enable the more efficient design of quality-control protocols for video streaming networks that reduce network operational costs while still delivering high-quality video content to the customers. Existing objective models that predict QoE are based on global video features, such as the number of stall events and their lengths, and are trained and validated on a small pool of ad hoc video datasets, most of which are not publicly available. The model we propose in this work goes beyond previous models as it also accounts for the fundamental effect that a viewer's recent level of satisfaction or dissatisfaction has on their overall viewing experience. In other words, the proposed model accounts for and adapts to the recency, or hysteresis effect caused by a stall event in addition to accounting for the lengths, frequency of occurrence, and the positions of stall events - factors that interact in a complex way to affect a user's QoE. On the recently introduced LIVE-Avvasi Mobile Video Database, which consists of 180 distorted videos of varied content that are afflicted solely with over 25 unique realistic stalling events, we trained and validated our model to accurately predict the QoE, attaining standout QoE prediction performance.

Oviposition strategies of temporary pool mosquitoes in relation to weather, tidal regime and land use in a temperate wetland.

PubMed

Cardo, M V; Vezzani, D; Carbajo, A E

2012-12-01

Wetlands have traditionally been associated with harbouring mosquitoes, a well-known nuisance and vectors of diseases. Within mosquito life cycle, oviposition is a determinant event by shaping their individual fitness and vectorial capacity. The study was conducted in one of the main temperate wetlands in South America. We used Generalized Linear Models to study the relation between temperature, precipitation, tidal regime, land use, microenvironment, and the occurrence of floodwater (Ochlerotatus and Psorophora spp.) and raft-laying (Culex and Uranotaenia spp.) mosquitoes using temporary pools as larval habitats. Pool occurrence was negatively associated with temperature, and positively related to precipitation and high tides. As regards the land use, it was lowest in domestic areas and plantations, intermediate in secondary forests, and highest in marshes. Each oviposition strategy was best modelled as a function of different environmental factors. The occurrence of floodwater mosquitoes was positively associated with high cumulative precipitation and low tide records. Raft-laying mosquitoes were related to low temperature records, while the effect of flooding varied with the land use. In view of these results, physical (water inputs and movement), chemical, and biological (egg and larval flushing, and predatory interactions) considerations are given to provide insight in the oviposition patterns of mosquitoes occurring in this complex wetland. We finally propose the generation of a tidal flow as a control measure against floodwater mosquitoes, which are the most anthropophilic in the study area.

Impact of concomitant dexamethasone dosing schedule on bortezomib-induced peripheral neuropathy in multiple myeloma.

PubMed

Kumar, Shaji K; Laubach, Jacob P; Giove, Thomas J; Quick, Maureen; Neuwirth, Rachel; Yung, Godwin; Rajkumar, S Vincent; Richardson, Paul G

2017-09-01

Peripheral neuropathy (PN) is the most troublesome adverse event associated with the proteasome inhibitor bortezomib. Studies suggest an inflammatory aetiology for bortezomib-induced PN (BiPN) and it has been hypothesized that reducing inflammation with concomitant dexamethasone may reduce BiPN incidence and/or severity. We retrospectively analysed PN rates from 32 studies (2697 patients with previously untreated multiple myeloma) incorporating bortezomib and differing dexamethasone schedules: partnered dosing (days of and after bortezomib), weekly dosing, and other dosing schedules (e.g. days 1-4, 8-11). Pooled overall PN rates were 45·5%, 63·9%, and 47·5%, respectively, with 5·3%, 11·0%, and 9·6% grade ≥3. Adjusting for potential confounders (age, gender, presence of thalidomide, bortezomib treatment duration), PN rates in patients on partnered dosing schedules appeared lower than in patients on weekly or other dosing schedules. Analyses conducted using patient-level data suggest that cumulative dexamethasone dose, a potential confounding factor, is unlikely to have influenced the analyses. Findings were similar in a separate pooled analysis excluding data from regimens incorporating thalidomide, when pooled overall PN rates were 50·1%, 63·9%, and 48·3%, respectively, with 4·2%, 11·0%, and 8·6% grade ≥3. These findings suggest that partnered dexamethasone dosing may result in less severe BiPN compared with alternative dexamethasone dosing schedules. © 2017 John Wiley & Sons Ltd.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors and fracture risk in patients with type 2 diabetes mellitus: A meta-analysis.

PubMed

Ruanpeng, Darin; Ungprasert, Patompong; Sangtian, Jutarat; Harindhanavudhi, Tasma

2017-09-01

Sodium-glucose cotransporter 2 (SGLT2) inhibitors could potentially alter calcium and phosphate homeostasis and may increase the risk of bone fracture. The current meta-analysis was conducted to investigate the fracture risk among patients with type 2 diabetes mellitus treated with SGLT2 inhibitors. Randomized controlled trials that compared the efficacy of SGLT2 inhibitors to placebo were identified. The risk ratios of fracture among patients who received SGLT2 inhibitors versus placebo were extracted from each study. Pooled risk ratios and 95% confidence intervals were calculated using a random-effect, Mantel-Haenszel analysis. A total of 20 studies with 8286 patients treated with SGLT2 inhibitors were included. The pooled risk ratio of bone fracture in patients receiving SGLT2 inhibitors versus placebo was 0.67 (95% confidence interval, 0.42-1.07). The pooled risk ratio for canagliflozin, dapagliflozin, and empagliflozin was 0.66 (95% confidence interval, 0.37-1.19), 0.84 (95% confidence interval, 0.22-3.18), and 0.57 (95% confidence interval, 0.20-1.59), respectively. Increased risk of bone fracture among patients with type 2 diabetes mellitus treated with SGLT2 inhibitors compared with placebo was not observed in this meta-analysis. However, the results were limited by short duration of treatment/follow-up and low incidence of the event of interest. Copyright © 2017 John Wiley & Sons, Ltd.

Shelf-Slope Exchanges near Submarine Canyons in the Southern Mid-Atlantic Bight

NASA Astrophysics Data System (ADS)

Wang, H.; Gong, D.

2016-02-01

Shelf-slope exchange processes are major physical drivers of biological productivity near the shelf-break. Observations from two Slocum ocean gliders in Fall 2013 are used to explore the driving mechanisms of cross-shelf-slope exchanges near Norfolk Canyon and Washington Canyon in the southern Mid-Atlantic Bight. Offshore excursion of bottom "cold pool" water, and shoreward intrusion of slope water at surface layer and thermocline depth occurred during northeasterly along-shelf winds. The saline intrusions of surface slope water resided between the cold pool and surface shelf water, and reached the bottom on the outer and mid-shelf, while the offshore excursion of cold pool water was found between the surface and intermediate slope-water over the canyon. Ekman transport calculation shows wind-driven cross-shelf transport can partially explain this interleaving pattern of intrusions. Scaling analysis of double diffusive processes demonstrate that they also likely played a role in the cross-shelf-slope exchange. A unique canyon upwelling event was captured in and around Washington Canyon during a period of southwesterly along-shelf wind and along-shelf flow to the northeast. The water mass distributions and isopycnal responses in both along-canyon and cross-canyon transects are consistent with scaling analysis and numerical studies of canyon upwelling. Temperature-Salinity properties of water masses in the canyon suggest active mixing between shelf and slope water masses near the canyon head. These results point to the importance of wind, double diffusion, and canyon topography on shelf-slope exchange in the MAB.

The Value of Risk Pooling for Mitigating Water Utility Financial Risks Arising From Water Scarcity

NASA Astrophysics Data System (ADS)

Baum, R.; Characklis, G. W.; Hughes, J.; Eskaf, S.

2015-12-01

Water utilities across the United States face growing supply risks as demand growth and extreme weather events make water scarcity more common. As it has become more difficult and expensive to build new supply capacity to accommodate these events, many utility managers respond by either imposing conservation measures, which reduces revenues, or acquiring additional water from other sources, which increases costs. These actions lead to changing financial trends that are difficult to predict and that utilities are currently ill-equipped to manage. As a result, adaptation strategies and tools are being developed to reduce utility vulnerabilities, ensuring both financial stability and continued access to low cost financing, a critical consideration for a capital intensive industry. Previous work in this area has involved the development of utility specific financial hedging tools. However, the time and informational requirements associated with developing these individualized strategies may be a limiting factor for widespread implementation. The objective of this research is to develop more generalized hedging instruments that can be applied simultaneously to multiple utilities across the United States, thereby increasing the potential for widespread implementation. This work first analyzes the financial risks of water scarcity for a large set of water utilities across the country and then proposes a financial hedging solution to mitigate these risks through hydrologic index-based financial insurance. Results provide insights into the most effective indices, the potential for risk pooling to reduce insurance costs, and the performance of these contracts in managing utility financial risk arising from drought.

Unraveling the mechanisms underlying pulse dynamics of soil respiration in tropical dry forests

DOE PAGES

Waring, Bonnie G.; Powers, Jennifer S.

2016-10-14

Tropical dry forests are already undergoing changes in the quantity and timing of rainfall, but there is great uncertainty over how these shifts will affect belowground carbon (C) cycling. While it has long been known that dry soils quickly release carbon dioxide (CO 2) upon rewetting, the mechanisms underlying the so-called 'Birch effect' are still debated. Here, we quantified soil respiration pulses and their biotic predictors in response to simulated precipitation events in a regenerating tropical dry forest in Costa Rica. We also simulated the observed rewetting CO 2 pulses with two soil carbon models: a conventional model assuming first-ordermore » decay rates of soil organic matter, and an enzyme-catalyzed model with Michaelis–Menten kinetics. We found that rewetting of dry soils produced an immediate and dramatic pulse of CO 2, accompanied by rapid immobilization of nitrogen into the microbial biomass. However, the magnitude of the rewetting CO 2 pulse was highly variable at fine spatial scales, and was well correlated with the size of the dissolved organic C pool prior to rewetting. Both the enzyme-catalyzed and conventional models were able to reproduce the Birch effect when respiration was coupled directly to microbial C uptake, although models differed in their ability to yield realistic estimates of SOC and microbial biomass pool sizes and dynamics. Lastly, our results suggest that changes in the timing and intensity of rainfall events in tropical dry forests will exert strong influence on ecosystem C balance by affecting the dynamics of microbial biomass growth.« less

Unraveling the mechanisms underlying pulse dynamics of soil respiration in tropical dry forests

DOE Office of Scientific and Technical Information (OSTI.GOV)

Waring, Bonnie G.; Powers, Jennifer S.

Tropical dry forests are already undergoing changes in the quantity and timing of rainfall, but there is great uncertainty over how these shifts will affect belowground carbon (C) cycling. While it has long been known that dry soils quickly release carbon dioxide (CO 2) upon rewetting, the mechanisms underlying the so-called 'Birch effect' are still debated. Here, we quantified soil respiration pulses and their biotic predictors in response to simulated precipitation events in a regenerating tropical dry forest in Costa Rica. We also simulated the observed rewetting CO 2 pulses with two soil carbon models: a conventional model assuming first-ordermore » decay rates of soil organic matter, and an enzyme-catalyzed model with Michaelis–Menten kinetics. We found that rewetting of dry soils produced an immediate and dramatic pulse of CO 2, accompanied by rapid immobilization of nitrogen into the microbial biomass. However, the magnitude of the rewetting CO 2 pulse was highly variable at fine spatial scales, and was well correlated with the size of the dissolved organic C pool prior to rewetting. Both the enzyme-catalyzed and conventional models were able to reproduce the Birch effect when respiration was coupled directly to microbial C uptake, although models differed in their ability to yield realistic estimates of SOC and microbial biomass pool sizes and dynamics. Lastly, our results suggest that changes in the timing and intensity of rainfall events in tropical dry forests will exert strong influence on ecosystem C balance by affecting the dynamics of microbial biomass growth.« less

Outcomes in elderly and young patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention with bivalirudin versus heparin: Pooled analysis from the EUROMAX and HORIZONS-AMI trials.

PubMed

Qaderdan, Khalid; Vos, Gerrit-Jan A; McAndrew, Thomas; Steg, Philippe Gabriel; Hamm, Christian W; Van't Hof, Arnoud; Mehran, Roxana; Deliargyris, Efthymios N; Bernstein, Debra; Stone, Gregg W; Ten Berg, Jurriën M

2017-12-01

Since older age is a strong predictor of not only bleeding but also of ischemic events, understanding the risk:benefit profile of bivalirudin in the elderly undergoing primary percutaneous coronary intervention (pPCI) for ST-segment elevation (STEMI) is important. For this, we aim to compare elderly with young patients, who all underwent pPCI for STEMI and randomly received either bivalirudin or heparin. We performed a patient-level pooled analysis (n=5800) of two large randomized trials. A total of 2149 (37.1%) elderly patients (>65 years of age) with STEMI were enrolled and randomly assigned to either bivalirudin or heparin with or without a GPI (control group) before pPCI. Clinical outcomes at 30 days were analyzed. In elderly patients, bivalirudin significantly reduced non-CABG major bleeding (7.1% vs 10.4%; P<.01), subacute ST (0.4% vs 1.5%; P<.01), and net adverse clinical events (NACE; composite of all-cause mortality, reinfarction, IDR, stroke or protocol-defined non-CABG major bleeding [13.7% vs 17.2%; P=.03]) with comparable rates of stroke, MI, acute ST, or all-cause death, when compared with heparin with or without GPI. In a large group of elderly patients enrolled in the EUROMAX and HORIZONS-AMI trials, bivalirudin was associated with lower 30-day rates of non-CABG major bleeding, subacute ST and NACE, with similar 30-day rates of acute ST and mortality. Copyright © 2017 Elsevier Inc. All rights reserved.

A review of land-based greenhouse gas flux estimates in Indonesia

NASA Astrophysics Data System (ADS)

Austin, Kemen G.; Harris, Nancy L.; Wijaya, Arief; Murdiyarso, Daniel; Harvey, Tom; Stolle, Fred; Kasibhatla, Prasad S.

2018-05-01

This study examines underlying reasons for differences among land-based greenhouse gas flux estimates in Indonesia, where six national inventories reported average emissions of between 0.4 and 1.1 Gt CO2e yr‑1 over the 2000–2012 period. The large range among estimates is only somewhat smaller than Indonesia’s GHG mitigation commitment. To determine the reasons for these differences, we compared input data and estimation methods, including the definitions and assumptions used for setting accounting boundaries, including emitting activities, incorporating fluxes from various carbon pools, and handling legacy fluxes. We also tested the sensitivity of methodological differences by generating our own reference emissions estimate and iteratively modifying individual components of the inventory. We found that the largest changes stem from the inclusion of legacy GHG emissions due to peat drainage (which increased emissions by at least +94% compared to the reference), methane emissions due to peat fires (+35%), and GHG emissions from belowground biomass and necromass carbon pools (+61%), modifications to assumptions of the mass of fuel burnt in peat fire events (+88%), and accounting for regrowth following a deforestation event (‑31%). These differences cumulatively explain more than half of the observed difference among inventory estimates. Understanding the various approaches to emissions estimation, and how these influence the magnitude of component GHG fluxes, is an important first step towards reconciling GHG inventories. The Indonesian government’s success in achieving its mitigation goal will depend on its ability to measure progress and evaluate the effectiveness of abatement actions, for which reliable harmonized greenhouse gas inventories are an essential foundation.

Unraveling the mechanisms underlying pulse dynamics of soil respiration in tropical dry forests

NASA Astrophysics Data System (ADS)

Waring, Bonnie G.; Powers, Jennifer S.

2016-10-01

Tropical dry forests are already undergoing changes in the quantity and timing of rainfall, but there is great uncertainty over how these shifts will affect belowground carbon (C) cycling. While it has long been known that dry soils quickly release carbon dioxide (CO2) upon rewetting, the mechanisms underlying the so-called ‘Birch effect’ are still debated. Here, we quantified soil respiration pulses and their biotic predictors in response to simulated precipitation events in a regenerating tropical dry forest in Costa Rica. We also simulated the observed rewetting CO2 pulses with two soil carbon models: a conventional model assuming first-order decay rates of soil organic matter, and an enzyme-catalyzed model with Michaelis-Menten kinetics. We found that rewetting of dry soils produced an immediate and dramatic pulse of CO2, accompanied by rapid immobilization of nitrogen into the microbial biomass. However, the magnitude of the rewetting CO2 pulse was highly variable at fine spatial scales, and was well correlated with the size of the dissolved organic C pool prior to rewetting. Both the enzyme-catalyzed and conventional models were able to reproduce the Birch effect when respiration was coupled directly to microbial C uptake, although models differed in their ability to yield realistic estimates of SOC and microbial biomass pool sizes and dynamics. Our results suggest that changes in the timing and intensity of rainfall events in tropical dry forests will exert strong influence on ecosystem C balance by affecting the dynamics of microbial biomass growth.

Pharmacokinetics, Pharmacodynamics, and Safety of Subcutaneous Bapineuzumab: A Single-Ascending-Dose Study in Patients With Mild to Moderate Alzheimer Disease.

PubMed

Lu, Ming; Brashear, H Robert

2018-06-19

This study was designed to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single ascending subcutaneous doses of bapineuzumab in patients with mild to moderate Alzheimer disease. Forty patients were randomized across 5 cohorts (5 mg, 10 mg, 20 mg, 40 mg, 80 mg; 8 patients each [bapineuzumab 6; placebo 2]). The incidence of treatment-emergent adverse events (TEAEs) was higher in pooled bapineuzumab cohorts (83%) than in the pooled placebo group (27.7%). Most common TEAEs in the bapineuzumab group were gastrointestinal disorders and musculoskeletal and connective tissue disorders (bapineuzumab 17% each; placebo 0%). Serious TEAEs were observed in 7% of bapineuzumab-treated patients without any deaths or adverse event-related discontinuation. The median times to reach peak measurable concentration (C max ) of bapineuzumab were 14 days for 5-, 10-, and 20-mg cohorts, 11 days for 40-mg, and 7 days for 80-mg cohorts. The apparent volume of distribution of bapineuzumab was 134.29 to 204.68 mL/kg. The total body clearance was consistent at 10 to 80 mg. The average terminal half-life ranged from 26 to 46 days (5- to 80-mg groups). Exposure to bapineuzumab increased dose-proportionally from 10 to 80 mg. There was a positive correlation between C max and area under the concentration-time curve to the last measurable concentration (AUC last ) of plasma amyloid-β, and between the C max and AUC last of serum bapineuzumab. © 2018, The American College of Clinical Pharmacology.

Experimental study of the spill and vaporization of a volatile liquid.

PubMed

Bohl, Douglas; Jackson, Gregory

2007-02-09

Pool and vapor cloud characteristics of an acetone spill issuing from the downstream wall of a flow obstruction oriented perpendicular to a uniform flow were investigated experimentally. Data indicate that the spill event was largely governed by the temperature of the surface in relation to the boiling point of the spilled liquid. The free stream velocity (ranging from 0.75 to 3.0m/s) also impacted the spreading of the spill. Planar laser-induced fluorescence (PLIF) was used to measure acetone vapor concentrations during the transient pool spreading and vaporization in a window 60cm long by 50cm high and located downstream of the 16cm high obstruction. The recirculation region induced by the flow obstruction caused upstream transport of the acetone vapor along the spill surface, after which it was convected vertically along the obstruction wall before being entrained into the flow and convected downstream. The recirculating flow caused regions of vapor within the flammability limits to be localized near the flow obstruction. These regions moved into and out of the measurement plane by large three-dimensional flow structures. The flammable region of the evolved vapor cloud was observed to grow well past the downstream edge of the measurement domain. With decreasing wind speeds, both the mass of acetone vapor within the flammability limits and the total spill event time increased significantly. The data presented herein provides a basis for validating future spill models of hazardous chemical releases, where complex turbulent flow modeling must be coupled with spill spreading and vaporization dynamics.

Temporal pattern of toxicity in runoff from the Tijuana River Watershed.

PubMed

Gersberg, Richard M; Daft, Daniel; Yorkey, Darryl

2004-02-01

Samples were collected from the Tijuana River under both dry weather (baseflow) conditions and during wet weather, and tested for toxicity using Ceriodaphnia dubia tests. Toxicity of waters in the Tijuana River was generally low under baseflow conditions, but increased markedly during high flow runoff events. In order to determine the temporal pattern of toxicity during individual rain events, sequential grab samples were collected using an autosampler at 5-7 h intervals after the start of the rain event, and tested for acute toxicity. In all cases, peak toxicity values (ranging from 2.8 to 5.8TU) for each storm occurred within the first 1-2 h of initiation of the rain event, and were statistically higher (using the 95% CL) for each of the pre-storm base flow values. However, there was no statistically significant correlation (p<0.05) between flow rate and toxicity when all storm data was pooled. Additionally, we used toxicity identification evaluation (TIE) procedures to attempt to identify the classes of chemicals that account for this early storm toxicity. Solid phase extraction was the only treatment that showed consistent and significant (P<0.05) removal of toxicity. These TIEs, conducted on the most toxic sample of the river's flow during runoff events, suggest that non-polar organics may be responsible for such toxicity. The temporal pattern of toxicity, both during a given storm event and seasonally, indicates that wash-off from the watershed by rainfall may deplete the supply of toxicity available for wash-off in subsequent events, so that a clearly consistent relationship between flow and toxicity was not evident.

Systematic review and meta-analysis: Multi-strain probiotics as adjunct therapy for Helicobacter pylori eradication and prevention of adverse events

PubMed Central

Huang, Ying; Wang, Lin; Malfertheiner, Peter

2015-01-01

Background Eradication rates with triple therapy for Helicobacter pylori infections have currently declined to unacceptable levels worldwide. Newer quadruple therapies are burdened with a high rate of adverse events. Whether multi-strain probiotics can improve eradication rates or diminish adverse events remains uncertain. Methods Relevant publications in which patients with H. pylori infections were randomized to a multi-strain probiotic or control were identified in PubMed, Cochrane Databases, and other sources from 1 January 1960–3 June 2015. Primary outcomes included eradication rates, incidence of any adverse event and the incidence of antibiotic-associated diarrhea. As probiotic efficacy is strain-specific, pooled relative risks and 95% confidence intervals were calculated using meta-analysis stratified by similar multi-strain probiotic mixtures. Results A total of 19 randomized controlled trials (20 treatment arms, n = 2730) assessing one of six mixtures of strains of probiotics were included. Four multi-strain probiotics significantly improved H. pylori eradication rates, five significantly prevented any adverse reactions and three significantly reduced antibiotic-associated diarrhea. Only two probiotic mixtures (Lactobacillus acidophilus/Bifidobacterium animalis and an eight-strain mixture) had significant efficacy for all three outcomes. Conclusions Our meta-analysis found adjunctive use of some multi-strain probiotics may improve H. pylori eradication rates and prevent the development of adverse events and antibiotic-associated diarrhea, but not all mixtures were effective. PMID:27536365

Rapid formation of a modern bedrock canyon by a single flood event

NASA Astrophysics Data System (ADS)

Lamb, Michael P.; Fonstad, Mark A.

2010-07-01

Deep river canyons are thought to form slowly over geological time (see, for example, ref. 1), cut by moderate flows that reoccur every few years. In contrast, some of the most spectacular canyons on Earth and Mars were probably carved rapidly during ancient megaflood events. Quantification of the flood discharge, duration and erosion mechanics that operated during such events is hampered because we lack modern analogues. Canyon Lake Gorge, Texas, was carved in 2002 during a single catastrophic flood. The event offers a rare opportunity to analyse canyon formation and test palaeo-hydraulic-reconstruction techniques under known topographic and hydraulic conditions. Here we use digital topographic models and visible/near-infrared aerial images from before and after the flood, discharge measured during the event, field measurements and sediment-transport modelling to show that the flood moved metre-sized boulders, excavated ~7m of limestone and transformed a soil-mantled valley into a bedrock canyon in just ~3days. We find that canyon morphology is strongly dependent on rock type: plucking of limestone blocks produced waterfalls, inner channels and bedrock strath terraces, whereas abrasion of cemented alluvium sculpted walls, plunge pools and streamlined islands. Canyon formation was so rapid that erosion might have been limited by the ability of the flow to transport sediment. We suggest that our results might improve hydraulic reconstructions of similar megafloods on Earth and Mars.

Nerve-muscle interactions during flight muscle development in Drosophila

NASA Technical Reports Server (NTRS)

Fernandes, J. J.; Keshishian, H.

1998-01-01

During Drosophila pupal metamorphosis, the motoneurons and muscles differentiate synchronously, providing an opportunity for extensive intercellular regulation during synapse formation. We examined the existence of such interactions by developmentally delaying or permanently eliminating synaptic partners during the formation of indirect flight muscles. When we experimentally delayed muscle development, we found that although adult-specific primary motoneuron branching still occurred, the higher order (synaptic) branching was suspended until the delayed muscle fibers reached a favourable developmental state. In reciprocal experiments we found that denervation caused a decrease in the myoblast pool. Furthermore, the formation of certain muscle fibers (dorsoventral muscles) was specifically blocked. Exceptions were the adult muscles that use larval muscle fibers as myoblast fusion targets (dorsal longitudinal muscles). However, when these muscles were experimentally compelled to develop without their larval precursors, they showed an absolute dependence on the motoneurons for their formation. These data show that the size of the myoblast pool and early events in fiber formation depend on the presence of the nerve, and that, conversely, peripheral arbor development and synaptogenesis is closely synchronized with the developmental state of the muscle.

Senate examines measures to improve nuclear safety following Japan disaster

NASA Astrophysics Data System (ADS)

Showstack, Randy

2012-03-01

One year after Japan suffered a devastating magnitude 9.0 earthquake and the resulting tsunami and nuclear disaster, the U.S. Nuclear Regulatory Commission (NRC) has taken a number of measures to try to ensure that nuclear plants in the United States are safe from natural hazards. At a U.S. Senate hearing on 15 March, NRC chair Gregory Jaczko announced that the commission had issued three key orders and several requests for information on 12 March that plant licensees must follow, and that NRC also plans to take additional actions. However, the commission is not moving quickly enough in some areas, such as ensuring that all plants are safe from seismic hazards, including those in areas with low seismic activity, according to Jaczko's testimony before the Senate Committee on Environment and Public Works (EPW) and the Subcommittee on Clean Air and Nuclear Safety. The 12 March orders require licensees to have strategies to maintain or restore core cooling, containment, and spent-fuel pool cooling capabilities "following a beyond-design-basis extreme natural event" and have a reliable indication of the water level in spent-fuel storage pools.

Effectiveness and safety of valsartan in children aged 6 to 16 years with hypertension.

PubMed

Wells, Thomas; Blumer, Jeffrey; Meyers, Kevin E C; Neto, Jose P R; Meneses, Rejane; Litwin, Mieczysław; Vande Walle, Johan; Solar-Yohay, Susan; Shi, Victor; Han, Guangyang

2011-05-01

The effectiveness and safety of valsartan have not been assessed in hypertensive children. Therefore, hypertensive patients aged 6 to 16 years (n=261) were randomized to receive weight-stratified low- (10/20 mg), medium- (40/80 mg), or high-dose (80/160 mg) valsartan for 2 weeks. After 2 weeks, patients were randomized to a 2-week placebo-controlled withdrawal phase. Dose-dependent reductions in sitting systolic blood pressure (SSBP) and sitting diastolic blood pressure (SDBP) were observed after 2 weeks (low dose, -7.9/-4.6 mm Hg; medium dose, -9.6/-5.8 mm Hg; high dose, -11.5/-7.4 mm Hg [P<.0001 for all groups]). During the withdrawal phase, SSBP and SDBP were both lower in the pooled valsartan group than in the pooled placebo group (SSBP, -2.7 mm Hg [P=.0368]; SDBP, -3.0 mm Hg [P=.0047]). Similar efficacy was observed in all subgroups. Valsartan was well tolerated and headache was the most commonly observed adverse event during both the double-blind and 52-week open-label phases. © 2011 Wiley Periodicals, Inc.

Gene Flow within and between Catchments in the Threatened Riparian Plant Myricaria germanica

PubMed Central

Werth, Silke; Scheidegger, Christoph

2014-01-01

One of the major distinctions of riparian habitats is their linearity. In linear habitats, gene flow is predicted to follow a one-dimensional stepping stone model, characterized by bidirectional gene flow between neighboring populations. Here, we studied the genetic structure of Myricaria germanica, a threatened riparian shrub which is capable of both wind and water dispersal. Our data led us to reject the ‘one catchment – one gene pool’ hypothesis as we found support for two gene pools, rather than four as expected in a study area including four catchments. This result also implies that in the history of the studied populations, dispersal across catchments has occurred. Two contemporary catchment-crossing migration events were detected, albeit between spatially proximate catchments. Allelic richness and inbreeding coefficients differed substantially between gene pools. There was significant isolation by distance, and our data confirmed the one-dimensional stepping-stone model of gene flow. Contemporary migration was bidirectional within the studied catchments, implying that dispersal vectors other than water are important for M. germanica. PMID:24932520

Variability of the western Pacific warm pool structure associated with El Niño

NASA Astrophysics Data System (ADS)

Hu, Shijian; Hu, Dunxin; Guan, Cong; Xing, Nan; Li, Jianping; Feng, Junqiao

2017-10-01

Sea surface temperature (SST) structure inside the western Pacific warm pool (WPWP) is usually overlooked because of its distinct homogeneity, but in fact it possesses a clear meridional high-low-high pattern. Here we show that the SST low in the WPWP is significantly intensified in July-October of El Niño years (especially extreme El Niño years) and splits the 28.5 °C-isotherm-defined WPWP (WPWP split for simplification). Composite analysis and heat budget analysis indicate that the enhanced upwelling due to positive wind stress curl anomaly and western propagating upwelling Rossby waves account for the WPWP split. Zonal advection at the eastern edge of split region plays a secondary role in the formation of the WPWP split. Composite analysis and results from a Matsuno-Gill model with an asymmetric cooling forcing imply that the WPWP split seems to give rise to significant anomalous westerly winds and intensify the following El Niño event. Lead-lag correlation shows that the WPWP split slightly leads the Niño 3.4 index.

Organic matter loading by hippopotami causes subsidy overload resulting in downstream hypoxia and fish kills.

PubMed

Dutton, Christopher L; Subalusky, Amanda L; Hamilton, Stephen K; Rosi, Emma J; Post, David M

2018-05-16

Organic matter and nutrient loading into aquatic ecosystems affects ecosystem structure and function and can result in eutrophication and hypoxia. Hypoxia is often attributed to anthropogenic pollution and is not common in unpolluted rivers. Here we show that organic matter loading from hippopotami causes the repeated occurrence of hypoxia in the Mara River, East Africa. We documented 49 high flow events over 3 years that caused dissolved oxygen decreases, including 13 events resulting in hypoxia, and 9 fish kills over 5 years. Evidence from experiments and modeling demonstrates a strong mechanistic link between the flushing of hippo pools and decreased dissolved oxygen in the river. This phenomenon may have been more widespread throughout Africa before hippopotamus populations were severely reduced. Frequent hypoxia may be a natural part of tropical river ecosystem function, particularly in rivers impacted by large wildlife.

Magnesium and the Risk of Cardiovascular Events: A Meta-Analysis of Prospective Cohort Studies

PubMed Central

Hao, Yongqiang; Li, Huiwu; Tang, Tingting; Wang, Hao; Yan, Weili; Dai, Kerong

2013-01-01

Background Prospective studies that have examined the association between dietary magnesium intake and serum magnesium concentrations and the risk of cardiovascular disease (CVD) events have reported conflicting findings. We undertook a meta-analysis to evaluate the association between dietary magnesium intake and serum magnesium concentrations and the risk of total CVD events. Methodology/Principal Findings We performed systematic searches on MEDLINE, EMBASE, and OVID up to February 1, 2012 without limits. Categorical, linear, and nonlinear, dose-response, heterogeneity, publication bias, subgroup, and meta-regression analysis were performed. The analysis included 532,979 participants from 19 studies (11 studies on dietary magnesium intake, 6 studies on serum magnesium concentrations, and 2 studies on both) with 19,926 CVD events. The pooled relative risks of total CVD events for the highest vs. lowest category of dietary magnesium intake and serum magnesium concentrations were 0.85 (95% confidence interval 0.78 to 0.92) and 0.77 (0.66 to 0.87), respectively. In linear dose-response analysis, only serum magnesium concentrations ranging from 1.44 to 1.8 mEq/L were significantly associated with total CVD events risk (0.91, 0.85 to 0.97) per 0.1 mEq/L (Pnonlinearity = 0.465). However, significant inverse associations emerged in nonlinear models for dietary magnesium intake (Pnonlinearity = 0.024). The greatest risk reduction occurred when intake increased from 150 to 400 mg/d. There was no evidence of publication bias. Conclusions/Significance There is a statistically significant nonlinear inverse association between dietary magnesium intake and total CVD events risk. Serum magnesium concentrations are linearly and inversely associated with the risk of total CVD events. PMID:23520480

Joint Effect of Alcohol Consumption and Educational Level on Alcohol-related Medical Events: A Danish Register-based Cohort Study.

PubMed

Christensen, Helene Nordahl; Diderichsen, Finn; Hvidtfeldt, Ulla Arthur; Lange, Theis; Andersen, Per Kragh; Osler, Merete; Prescott, Eva; Tjønneland, Anne; Rod, Naja Hulvej; Andersen, Ingelise

2017-11-01

Alcohol-related mortality is more pronounced in lower than in higher socioeconomic groups in Western countries. Part of the explanation is differences in drinking patterns. However, differences in vulnerability to health consequences of alcohol consumption across socioeconomic groups may also play a role. We investigated the joint effect of alcohol consumption and educational level on the rate of alcohol-related medical events. We pooled seven prospective cohorts from Denmark that enrolled 74,278 men and women age 30-70 years (study period, 1981 to 2009). We measured alcohol consumption at baseline using self-administrated questionnaires. Information on highest attained education 1 year before study entry and hospital and mortality data on alcohol-related medical events were obtained through linkage to nationwide registries. We performed analyses using the Aalen additive hazards model. During follow-up (1,085,049 person-years), a total of 1718 alcohol-related events occurred. The joint effect of very high alcohol consumption (>21 [>28] drinks per week in women [men]) and low education on alcohol-related events exceeded the sum of their separate effects. Among men, we observed 289 (95% confidence interval = 123, 457) extra events per 100,000 person-years owing to education-alcohol interaction (P < 0.001). Similarly, among women, we observed 239 (95% confidence interval = 90, 388) extra events per 100,000 person-years owing to this interaction (P < 0.001). High alcohol consumption is associated with a higher risk of alcohol-related medical events among those with low compared with high education. This interaction may be explained by differences in vulnerability and drinking patterns across educational groups.See video abstract at, http://links.lww.com/EDE/B267.

Impacts of anthropogenic emissions and cold air pools on urban to montane gradients of snowpack ion concentrations in the Wasatch Mountains, Utah

NASA Astrophysics Data System (ADS)

Hall, Steven J.; Maurer, Gregory; Hoch, Sebastian W.; Taylor, Raili; Bowling, David R.

2014-12-01

Urban montane valleys are often characterized by periodic wintertime temperature inversions (cold air pools) that increase atmospheric particulate matter concentrations, potentially stimulating the deposition of major ions to these snow-covered ecosystems. We assessed spatial and temporal patterns of ion concentrations in snow across urban to montane gradients in Salt Lake City, Utah, USA, and the adjacent Wasatch Mountains during January 2011, a period of several persistent cold air pools. Ion concentrations in fresh snow samples were greatest in urban sites, and were lower by factors of 4-130 in a remote high-elevation montane site. Adjacent undeveloped canyons experienced significant incursions of particulate-rich urban air during stable atmospheric conditions, where snow ion concentrations were lower but not significantly different from urban sites. Surface snow ion concentrations on elevation transects in and adjacent to Salt Lake City varied with temporal and spatial trends in aerosol concentrations, increasing following exposure to particulate-rich air as cold air pools developed, and peaking at intermediate elevations (1500-1600 m above sea level, or 200-300 m above the valley floor). Elevation trends in ion concentrations, especially NH4+ and NO3-, corresponded with patterns of aerosol exposure inferred from laser ceilometer data, suggesting that high particulate matter concentrations stimulated fog or dry ion deposition to snow-covered surfaces at the top of the cold air pools. Fog/dry deposition inputs were similar to wet deposition at mid-elevation montane sites, but appeared negligible at lower and higher-elevation sites. Overall, snow ion concentrations in our urban and adjacent montane sites exceeded many values reported from urban precipitation in North America, and greatly exceeded those reported for remote snowpacks. Sodium, Cl-, NH4+, and NO3- concentrations in fresh snow were high relative to previously measured urban precipitation, with means of 120, 117, 42, and 39 μeq l-1, respectively. After exposure to atmospheric particulate matter during cold pool events, surface snow concentrations peaked at 2500, 3600, 93, and 90 μeq l-1 for these ions. Median nitrogen (N) deposition in fresh urban snow samples measured 0.8 kg N ha-1 during January 2011, with similar fog/dry deposition inputs at mid-elevation montane sites. Wintertime anthropogenic air pollution represents a significant source of ions to snow-covered ecosystems proximate to urban montane areas, with important implications for ecosystem function.

Differential Medial Temporal Lobe and Parietal Cortical Contributions to Real-world Autobiographical Episodic and Autobiographical Semantic Memory.

PubMed

Brown, Thackery I; Rissman, Jesse; Chow, Tiffany E; Uncapher, Melina R; Wagner, Anthony D

2018-04-18

Autobiographical remembering can depend on two forms of memory: episodic (event) memory and autobiographical semantic memory (remembering personally relevant semantic knowledge, independent of recalling a specific experience). There is debate about the degree to which the neural signals that support episodic recollection relate to or build upon autobiographical semantic remembering. Pooling data from two fMRI studies of memory for real-world personal events, we investigated whether medial temporal lobe (MTL) and parietal subregions contribute to autobiographical episodic and semantic remembering. During scanning, participants made memory judgments about photograph sequences depicting past events from their life or from others' lives, and indicated whether memory was based on episodic or semantic knowledge. Results revealed several distinct functional patterns: activity in most MTL subregions was selectively associated with autobiographical episodic memory; the hippocampal tail, superior parietal lobule, and intraparietal sulcus were similarly engaged when memory was based on retrieval of an autobiographical episode or autobiographical semantic knowledge; and angular gyrus demonstrated a graded pattern, with activity declining from autobiographical recollection to autobiographical semantic remembering to correct rejections of novel events. Collectively, our data offer insights into MTL and parietal cortex functional organization, and elucidate circuitry that supports different forms of real-world autobiographical memory.

On the relative role of meridional convergence and downwelling motion during the heat buildup leading to El Niño events

NASA Astrophysics Data System (ADS)

Ballester, Joan; Bordoni, Simona; Petrova, Desislava; Rodó, Xavier

2015-04-01

Despite steady progress in the understanding of El Niño-Southern Oscillation (ENSO) in the past decades, questions remain on the exact mechanisms leading to the onset of El Niño (EN) events. Several authors have highlighted how the subsurface heat buildup in the western tropical Pacific and the recharged phase in equatorial heat content are intrinsic elements of ENSO variability, leading to those changes in zonal wind stress, sea surface temperature and thermocline tilt that characterize the growing and mature phases of EN. Here we use an ensemble of ocean and atmosphere assimilation products to identify the mechanisms contributing to the heat buildup that precedes EN events by about 18-24 months on average. Anomalous equatorward subsurface mass convergence due to meridional Sverdrup transport is found to be an important mechanism of thermocline deepening near and to the east of the dateline. In the warm pool, instead, surface horizontal convergence and downwelling motion have a leading role in subsurface warming, since equatorward mass convergence is weaker and counterbalanced by subsurface zonal divergence. The picture emerging from our results highlights the complexity of the three dimensional dynamic and thermodynamic structure of the tropical Pacific during the heat buildup leading to EN events.

Short versus prolonged dual antiplatelet therapy (DAPT) duration after coronary stent implantation: A comparison between the DAPT study and 9 other trials evaluating DAPT duration

PubMed Central

Toyota, Toshiaki; Shiomi, Hiroki; Morimoto, Takeshi; Natsuaki, Masahiro; Kimura, Takeshi

2017-01-01

Aims The Dual Antiplatelet Therapy (DAPT) study demonstrated that DAPT beyond 1-year after drug-eluting stent (DES) implantation, as compared with aspirin therapy alone, significantly reduced the risk of major cardiovascular and cerebrovascular events, which was mainly driven by the large risk reduction for myocardial infarction (MI). We sought to compare the largest DAPT study with other trials evaluating DAPT durations after DES implantation. Methods and results By a systematic literature search, we identified 9 trials comparing prolonged- versus short-DAPT in addition to the DAPT study. The result from the DAPT study (N = 9961) with public–private collaboration was different from the pooled result of the 9 other investigator-driven trials (N = 22174) in terms of the effect of prolonged-DAPT on MI (odds ratio [OR] 0.48 [95%CI 0.38–0.62] versus pooled OR 0.88 [95%CI 0.67–1.15]: P = 0.001 for difference), while the trends for excess risk of prolonged-DAPT relative to short-DAPT for all-cause death (OR 1.31 [95%CI 0.97–1.78] versus pooled OR 1.16 [95%CI 0.92–1.45]: P = 0.53 for difference), and bleeding (OR 1.62 [95%CI 1.21–2.17] versus pooled OR 2.08 [95%CI 1.51–2.84]: P = 0.25 for difference) were consistently seen in both the DAPT and other trials. The annual rate of MI during aspirin mono-therapy in the DAPT study was much higher than that those in the other trials (2.7% versus 0.6–1.6%). Conclusions Given the difference between the DAPT study and other trials, future studies should focus on certain subgroups of patients that are more or less likely to benefit from longer duration DAPT. PMID:28931015

Association of extremely high levels of high-density lipoprotein cholesterol with cardiovascular mortality in a pooled analysis of 9 cohort studies including 43,407 individuals: The EPOCH-JAPAN study.

PubMed

Hirata, Aya; Sugiyama, Daisuke; Watanabe, Makoto; Tamakoshi, Akiko; Iso, Hiroyasu; Kotani, Kazuhiko; Kiyama, Masahiko; Yamada, Michiko; Ishikawa, Shizukiyo; Murakami, Yoshitaka; Miura, Katsuyuki; Ueshima, Hirotsugu; Okamura, Tomonori

2018-02-08

The effect of very high or extremely high levels of high-density lipoprotein cholesterol (HDL-C) on cardiovascular disease (CVD) is not well described. Although a few recent studies have reported the adverse effects of extremely high levels of HDL-C on CVD events, these did not show a statistically significant association between extremely high levels of HDL-C and cause-specific CVD mortality. In addition, Asian populations have not been studied. We examine the impact of extremely high levels of HDL-C on cause-specific CVD mortality using pooled data of Japanese cohort studies. We performed a large-scale pooled analysis of 9 Japanese cohorts including 43,407 participants aged 40-89 years, dividing the participants into 5 groups by HDL-C levels, including extremely high levels of HDL-C ≥2.33 mmol/L (≥90 mg/dL). We estimated the adjusted hazard ratio of each HDL-C category for all-cause death and cause-specific deaths compared with HDL-C 1.04-1.55 mmol/L (40-59 mg/dL) using a cohort-stratified Cox proportional hazards model. During a 12.1-year follow-up, 4995 all-cause deaths and 1280 deaths due to overall CVD were identified. Extremely high levels of HDL-C were significantly associated with increased risk of atherosclerotic CVD mortality (hazard ratio = 2.37, 95% confidence interval: 1.37-4.09 for total) and increased risk for coronary heart disease and ischemic stroke. In addition, the risk for extremely high HDL-C was more evident among current drinkers. We showed extremely high levels of HDL-C had an adverse effect on atherosclerotic CVD mortality in a pooled analysis of Japanese cohorts. Copyright © 2018 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Tissue angiotensin-converting enzyme inhibitors for the prevention of cardiovascular disease in patients with diabetes mellitus without left ventricular systolic dysfunction or clinical evidence of heart failure: a pooled meta-analysis of randomized placebo-controlled clinical trials.

PubMed

Saha, S A; Molnar, J; Arora, R R

2008-01-01

The aim of this study was to determine the role of tissue angiotensin-converting enzyme (ACE) inhibitors in the prevention of cardiovascular disease in patients with diabetes mellitus without left ventricular systolic dysfunction or clinical evidence of heart failure in randomized placebo-controlled clinical trials using pooled meta-analysis techniques. Randomized placebo-controlled clinical trials of at least 12 months duration in patients with diabetes mellitus without left ventricular systolic dysfunction or heart failure who had experienced a prior cardiovascular event or were at high cardiovascular risk were selected. A total of 10 328 patients (43 517 patient-years) from four selected trials were used for meta-analysis. Relative risk estimations were made using data pooled from the selected trials and statistical significance was determined using the Chi-squared test (two-sided alpha error <0.05). The number of patients needed to treat was also calculated. Tissue ACE inhibitors significantly reduced the risk of cardiovascular mortality by 14.9% (p = 0.022), myocardial infarction by 20.8% (p = 0.002) and the need for invasive coronary revascularization by 14% (p = 0.015) when compared to placebo. The risk of all-cause mortality also tended to be lower among patients randomized to tissue ACE inhibitors, whereas the risks of stroke and hospitalization for heart failure were not significantly affected. Treating about 65 patients with tissue ACE inhibitors for about 4.2 years would prevent one myocardial infarction, whereas treating about 85 patients would prevent one cardiovascular death. Pooled meta-analysis of randomized placebo-controlled trials suggests that tissue ACE inhibitors modestly reduce the risk of myocardial infarction and cardiovascular death and tend to reduce overall mortality in diabetic patients without left ventricular systolic dysfunction or heart failure.

Uniparental Genetic Heritage of Belarusians: Encounter of Rare Middle Eastern Matrilineages with a Central European Mitochondrial DNA Pool

PubMed Central

Kushniarevich, Alena; Sivitskaya, Larysa; Danilenko, Nina; Novogrodskii, Tadeush; Tsybovsky, Iosif; Kiseleva, Anna; Kotova, Svetlana; Chaubey, Gyaneshwer; Metspalu, Ene; Sahakyan, Hovhannes; Bahmanimehr, Ardeshir; Reidla, Maere; Rootsi, Siiri; Parik, Jüri; Reisberg, Tuuli; Achilli, Alessandro; Hooshiar Kashani, Baharak; Gandini, Francesca; Olivieri, Anna; Behar, Doron M.; Torroni, Antonio; Davydenko, Oleg; Villems, Richard

2013-01-01

Ethnic Belarusians make up more than 80% of the nine and half million people inhabiting the Republic of Belarus. Belarusians together with Ukrainians and Russians represent the East Slavic linguistic group, largest both in numbers and territory, inhabiting East Europe alongside Baltic-, Finno-Permic- and Turkic-speaking people. Till date, only a limited number of low resolution genetic studies have been performed on this population. Therefore, with the phylogeographic analysis of 565 Y-chromosomes and 267 mitochondrial DNAs from six well covered geographic sub-regions of Belarus we strove to complement the existing genetic profile of eastern Europeans. Our results reveal that around 80% of the paternal Belarusian gene pool is composed of R1a, I2a and N1c Y-chromosome haplogroups – a profile which is very similar to the two other eastern European populations – Ukrainians and Russians. The maternal Belarusian gene pool encompasses a full range of West Eurasian haplogroups and agrees well with the genetic structure of central-east European populations. Our data attest that latitudinal gradients characterize the variation of the uniparentally transmitted gene pools of modern Belarusians. In particular, the Y-chromosome reflects movements of people in central-east Europe, starting probably as early as the beginning of the Holocene. Furthermore, the matrilineal legacy of Belarusians retains two rare mitochondrial DNA haplogroups, N1a3 and N3, whose phylogeographies were explored in detail after de novo sequencing of 20 and 13 complete mitogenomes, respectively, from all over Eurasia. Our phylogeographic analyses reveal that two mitochondrial DNA lineages, N3 and N1a3, both of Middle Eastern origin, might mark distinct events of matrilineal gene flow to Europe: during the mid-Holocene period and around the Pleistocene-Holocene transition, respectively. PMID:23785503

Short versus prolonged dual antiplatelet therapy (DAPT) duration after coronary stent implantation: A comparison between the DAPT study and 9 other trials evaluating DAPT duration.

PubMed

Toyota, Toshiaki; Shiomi, Hiroki; Morimoto, Takeshi; Natsuaki, Masahiro; Kimura, Takeshi

2017-01-01

The Dual Antiplatelet Therapy (DAPT) study demonstrated that DAPT beyond 1-year after drug-eluting stent (DES) implantation, as compared with aspirin therapy alone, significantly reduced the risk of major cardiovascular and cerebrovascular events, which was mainly driven by the large risk reduction for myocardial infarction (MI). We sought to compare the largest DAPT study with other trials evaluating DAPT durations after DES implantation. By a systematic literature search, we identified 9 trials comparing prolonged- versus short-DAPT in addition to the DAPT study. The result from the DAPT study (N = 9961) with public-private collaboration was different from the pooled result of the 9 other investigator-driven trials (N = 22174) in terms of the effect of prolonged-DAPT on MI (odds ratio [OR] 0.48 [95%CI 0.38-0.62] versus pooled OR 0.88 [95%CI 0.67-1.15]: P = 0.001 for difference), while the trends for excess risk of prolonged-DAPT relative to short-DAPT for all-cause death (OR 1.31 [95%CI 0.97-1.78] versus pooled OR 1.16 [95%CI 0.92-1.45]: P = 0.53 for difference), and bleeding (OR 1.62 [95%CI 1.21-2.17] versus pooled OR 2.08 [95%CI 1.51-2.84]: P = 0.25 for difference) were consistently seen in both the DAPT and other trials. The annual rate of MI during aspirin mono-therapy in the DAPT study was much higher than that those in the other trials (2.7% versus 0.6-1.6%). Given the difference between the DAPT study and other trials, future studies should focus on certain subgroups of patients that are more or less likely to benefit from longer duration DAPT.

Faecal Microbiota Transplantation for Inflammatory Bowel Disease: A Systematic Review and Meta-analysis.

PubMed

Paramsothy, Sudarshan; Paramsothy, Ramesh; Rubin, David T; Kamm, Michael A; Kaakoush, Nadeem O; Mitchell, Hazel M; Castaño-Rodríguez, Natalia

2017-10-01

Faecal microbiota transplantation [FMT] has been investigated as a potential treatment for inflammatory bowel disease [IBD]. We thus performed a systematic review and meta-analysis assessing the effectiveness and safety of FMT in IBD. A systematic review was conducted until January 2017. Studies were excluded if patients had co-infection or data were pooled across disease subtypes (ulcerative colitis [UC], Crohn's disease [CD], pouchitis). Clinical remission was established as the primary outcome. Pooled effect sizes and 95% confidence intervals were obtained using the random effects model. In all, 53 studies were included [41 in UC, 11 in CD, 4 in pouchitis]. Overall, 36% [201/555] of UC, 50.5% [42/83] of CD, and 21.5% [5/23] of pouchitis patients achieved clinical remission. Among cohort studies, the pooled proportion achieving clinical remission was 33% (95% confidence interval [CI] = 23%-43%] for UC and 52% [95% CI = 31%-72%] for CD, both with moderate risk of heterogeneity. For four RCTs in UC, significant benefit in clinical remission (pooled odds ratios [[P-OR] = 2.89, 95% CI = 1.36-6.13, p = 0.006) with moderate heterogeneity [Cochran's Q, p = 0.188; I2 = 37%] was noted. Sub-analyses suggest remission in UC improved with increased number of FMT infusions and lower gastrointestinal tract administration. Most adverse events were transient gastrointestinal complaints. Microbiota analysis was performed in 24 studies, with many identifying increased diversity and a shift in recipient microbiota profile towards the donor post-FMT. FMT appears effective in UC remission induction, but long-term durability and safety remain unclear. Additional well-designed controlled studies of FMT in IBD are needed, especially in CD and pouchitis. Copyright © 2017 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com

Effects of Neck Radiation Therapy on Extra-Cranial Carotid Arteries Atherosclerosis Disease Prevalence: Systematic Review and a Meta-Analysis

PubMed Central

Bashar, Khalid; Healy, Donagh; Clarke-Moloney, Mary; Burke, Paul; Kavanagh, Eamon; Walsh, Stewart-Redmond

2014-01-01

Introduction Radiation arteritis following neck irradiation as a treatment for head and neck malignancy has been well documented. The long-term sequelae of radiation exposure of the carotid arteries may take years to manifest clinically, and extra-cranial carotid artery (ECCA) stenosis is a well-recognised vascular complication. These carotid lesions should not be regarded as benign and should be treated in the same manner as standard carotid stenosis. Previous studies have noted increased cerebrovascular events such as stroke in this cohort of patients because of high-grade symptomatic carotid stenosis resulting in emboli. Aim To evaluate the effect of radiation therapy on ECCA atherosclerosis progression. Methods Online search for case-control studies and randomised clinical trials that reported on stenosis in extra-cranial carotid arteries in patients with neck malignancies who received radiation therapy (RT) comparing them to patients with neck malignancies who did not receive RT. Results Eight studies were included in the final analysis with total of 1070 patients – 596 received RT compared to 474 in the control group. There was statistically significant difference in overall stenosis rate (Pooled risk ratio  =  4.38 [2.98, 6.45], P  =  0.00001) and severe stenosis (Pooled risk ratio  =  7.51 [2.78, 20.32], P <0.0001), both being higher in the RT group. Pooled analysis of the five studies that reported on mild stenosis also showed significant difference (Pooled risk ratio  =  2.74 [1.75, 4.30], 95% CI, P  =  0.0001). Conclusion The incidence of severe ECCA stenosis is higher among patients who received RT for neck malignancies. Those patients should be closely monitored and screening programs should be considered in all patients who receive neck RT. PMID:25329500

The response of a simulated mesoscale convective system to increased aerosol pollution: Part II: Derecho characteristics and intensity in response to increased pollution

NASA Astrophysics Data System (ADS)

Clavner, Michal; Grasso, Lewis D.; Cotton, William R.; van den Heever, Susan C.

2018-01-01

Mesoscale Convective Systems (MCS) are important contributors to rainfall as well as producers of severe weather such as hail, tornados, and straight-line wind events known as derechos. In this study, different aerosol concentrations and their effects on a derecho event are examined by simulating a case study, the 8 May 2009 "Super-Derecho", using the Regional Atmospheric Modeling System (RAMS), a cloud-resolving model with sophisticated aerosol and cloud microphysics. Three simulations were conducted that differed in the initial aerosol concentrations, spatial distribution and chemical composition as derived from output of GEOS-Chem, a 3D chemical transport model. In order to understand the impact of changes in aerosol concentrations on the derecho characteristics, the dynamical processes that produced the strong surface wind were determined by performing back-trajectory analysis during two periods of the simulated storm: the development and the onset of dissipation. A time dependent and non-monotonic trend was found between the intensity of the derecho and the increased aerosol concentrations that served as cloud condensation nuclei. During the formation period of the MCS, the non-monotonic trend was attributed to the microphysical impact of aerosol loading on the intensity of the cold pool; that is, the impact of aerosols on both the melting and evaporation rates of hydrometeors. The subsequent intensity changes within the cold pool modified the balance between the horizontal vorticity generated by the cold pool and that of the environment, thereby impacting the orientation of the convective updraft at the leading line. This, in turn, altered the primary flow that contributed to the formation of the derecho-strength surface winds. The simulation with no anthropogenic aerosols exhibited the strongest cold pool and the primary flow was associated with a descending rear inflow jet that produced the derecho winds over a larger region. The simulation with the highest amount of anthropogenic aerosols featured a stronger mesovortex and the derecho winds were primarily due to stronger convective downbursts. As the simulated storm matured, the changes in the derecho winds were found to be associated with the strength of the mesovortex at the gust front. During the period when the simulated storm began to dissipate, the non-monotonic trend in derecho intensity was associated with a non-monotonic response in mesovortex strength to increased aerosol concentrations. A moderate increase in aerosol concentrations led to the formation of a weaker mesovortex while a greater increase in aerosol concentration led to the formation of a stronger mesovortex. The formation of a stronger mesovortex was found to increase the contribution of the derecho winds following a convective downburst associated with an "up-down" downdraft trajectory.

Pyroclastic flow generated by crater-wall collapse and outpouring of the lava pool of Arenal Volcano, Costa Rica

NASA Astrophysics Data System (ADS)

Alvarado, Guillermo E.; Soto, Gerardo J.

2002-01-01

The pyroclastic flow that issued from the Arenal summit crater on 28 August 1993 came from the collapse of the crater wall of the cone and the drainage of a lava pool. The 3-km-long pyroclastic flow, 2.2±0.8×106 m3 in volume, was confined to narrow valleys (30-100 m wide). The thickness of the pyroclastic deposit ranged from 1 to 10 m, and its temperature was about 400 °C, although single bombs were up to 1,000 °C. The deposit is clast-supported, has a bimodal grain size distribution, and consists of an intimate mixture of finely pulverized rock ash, lapilli, small blocks, and cauliflower bread-crusted bombs, in which are set meter-size lava fragments and juvenile and non-juvenile angular blocks, and bombs up to 7 m in diameter. Large faceted blocks make up 50% of the total volume of the deposit. The cauliflower bombs have deep and intricate bread-crust texture and post-depositional vesiculation. It is proposed that the juvenile material was produced entirely from a lava pool, whereas faceted non-juvenile blocks come from the crater-wall collapse. The concentration and maximum diameter of cauliflower bread-crusted bombs increases significantly from the base (rockslide + pyroclastic flow) to the top (the pyroclastic flow) of the deposit. An ash cloud deposited accretionary lapilli in the proximal region (outside of the pyroclastic flow deposit), and very fine ash fell in the distal region (between 5 and 30 km). The accretionary lapilli deposit is derived from the fine, elutriated products of the flow as it moved. A turbulent overriding surge blew down the surrounding shrubbery in the flow direction. The pyroclastic flow from August 1993, similar to the flows of June 1975, May 1998, August 2000, and March 2001, slid and rolled rather than being buoyed up by gas. They grooved, scratched, and polished the surfaces over which they swept, similar to a Merapi-type pyroclastic flow. However, the mechanism of the outpouring of a lava pool and the resulting flows composed of high- to moderate-vesiculated, cauliflower bread-crusted bombs and juvenile blocks have not been described before. High-frequency earthquake swarms, followed by an increase in low-frequency volcanic events, preceded the 1975, 1993, and 2000 eruptions 2-4 months before. These pyroclastic flow events, therefore, may be triggered by internal expansion of the unstable cone in the upper part because of a slight change in the pressure of the magma column (gas content and/or effusive rate). This phenomenon has important short-term, volcanic hazard implications for touristic development of some parts on the flanks of the volcano.

STS-56 MS1 Foale, in LES/LEH, floats during bailout exercises in JSC WETF

NASA Technical Reports Server (NTRS)

1993-01-01

STS-56 Discovery, Orbiter Vehicle (OV) 103, Mission Specialist 1 (MS1) Michael Foale, wearing launch and entry suit (LES) and launch and entry helmet (LEH), floats in a single person life raft during launch emergency egress (bailout) exercises in JSC's Weightless Environment Training Facility (WETF) Bldg 29 pool. Foale's body is covered with the life raft tarp. His head and the space shuttle search and rescue satellite aided tracking (SARSAT) antenna protrude above the tarp. This simulation prepares the astronauts for the event of an emergency egress and subsequent water landing during launch.

STS-52 MS Veach and Payload Specialist MacLean during JSC bailout exercises

NASA Technical Reports Server (NTRS)

1992-01-01

STS-52 Columbia, Orbiter Vehicle (OV) 102, Mission Specialist (MS) Charles Lacy Veach (left) and Canadian Payload Specialist Steven G. MacLean listen to a briefing during emergency egress (bailout) training exercises in JSC's Weightless Environment Training Facility (WETF) Bldg 29. Veach and MacLean are fully outfitted in launch and entry suits (LESs), launch and entry helmets (LEHs), parachutes, and water survival equipment including a life jacket. The WETF's 25-ft deep pool will simulate the ocean as the crewmember's prepare for the event of a water landing. MacLean represents the Canadian Space Agency (CSA).

The role of sea surface salinity in ENSO related water cycle anomaly

NASA Astrophysics Data System (ADS)

Tang, Wenqing; Yueh, Simon

2017-04-01

This study investigates the role of sea surface salinity (SSS) in the water cycle anomaly associated with El Niño Southern Oscillation (ENSO). The 2015-16 El Niño, one of the strongest ENSO events observed in centuries, coincident with unprecedented coverage of spacebased remote sensing of SSS over global oceans. We analyze three SSS data sets: from the NASA's missions of SMAP and Aquarius, and the ESA's Soil Moisture and Ocean Salinity (SMOS). One typical characteristics of an ENSO event is the zonal displacement of the Western equatorial Pacific Fresh Pool (WPFP). The edge of the pool extends eastward during El Niño, retreats westward during La Niña. For super El Niño, the eastern edge of WPFP extends much more east across the equatorial Pacific. Indeed, SSS from SMAP reveals much stronger eastward migration of WPFP starting in April 2015. The eastern edge of WPFP reached 140°W in March 2016, about 40° more eastward extension than Aquarius observed in previous years. In the following months from March to June 2016, WPFP retreated westward, coincident with the ending of this strong El Niño event [WMO, El Nino/La Nina update, 2016]. SMOS data shows similar feature, confirming that there is no systematic biases between SMAP and Aquarius retrievals. We examine the linkage between the observed SSS variation and ENSO related water cycle anomaly by integrated analysis of SSS data sets in conjunction with other satellite and in situ measurements on rain, wind, evaporation and ocean currents. Based on the governing equation of the mixed layer salt budget, the freshwater exchange between air-sea interfaces is estimated as residual of the mixed-layer salinity (MLS) temporal change and advection (Focean), as an alternative to evaporation minus precipitation (FE-P). We analyzed the spatial and temporal variation of Focean and FE-P to explore the anomalous signature in the oceanic and atmospheric branches of the water cycle associated with 2015/16 ENSO. The maximum anomalous along the Equator shown in Focean occurred a few weeks ahead of FE-P, suggesting that salinity is not only a passive tracer but also plays an active role in the onset and evolvement of an ENSO event.

Memory effect triggered by exceptional event: the Rio Cordon study case

NASA Astrophysics Data System (ADS)

Rainato, Riccardo; Mao, Luca; Picco, Lorenzo; Garcia-Rama, Adriana; Aristide Lenzi, Mario

2016-04-01

In the mountain environment, the steep channels play a key-role in the drainage networks. Notably, the sediment transport processes that here occur, can affect aspects as the geomorphic changes, channel evolution, reservoir management, infrastructure design and hazard assessment. Due to the complex and changeable hydraulic and morphological features that characterize the mountain environment, the steep channels can exhibit fluvial and/or debris-flow transport with magnitude of sediment delivery that, in the same basin, may strongly vary from event to event. In the light of these challenging conditions, appears clear as an accurate monitoring and investigation of sediment dynamics is of critical importance in the steep mountain channels. Such monitoring has even more significance if it is maintained over long-period, enabling to investigate even the role of high magnitude/low frequency events. Using a dataset 29 years-wide, this work aims to investigate the temporal trend of sediment dynamic in the Rio Cordon (Eastern Italian Alps). The Rio Cordon is a steep mountain channel (mean slope = 13%) characterized by step-pool and riffle-pool morphology. The basin (5 km2)exhibits a prevalent nivo-pluvial runoff regime. Since 1986, the catchment is equipped with a monitoring station, that continuously records water discharge, bedload and suspended load (at 1 hr intervals, and 5 min intervals during floods). In September 1994 an exceptional event (RI > 100 years) occurred in the study site, mobilizing about 4000 tons of material. Currently, the structure is managed by ARPA Veneto - Regional Department for Land Safety. In terms of magnitude, the 31 floods recorded by the monitoring station show a wide range of hydraulic forcing (i.e. peak discharge and effective runoff) and amount transported. Specifically, Qpeak ranges within one order of magnitude (1.02 - 10.42 m3 s-1), while the amount of bedload and suspended load varies by more than 3 orders (i.e. 0.9 t < BL < 1541.7 t). The amounts transported by the floods are investigated as a function of Qpeak, using a power-law regression. Bedload (r2= 0.739) and suspended load (r2= 0.565) appear positively correlated with Qpeak, also showing that floods of a certain magnitude transported more sediments after the exceptional 1994 flood. A comparable behavior can be observed by the Qpeak/D50 relationship (r2= 0.688). The ratio between sediment load and effective runoff of the events allowed the temporal trend of transport efficiency to be inferred. The results highlight that nearly a decade with high transport efficiency appears to have occurred subsequently to the September 1994 event. This result confirms that exceptional floods, rarely assessed by short-term monitoring programs, can strongly affect the long-term sediment fluxes. In the case of Rio Cordon, the exceptional event triggered a "memory effect" in the basin, altering the sediment dynamics for roughly 10 years. This research was supported by the Italian Research Project of Relevant Interest PRIN2010-2011, prot. 20104ALME4, ITSE; and by the University of Padova Research Project CPDA149091- WoodAlp.

13 CFR 120.611 - Pools backing Pool Certificates.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 13 Business Credit and Assistance 1 2011-01-01 2011-01-01 false Pools backing Pool Certificates. 120.611 Section 120.611 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Secondary Market Certificates § 120.611 Pools backing Pool Certificates. (a) Pool characteristics. As set...

13 CFR 120.611 - Pools backing Pool Certificates.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Pools backing Pool Certificates. 120.611 Section 120.611 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Secondary Market Certificates § 120.611 Pools backing Pool Certificates. (a) Pool characteristics. As set...

Why continuous simulation? The role of antecedent moisture in design flood estimation

NASA Astrophysics Data System (ADS)

Pathiraja, S.; Westra, S.; Sharma, A.

2012-06-01

Continuous simulation for design flood estimation is increasingly becoming a viable alternative to traditional event-based methods. The advantage of continuous simulation approaches is that the catchment moisture state prior to the flood-producing rainfall event is implicitly incorporated within the modeling framework, provided the model has been calibrated and validated to produce reasonable simulations. This contrasts with event-based models in which both information about the expected sequence of rainfall and evaporation preceding the flood-producing rainfall event, as well as catchment storage and infiltration properties, are commonly pooled together into a single set of "loss" parameters which require adjustment through the process of calibration. To identify the importance of accounting for antecedent moisture in flood modeling, this paper uses a continuous rainfall-runoff model calibrated to 45 catchments in the Murray-Darling Basin in Australia. Flood peaks derived using the historical daily rainfall record are compared with those derived using resampled daily rainfall, for which the sequencing of wet and dry days preceding the heavy rainfall event is removed. The analysis shows that there is a consistent underestimation of the design flood events when antecedent moisture is not properly simulated, which can be as much as 30% when only 1 or 2 days of antecedent rainfall are considered, compared to 5% when this is extended to 60 days of prior rainfall. These results show that, in general, it is necessary to consider both short-term memory in rainfall associated with synoptic scale dependence, as well as longer-term memory at seasonal or longer time scale variability in order to obtain accurate design flood estimates.

Who is driving continuing medical education for family medicine?

PubMed

Klein, Douglas; Allan, G Michael; Manca, Donna; Sargeant, Joan; Barnett, Carly

2009-01-01

Considerable time and money are invested in continuing medical education (CME) for family physicians (FPs) but the effectiveness is uncertain. The participation of FPs as coordinators and teachers is not well known. The goal of this project was to describe the role of FPs in organizing and teaching CME events that are accredited for FPs. Information about accredited CME events occurring in Alberta and Nova Scotia was requested from universities, provincial chapters of the College of Family Physicians of Canada, and pharmaceutical companies. Location, coordinating site, organizing committee members, teaching faculty, and format were recorded from each event. The number and proportion of FPs involved in both organizing and teaching CME events accredited for FPs were calculated and compared. A total of 314 CME events were collected, comprising a total of 1,472 hours of CME. From the CME events collected, there were 1,730 organizing committee members and 1,647 teachers. FPs constitute 59% of the organizing committees and 17% of the teachers. Significant differences in the numbers of FP planners and teachers were related to organizing group, format, location, and expected audience composition. The accreditation requirement for FPs on organizing committees likely helps preserve a reasonable proportion of FP organizers but not teachers in FP CME. The proportions of true FP planners and teachers may actually be lower than planning documents indicate. Low level of family physician teachers in CME may be due to FPs' not selecting FP teachers, the FP teaching pool's being inadequate, or the organizing committee's being unaware of FPs who are knowledgeable in particular areas.

A voluntary program to curtail boat disturbance to waterfowl during migration

USGS Publications Warehouse

Kenow, Kevin P.; Korschgen, Carl E.; Nissen, James M.; Elfessi, Abdulaziz; Steinbach, Richard

2003-01-01

A voluntary waterfowl avoidance area (VWAA) was established on Lake Onalaska in Navigation Pool 7 of the Upper Mississippi River, Wisconsin, USA, in 1986, to reduce boating disturbance to migratory waterfowl. We monitored boater compliance with the VWAA program in 1993 and 1997. Of 1,664 "boating events" observed on Lake Onalaska, boats intruded into the VWAA on 127 occasions. Boating events have increased from 1.82 boating events/h in 1986-88 to 1.97 in 1993 and 2.58 in 1997. Despite a 60% increase in boating traffic, the lake-wide disturbance rates in 1997 were comparable to that in 1981. We attribute this to a significant reduction in the proportion of lake-wide boating events that resulted in disturbance, a direct consequence of the VWAA program. Rate of intrusion into the VWAA was 0.11 per boating event in 1997 compared to 0.18 per boating event in 1986-88. Boating disturbances to waterfowl within the VWAA occurred at about half the rate (0.24 to 0.28 disturbances∙hr-1) observed prior to establishment of the program (0.48 disturbances∙hr-1). We also identified access points used by boaters and boating activities that were most likely to result in intrusion into the VWAA and associated disturbance to waterfowl. Results of these analyses have provided useful information to resource managers for targeting public education efforts. The VWAA program has contributed to the value of Lake Onalaska as a waterfowl refuge and demonstrates an effective collaboration among government agencies and non-governmental organizations.

A voluntary program to curtail boat disturbance to waterfowl during migration

USGS Publications Warehouse

Kenow, K.P.; Korschgen, C.E.; Nissen, J.M.; Elfessi, A.; Steinbach, R.

2003-01-01

A voluntary waterfowl avoidance area (VWAA) was established on Lake Onalaska in Navigation Pool 7 of the Upper Mississippi River, Wisconsin, USA, in 1986, to reduce boating disturbance to migratory waterfowl. We monitored boater compliance with the VWAA program in 1993 and 1997. Of 1,664 "boating events" observed on Lake Onalaska, boats intruded into the VWAA on 127 occasions. Boating events have increased from 1.82 boating events/h in 1986-88 to 1.97 in 1993 and 2.58 in 1997. Despite a 60% increase in boating traffic, the lake-wide disturbance rates in 1997 were comparable to that in 1981. We attribute this to a significant reduction in the proportion of lake-wide boating events that resulted in disturbance, a direct consequence of the VWAA program. Rate of intrusion into the VWAA was 0.11 per boating event in 1997 compared to 0.18 per boating event in 1986-88. Boating disturbances to waterfowl within the VWAA occurred at about half the rate (0.24 to 0.28 disturbances ?? hr1) observed prior to establishment of the program (0.48 disturbances ?? hr1 . We also identified access points used by boaters and boating activities that were most likely to result in intrusion into the VWAA and associated disturbance to waterfowl. Results of these analyses have provided useful information to resource managers for targeting public education efforts. The VWAA program has contributed to the value of Lake Onalaska as a waterfowl refuge and demonstrates an effective collaboration among government agencies and non-governmental organizations.

Development and validation of the Questionnaire of Stressful Life Events (QSLE).

PubMed

Butjosa, Anna; Gómez-Benito, Juana; Myin-Germeys, Inez; Barajas, Ana; Baños, Iris; Usall, Judith; Grau, Norma; Granell, Luis; Sola, Andrea; Carlson, Janina; Dolz, Montserrat; Sánchez, Bernardo; Haro, Josep Maria; Ochoa, Susana

2017-12-01

Stressful life events (SLEs) are important indicators prior to the onset of first-episode psychosis (FEP). Although there are well-validated interviews and self-reports for assessing SLE on proximate events, unfortunately there are no instruments to assess SLE covering an entire lifetime. This study includes detailed specific items of childhood, adolescence, and adulthood focused on the presence of SLE, emotional impact (stressfulness), and the age at which the event occurred. Our research describes 2 studies designed to develop and validate a new scale to assess SLE: the Questionnaire of Stressful Life Events (QSLE). In Study 1, an over-inclusive item pool was generated based on review of group of experts at Parc Sanitari Sant Joan de Déu and content validity was examined by an Expert Survey. The whole scale represents the content domain. In Study 2, item-level analyses revealed good distributional properties, intra-rater reliability, and convergent and discriminant validity. In the sensitivity and specificity analysis, 18 items had high relevance in the discriminability between patients with FEP and healthy controls. We note that there was an AUC of 0.676, indicating a good predictor. Using 7 as a cutoff to predict an individual as a patient would yield a sensitivity of 64.8% and a specificity of 65%. Overall, the QSLE displayed satisfactory psychometric characteristics in a Spanish population. These results suggest that QSLE gives us the opportunity to investigate childhood, adolescent, and adult life events by measuring the stress and age at the moment on a continuous scale. Copyright © 2017 Elsevier Ltd. All rights reserved.

Identifying black swans in NextGen: predicting human performance in off-nominal conditions.

PubMed

Wickens, Christopher D; Hooey, Becky L; Gore, Brian F; Sebok, Angelia; Koenicke, Corey S

2009-10-01

The objective is to validate a computational model of visual attention against empirical data--derived from a meta-analysis--of pilots' failure to notice safety-critical unexpected events. Many aircraft accidents have resulted, in part, because of failure to notice nonsalient unexpected events outside of foveal vision, illustrating the phenomenon of change blindness. A model of visual noticing, N-SEEV (noticing-salience, expectancy, effort, and value), was developed to predict these failures. First, 25 studies that reported objective data on miss rate for unexpected events in high-fidelity cockpit simulations were identified, and their miss rate data pooled across five variables (phase of flight, event expectancy, event location, presence of a head-up display, and presence of a highway-in-the-sky display). Second, the parameters of the N-SEEV model were tailored to mimic these dichotomies. The N-SEEV model output predicted variance in the obtained miss rate (r = .73). The individual miss rates of all six dichotomous conditions were predicted within 14%, and four of these were predicted within 7%. The N-SEEV model, developed on the basis of an independent data set, was able to successfully predict variance in this safety-critical measure of pilot response to abnormal circumstances, as collected from the literature. As new technology and procedures are envisioned for the future airspace, it is important to predict if these may compromise safety in terms of pilots' failing to notice unexpected events. Computational models such as N-SEEV support cost-effective means of making such predictions.

Late Holocene environmental reconstructions and the implications on flood events, typhoon patterns, and agriculture activities in NE Taiwan

NASA Astrophysics Data System (ADS)

Wang, L.-C.; Behling, H.; Lee, T.-Q.; Li, H.-C.; Huh, C.-A.; Shiau, L.-J.; Chang, Y.-P.

2014-05-01

In this study, we reconstructed the paleoenvironmental changes from a sediment archive of the floodplain lake in Ilan Plain of NE Taiwan on multi-decadal resolution for the last ca. 1900 years. On the basis of pollen and diatom records, we evaluated the record of past vegetation, floods, typhoons and agriculture activities of this area, which is sensitive to the hydrological conditions of the West Pacific. High sedimentation rates with low microfossil preservations reflected multiple flood events and humid climatic conditions during 100-1400 AD. A shortly interrupted dry phase can be found during 940-1010 AD. The driest phase corresponds to the Little Ice Age phase 1 (LIA1, 1400-1620 AD) with less disturbance by flood events, which enhanced the occurrence of wetlands (Cyperaceae) and diatom depositions. Humid phases with frequent typhoons are inferred by high percentages of Lagerstroemia and high ratios of planktonic/benthic diatoms, respectively, during 500-700 AD and Little Ice Age phase 2 (LIA2, 1630-1850 AD). The occurrences of cultivated Poaceae (Oryza) during 1250-1300 AD and the last ~400 years, reflect agriculture activities, which seems to implicate strongly with the environmental stability. Finally, we found flood events which dominated during the El Niño-like stage, but dry events as well as frequent typhoon events happened during the La Niña-like stage. After comparing our results with the reconstructed proxy for tropical hydrological conditions, we suggested that the local hydrology in coastal East Asia were strongly affected by the typhoon-triggered heavy rainfalls which were influenced by the variation of global temperature, expansion of the Pacific warm pool and intensification of ENSO events.

POOL WATER TREATMENT AND COOLING SYSTEM DESCRIPTION DOCUMENT

DOE Office of Scientific and Technical Information (OSTI.GOV)

V. King

2000-06-19

The Pool Water Treatment and Cooling System is located in the Waste Handling Building (WHB), and is comprised of various process subsystems designed to support waste handling operations. This system maintains the pool water temperature within an acceptable range, maintains water quality standards that support remote underwater operations and prevent corrosion, detects leakage from the pool liner, provides the capability to remove debris from the pool, controls the pool water level, and helps limit radiological exposure to personnel. The pool structure and liner, pool lighting, and the fuel staging racks in the pool are not within the scope of themore » Pool Water Treatment and Cooling System. Pool water temperature control is accomplished by circulating the pool water through heat exchangers. Adequate circulation and mixing of the pool water is provided to prevent localized thermal hotspots in the pool. Treatment of the pool water is accomplished by a water treatment system that circulates the pool water through filters, and ion exchange units. These water treatment units remove radioactive and non-radioactive particulate and dissolved solids from the water, thereby providing the water clarity needed to conduct waste handling operations. The system also controls pool water chemistry to prevent advanced corrosion of the pool liner, pool components, and fuel assemblies. Removal of radioactivity from the pool water contributes to the project ALARA (as low as is reasonably achievable) goals. A leak detection system is provided to detect and alarm leaks through the pool liner. The pool level control system monitors the water level to ensure that the minimum water level required for adequate radiological shielding is maintained. Through interface with a demineralized water system, adequate makeup is provided to compensate for loss of water inventory through evaporation and waste handling operations. Interface with the Site Radiological Monitoring System provides continuous radiological monitoring of the pool water. The Pool Water Treatment and Cooling System interfaces with the Waste Handling Building System, Site-Generated Radiological Waste Handling System, Site Radiological Monitoring System, Waste Handling Building Electrical System, Site Water System, and the Monitored Geologic Repository Operations Monitoring and Control System.« less

Risk factors for hospital re-presentation among older adults following fragility fractures: a systematic review and meta-analysis.

PubMed

Mathew, Saira A; Gane, Elise; Heesch, Kristiann C; McPhail, Steven M

2016-09-12

Older adults hospitalized with fragility fractures are at high risk of negative events that can culminate in re-presentations to hospital emergency departments or readmissions to hospital. This systematic review aimed to identify patient, clinical, or hospital-related factors that are identifiable at the index admission and that may be associated with re-presentations to hospital emergency departments or hospital readmissions in older adults following fragility fractures. Four electronic databases (PubMed, CINAHL, Embase, and Scopus) were searched. A suite of search terms identified peer-reviewed English-language articles that examined potential correlates of hospital re-presentation in older adults (mean age ≥ 65 years) who were discharged from hospital following treatment for fragility fractures. A three-stage screening process (titles, abstracts, full text) was conducted by two researchers independently. Participant characteristics, study design, potential correlates examined, analyses, and findings were extracted for studies included in the review. Quality and risk of bias were assessed with the Effective Public Health Practice Project Quality Assessment Tool. The strength of evidence was incorporated into a best evidence synthesis, and meta-analysis was conducted where effect pooling was possible. Eleven of 35 eligible studies were categorized as high quality studies. These studies reported that age, higher Cumulative Illness Rating scores, American Society of Anesthesiologists scores > 3, longer length of stay, male sex, cardiovascular disease, low post-operative hemoglobin, kidney disease, dementia and cancer were factors identified at the index admission that were predictive of subsequent re-presentation to hospital. Age was the only predictor for which pooling of effects across studies was possible: pooling was conducted for re-presentation ≤ 30 days (pooled OR, 1.27; 95 % CI, 1.14-1.43) and > 30 days (pooled OR, 1.23; 95 % CI, 1.01-1.50). The best-evidence synthesis, in addition to the meta-analysis, identified a range of factors that may have utility in guiding clinical practice and policy guidelines for targeted interventions to reduce the need for re-presentation to hospital among this frail clinical population. The paucity of studies investigating re-presentations to hospital emergency departments without admission was an important gap in the literature identified in this review. Key limitations were exclusion of non-English language studies and grey literature. PROSPERO CRD42015019379 .

Towards a consistent approach of measuring and modelling CO2 exchange with manual chambers

NASA Astrophysics Data System (ADS)

Huth, Vytas; Vaidya, Shrijana; Hoffmann, Mathias; Jurisch, Nicole; Günther, Anke; Gundlach, Laura; Hagemann, Ulrike; Elsgaard, Lars; Augustin, Jürgen

2016-04-01

Determining ecosystem CO2 exchange with the manual closed chamber method has been applied in the past for e.g. plant, soil or treatment on a wide range of terrestrial ecosystems. Its major limitation is the discontinuous data acquisation challenging any gap-filling procedures. In addition, both data acquisition and gap-filling of closed chamber data have been carried out in different ways in the past. The reliability and comparability of the derived results from different closed chamber studies has therefore remained unclear. Hence, this study compares two different approaches of obtaining fluxes of gross primary production (GPP) either via sunrise to noon or via gradually-shaded mid-day measurements of transparent chamber fluxes (i.e. net ecosystem exchange, NEE) and opaque chamber fluxes (i.e., ecosystem respiration, RECO) on a field experiment plot in NE Germany cropped with a lucerne-clover-grass mix. Additionally, we compare three approaches of pooling RECO data for consecutive modelling of annual balances of NEE, i.e. campaign-wise (single measurement day RECO models), seasonal-wise (one RECO model for the entire study period), and cluster-wise (two RECO models representing low-/high-vegetation-stage data) modelling. The annual NEE balances of the sunrise to noon measurements are insensitive towards differing RECO modelling approaches (-101 to -131 g C m-2), whereas the choice of modelling annual NEE balances with the shaded mid-day measurements must be taken carefully (-200 to 425 g C m-2). In addition, the campaign-wise RECO modelling approach is very sensitive to daily data pooling (sunrise vs. mid-day) and only advisable when the diurnal variability of CO2 fluxes and environmental parameters (i.e. photosynthetically active radiation, temperature) is sufficiently covered. The seasonal- and cluster-wise approaches lead to robust NEE balances with only little variation in terms of daily data collection. We therefore recommend sunrise to noon measurements and data pooling from adjacent measurement campaigns as long as pooling over e.g. harvest events and significant changes in plant development can be omitted. If, e.g. for extensive treatment comparisons, the sunrise to noon measurements are not feasible due to their higher workload, data pooling accounting for plant development is necessary.

Degraded Litter Leachates as a Potential Control on Streamwater Nitrogen Dynamics

NASA Astrophysics Data System (ADS)

Hernes, P. J.; O'Geen, A. T.; Dahlgren, R. A.

2008-12-01

Dissolved organic nitrogen (DON) export from catchments is a critical element of overall nutrient cycling. An underlying assumption in most studies investigating DON export is that the source of this DON is from an aged soil organic matter (SOM) pool. However, recent investigations of dissolved organic carbon (DOC) have called into question the idea that dissolved organic matter (DOM) in streams is derived primarily from aged SOM. Evidence includes riverine DOC 14C ages (~5 years) that are much younger than SOM within the catchment as well as the riverine particulate organic matter (POM) pool (decades to 100s of years). Molecular fractionation due to litter leaching and sorption to mineral surfaces can completely account for the degraded molecular signatures observed in dissolved amino acid and dissolved lignin compositions within the DOM pool. Thus it is feasible that a significant portion of exported DON from catchments could come from a younger, less degraded organic matter pool such as litters. To evaluate this potential, we conducted a leaching incubation experiment using litters and degraded "duff" litters (estimated 2-5 yrs of degradation) from four vegetation types (live and blue oak leaves, foothill pine needles, and mixed annual grasses) in an oak woodland ecosystem in the foothills of the Sierra mountains of California. Litters and duffs were placed on sieves within funnels throughout the catchment, and leachates were collected during each rainfall event from Dec. 1, 2006 through May 31, 2007. DON accounted for 50-70% of nitrogen released from litters and DON plus particulate organic nitrogen (PON) constituted >90% of released nitrogen. In contrast, dissolved inorganic nitrogen (DIN) made up 60-80% of released nitrogen in the duff materials with the majority as ammonia. When scaled to the entire watershed, overall yields of dissolved nitrogen in leachates was estimated at 6.0 kg ha-1 for DON, 7.3 kg ha-1 for NH4-N, and 8.8 kg ha-1 for NO3-N, with 90% of the DON and 99% of the DIN derived from the duff materials. Areal yields are up to an order of magnitude greater than reported stream/riverine exports from catchments, indicating that much of this leachate must be degraded or sorbed along hydrologic flowpaths to streams, but that leachates could constitute a significant component of the DON/DOM pool within streams.

Pegvaliase for the treatment of phenylketonuria: A pivotal, double-blind randomized discontinuation Phase 3 clinical trial.

PubMed

Harding, Cary O; Amato, R Stephen; Stuy, Mary; Longo, Nicola; Burton, Barbara K; Posner, John; Weng, Haoling H; Merilainen, Markus; Gu, Zhonghua; Jiang, Joy; Vockley, Jerry

2018-05-01

Pegvaliase is a recombinant Anabaena variabilis phenylalanine ammonia lyase (PAL) enzyme under investigation for treatment of adult phenylketonuria (PKU). This manuscript describes results of a randomized discontinuation trial (RDT) designed to evaluate the effects of pegvaliase treatment on blood phenylalanine (Phe) and neuropsychiatric outcomes in adults with PKU. PRISM-2 is a 4-part, Phase 3 study that enrolled adults with PKU receiving pegvaliase treatment (initiated in a prior Phase 2 or Phase 3 study). The RDT, Part 2 of PRISM-2, was an 8-week trial that evaluated change in blood Phe concentrations, neuropsychiatric and neurocognitive measures, and safety outcomes in PRISM-2 participants who had achieved at least a 20% blood Phe reduction from pre-treatment baseline with pegvaliase treatment. Participants were randomized 2:1 to either continue pegvaliase (20 mg/day or 40 mg/day) or switch to matching placebo. The pooled pegvaliase group enrolled 66 participants and each placebo group enrolled 14 participants. The primary endpoint of change in blood Phe concentration from RDT entry to RDT Week 8 was met with clinically meaningful and statistically significant differences between the pegvaliase and placebo groups. Mean (SD) blood Phe at the beginning of the RDT when all participants were receiving pegvaliase was 563.9 μM (504.6) in the group assigned to the 20 mg/day placebo group (n = 14), 508.2 μM (363.7) in those assigned to the 40 mg/day placebo group (n = 14), and 503.9 μM (520.3) in those assigned to continue pegvaliase treatment (n = 58). At Week 8 of the RDT, the least squares mean change (95% confidence interval) in blood Phe was 949.8 μM (760.4 to 1139.1) for the 20 mg/day placebo group and 664.8 μM (465.5 to 864.1) for the 40 mg/day placebo group in comparison to 26.5 μM (-68.3 to 121.3) for the pooled (20 mg/day and 40 mg/day) pegvaliase group (P < 0.0001 for pooled pegvaliase group vs each placebo group). Adverse events (AEs) were usually lower in the pooled placebo group when compared to the pooled pegvaliase group. The most common AEs for the pooled pegvaliase and pooled placebo groups were arthralgia (13.6% and 10.3%, respectively), headache (12.1% and 24.1%), anxiety (10.6% and 6.9%), fatigue (10.6% and 10.3%), and upper respiratory tract infection (1.5% and 17.2%). Mean blood Phe reduction was sustained in the pegvaliase group, while placebo groups had mean blood Phe concentration increase toward pre-treatment baseline levels. Results from this study confirmed the efficacy of pegvaliase in maintaining reduced blood Phe concentrations with a manageable safety profile for most participants. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Rank-based pooling for deep convolutional neural networks.

PubMed

Shi, Zenglin; Ye, Yangdong; Wu, Yunpeng

2016-11-01

Pooling is a key mechanism in deep convolutional neural networks (CNNs) which helps to achieve translation invariance. Numerous studies, both empirically and theoretically, show that pooling consistently boosts the performance of the CNNs. The conventional pooling methods are operated on activation values. In this work, we alternatively propose rank-based pooling. It is derived from the observations that ranking list is invariant under changes of activation values in a pooling region, and thus rank-based pooling operation may achieve more robust performance. In addition, the reasonable usage of rank can avoid the scale problems encountered by value-based methods. The novel pooling mechanism can be regarded as an instance of weighted pooling where a weighted sum of activations is used to generate the pooling output. This pooling mechanism can also be realized as rank-based average pooling (RAP), rank-based weighted pooling (RWP) and rank-based stochastic pooling (RSP) according to different weighting strategies. As another major contribution, we present a novel criterion to analyze the discriminant ability of various pooling methods, which is heavily under-researched in machine learning and computer vision community. Experimental results on several image benchmarks show that rank-based pooling outperforms the existing pooling methods in classification performance. We further demonstrate better performance on CIFAR datasets by integrating RSP into Network-in-Network. Copyright © 2016 Elsevier Ltd. All rights reserved.

Acceptability of the aquatic environment for exercise training by people with chronic obstructive pulmonary disease with physical comorbidities: Additional results from a randomised controlled trial.

PubMed

McNamara, Renae J; McKeough, Zoe J; McKenzie, David K; Alison, Jennifer A

2015-06-01

Water-based exercise training is a relatively new concept in the management of people with COPD. This study aimed to examine the acceptability of the aquatic environment as a medium for exercise training in people with COPD with physical comorbidities. Following a supervised eight week, three times a week, water-based exercise training programme conducted in a hospital hydrotherapy pool as part of a randomised controlled trial, participants completed a questionnaire about their experience with exercise training in the pool including adverse events, barriers and factors enabling exercise programme completion, satisfaction with the aquatic environment and their preference for an exercise training environment. All 18 participants (mean (SD) age 72 (10) years; FEV1% predicted 60 (10) %) who commenced the water-based exercise training programme completed the questionnaire. Three participants withdrew from training. High acceptability of the water and air temperature, shower and change-room facilities, staff assistance and modes of pool entry was reported (94% to 100%). Six factors were highly rated as enabling exercise programme adherence and completion: staff support (chosen by 93% of participants), enjoyment (80%), sense of achievement (80%), noticeable improvements (73%), personal motivation (73%) and participant support (53%). Eighty-nine percent of the participants indicated they would continue with water-based exercise. This study provides the first insight into the acceptability of the aquatic environment for exercise training in people with COPD and indicates water-based exercise and the aquatic environment is well accepted. Copyright © 2014 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

Aquatic exercise in a chest-high pool for hormone therapy-induced arthralgia in breast cancer survivors: a pragmatic controlled trial.

PubMed

Cantarero-Villanueva, I; Fernández-Lao, C; Caro-Morán, E; Morillas-Ruiz, J; Galiano-Castillo, N; Díaz-Rodríguez, L; Arroyo-Morales, M

2013-02-01

To investigate the impact of aquatic exercise on pressure pain threshold in breast cancer survivors with hormone therapy-associated arthralgia. Single-blind, controlled trial. Two major metropolitan hospitals and a Sport and Spa Club in Granada, Spain. Forty women aged 29-71 years with stage I-III breast cancer who reported arthralgia. Patients were allocated alternately to either aquatic exercise in a chest-high pool or usual care while on the waiting list; control patients received treatment later. The two-month hydrotherapy intervention consisted of 24 sessions 3 days per week. Each session included 5 minutes of warm-up, 15-20 minutes of aerobic exercise, 15 minutes of mobility exercise and 20 minutes of recovery techniques. Pressure pain threshold at neck, shoulder, hand and leg were evaluated as primary outcomes. Cancer-related fatigue, as measured by the Piper Fatigue Scale, body mass index and waist circumference were secondary outcomes. A 2 × 2 repeated-measure ANCOVA was used in this study. No adverse events or development of worsening of pain was observed. Almost all the participants in the intervention group (89%) adhered to the hydrotherapy programme. Participants experienced a decrease in pressure pain threshold measured in neck, hand, shoulder and leg, as measured by algometry pressure, and waist circumference; all P < 0.05. Cancer-related fatigue (P = 0.06) and body mass index (P = 0.42) did not show significant improvement. These data suggest that hydrotherapy in a chest-high pool may reduce the pain threshold and waist circumference in breast cancer survivors with hormone therapy-associated arthralgia.

Ventilator-associated pneumonia rates in critical care units in 3 Arabian Gulf countries: A 6-year surveillance study.

PubMed

El-Saed, Aiman; Al-Jardani, Amina; Althaqafi, Abdulhakeem; Alansari, Huda; Alsalman, Jameela; Al Maskari, Zaina; El Gammal, Ayman; Al Nasser, Wafa; Al-Abri, Seif S; Balkhy, Hanan H

2016-07-01

Data estimating the rates of ventilator-associated pneumonia (VAP) in critical patients in Gulf Cooperation Council (GCC) countries are very limited. The aim of this study was to estimate VAP rates in GCC hospitals and to compare rates with published reports of the U.S. National Healthcare Safety Network (NHSN) and International Nosocomial Infection Control Consortium (INICC). VAP rates and ventilator utilization between 2008 and 2013 were calculated from aggregate VAP surveillance data using NHSN methodology pooled from 6 hospitals in 3 GCC countries: Saudi Arabia, Oman, and Bahrain. The standardized infection ratios of VAP in GCC hospitals were compared with published reports of the NHSN and INICC. A total of 368 VAP events were diagnosed during a 6-year period covering 76,749 ventilator days and 134,994 patient days. The overall VAP rate was 4.8 per 1,000 ventilator days (95% confidence interval, 4.3-5.3), with an overall ventilator utilization of 0.57. The VAP rates showed a wide variability between different types of intensive care units (ICUs) and were decreasing over time. After adjusting for the differences in ICU type, the risk of VAP in GCC hospitals was 217% higher than NHSN hospitals and 69% lower than INICC hospitals. The risk of VAP in ICU patients in GCC countries is higher than pooled U.S. VAP rates but lower than pooled rates from developing countries participating in the INICC. Copyright © 2016 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Movements and habitat use by PIT-tagged Atlantic salmon parr in early winter: The influence of anchor ice

USGS Publications Warehouse

Roussel, J.-M.; Cunjak, R.A.; Newbury, R.; Caissie, D.; Haro, A.

2004-01-01

1. Movements and habitat use by Atlantic salmon parr in Catamaran Brook, New Brunswick, were studied using Passive Integrated Transponder technology. The fish were tagged in the summer of 1999, and a portable reading system was used to collect data on individual positions within a riffle-pool sequence in the early winter of 1999. Two major freezing events occurred on November 11-12 (Ice 1) and November 18-19 (Ice 2) that generated significant accumulations of anchor ice in the riffle. 2. Individually tagged parr (fork length 8.4-12.6 cm, n = 15) were tracked from 8 to 24 November 1999. Over this period, emigration (40%) was higher from the pool than from the riffle. Of the nine parr that were consistently located, seven parr moved <5 m up- or downstream, and two parr moved more than 10 m (maximum 23 m). Parr moved significantly more by night than by day, and diel habitat shifts were more pronounced in the pool with some of the fish moving closer to the bank at night. 3. During Ice 2, there was relatively little movement by most of the parr in the riffle beneath anchor ice up to 10 cm in thickness. Water temperature was 0.16??C above the freezing point beneath anchor ice, suggesting the existence of suitable habitats where salmon parr can avoid supercooling conditions and where they can have access to low velocity shelters. To our knowledge, these are the first data on habitat use by Atlantic salmon parr under anchor ice.

Stereotactic radiosurgery for the treatment of mesial temporal lobe epilepsy.

PubMed

Feng, E-S; Sui, C-B; Wang, T-X; Sun, G-L

2016-12-01

Stereotactic radiosurgery (RS) is a potential option for some patients with temporal lobe epilepsy (TLE). The aim of this meta-analysis was to determine the pooled seizure-free rate and the time interval to seizure cessation in patients with lesions in the mesial temporal lobe, and who were eligible for either stereotactic or gamma knife RS. We searched the Medline, Cochrane, EMBASE, and Google Scholar databases using combinations of the following terms: RS, stereotactic radiosurgery, gamma knife, and TLE. We screened 103 articles and selected 13 for inclusion in the meta-analysis. Significant study heterogeneity was detected; however, the included studies displayed an acceptable level of quality. We show that approximately half of the patients were seizure free over a follow-up period that ranged from 6 months to 9 years [pooled estimate: 50.9% (95% confidence interval: 0.381-0.636)], with an average of 14 months to seizure cessation [pooled estimate: 14.08 months (95% confidence interval: 11.95-12.22 months)]. Nine of 13 included studies reported data for adverse events (AEs), which included visual field deficits and headache (the two most common AEs), verbal memory impairment, psychosis, psychogenic non-epileptic seizures, and dysphasia. Patients in the individual studies experienced AEs at rates that ranged from 8%, for non-epileptic seizures, to 85%, for headache. Our findings indicate that RS may have similar or slightly less efficacy in some patients compared with invasive surgery. Randomized controlled trials of both treatment regimens should be undertaken to generate an evidence base for patient decision-making. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

AST: an automated sequence-sampling method for improving the taxonomic diversity of gene phylogenetic trees.

PubMed

Zhou, Chan; Mao, Fenglou; Yin, Yanbin; Huang, Jinling; Gogarten, Johann Peter; Xu, Ying

2014-01-01

A challenge in phylogenetic inference of gene trees is how to properly sample a large pool of homologous sequences to derive a good representative subset of sequences. Such a need arises in various applications, e.g. when (1) accuracy-oriented phylogenetic reconstruction methods may not be able to deal with a large pool of sequences due to their high demand in computing resources; (2) applications analyzing a collection of gene trees may prefer to use trees with fewer operational taxonomic units (OTUs), for instance for the detection of horizontal gene transfer events by identifying phylogenetic conflicts; and (3) the pool of available sequences is biased towards extensively studied species. In the past, the creation of subsamples often relied on manual selection. Here we present an Automated sequence-Sampling method for improving the Taxonomic diversity of gene phylogenetic trees, AST, to obtain representative sequences that maximize the taxonomic diversity of the sampled sequences. To demonstrate the effectiveness of AST, we have tested it to solve four problems, namely, inference of the evolutionary histories of the small ribosomal subunit protein S5 of E. coli, 16 S ribosomal RNAs and glycosyl-transferase gene family 8, and a study of ancient horizontal gene transfers from bacteria to plants. Our results show that the resolution of our computational results is almost as good as that of manual inference by domain experts, hence making the tool generally useful to phylogenetic studies by non-phylogeny specialists. The program is available at http://csbl.bmb.uga.edu/~zhouchan/AST.php.

Association Between Marijuana Use and Condom Use: A Meta-Analysis of Between-Subject Event-Based Studies.

PubMed

Schumacher, Amy; Marzell, Miesha; Toepp, Angela J; Schweizer, Marin L

2018-05-01

With the current public health burden of sexually transmitted infections, it is important to identify factors affecting condom use. The association between marijuana use and condom use is especially important because of the increasing number of U.S. states legalizing marijuana; however, relevant research findings are mixed. The goal of this study was to perform a meta-analysis assessing the relationship between marijuana and condom use at instances of sexual intercourse. A systematic search of four databases was performed. Data were extracted and pooled estimates were calculated using random-effects models with inverse variance weighting. Heterogeneity was evaluated using the Cochran Q chi-square test. Eleven studies were included. There was a statistically significant relationship between marijuana and condom use in the overall pooled analysis (odds ratio [OR] = 0.71, 95% CI [0.56, 0.89]), and studies were homogeneous, I 2 = 12%, χ 2 (10) = 11.37, p = .33. Stratified analyses showed that although the pooled OR was not significant for adults (OR = 0.92, 95% CI [0.64, 1.33]), there was a significant relationship between condom use and marijuana use for adolescents (OR = 0.62, 95% CI [0.47, 0.82]). This meta-analysis found that the odds of condom use were lower for those who used marijuana around the time of intercourse than for those who did not, with this effect only significant for adolescents in a subgroup analysis. As the adolescent populations in this analysis were not representative of a general population of adolescents, future research should focus not only on those considered high risk.

AST: An Automated Sequence-Sampling Method for Improving the Taxonomic Diversity of Gene Phylogenetic Trees

PubMed Central

Zhou, Chan; Mao, Fenglou; Yin, Yanbin; Huang, Jinling; Gogarten, Johann Peter; Xu, Ying

2014-01-01

A challenge in phylogenetic inference of gene trees is how to properly sample a large pool of homologous sequences to derive a good representative subset of sequences. Such a need arises in various applications, e.g. when (1) accuracy-oriented phylogenetic reconstruction methods may not be able to deal with a large pool of sequences due to their high demand in computing resources; (2) applications analyzing a collection of gene trees may prefer to use trees with fewer operational taxonomic units (OTUs), for instance for the detection of horizontal gene transfer events by identifying phylogenetic conflicts; and (3) the pool of available sequences is biased towards extensively studied species. In the past, the creation of subsamples often relied on manual selection. Here we present an Automated sequence-Sampling method for improving the Taxonomic diversity of gene phylogenetic trees, AST, to obtain representative sequences that maximize the taxonomic diversity of the sampled sequences. To demonstrate the effectiveness of AST, we have tested it to solve four problems, namely, inference of the evolutionary histories of the small ribosomal subunit protein S5 of E. coli, 16 S ribosomal RNAs and glycosyl-transferase gene family 8, and a study of ancient horizontal gene transfers from bacteria to plants. Our results show that the resolution of our computational results is almost as good as that of manual inference by domain experts, hence making the tool generally useful to phylogenetic studies by non-phylogeny specialists. The program is available at http://csbl.bmb.uga.edu/~zhouchan/AST.php. PMID:24892935

Silent Circulation of St. Louis Encephalitis Virus Prior to an Encephalitis Outbreak in Cordoba, Argentina (2005)

PubMed Central

Díaz, Luis Adrian; Albrieu Llinás, Guillermo; Vázquez, Ana; Tenorio, Antonio; Contigiani, Marta Silvia

2012-01-01

St. Louis encephalitis virus is a complex zoonoses. In 2005, 47 laboratory-confirmed and probable clinical cases of SLEV infection were reported in Córdoba, Argentina. Although the causes of 2005 outbreak remain unknown, they might be related not only to virological factors, but also to ecological and environmental conditions. We hypothesized that one of the factors for SLE reemergence in Córdoba, Argentina, was the introduction of a new SLEV genotype (SLEV genotype III), with no previous activity in the area. In order to evaluate this hypothesis we carried out a molecular characterization of SLEV detections from mosquitoes collected between 2001 and 2004 in Córdoba city. A total of 315 mosquito pools (11,002 individuals) including 12 mosquitoes species were analyzed. Overall, 20 pools (8 mosquitoes species) were positive for SLEV. During this study, genotypes II, V and VII were detected. No mosquito pool infected with genotype III was detected before the 2005 outbreak. Genotype V was found every year and in the 8 sampled sites. Genotypes II and VII showed limited temporal and spatial activities. We cannot dismiss the association of genotype II and V as etiological agents during the outbreak. However, the silent circulation of other SLEV strains in Córdoba city before the 2005 outbreak suggests that the introduction of genotype III was an important factor associated to this event. Not mutually exclusive, other factors such as changes in avian hosts and mosquitoes vectors communities, driven by climatic and environmental modifications, should also be taken into consideration in further studies. PMID:22303490

Interactions between pool geometry and hydraulics

USGS Publications Warehouse

Thompson, Douglas M.; Nelson, Jonathan M.; Wohl, Ellen E.

1998-01-01

An experimental and computational research approach was used to determine interactions between pool geometry and hydraulics. A 20-m-long, 1.8-m-wide flume was used to investigate the effect of four different geometric aspects of pool shape on flow velocity. Plywood sections were used to systematically alter constriction width, pool depth, pool length, and pool exit-slope gradient, each at two separate levels. Using the resulting 16 unique geometries with measured pool velocities in four-way factorial analyses produced an empirical assessment of the role of the four geometric aspects on the pool flow patterns and hence the stability of the pool. To complement the conclusions of these analyses, a two-dimensional computational flow model was used to investigate the relationships between pool geometry and flow patterns over a wider range of conditions. Both experimental and computational results show that constriction and depth effects dominate in the jet section of the pool and that pool length exhibits an increasing effect within the recirculating-eddy system. The pool exit slope appears to force flow reattachment. Pool length controls recirculating-eddy length and vena contracta strength. In turn, the vena contracta and recirculating eddy control velocities throughout the pool.

Stent migration following endoscopic suture fixation of esophageal self-expandable metal stents: a systematic review and meta-analysis.

PubMed

Law, Ryan; Prabhu, Anoop; Fujii-Lau, Larissa; Shannon, Carol; Singh, Siddharth

2018-02-01

Covered self-expandable metal stents (SEMS) are utilized for the management of benign and malignant esophageal conditions; however, covered SEMS are prone to migration. Endoscopic suture fixation may mitigate the migration risk of covered esophageal SEMS. Hence, we conducted a systematic review and meta-analysis to evaluate the effectiveness and safety of endoscopic suture fixation for covered esophageal SEMS. Following PRISMA guidelines, we performed a systematic review from 2011 to 2016 to identify studies (case control/case series) reporting the technical success and migration rate of covered esophageal SEMS following endoscopic suture fixation. We searched multiple electronic databases and conference proceedings. We calculated pooled rates (and 95% confidence intervals [CI]) of technical success and stent migration using a random effects model. We identified 14 studies (212 patients) describing covered esophageal SEMS placement with endoscopic suture fixation. When reported, SEMS indications included leak/fistula (n = 75), stricture (n = 65), perforation (n = 10), and achalasia (n = 4). The pooled technical success rate was 96.7% (95% CI 92.3-98.6), without heterogeneity (I 2  = 0%). We identified 29 SEMS migrations at rate of 15.9% (95% CI 11.4-21.6), without heterogeneity (I 2  = 0%). Publication bias was observed, and using the trim-and-fill method, a more conservative estimate for stent migration was 17.0%. Suture-related adverse events were estimated to occur in 3.7% (95% CI 1.6-8.2) of cases. Endoscopic suture fixation of covered esophageal SEMS appears to reduce stent migration when compared to published rates of non-anchored SEMS. However, SEMS migration still occurs in approximately 1 out of 6 cases despite excellent immediate technical success and low risk of suture-related adverse events.

Is Tamsulosin 0.2 mg Effective and Safe as a First-Line Treatment Compared with Other Alpha Blockers?: A Meta-Analysis and a Moderator Focused Study

PubMed Central

Shim, Sung Ryul; Chang, In Ho; Shin, In Soo; Hwang, Sung Dong; Kim, Khae Hwan; Yoon, Sang Jin; Song, Yun Seob

2016-01-01

Purpose Tamsulosin 0.2 mg is used widely in Asian people, but the low dose has been studied less than tamsulosin 0.4 mg or other alpha blockers of standard dose. This study investigated the efficacy and safety of tamsulosin 0.2 mg by a meta-analysis and meta-regression. Materials and Methods We conducted a meta-analysis of efficacy of tamsulosin 0.2 mg using International Prostate Symptom Score (IPSS), maximal urinary flow rate (Qmax), post-voided residual volume (PVR), and quality of life (QoL). Safety was analyzed using adverse events. Relevant studies were searched using MEDLINE, EMBASE, and Cochrane library from January 1980 to June 2013. Results Ten studies were included with a total sample size of 1418 subjects [722 tamsulosin 0.2 mg group and 696 other alpha-blockers (terazosin, doxazosin, naftopidil, silodosin) group]. Study duration ranged from 4 to 24 weeks. The pooled overall standardized mean differences (SMD) in the mean change of IPSS from baseline for the tamsulosin group versus the control group was 0.02 [95% confidence interval (CI); -0.20, 0.25]. The pooled overall SMD in the mean change of QoL from baseline for the tamsulosin group versus the control group was 0.16 (95% CI; -0.16, 0.48). The regression analysis with the continuous variables (number of patients, study duration) revealed no significance in all outcomes as IPSS, QoL, and Qmax. Conclusion This study clarifies that tamsulosin 0.2 mg has similar efficacy and fewer adverse events compared with other alpha-blockers as an initial treatment strategy for men with lower urinary tract symptoms. PMID:26847294

Efficacy and safety of clindamycin phosphate 1.2%/tretinoin 0.025% formulation for the treatment of acne vulgaris: pooled analysis of data from three randomised, double-blind, parallel-group, phase III studies.

PubMed

Dréno, Brigitte; Bettoli, Vincenzo; Ochsendorf, Falk; Layton, Alison M; Perez, Montserrat; Dakovic, Rada; Gollnick, Harald

2014-01-01

The efficacy and safety of clindamycin phosphate 1.2%/tretinoin 0.025% (Clin-RA) were evaluated in three 12-week randomised studies. To perform a pooled analysis of data from these studies to evaluate Clin-RA's efficacy and safety in a larger overall population, in subgroups of adolescents and according to acne severity. 4550 patients were randomised to Clin-RA, clindamycin, tretinoin and vehicle. Evaluations included percentage change in lesions, treatment success rate, proportions of patients with ≥50% or ≥80% continuous reduction in lesions, adverse events and cutaneous tolerability. In the overall population, the percentage reduction in inflammatory, non-inflammatory and total lesions and the treatment success rate were significantly greater with Clin-RA compared with clindamycin, tretinoin and vehicle alone (all p<0.01). The percentage reduction in all types of lesions was also significantly greater with Clin-RA in the adolescent subgroup (2915 patients, p<0.002) and in patients with mild/moderate acne (3662 patients, p<0.02) versus comparators. In patients with severe acne (n = 880), the percentage reduction in all lesion types was significantly greater with Clin-RA versus vehicle (p<0.0001). A greater proportion of Clin-RA treated patients had a ≥50% or ≥80% continuous reduction in all types of lesions at week 12 compared with clindamycin, tretinoin and vehicle. Adverse event frequencies in the active and vehicle groups were similar. Baseline-adjusted mean tolerability scores over time were <1 (mild) and similar in all groups. Clin-RA is safe, has superior efficacy to its component monotherapies and should be considered as one of the first-line therapies for mild-to-moderate facial acne.

Treatment effect, adherence, and safety of high fluid intake for the prevention of incident and recurrent kidney stones: a systematic review and meta-analysis.

PubMed

Cheungpasitporn, Wisit; Rossetti, Sandro; Friend, Keith; Erickson, Stephen B; Lieske, John C

2016-04-01

The objective of this systematic review and meta-analysis were to evaluate the effectiveness of high fluid intake for the prevention of incident and recurrent kidney stones, as well as its adherence and safety. A literature search was performed encompassing 1980 through July 2014. Studies that reported relative risks, odds ratios, or hazard ratios comparing the risk of kidney stone events in patients with high vs inadequate fluid intake were included. Pooled risk ratios (RRs) and 95 % confidence intervals (CIs) were calculated using a random-effect, generic inverse variance method. Nine studies [2 randomized controlled trials (RCTs) with 269 patients; 7 observational studies with 273,685 individuals] were included in the meta-analysis. Pooled RRs of kidney stones in individuals with high-fluid intake were 0.40 (95 % CI 0.20-0.79) and 0.49 (0.34-0.71) in RCTs and observational studies, respectively. High fluid intake was significantly associated with reduced risk of recurrent kidney stones: RRs 0.40 (95 % CI 0.20-0.79) and 0.20 (0.09-0.44) in RCTs and observational studies, respectively. Adherence and safety data on high fluid intake treatment were limited; 1 RCT reported no withdrawals due to adverse events. This analysis demonstrated a significantly reduced risk of incident kidney stones among individuals with high fluid consumption. High fluid consumption also reduced the risk of recurrent kidney stones. Furthermore, the magnitude of risk reduction was high. Although increased water intake appears to be safe, future studies on its safety in patients with high risk of volume overload or hyponatremia may be indicated.

Effects of low-dose paroxetine 7.5 mg on weight and sexual function during treatment of vasomotor symptoms associated with menopause

PubMed Central

Portman, David J.; Kaunitz, Andrew M.; Kazempour, Kazem; Mekonnen, Hana; Bhaskar, Sailaja; Lippman, Joel

2014-01-01

Abstract Objective Two phase 3, randomized, placebo-controlled trials demonstrated that low-dose paroxetine 7.5 mg reduced the frequency and severity of vasomotor symptoms (VMS) associated with menopause and had a favorable tolerability profile. The impact of paroxetine 7.5 mg on body weight and sexual function was evaluated in a pooled analysis. Methods Postmenopausal women aged 40 years or older who had moderate to severe VMS were randomly assigned to receive paroxetine 7.5 mg or placebo once daily for 12 or 24 weeks. Assessments included changes in body mass index (BMI) and weight, Arizona Sexual Experiences Scale score, Hot Flash–Related Daily Interference Scale sexuality subscore, and adverse events related to weight or sexual dysfunction. Results Pooled efficacy and safety populations comprised 1,174 and 1,175 participants, respectively. Baseline values were similar for median weight (∼75 kg), median BMI (∼28 kg/m2), and the proportion of women with sexual dysfunction (∼58%). No clinically meaningful or statistically significant changes from baseline in weight or sexual function assessments occurred in the paroxetine 7.5 mg group. Small but statistically significant increases in weight and BMI were observed in the placebo group only on week 4. No significant difference between treatment groups was observed in the proportion of participants who had 7% or higher gain in body weight on week 4, 12, or 24. Rates of adverse events suggestive of sexual dysfunction were low and similar in both treatment groups. Conclusions Paroxetine 7.5 mg does not cause weight gain or negative changes in libido when used to treat menopause-associated VMS in postmenopausal women. PMID:24552977

Tofacitinib, an oral Janus kinase inhibitor, in patients from Mexico with rheumatoid arthritis: Pooled efficacy and safety analyses from Phase 3 and LTE studies.

PubMed

Burgos-Vargas, Ruben; Cardiel, Mario; Xibillé, Daniel; Pacheco-Tena, César; Pascual-Ramos, Virginia; Abud-Mendoza, Carlos; Mahgoub, Ehab; Rahman, Mahboob; Fan, Haiyun; Rojo, Ricardo; García, Erika; Santana, Karina

2017-05-25

Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We characterized efficacy and safety of tofacitinib in Mexican patients from RA Phase 3 and long-term extension (LTE) studies. Data from Mexican patients with RA and an inadequate response to disease-modifying antirheumatic drugs (DMARDs) were taken from four Phase 3 studies (pooled across studies) and one open-label LTE study of tofacitinib. Patients received tofacitinib 5 or 10mg twice daily, adalimumab (one Phase 3 study) or placebo (four Phase 3 studies) as monotherapy or in combination with conventional synthetic DMARDs. Efficacy up to Month 12 (Phase 3) and Month 36 (LTE) was assessed by American College of Rheumatology 20/50/70 response rates, Disease Activity Score (erythrocyte sedimentation rate), and Health Assessment Questionnaire-Disability Index. Safety, including incidence rates (IRs; patients with events/100 patient-years) for adverse events (AEs) of special interest, was assessed throughout the studies. 119 and 212 Mexican patients were included in the Phase 3 and LTE analyses, respectively. Tofacitinib-treated patients in Phase 3 had numerically greater improvements in efficacy responses versus placebo at Month 3. Efficacy was sustained in Phase 3 and LTE studies. IRs for AEs of special interest were similar to those with tofacitinib in the global and Latin American RA populations. In Mexican patients from the tofacitinib global RA program, tofacitinib efficacy was demonstrated up to Month 12 in Phase 3 studies and Month 36 in the LTE study, with a safety profile consistent with tofacitinib global population. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Secukinumab long-term safety experience: A pooled analysis of 10 phase II and III clinical studies in patients with moderate to severe plaque psoriasis.

PubMed

van de Kerkhof, Peter C M; Griffiths, Christopher E M; Reich, Kristian; Leonardi, Craig L; Blauvelt, Andrew; Tsai, Tsen-Fang; Gong, Yankun; Huang, Jiaqing; Papavassilis, Charis; Fox, Todd

2016-07-01

Secukinumab, a fully human anti-interleukin-17A monoclonal antibody, has demonstrated efficacy and safety in patients with moderate to severe plaque psoriasis. We reviewed safety data from the secukinumab psoriasis phase II/III program. Data were pooled from 10 phase II/III secukinumab psoriasis studies. Analysis included 3993 subjects; 3430 received secukinumab, representing 2725 subject-years (SYs) of exposure. Over 52 weeks, for secukinumab 300 mg, 150 mg, and etanercept, respectively, exposure-adjusted incidence rates (IRs) per 100 SYs were comparable across treatments for total adverse events (AEs; 236.1, 239.9, and 243.4, respectively); infections (91.1, 85.3, and 93.7, respectively); serious AEs (7.4, 6.8, and 7.0, respectively); serious infections (1.4, 1.1, and 1.4, respectively); malignant or unspecified tumors (0.77, 0.97, and 0.68, respectively); and adjudicated major adverse cardiovascular events (0.42, 0.35, and 0.34, respectively). AEs were not dose-related except for nonserious, mild/moderate, skin/mucosal candidiasis (IRs 3.55, 1.85, and 1.37 for secukinumab 300 mg, 150 mg, and etanercept, respectively). There was a limited number of patients in comparator groups and the exposure to placebo was short. Secukinumab had a favorable safety profile, had no meaningful difference between the 300- and 150-mg doses and, in terms of safety, was comparable to etanercept over 52 weeks in patients with moderate to severe plaque psoriasis. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

First-Line Matched Related Donor Hematopoietic Stem Cell Transplantation Compared to Immunosuppressive Therapy in Acquired Severe Aplastic Anemia

PubMed Central

Peinemann, Frank; Grouven, Ulrich; Kröger, Nicolaus; Bartel, Carmen; Pittler, Max H.; Lange, Stefan

2011-01-01

Introduction Acquired severe aplastic anemia (SAA) is a rare and progressive disease characterized by an immune-mediated functional impairment of hematopoietic stem cells. Transplantation of these cells is a first-line treatment option if HLA-matched related donors are available. First-line immunosuppressive therapy may be offered as alternative. The aim was to compare the outcome of these patients in controlled trials. Methods A systematic search was performed in the bibliographic databases MEDLINE, EMBASE, and The Cochrane Library. To show an overview of various outcomes by treatment group we conducted a meta-analysis on overall survival. We evaluated whether studies reported statistically significant factors for improved survival. Results 26 non-randomized controlled trials (7,955 patients enrolled from 1970 to 2001) were identified. We did not identify any RCTs. Risk of bias was high except in 4 studies. Young age and recent year of treatment were identified as factors for improved survival in the HSCT group. Advanced age, SAA without very severe aplastic anemia, and combination of anti-lymphocyte globulin with cyclosporine A were factors for improved survival in the IST group. In 19 studies (4,855 patients), summary statistics were sufficient to be included in meta-analysis. Considerable heterogeneity did not justify a pooled estimate. Adverse events were inconsistently reported and varied significantly across studies. Conclusions Young age and recent year of treatment were identified as factors for improved survival in the transplant group. Advanced age, SAA without very severe aplastic anemia, and combination of anti-lymphocyte globulin with cyclosporine A were factors for improved survival in the immunosuppressive group. Considerable heterogeneity of non-randomized controlled studies did not justify a pooled estimate. Adverse events were inconsistently reported and varied significantly across studies. PMID:21541024

Efficacy and Safety of ATX-101 by Treatment Session: Pooled Analysis of Data from the Phase 3 REFINE Trials.

PubMed

Dayan, Steven H; Schlessinger, Joel; Beer, Kenneth; Donofrio, Lisa M; Jones, Derek H; Humphrey, Shannon; Carruthers, Jean; Lizzul, Paul F; Gross, Todd M; Beddingfield, Frederick C; Somogyi, Christine

2018-02-01

ATX-101 (deoxycholic acid injection) is the only injectable drug approved for submental fat (SMF) reduction. In the phase 3 REFINE trials, adults with moderate or severe SMF who were dissatisfied with the appearance of their face/chin were eligible to receive up to 6 treatment sessions with ATX-101 (2 mg/cm2) or placebo. Primary and secondary endpoints, evaluated at 12 weeks after last treatment, significantly favored ATX-101 supporting its efficacy for reducing SMF and the psychological impact of SMF, and increasing satisfaction with the appearance of the face/chin. To evaluate the efficacy and safety of ATX-101 by treatment session. This post-hoc analysis used pooled data from the REFINE trials to evaluate efficacy endpoints and adverse events following each treatment session to further characterize the ATX-101 treatment response and safety profile. In both treatment groups, mean injection volume declined over subsequent treatment sessions, though more markedly in the ATX-101 group. The majority of ATX-101-treated subjects achieved a ≥1-grade improvement in SMF within 2 to 4 treatment sessions based on either clinician or subject assessment. Furthermore, 19.1% of ATX-101-treated subjects (vs 3.9% of placebo-treated subjects) received fewer than 6 treatment sessions owing to subject satisfaction with treatment or lack of sufficient SMF for further treatment. In both treatment groups, the incidence/severity of common injection-site adverse events declined over subsequent treatment sessions. Although up to 6 treatment sessions were permitted in the REFINE trials, most ATX-101-treated subjects achieved an improvement in SMF within 2 to 4 treatment sessions. © 2018 The American Society for Aesthetic Plastic Surgery, Inc.

Reconstructing the geomorphic history of Liang Bua, Flores, Indonesia: a stratigraphic interpretation of the occupational environment.

PubMed

Westaway, K E; Sutikna, T; Saptomo, W E; Jatmiko; Morwood, M J; Roberts, R G; Hobbs, D R

2009-11-01

Liang Bua, in Flores, Indonesia, was formed as a subterranean chamber over 600ka. From this time to the present, a series of geomorphic events influenced the structure of the cave and cave deposits, creating a complex stratigraphy. Within these deposits, nine main sedimentary units have been identified. The stratigraphic relationships between these units provide the evidence needed to reconstruct the geomorphic history of the cave. This history was dominated by water action, including slope wash processes, channel formation, pooling of water, and flowstone precipitation, which created waterfalls, cut-and-fill stratigraphy, large pools of water, and extensive flowstone cappings. The reconstructed sequence of events over the last 190k.yr. has been summarized by a series of time slices that demonstrate the nature of the occupational environment in Liang Bua. The earliest artifacts at the site, dated to approximately 190ka, testify to hominin presence in the area, but the reconstructions suggest that occupation of the cave itself may not have been possible until after approximately 100ka. At approximately 95ka, channel erosion of a basal unit, which displays evidence of deposition in a pond environment, created a greater relief on the cave floor, and formed remanent areas of higher ground that later became a focus for hominin occupation from 74-61ka by the west wall and in the center of the cave, and from approximately 18-17ka by the east wall. These zones have been identified according to the sloping nature of the stratigraphy and the distribution of artifacts, and their locations have implications for the archaeological interpretation of the site.

Composite Sampling Approaches for Bacillus anthracis Surrogate Extracted from Soil

PubMed Central

France, Brian; Bell, William; Chang, Emily; Scholten, Trudy

2015-01-01

Any release of anthrax spores in the U.S. would require action to decontaminate the site and restore its use and operations as rapidly as possible. The remediation activity would require environmental sampling, both initially to determine the extent of contamination (hazard mapping) and post-decon to determine that the site is free of contamination (clearance sampling). Whether the spore contamination is within a building or outdoors, collecting and analyzing what could be thousands of samples can become the factor that limits the pace of restoring operations. To address this sampling and analysis bottleneck and decrease the time needed to recover from an anthrax contamination event, this study investigates the use of composite sampling. Pooling or compositing of samples is an established technique to reduce the number of analyses required, and its use for anthrax spore sampling has recently been investigated. However, use of composite sampling in an anthrax spore remediation event will require well-documented and accepted methods. In particular, previous composite sampling studies have focused on sampling from hard surfaces; data on soil sampling are required to extend the procedure to outdoor use. Further, we must consider whether combining liquid samples, thus increasing the volume, lowers the sensitivity of detection and produces false negatives. In this study, methods to composite bacterial spore samples from soil are demonstrated. B. subtilis spore suspensions were used as a surrogate for anthrax spores. Two soils (Arizona Test Dust and sterilized potting soil) were contaminated and spore recovery with composites was shown to match individual sample performance. Results show that dilution can be overcome by concentrating bacterial spores using standard filtration methods. This study shows that composite sampling can be a viable method of pooling samples to reduce the number of analysis that must be performed during anthrax spore remediation. PMID:26714315

Patient characteristics associated with venous thromboembolic events: a cohort study using pooled electronic health record data

PubMed Central

Foster, Wendy; Gilder, Jason; Love, Thomas E; Jain, Anil K

2012-01-01

Objective To demonstrate the potential of de-identified clinical data from multiple healthcare systems using different electronic health records (EHR) to be efficiently used for very large retrospective cohort studies. Materials and methods Data of 959 030 patients, pooled from multiple different healthcare systems with distinct EHR, were obtained. Data were standardized and normalized using common ontologies, searchable through a HIPAA-compliant, patient de-identified web application (Explore; Explorys Inc). Patients were 26 years or older seen in multiple healthcare systems from 1999 to 2011 with data from EHR. Results Comparing obese, tall subjects with normal body mass index, short subjects, the venous thromboembolic events (VTE) OR was 1.83 (95% CI 1.76 to 1.91) for women and 1.21 (1.10 to 1.32) for men. Weight had more effect then height on VTE. Compared with Caucasian, Hispanic/Latino subjects had a much lower risk of VTE (female OR 0.47, 0.41 to 0.55; male OR 0.24, 0.20 to 0.28) and African-Americans a substantially higher risk (female OR 1.83, 1.76 to 1.91; male OR 1.58, 1.50 to 1.66). This 13-year retrospective study of almost one million patients was performed over approximately 125 h in 11 weeks, part time by the five authors. Discussion As research informatics tools develop and more clinical data become available in EHR, it is important to study and understand unique opportunities for clinical research informatics to transform the scale and resources needed to perform certain types of clinical research. Conclusions With the right clinical research informatics tools and EHR data, some types of very large cohort studies can be completed with minimal resources. PMID:22759621

Prevalence of Functional Defecation Disorders in Children: A Systematic Review and Meta-Analysis.

PubMed

Koppen, Ilan J N; Vriesman, Mana H; Saps, Miguel; Rajindrajith, Shaman; Shi, Xiaoxia; van Etten-Jamaludin, Faridi S; Di Lorenzo, Carlo; Benninga, Marc A; Tabbers, Merit M

2018-04-12

To systematically review the literature regarding the epidemiology of functional constipation and functional nonretentive fecal incontinence (FNRFI) in children. Secondary objectives were to assess the geographical, age, and sex distribution of functional constipation and FNRFI and to evaluate associated factors. The Cochrane Library, PubMed, and Embase databases were searched from 2006 until September 2017. The following inclusion criteria were applied: (1) prospective studies of population-based samples; (2) reporting on the prevalence of functional constipation or FNRFI according to the Rome III/IV criteria; (3) in children aged 0-18 years; and (4) published in full manuscript form. A quality assessment of included studies was conducted. Random effect meta-analyses with meta-regression analyses of study characteristics were performed. Thirty-seven studies were included, of which 35 reported on the prevalence of functional constipation and 15 of FNRFI. The reported prevalence of functional constipation ranged from 0.5% to 32.2%, with a pooled prevalence of 9.5% (95% CI 7.5-12.1). The prevalence of FRNFI ranged from 0.0% to 1.8%, with a pooled prevalence of 0.4% (95% CI 0.2-0.7). The prevalence of functional constipation was 8.6% in boys compared with 8.9% in girls (OR 0.99, 95% CI 0.9-1.4). Geographical location, dietary habits, and exposure to stressful life events were reported to be associated with the prevalence of functional constipation. Data on FNRFI were scarce and no associated factors were identified. Functional constipation is common in childhood and is associated with geographical location, lifestyle factors, and stressful life events. FNRFI is rare, and no associated factors were identified. Copyright © 2018 Elsevier Inc. All rights reserved.

Alternative Splice in Alternative Lice

PubMed Central

Tovar-Corona, Jaime M.; Castillo-Morales, Atahualpa; Chen, Lu; Olds, Brett P.; Clark, John M.; Reynolds, Stuart E.; Pittendrigh, Barry R.; Feil, Edward J.; Urrutia, Araxi O.

2015-01-01

Genomic and transcriptomics analyses have revealed human head and body lice to be almost genetically identical; although con-specific, they nevertheless occupy distinct ecological niches and have differing feeding patterns. Most importantly, while head lice are not known to be vector competent, body lice can transmit three serious bacterial diseases; epidemictyphus, trench fever, and relapsing fever. In order to gain insights into the molecular bases for these differences, we analyzed alternative splicing (AS) using next-generation sequencing data for one strain of head lice and one strain of body lice. We identified a total of 3,598 AS events which were head or body lice specific. Exon skipping AS events were overrepresented among both head and body lice, whereas intron retention events were underrepresented in both. However, both the enrichment of exon skipping and the underrepresentation of intron retention are significantly stronger in body lice compared with head lice. Genes containing body louse-specific AS events were found to be significantly enriched for functions associated with development of the nervous system, salivary gland, trachea, and ovarian follicle cells, as well as regulation of transcription. In contrast, no functional categories were overrepresented among genes with head louse-specific AS events. Together, our results constitute the first evidence for transcript pool differences in head and body lice, providing insights into molecular adaptations that enabled human lice to adapt to clothing, and representing a powerful illustration of the pivotal role AS can play in functional adaptation. PMID:26169943

Apparatus for draining lower drywell pool water into suppresion pool in boiling water reactor

DOEpatents

Gluntz, Douglas M.

1996-01-01

An apparatus which mitigates temperature stratification in the suppression pool water caused by hot water drained into the suppression pool from the lower drywell pool. The outlet of a spillover hole formed in the inner bounding wall of the suppression pool is connected to and in flow communication with one end of piping. The inlet end of the piping is above the water level in the suppression pool. The piping is routed down the vertical downcomer duct and through a hole formed in the thin wall separating the downcomer duct from the suppression pool water. The piping discharge end preferably has an elevation at or near the bottom of the suppression pool and has a location in the horizontal plane which is removed from the point where the piping first emerges on the suppression pool side of the inner bounding wall of the suppression pool. This enables water at the surface of the lower drywell pool to flow into and be discharged at the bottom of the suppression pool.

Self-formed waterfall plunge pools in homogeneous rock

NASA Astrophysics Data System (ADS)

Scheingross, Joel S.; Lo, Daniel Y.; Lamb, Michael P.

2017-01-01

Waterfalls are ubiquitous, and their upstream propagation can set the pace of landscape evolution, yet no experimental studies have examined waterfall plunge pool erosion in homogeneous rock. We performed laboratory experiments, using synthetic foam as a bedrock simulant, to produce self-formed waterfall plunge pools via particle impact abrasion. Plunge pool vertical incision exceeded lateral erosion by approximately tenfold until pools deepened to the point that the supplied sediment could not be evacuated and deposition armored the pool bedrock floor. Lateral erosion of plunge pool sidewalls continued after sediment deposition, but primarily at the downstream pool wall, which might lead to undermining of the plunge pool lip, sediment evacuation, and continued vertical pool floor incision in natural streams. Undercutting of the upstream pool wall was absent, and our results suggest that vertical drilling of successive plunge pools is a more efficient waterfall retreat mechanism than the classic model of headwall undercutting and collapse in homogeneous rock.

Sugammadex for reversal of rocuronium-induced neuromuscular blockade in pediatric patients: A systematic review and meta-analysis.

PubMed

Won, Young Ju; Lim, Byung Gun; Lee, Dong Kyu; Kim, Heezoo; Kong, Myoung Hoon; Lee, Il Ok

2016-08-01

Previous studies have shown that sugammadex, a modified γ-cyclodextrin, is a well-tolerated agent for the reversal of neuromuscular blockade (NMB) induced by a steroidal neuromuscular blocking drug in adult patients. However, its use has not been reviewed in pediatric patients. The aim of this meta-analysis was to evaluate the efficacy and safety of sugammadex in the reversal of rocuronium-induced NMB during surgery under general anesthesia in pediatric patients. A literature search was performed using the Pubmed, EMBASE: Drugs and pharmacology, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews. Analysis was conducted using RevMan 5.3. Data collected from different trials were pooled; the weighted mean difference or the pooled risk ratio and the corresponding 95% confidence interval (CI) were used for analysis, and heterogeneity (I) assessment was performed. Six randomized controlled trials comparing 253 pediatric patients (age range, 2-18 years) were included in the final analysis. The mean time taken to reach a train-of-four ratio of ≥0.9 was significantly shorter in the sugammadex groups (2 and 4 mg/kg) than in the control group (neostigmine or placebo), although the heterogeneity was high. The weighted mean differences of the 2 and 4 mg/kg sugammadex groups were -7.15 (95% CI: -10.77 to -3.54; I = 96%; P = 0.0001) and -17.32 (95% CI: -29.31 to -5.32; I = 98%; P = 0.005), respectively. The extubation time in the sugammadex group was shorter than that in the control group; the weighted mean difference of the sugammadex group was -6.00 (95% CI: -11.46 to -0.53; I = 99%; P = 0.03). There was no significant difference between the groups in terms of the incidence of postanesthetic adverse events; the pooled risk ratio was 0.67 (95% CI: 0.27-1.71; I = 59%; P = 0.41). We suggest that sugammadex is fast and effective in reversing rocuronium-induced NMB in pediatric patients. Although there was no evidence of a higher incidence of adverse events with sugammadex compared to that with neostigmine or placebo, much more data regarding the safety of sugammadex in pediatric patients may be still required.

A multicentre randomized controlled trial of the efficacy and safety of single-dose praziquantel at 40 mg/kg vs. 60 mg/kg for treating intestinal schistosomiasis in the Philippines, Mauritania, Tanzania and Brazil.

PubMed

Olliaro, Piero L; Vaillant, Michel T; Belizario, Vincente J; Lwambo, Nicholas J S; Ouldabdallahi, Mohamed; Pieri, Otavio S; Amarillo, Maria L; Kaatano, Godfrey M; Diaw, Mamadou; Domingues, Analucia C; Favre, Tereza C; Lapujade, Olivier; Alves, Fabiana; Chitsulo, Lester

2011-06-01

Praziquantel at 40 mg/kg in a single dose is the WHO recommended treatment for all forms of schistosomiasis, but 60 mg/kg is also deployed nationally. Four trial sites in the Philippines, Mauritania, Tanzania and Brazil enrolled 856 patients using a common protocol, who were randomised to receive praziquantel 40 mg/kg (n  =  428) or 60 mg/kg (n  =  428). While the sites differed for transmission and infection intensities (highest in Tanzania and lowest in Mauritania), no bias or heterogeneity across sites was detected for the main efficacy outcomes. The primary efficacy analysis was the comparison of cure rates on Day 21 in the intent-to-treat population for the pooled data using a logistic model to calculate Odd Ratios allowing for baseline characteristics and study site. Both doses were highly effective: the Day 21 cure rates were 91.7% (86.6%-98% at individual sites) with 40 mg/kg and 92.8% (88%-97%) with 60 mg/kg. Secondary parameters were eggs reduction rates (ERR), change in intensity of infection and reinfection rates at 6 and 12 months. On Day 21 the pooled estimate of the ERR was 91% in both arms. The Hazard Ratio for reinfections was only significant in Brazil, and in favour of 60 mg/kg on the pooled estimate (40 mg/kg: 34.3%, 60 mg/kg: 23.9%, HR  =  0.78, 95% CI  = [0.63;0.96]). Analysis of safety could not distinguish between disease- and drug-related events. 666 patients (78%) reported 1327 adverse events (AE) 4 h post-dosing. The risk of having at least one AE was higher in the 60 than in the 40 mg/kg group (83% vs. 73%, p<0.001). At 24 h post-dosing, 456 patients (54%) had 918 AEs with no difference between arms. The most frequent AE was abdominal pain at both 4 h and 24 h (40% and 24%). A higher dose of 60 mg/kg of praziquantel offers no significant efficacy advantage over standard 40 mg/kg for treating intestinal schistosomiasis caused by either S. mansoni or S. japonicum. The results of this study support WHO recommendation and should be used to inform policy decisions in the countries.

A Systematic Review and Meta-analysis of Thrombotic Events Following Endovenous Thermal Ablation of the Great Saphenous Vein.

PubMed

Healy, Donagh A; Kimura, Shiori; Power, David; Elhaj, Abubaker; Abdeldaim, Yasser; Cross, Keith S; McGreal, Gerard T; Burke, Paul E; Moloney, Tony; Manning, Brian J; Kavanagh, Eamon G

2018-06-09

A systematic review and meta-analysis was performed to determine the incidence of thrombotic events following great saphenous vein (GSV) endovenous thermal ablation (EVTA). MEDLINE, Embase and conference abstracts were searched. Eligible studies were randomised controlled trials and case series that included at least 100 patients who underwent GSV EVTA (laser ablation or radiofrequency ablation [RFA]) with duplex ultrasound (DUS) within 30 days. The systematic review focused on the complications of endovenous heat induced thrombosis (EHIT), deep venous thrombosis (DVT), and pulmonary embolism (PE). The primary outcome for the meta-analysis was deep venous thrombotic events which were defined as DVT or EHIT Type 2, 3, or 4. Secondary outcomes for the meta-analysis were EHIT Type 2, 3, or 4, DVT and PE. Subgroup analyses were performed for both the RFA and EVLA groups. Pooled proportions were calculated using random effects modelling. Fifty-two studies (16,398 patients) were included. Thrombotic complications occurred infrequently. Deep venous thrombotic events occurred in 1.7% of cases (95% CI 0.9-2.7%) (25 studies; 10,012 patients; 274 events). EHIT Type 2, 3, or 4 occurred in 1.4% of cases (95% CI 0.8-2.3%) (26 studies; 10,225 patients; 249 events). DVT occurred in 0.3% of cases (95% CI = 0.2%-0.5%) (49 studies; 15,676 patients; 48 events). PE occurred in 0.1% of cases (95% CI = 0.1-0.2%) (29 studies; 8223 patients; 3 events). Similar results were found when the RFA and EVLA groups were analysed separately. Thrombotic events occur infrequently following GSV EVTA. Given the large numbers of procedures worldwide and the potential for serious consequences, further research is needed on the burden of these complications and their management. Copyright © 2018 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.

Early-life nutritional effects on the female reproductive system.

PubMed

Chan, K A; Tsoulis, M W; Sloboda, D M

2015-02-01

There is now considerable epidemiological and experimental evidence indicating that early-life environmental conditions, including nutrition, affect subsequent development in later life. These conditions induce highly integrated responses in endocrine-related homeostasis, resulting in persistent changes in the developmental trajectory producing an altered adult phenotype. Early-life events trigger processes that prepare the individual for particular circumstances that are anticipated in the postnatal environment. However, where the intrauterine and postnatal environments differ markedly, such modifications to the developmental trajectory may prove maladaptive in later life. Reproductive maturation and function are similarly influenced by early-life events. This should not be surprising, because the primordial follicle pool is established early in life and is thus vulnerable to early-life events. Results of clinical and experimental studies have indicated that early-life adversity is associated with a decline in ovarian follicular reserve, changes in ovulation rates, and altered age at onset of puberty. However, the underlying mechanisms regulating the relationship between the early-life developmental environment and postnatal reproductive development and function are unclear. This review examines the evidence linking early-life nutrition and effects on the female reproductive system, bringing together clinical observations in humans and experimental data from targeted animal models. © 2015 Society for Endocrinology.

Short-term effect and adverse events of adalimumab versus placebo in inducing remission for moderate-to-severe ulcerative colitis: a meta-analysis.

PubMed

Yang, Zheng; Ye, Xiao-Qing; Zhu, Yu-Zhen; Liu, Zhou; Zou, Ying; Deng, Ying; Guo, Can-Can; Garg, Sushil Kumar; Feng, Jin-Shan

2015-01-01

Adalimumab is used in an attempt to maintain remission for Ulcerative colitis. This study was to evaluate the efficacy and adverse events of adalimumab compared with placebo in inducing remission of Ulcerative colitis. MEDLINE, EMBASE, the Cochrane Controlled Trials Register, OVID, BIOSIS, CNKI, and Google were searched. All randomized trials comparing adalimumab with placebo in inducing remission of moderate-to-severe ulcerative colitis were included. Two randomized controlled trials with a total of 754 participants met the inclusion criteria. The pooled risk ratio (RR) of clinical remission was 1.85 (95% confidence interval (CI) 1.26 to 2.72) following adalimumab treatment. RR of clinical response was 1.40 (95% CI 1.19 to 1.65) while that of mucosal healing was 1.23 (95% CI 1.03 to 1.47). RR of any adverse events was 1.00 (95% CI 0.93 to 1.09). Compared with placebo, administration of adalimumab may increase the proportion of patients with moderate-to-severe ulcerative colitis attaining clinical remission, clinical response and mucosal healing. Adalimumab is also tolerated well in these patients.

Air quality at outdoor community events: findings from fine particulate (PM2.5) sampling at festivals in Edmonton, Alberta.

PubMed

Collins, Damian; Parsons, Marc; Zinyemba, Chaka

2014-01-01

Exposure to fine particulate matter (PM2.5) is associated with a broad range of health risks. This study assessed the impacts of cooking smoke and environmental tobacco smoke on air quality at outdoor community events in Edmonton, Alberta (Canada). Data were collected at three festivals in July-August 2011 using a portable real-time airborne particle monitor. The pooled mean PM2.5 level was 12.41 μg/m(3). Peak readings varied from 52 to 1877 μg/m(3). Mean PM2.5 near food stalls was 35.42 μg/m(3), which exceeds the WHO limit for 24 h exposure. Mean PM2.5 levels with smokers present were 16.39 μg/m(3) (all points) and 9.64 μg/m(3) (excluding points near food stalls). Although some smokers withdrew from common spaces, on average 20 smokers/hour were observed within 3 m. Extending smoking bans would improve air quality and address related concerns. However, food preparation is a more pressing area for policy action to reduce PM2.5 exposure at these community events.

Nocturnal air, road, and rail traffic noise and daytime cognitive performance and annoyance.

PubMed

Elmenhorst, Eva-Maria; Quehl, Julia; Müller, Uwe; Basner, Mathias

2014-01-01

Various studies indicate that at the same noise level and during the daytime, annoyance increases in the order of rail, road, and aircraft noise. The present study investigates if the same ranking can be found for annoyance to nocturnal exposure and next day cognitive performance. Annoyance ratings and performance change during combined noise exposure were also tested. In the laboratory 72 participants were exposed to air, road, or rail traffic noise and all combinations. The number of noise events and LAS,eq were kept constant. Each morning noise annoyance questionnaires and performance tasks were administered. Aircraft noise annoyance ranked first followed by railway and road noise. A possible explanation is the longer duration of aircraft noise events used in this study compared to road and railway noise events. In contrast to road and rail traffic, aircraft noise annoyance was higher after nights with combined exposure. Pooled noise exposure data showed small but significant impairments in reaction times (6 ms) compared to nights without noise. The noise sources did not have a differential impact on performance. Combined exposure to multiple traffic noise sources did not induce stronger impairments than a single noise source. This was reflected also in low workload ratings.

Pooled analysis of large and long-term safety data from the human papillomavirus-16/18-AS04-adjuvanted vaccine clinical trial programme

PubMed Central

Angelo, Maria-Genalin; David, Marie-Pierre; Zima, Julia; Baril, Laurence; Dubin, Gary; Arellano, Felix; Struyf, Frank

2014-01-01

Purpose The purpose of this study is to further evaluate the safety of the human papillomavirus (HPV)-16/18-AS04-adjuvanted vaccine (HPV-16/18-vaccine Cervarix®, GlaxoSmithKline, Belgium) through a pooled analysis of data from 42 completed/ongoing clinical studies. Methods Unsolicited adverse events (AEs) were reported for 30 days after each dose. Medically significant conditions, serious AEs (SAEs), potential immune-mediated diseases (pIMDs) and pregnancy outcomes were captured until study completion. Events leading to subject withdrawal were reviewed. Relative risks compared incidences of spontaneous abortion and pIMDs in controlled studies. Results Thirty one thousand one hundred seventy-three adolescent girls/women received HPV-16/18-vaccine alone (HPV group), 2166 received HPV-16/18-vaccine coadministered with another vaccine and 24 241 were controls. Mean follow-up was 39 months (range 0–113.3). Incidences of unsolicited AEs reported within 30 days after any dose were similar between HPV and Control groups (30.8%/29.7%). During the entire study period, reports of medically significant conditions (25.0%/28.3%) and SAEs (7.9%/9.3%) were also similarly distributed between groups. Deaths were rare: HPV (alone/coadministered) n = 25, controls n = 20 (n = 18 in blinded groups). pIMDs within 1 year were reported by 0.2% of HPV-16/18 vaccinees and controls. For each pIMD event category, no increased relative risks were reported for HPV-16/18 vaccinees versus controls. Coadministration did not change the overall safety profile. Pregnancy outcomes and withdrawal rates were similar between groups. Conclusions Analysis of safety data arising from 57 580 subjects and 96 704 HPV-16/18-vaccine doses shows that the incidences and distribution of AEs were similar among HPV-16/18-vaccine recipients and controls. No new safety signals were identified. The data confirm previous findings that HPV-16/18-vaccine has an acceptable benefit-risk profile in adolescent girls and adult women. PMID:24644063

Smouldering Subsurface Fires in the Earth System

NASA Astrophysics Data System (ADS)

Rein, Guillermo

2010-05-01

Smouldering fires, the slow, low-temperature, flameless form of combustion, are an important phenomena in the Earth system. These fires propagate slowly through organic layers of the forest ground and are responsible for 50% or more of the total biomass consumed during wildfires. Only after the 2002 study of the 1997 extreme haze event in South-East Asia, the scientific community recognised the environmental and economic threats posed by subsurface fires. This was caused by the spread of vast biomass fires in Indonesia, burning below the surface for months during the El Niño climate event. It has been calculated that these fires released between 0.81 and 2.57 Gton of carbon gases (13-40% of global emissions). Large smouldering fires are rare events at the local scale but occur regularly at a global scale. Once ignited, they are particularly difficult to extinguish despite extensive rains or fire-fighting attempts and can persist for long periods of time (months, years) spreading over very extensive areas of forest and deep into the soil. Indeed, these are the oldest continuously burning fires on Earth. Earth scientists are interested in smouldering fires because they destroy large amounts of biomass and cause greater damage to the soil ecosystem than flaming fires do. Moreover, these fires cannot be detected with current satellite remote sensing technologies causing inconsistencies between emission inventories and model predictions. Organic soils sustain smouldering fire (hummus, duff, peat and coal) which total carbon pool exceeds that of the world's forests or the atmosphere. This have important implications for climate change. Warmer temperatures at high latitudes are resulting in unprecedented permafrost thaw that is leaving large soil carbon pools exposed to fires. Because the CO2 flux from peat fires has been measured to be about 3000 times larger that the natural degradation flux, permafrost thaw is a risk for greater carbon release by fire and subsequently influence carbon-climate feedbacks. This presentation will revise the current knowledge on smouldering fires in the Earth system regarding ignition, spread patterns and emissions. It will explain the key differences between shallow and deep fires, and flaming fires.

Characterizing convective cold pools: Characterizing Convective Cold Pools

DOE PAGES

Drager, Aryeh J.; van den Heever, Susan C.

2017-05-09

Cold pools produced by convective storms play an important role in Earth's climate system. However, a common framework does not exist for objectively identifying convective cold pools in observations and models. The present study investigates convective cold pools within a simulation of tropical continental convection that uses a cloud-resolving model with a coupled land-surface model. Multiple variables are assessed for their potential in identifying convective cold pool boundaries, and a novel technique is developed and tested for identifying and tracking cold pools in numerical model simulations. This algorithm is based on surface rainfall rates and radial gradients in the densitymore » potential temperature field. The algorithm successfully identifies near-surface cold pool boundaries and is able to distinguish between connected cold pools. Once cold pools have been identified and tracked, composites of cold pool evolution are then constructed, and average cold pool properties are investigated. Wet patches are found to develop within the centers of cold pools where the ground has been soaked with rainwater. These wet patches help to maintain cool surface temperatures and reduce cold pool dissipation, which has implications for the development of subsequent convection.« less

Characterizing convective cold pools: Characterizing Convective Cold Pools

DOE Office of Scientific and Technical Information (OSTI.GOV)

Drager, Aryeh J.; van den Heever, Susan C.

Cold pools produced by convective storms play an important role in Earth's climate system. However, a common framework does not exist for objectively identifying convective cold pools in observations and models. The present study investigates convective cold pools within a simulation of tropical continental convection that uses a cloud-resolving model with a coupled land-surface model. Multiple variables are assessed for their potential in identifying convective cold pool boundaries, and a novel technique is developed and tested for identifying and tracking cold pools in numerical model simulations. This algorithm is based on surface rainfall rates and radial gradients in the densitymore » potential temperature field. The algorithm successfully identifies near-surface cold pool boundaries and is able to distinguish between connected cold pools. Once cold pools have been identified and tracked, composites of cold pool evolution are then constructed, and average cold pool properties are investigated. Wet patches are found to develop within the centers of cold pools where the ground has been soaked with rainwater. These wet patches help to maintain cool surface temperatures and reduce cold pool dissipation, which has implications for the development of subsequent convection.« less

Supercritical strata in Lower Paleozoic fluvial rocks: a super critical link to upper flow regime processes and preservation in nature

NASA Astrophysics Data System (ADS)

Lowe, David; Arnott, Bill

2015-04-01

Recent experimental work has much improved our understanding of the lithological attributes of open-channel supercritical flow deposits, namely those formed by antidunes, chutes-and-pools and cyclic steps. However their limited documentation in the ancient sedimentary record brings into question details about their geological preservation. Antidune, chute-and-pool and cyclic step deposits are well developed in sandy ephemeral fluvial deposits of the Upper Cambrian - Lower Ordovician Potsdam Group in the Ottawa Embayment of eastern North America. These high energy fluvial strata form dm- to a few m-thick units intercalated within thick, areally expansive successions of sheet sandstones consisting mostly of wind ripple and adhesion stratification with common deflation lags. Collectively these strata record deposition in a semi-arid environment in which rare, episodic high-energy fluvial events accounted for most of the influx of sediment from upland sources. Following deposition, however, extensive aeolian processes reworked the sediment pile, and hence modified profoundly the preserved stratigraphic record. Antidune deposits occur as 0.2 - 1.6 m thick cosets made up of 2 - 15 cm thick lenticular sets of low angle (≤ 20o) cross-stratified, medium- to coarse-grained sandstone bounded by low-angle (5 - 15o) concave-upward scours and, in many cases, capped by low angle (10 - 15o) convex-upwards symmetrical formsets. Chute-and-pool deposits form single sets, 5 - 55 cm thick and 0.6 - 6 m wide, with scoured bases and low to high angle (5 - 25o) sigmoidal cross-strata consisting of medium- to coarse-grained sandstone. Cyclic step deposits consist of trough cross-stratified sets, 20 cm - 1.6 m thick, 2.5 - 12 m long and 7 - 35 m wide, typically forming trains that laterally are erosively juxtaposed at regularly-spaced intervals. They are composed of medium- to coarse-grained sandstone with concave-up, moderate to high angle (15 - 35o) cross-strata with tangential bases that conform to the shape of the basal bounding surface of the set. Antidune and cyclic step deposits are common and fill 0.4 - 1.8 m deep channels, which then are generally overlain by extensive (>1 km) aeolian deflation surfaces. Chute-and-pool strata, however, are rare and only occur as isolated scour-filling sets within unconfined floodplain deposits. Nowhere in outcrop do different kinds of supercritical bedform deposits interfinger or appear related to the same flow event, suggesting that individual packages of supercritical strata were deposited by discreet, rapidly waning flows with little time for incremental growth or deposition under changing flow conditions. The stratal characteristics and geometries of channel-filling antidune and cyclic step cosets in the Potsdam are similar to those produced in steady experimental flows with high rates of aggradation. Similar conditions in the Potsdam were probably attained because the flows were channelized, which also caused the freshly deposited sediment to lie beneath the water table, and hence beneath the effects of extensive post-flood aeolian deflation. Conversely, scour-filling chute-and-pool deposits formed on the floodplain where highly unsteady, erosive and rapidly waning unconfined flows formed isolated, partly-filled, erosively-based, ephemeral structures. Moreover, being formed on the surface of the floodplain subjected these deposits to extensive post-depositional reworking, and as a consequence caused them to be poorly preserved.

Autophagy requires poly(adp-ribosyl)ation-dependent AMPK nuclear export

PubMed Central

Rodríguez-Vargas, José M; Rodríguez, María I; Majuelos-Melguizo, Jara; García-Diaz, Ángel; González-Flores, Ariannys; López-Rivas, Abelardo; Virág, László; Illuzzi, Giuditta; Schreiber, Valerie; Dantzer, Françoise; Oliver, F Javier

2016-01-01

AMPK is a central energy sensor linking extracellular milieu fluctuations with the autophagic machinery. In the current study we uncover that Poly(ADP-ribosyl)ation (PARylation), a post-translational modification (PTM) of proteins, accounts for the spatial and temporal regulation of autophagy by modulating AMPK subcellular localisation and activation. More particularly, we show that the minority AMPK pool needs to be exported to the cytosol in a PARylation-dependent manner for optimal induction of autophagy, including ULK1 phosphorylation and mTORC1 inactivation. PARP-1 forms a molecular complex with AMPK in the nucleus in non-starved cells. In response to nutrient deprivation, PARP-1 catalysed PARylation, induced the dissociation of the PARP-1/AMPK complex and the export of free PARylated nuclear AMPK to the cytoplasm to activate autophagy. PARP inhibition, its silencing or the expression of PARylation-deficient AMPK mutants prevented not only the AMPK nuclear-cytosolic export but also affected the activation of the cytosolic AMPK pool and autophagosome formation. These results demonstrate that PARylation of AMPK is a key early signal to efficiently convey extracellular nutrient perturbations with downstream events needed for the cell to optimize autophagic commitment before autophagosome formation. PMID:27689873

The prevalence of oral anticoagulation in patients with atrial fibrillation in Portugal: Systematic review and meta-analysis of observational studies.

PubMed

Caldeira, Daniel; Barra, Márcio; David, Cláudio; Costa, João; Ferreira, Joaquim J; Pinto, Fausto J

2014-09-01

Oral anticoagulation (OAC) is an effective treatment in the prevention of thromboembolic events in patients with atrial fibrillation (AF). The aim of this review was to estimate the prevalence of OAC therapy in patients with AF in Portugal. MEDLINE, the Index of Portuguese Medical Journals and SIBUL (the Bibliographic Catalog of the Integrated Library System of the University of Lisbon) were searched for Portuguese observational studies reporting the proportion of anticoagulated patients with AF. The pooled estimated prevalence of anticoagulated patients and respective 95% confidence interval (CI) were determined by means of a meta-analysis. Seven studies were included for analysis, of which four were conducted in a hospital environment and three in the general community. These studies enrolled a total of 891 patients with AF. The pooled estimated prevalence of anticoagulated patients was 40% (95% CI: 32-48%). The prevalence of OAC in Portuguese AF patients is low. There is a need to promote change in OAC prescribing habits for AF patients in Portugal, in accordance with international guidelines. Copyright © 2014 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Solar radiation, phytoplankton pigments and the radiant heating of the equatorial Pacific warm pool

NASA Technical Reports Server (NTRS)

Siegel, David A.; Ohlmann, J. Carter; Washburn, Libe; Bidigare, Robert R.; Nosse, Craig T.; Fields, Erik; Zhou, Yimei

1995-01-01

Recent optical, physical, and biological oceanographic observations are used to assess the magnitude and variability of the penetrating flux of solar radiation through the mixed layer of the warm water pool (WWP) of the western equatorial Pacific Ocean. Typical values for the penetrative solar flux at the climatological mean mixed layer depth for the WWP (30 m) are approx. 23 W/sq m and are a large fraction of the climatological mean net air-sea heat flux (approx. 40 W/sq m). The penetrating solar flux can vary significantly on synoptic timescales. Following a sustained westerly wind burst in situ solar fluxes were reduced in response to a near tripling of mixed layer phytoplankton pigment concentrations. This results in a reduction in the penetrative flux at depth (5.6 W/sq m at 30 m) and corresponds to a biogeochemically mediated increase in the mixed layer radiant heating rate of 0.13 C per month. These observations demonstrate a significant role of biogeochemical processes on WWP thermal climate. We speculate that this biogeochemically mediated feedback process may play an important role in enhancing the rate at which the WWP climate system returns to normal conditions following a westerly wind burst event.

[Molecular responses of photosynthetic apparatus of plants to long term irradiance changes].

PubMed

Adamiec, Małgorzata; Jackowski, Grzegorz

2008-01-01

In response to long term (at least 1-3 h) irradiance changes the responses are elicited at the level of structure and function of photosynthetic apparatus of plants which are thought to be aimed to keep the balance between the level of excitation energy funneled to the reaction centers of the photosystems by energetic antennae and the utilization of this energy in the form of photosynthetic electron transfer and dark reactions. At high vs medium irradiances the rate of excitation energy transfer via LHCII is reduced while the rate of electron flow and photosynthetic dark reactions is increased. The reaction at LHCII level stems from the reduction of its pool per PSII reaction center and the regulatory events comprise changes in the expression of LHCII apoproteins and/or chi b biosynthesis. The basis for higher electron flow capabilities lies in significant increases in the content of some electron carriers and the catalytic activity of ATP synthase. The upregulation of photosynthetic dark reaction in turn is due to the activation of signaling pathways leading to the increase in the pool and catalytic activities of rubisco and other Calvin cycle enzymes.

"Super-quenching" state protects Symbiodinium from thermal stress - Implications for coral bleaching.

PubMed

Slavov, Chavdar; Schrameyer, Verena; Reus, Michael; Ralph, Peter J; Hill, Ross; Büchel, Claudia; Larkum, Anthony W D; Holzwarth, Alfred R

2016-06-01

The global rise in sea surface temperatures causes regular exposure of corals to high temperature and high light stress, leading to worldwide disastrous coral bleaching events (loss of symbiotic dinoflagellates (Symbiodinium) from reef-building corals). Our picosecond chlorophyll fluorescence experiments on cultured Symbiodinium clade C cells exposed to coral bleaching conditions uncovered the transformations of the alga's photosynthetic apparatus (PSA) that activate an extremely efficient non-photochemical "super-quenching" mechanism. The mechanism is associated with a transition from an initially heterogeneous photosystem II (PSII) pool to a homogeneous "spillover" pool, where nearly all excitation energy is transferred to photosystem I (PSI). There, the inherently higher stability of PSI and high quenching efficiency of P(700)(+) allow dumping of PSII excess excitation energy into heat, resulting in almost complete cessation of photosynthetic electron transport (PET). This potentially reversible "super-quenching" mechanism protects the PSA against destruction at the cost of a loss of photosynthetic activity. We suggest that the inhibition of PET and the consequent inhibition of organic carbon production (e.g. sugars) in the symbiotic Symbiodinium provide a trigger for the symbiont expulsion, i.e. bleaching. Copyright © 2016. Published by Elsevier B.V.

Molecular evidence of RNA polymerase II gene reveals the origin of worldwide cultivated barley

PubMed Central

Wang, Yonggang; Ren, Xifeng; Sun, Dongfa; Sun, Genlou

2016-01-01

The origin and domestication of cultivated barley have long been under debate. A population-based resequencing and phylogenetic analysis of the single copy of RPB2 gene was used to address barley domestication, to explore genetic differentiation of barley populations on the worldwide scale, and to understand gene-pool exchanges during the spread and subsequent development of barley cultivation. Our results revealed significant genetic differentiation among three geographically distinct wild barley populations. Differences in haplotype composition among populations from different geographical regions revealed that modern cultivated barley originated from two major wild barley populations: one from the Near East Fertile Crescent and the other from the Tibetan Plateau, supporting polyphyletic origin of cultivated barley. The results of haplotype frequencies supported multiple domestications coupled with widespread introgression events that generated genetic admixture between divergent barley gene pools. Our results not only provide important insight into the domestication and evolution of cultivated barley, but also enhance our understanding of introgression and distinct selection pressures in different environments on shaping the genetic diversity of worldwide barley populations, thus further facilitating the effective use of the wild barley germplasm. PMID:27786300

Genomics of high molecular weight plasmids isolated from an on-farm biopurification system.

PubMed

Martini, María C; Wibberg, Daniel; Lozano, Mauricio; Torres Tejerizo, Gonzalo; Albicoro, Francisco J; Jaenicke, Sebastian; van Elsas, Jan Dirk; Petroni, Alejandro; Garcillán-Barcia, M Pilar; de la Cruz, Fernando; Schlüter, Andreas; Pühler, Alfred; Pistorio, Mariano; Lagares, Antonio; Del Papa, María F

2016-06-20

The use of biopurification systems (BPS) constitutes an efficient strategy to eliminate pesticides from polluted wastewaters from farm activities. BPS environments contain a high microbial density and diversity facilitating the exchange of information among bacteria, mediated by mobile genetic elements (MGEs), which play a key role in bacterial adaptation and evolution in such environments. Here we sequenced and characterized high-molecular-weight plasmids from a bacterial collection of an on-farm BPS. The high-throughput-sequencing of the plasmid pool yielded a total of several Mb sequence information. Assembly of the sequence data resulted in six complete replicons. Using in silico analyses we identified plasmid replication genes whose encoding proteins represent 13 different Pfam families, as well as proteins involved in plasmid conjugation, indicating a large diversity of plasmid replicons and suggesting the occurrence of horizontal gene transfer (HGT) events within the habitat analyzed. In addition, genes conferring resistance to 10 classes of antimicrobial compounds and those encoding enzymes potentially involved in pesticide and aromatic hydrocarbon degradation were found. Global analysis of the plasmid pool suggest that the analyzed BPS represents a key environment for further studies addressing the dissemination of MGEs carrying catabolic genes and pathway assembly regarding degradation capabilities.

Quantification of α-tubulin isotypes by sandwich ELISA with signal amplification through biotinyl-tyramide or immuno-PCR.

PubMed

Dráberová, Eduarda; Stegurová, Lucie; Sulimenko, Vadym; Hájková, Zuzana; Dráber, Petr; Dráber, Pavel

2013-09-30

Microtubules formed by αβ-tubulin dimers represent cellular structures that are indispensable for the maintenance of cell morphology and for cell motility generation. Microtubules in intact cells are in highly regulated equilibrium with cellular pools of soluble tubulin dimers. Sensitive, reproducible and rapid assays are necessary to monitor tubulin changes in cytosolic pools after treatment with anti-mitotic drugs, during the cell cycle or activation and differentiation events. Here we describe new assays for α-tubulin quantification. The assays are based on sandwich ELISA, and the signal is amplified with biotinyl-tyramide or immuno-PCR. Matching monoclonal antibody pair recognizes phylogenetically highly conserved epitopes localized outside the C-terminal isotype-defining region. This makes it possible to detect α-tubulin isotypes in different cell types of various species. Biotinyl-tyramide amplification and immuno-PCR amplification enable detection of tubulin at concentrations 2.5ng/ml and 0.086ng/ml, respectively. Immuno-PCR detection shows enhanced sensitivity and wider dynamic range when compared to ELISA with biotinyl-tyramide detection. Our results on taxol-treated and activated bone marrow-derived mast cells demonstrate, that the assays allow sensitive quantification of tubulin in complex biological fluids. © 2013.

Gravin orchestrates PKA and β2-adrenergic receptor signaling critical for synaptic plasticity and memory

PubMed Central

Havekes, Robbert; Canton, David A.; Park, Alan J.; Huang, Ted; Nie, Ting; Day, Jonathan P.; Guercio, Leonardo A.; Grimes, Quinn; Luczak, Vincent; Gelman, Irwin H.; Baillie, George S.; Scott, John D.; Abel, Ted

2012-01-01

A kinase-anchoring proteins (AKAPs) organize compartmentalized pools of Protein Kinase A (PKA) to enable localized signaling events within neurons. However, it is unclear which of the many expressed AKAPs in neurons target PKA to signaling complexes important for long-lasting forms of synaptic plasticity and memory storage. In the forebrain, the anchoring protein gravin recruits a signaling complex containing PKA, PKC, calmodulin, and PDE4D to the β2-adrenergic receptor. Here, we show that mice lacking the α-isoform of gravin have deficits in PKA-dependent long-lasting forms of hippocampal synaptic plasticity including β2-adrenergic receptor-mediated plasticity, and selective impairments of long-term memory storage. Further, both hippocampal β2-adrenergic receptor phosphorylation by PKA, and learning-induced activation of ERK, are attenuated in the CA1 region of the hippocampus in mice lacking gravin-α. We conclude that gravin compartmentalizes a significant pool of PKA that regulates learning-induced β2-adrenergic receptor signaling and ERK activation in the hippocampus in vivo, organizing molecular interactions between glutamatergic and noradrenergic signaling pathways for long-lasting synaptic plasticity, and memory storage. PMID:23238728

The spatial variability of water chemistry and DOC in bog pools: the importance of slope position, diurnal turnover and pool type

NASA Astrophysics Data System (ADS)

Holden, Joseph; Turner, Ed; Baird, Andy; Beadle, Jeannie; Billett, Mike; Brown, Lee; Chapman, Pippa; Dinsmore, Kerry; Dooling, Gemma; Grayson, Richard; Moody, Catherine; Gee, Clare

2017-04-01

We have previously shown that marine influence is an important factor controlling regional variability of pool water chemistry in blanket peatlands. Here we examine within-site controls on pool water chemistry. We surveyed natural and artificial (restoration sites) bog pools at blanket peatland sites in northern Scotland and Sweden. DOC, pH, conductivity, dissolved oxygen, temperature, cations, anions and absorbance spectra from 220-750nm were sampled. We sampled changes over time but also conducted intensive spatial surveys within individual pools and between pools on the same sampling days at individual study sites. Artificial pools had significantly greater DOC concentrations and different spectral absorbance characteristics when compared to natural pools at all sites studied. Within-pool variability in water chemistry tended to be small, even for very large pools ( 400 m2), except where pools had a layer of loose, mobile detritus on their beds. In these instances rapid changes took place between the overlying water column and the mobile sediment layer wherein dissolved oxygen concentrations dropped from values of around 12-10 mg/L to values less than 0.5 mg/L over just 2-3 cm of the depth profile. Such strong contrasts were not observed for pools which had a hard peat floor and which lacked a significant detritus layer. Strong diurnal turnover occurred within the pools on summer days, including within small, shallow pools (e.g. < 30 cm deep, 1 m2 area). For many pools on these summer days there was an evening spike in dissolved oxygen concentrations which originated at the surface and was then cycled downwards as the pool surface waters cooled. Slope location was a significant control on several pool water chemistry variables including pH and DOC concentration with accumulation (higher concentrations) in pools that were located further downslope in both natural and artificial pool systems. These processes have important implications for our interpretation of water chemistry and gas flux data from pool systems, how we design our sampling strategies and how we upscale results.

Animal and vegetation patterns in natural and man-made bog pools: implications for restoration

USGS Publications Warehouse

Mazerolle, M.J.; Poulin, M.; Lavoie, C.; Rochefort, L.; Desrochers, A.; Drolet, B.

2006-01-01

1. Peatlands have suffered great losses following drainage for agriculture, forestry, urbanisation, or peat mining, near inhabited areas. We evaluated the faunal and vegetation patterns after restoration of a peatland formerly mined for peat. We assessed whether bog pools created during restoration are similar to natural bog pools in terms of water chemistry, vegetation structure and composition, as well as amphibian and arthropod occurrence patterns. 2. Both avian species richness and peatland vegetation cover at the site increased following restoration. Within bog pools, however, the vegetation composition differed between natural and man-made pools. The cover of low shrubs, Sphagnum moss, submerged, emergent and floating vegetation in man-made pools was lower than in natural pools, whereas pH was higher than in typical bog pools. Dominant plant species also differed between man-made and natural pools. 3. Amphibian tadpoles, juveniles and adults occurred more often in man-made pools than natural bog pools. Although some arthropods, including Coleoptera bog specialists, readily colonised the pools, their abundance was two to 26 times lower than in natural bog pools. Plant introduction in bog pools, at the stocking densities we applied, had no effect on the occurrence of most groups. 4. We conclude that our restoration efforts were partially successful. Peatland-wide vegetation patterns following restoration mimicked those of natural peatlands, but 4 years were not sufficient for man-made pools to fully emulate the characteristics of natural bog pools.

Environmental controls of C, N and P biogeochemistry in peatland pools.

PubMed

Arsenault, Julien; Talbot, Julie; Moore, Tim R

2018-08-01

Pools are common in northern peatlands but studies have seldom focused on their nutrient biogeochemistry, especially in relation to their morphological characteristics and through seasons. We determined the environmental characteristics controlling carbon (C), nitrogen (N) and phosphorus (P) biogeochemistry in pools and assessed their evolution over the course of the 2016 growing season in a subboreal ombrotrophic peatland of eastern Canada. We showed that water chemistry variations in 62 pools were significantly explained by depth (81.9%) and the surrounding vegetation type (14.8%), but not by pool area or shape. Shallow pools had larger dissolved organic carbon (DOC) and total nitrogen (TN) concentrations and lower pH than deep pools, while pools surrounded by coniferous trees had more recalcitrant DOC than pools where vegetation was dominated by mosses. The influence of depth on pool biogeochemistry was confirmed by the seasonal survey of pools of different sizes with 47.1% of the variation in pool water chemistry over time significantly explained. Of this, 67.3% was explained by the interaction between time and pool size and 32.7% by pool size alone. P concentrations were small in all pools all summer long and combined with high N:P ratios, are indicative of P-limitation. Our results show that pool biogeochemistry is influenced by internal processes and highlight the spatial and temporal heterogeneity of nutrient biogeochemistry in ombrotrophic peatlands. Copyright © 2018 Elsevier B.V. All rights reserved.

75 FR 19964 - Notice of Staff Attendance at Southwest Power Pool Regional State Committee Meeting and Southwest...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-16

... Power Pool, Inc. Docket No. ER10-696, Southwest Power Pool, Inc. Docket No. ER10-697, Southwest Power Pool, Inc. Docket No. ER10-698, Southwest Power Pool, Inc. Docket No. ER10-700, Southwest Power Pool...

Simple stochastic model for El Niño with westerly wind bursts

PubMed Central

Thual, Sulian; Majda, Andrew J.; Chen, Nan; Stechmann, Samuel N.

2016-01-01

Atmospheric wind bursts in the tropics play a key role in the dynamics of the El Niño Southern Oscillation (ENSO). A simple modeling framework is proposed that summarizes this relationship and captures major features of the observational record while remaining physically consistent and amenable to detailed analysis. Within this simple framework, wind burst activity evolves according to a stochastic two-state Markov switching–diffusion process that depends on the strength of the western Pacific warm pool, and is coupled to simple ocean–atmosphere processes that are otherwise deterministic, stable, and linear. A simple model with this parameterization and no additional nonlinearities reproduces a realistic ENSO cycle with intermittent El Niño and La Niña events of varying intensity and strength as well as realistic buildup and shutdown of wind burst activity in the western Pacific. The wind burst activity has a direct causal effect on the ENSO variability: in particular, it intermittently triggers regular El Niño or La Niña events, super El Niño events, or no events at all, which enables the model to capture observed ENSO statistics such as the probability density function and power spectrum of eastern Pacific sea surface temperatures. The present framework provides further theoretical and practical insight on the relationship between wind burst activity and the ENSO. PMID:27573821

Nutrition considerations for open-water swimming.

PubMed

Shaw, Gregory; Koivisto, Anu; Gerrard, David; Burke, Louise M

2014-08-01

Open-water swimming (OWS) is a rapidly developing discipline. Events of 5-25 km are featured at FINA World Championships, and the international circuit includes races of 5-88 km. The Olympic OWS event, introduced in 2008, is contested over 10 km. Differing venues present changing environmental conditions, including water and ambient temperatures, humidity, solar radiation, and unpredictable tides. Furthermore, the duration of most OWS events (1-6 hr) creates unique physiological challenges to thermoregulation, hydration status, and muscle fuel stores. Current nutrition recommendations for open-water training and competition are either an extension of recommendations from pool swimming or are extrapolated from other athletic populations with similar physiological requirements. Competition nutrition should focus on optimizing prerace hydration and glycogen stores. Although swimmers should rely on self-supplied fuel and fluid sources for shorter events, for races of 10 km or greater, fluid and fuel replacement can occur from feeding pontoons when tactically appropriate. Over the longer races, feeding pontoons should be used to achieve desirable targets of up to 90 g/ hr of carbohydrates from multitransportable sources. Exposure to variable water and ambient temperatures will play a significant role in determining race nutrition strategies. For example, in extreme environments, thermoregulation may be assisted by manipulating the temperature of the ingested fluids. Swimmers are encouraged to work with nutrition experts to develop effective and efficient strategies that enhance performance through appropriate in-competition nutrition.

Late Holocene environmental reconstructions and their implications on flood events, typhoon, and agricultural activities in NE Taiwan

NASA Astrophysics Data System (ADS)

Wang, L.-C.; Behling, H.; Lee, T.-Q.; Li, H.-C.; Huh, C.-A.; Shiau, L.-J.; Chang, Y.-P.

2014-10-01

We reconstructed paleoenvironmental changes from a sediment archive of a lake in the floodplain of the Ilan Plain of NE Taiwan on multi-decadal resolution for the last ca. 1900 years. On the basis of pollen and diatom records, we evaluated past floods, typhoons, and agricultural activities in this area which are sensitive to the hydrological conditions in the western Pacific. Considering the high sedimentation rates with low microfossil preservations in our sedimentary record, multiple flood events were. identified during the period AD 100-1400. During the Little Ice Age phase 1 (LIA 1 - AD 1400-1620), the abundant occurrences of wetland plant (Cyperaceae) and diatom frustules imply less flood events under stable climate conditions in this period. Between AD 500 and 700 and the Little Ice Age phase 2 (LIA 2 - AD 1630-1850), the frequent typhoons were inferred by coarse sediments and planktonic diatoms, which represented more dynamical climate conditions than in the LIA 1. By comparing our results with the reconstructed changes in tropical hydrological conditions, we suggested that the local hydrology in NE Taiwan is strongly influenced by typhoon-triggered heavy rainfalls, which could be influenced by the variation of global temperature, the expansion of the Pacific warm pool, and the intensification of El Niño-Southern Oscillation (ENSO) events.

ECS DAAC Data Pools

NASA Astrophysics Data System (ADS)

Kiebuzinski, A. B.; Bories, C. M.; Kalluri, S.

2002-12-01

As part of its Earth Observing System (EOS), NASA supports operations for several satellites including Landsat 7, Terra, and Aqua. ECS (EOSDIS Core System) is a vast archival and distribution system and includes several Distributed Active Archive Centers (DAACs) located around the United States. EOSDIS reached a milestone in February when its data holdings exceeded one petabyte (1,000 terabytes) in size. It has been operational since 1999 and originally was intended to serve a large community of Earth Science researchers studying global climate change. The Synergy Program was initiated in 2000 with the purpose of exploring and expanding the use of remote sensing data beyond the traditional research community to the applications community including natural resource managers, disaster/emergency managers, urban planners and others. This included facilitating data access at the DAACs to enable non-researchers to exploit the data for their specific applications. The combined volume of data archived daily across the DAACs is of the order of three terabytes. These archived data are made available to the research community and to general users of ECS data. Currently, the average data volume distributed daily is two terabytes, which combined with an ever-increasing need for timely access to these data, taxes the ECS processing and archival resources for more real-time use than was previously intended for research purposes. As a result, the delivery of data sets to users was being delayed in many cases, to unacceptable limits. Raytheon, under the auspices of the Synergy Program, investigated methods at making data more accessible at a lower cost of resources (processing and archival) at the DAACs. Large on-line caches (as big as 70 Terabytes) of data were determined to be a solution that would allow users who require contemporary data to access them without having to pull it from the archive. These on-line caches are referred to as "Data Pools." In the Data Pool concept, data is inserted via subscriptions based on ECS events, for example, arrival of data matching a specific spatial context. Upon acquisition, these data are written to the Data Pools as well as to the permanent archive. The data is then accessed via a public Web interface, which provides a drilldown search, using data group, spatial, temporal and other flags. The result set is displayed as a list of ftp links to the data, which the user can click and directly download. Data Pool holdings are continuously renewed as the data is allowed to expire and is replaced by more current insertions. In addition, the Data Pool may also house data sets that though not contemporary, receive significant user attention, i.e. a Chernobyl-type of incident, a flood, or a forest fire. The benefits are that users who require contemporary data can access the data immediately (within 24 hours of acquisition) under a much improved access technique. Users not requiring contemporary data, benefit from the Data Pools by having greater archival and processing resources (and a shorter processing queue) made available to them. All users benefit now from the capability to have standing data orders for data matching a geographic context (spatial subscription), a capability also developed under the Synergy program. The Data Pools are currently being installed and checked at each of the DAACs. Additionally, several improvements to the search capabilities, data manipulation tools and overall storage capacity are being developed and will be installed in the First Quarter of 2003.

Inclusions in diamonds constrain thermo-chemical conditions during Mesozoic metasomatism of the Kaapvaal cratonic mantle

NASA Astrophysics Data System (ADS)

Weiss, Yaakov; Navon, Oded; Goldstein, Steven L.; Harris, Jeff W.

2018-06-01

Fluid/melt inclusions in diamonds, which were encapsulated during a metasomatic event and over a short period of time, are isolated from their surrounding mantle, offering the opportunity to constrain changes in the sub-continental lithospheric mantle (SCLM) that occurred during individual thermo-chemical events, as well as the composition of the fluids involved and their sources. We have analyzed a suite of 8 microinclusion-bearing diamonds from the Group I De Beers Pool kimberlites, South Africa, using FTIR, EPMA and LA-ICP-MS. Seven of the diamonds trapped incompatible-element-enriched saline high density fluids (HDFs), carry peridotitic mineral microinclusions, and substitutional nitrogen almost exclusively in A-centers. This low-aggregation state of nitrogen indicates a short mantle residence times and/or low mantle ambient temperature for these diamonds. A short residence time is favored because, elevated thermal conditions prevailed in the South African lithosphere during and following the Karoo flood basalt volcanism at ∼180 Ma, thus the saline metasomatism must have occurred close to the time of kimberlite eruptions at ∼85 Ma. Another diamond encapsulated incompatible-element-enriched silicic HDFs and has 25% of its nitrogen content residing in B-centers, implying formation during an earlier and different metasomatic event that likely relates to the Karoo magmatism at ca. 180 Ma. Thermometry of mineral microinclusions in the diamonds carrying saline HDFs, based on Mg-Fe exchange between garnet-orthopyroxene (Opx)/clinopyroxene (Cpx)/olivine and the Opx-Cpx thermometer, yield temperatures between 875-1080 °C at 5 GPa. These temperatures overlap with conditions recorded by touching inclusion pairs in diamonds from the De Beers Pool kimberlites, which represent the mantle ambient conditions just before eruption, and are altogether lower by 150-250 °C compared to P-T gradients recorded by peridotite xenoliths from the same locality. Oxygen fugacity (fO2) differs as well. The fO2 calculated for the saline HDF compositions (Δlog ⁡ fO 2 (FMQ) = - 2.47 to -1.34) are higher by about a log unit compared with that recorded by xenoliths at 4-7 GPa. We conclude that enriched saline HDFs mediated the metasomatism that preceded Group I kimberlite eruptions in the southwestern Kaapvaal craton, and that their 'cold and oxidized' nature reflects their derivation from a deep subducting slab. This event had little impact on the temperature and redox state of the Kaapvaal lithosphere as a reservoir, however, it likely affected its properties along limited metasomatized veins and their wall rock. To reconcile the temperature and oxygen fugacity discrepancy between inclusions in diamonds and xenoliths, we argue that xenoliths did not equilibrate during the last saline metasomatic event or kimberlite eruption. Thus the P-T- fO2 gradients they record express pre-existing lithospheric conditions that were likely established during the last major thermal event in the Kaapvaal craton (i.e. the Karoo magmatism at ca. 180 Ma).

2011 Summary: Coastal wetland restoration research

USGS Publications Warehouse

Kowalski, Kurt P.; Wiley, Michael J.; Wilcox, Douglas A.; Carlson Mazur, Martha L.; Czayka, Alex; Dominguez, Andrea; Doty, Susan; Eggleston, Mike; Green, Sean; Sweetman, Amanda

2014-01-01

The Great Lakes Restoration Initiative (GLRI) projects currently taking place in Great Lakes coastal wetlands provide a unique opportunity to study ecosystem response to management actions as practitioners strive to improve wetland function and increase ecosystem services. Through a partnership between the U.S. Geological Survey – Great Lakes Science Center (GLSC), U.S. Fish and Wildlife Service (USFWS), and Ducks Unlimited, a GLRI-funded project has reestablished the hydrologic connection between an intensively managed impounded wetland (Pool 2B) and Crane Creek, a small Lake Erie tributary, by building a water-control structure that was opened in the spring of 2011. The study site is located within the USFWS Ottawa National Wildlife Refuge (ONWR) and lies within the boundaries of the U.S. Environmental Protection Agency (EPA)-designated Maumee River Area of Concern. The broad objective of the project is to evaluate how hydrologically reconnecting a previously diked wetland impacts fish, mollusks, and other biota and affects nutrient transport, nutrient cycling, water quality, flood storage, and many other abiotic conditions. The results from this project suggest large system-wide benefits from sustainable reestablishment of lake-driven hydrology in this and other similar systems. We comprehensively sampled water chemistry, fish, birds, plants, and invertebrates in Crane Creek coastal wetlands, Pool 2A (a reference diked wetland), and Pool 2B (the reconnected wetland) in 2010 and 2011 to: 1) Characterize spatial and seasonal patterns for these parameters. 2) Examine ecosystem response to the opening of a water-control structure that allows fish passage Our sampling efforts have yielded data that reveal striking changes in water quality, hydrology, and fish assemblages in our experimental unit (2B). Prior to the reconnection, the water chemistry in pools 2A and 2B were very similar. Afterwards, we found that the water chemistry in reconnected Pool 2B was more similar to Crane Creek (e.g., greater turbidity, higher concentration of nitrogen). Sites closest to the structure showed the most creek influence with that influence decreasing with distance from the structure, suggesting that input water from Crane Creek is not mixing fully with the pool water. We also found that water level fluctuations were much greater in the reconnected wetland due to the influence of seiches in Lake Erie. We measured the nutrient concentrations of water flowing into and out of Pool 2B during seiche events and found that the phosphorous and nitrogen concentrations generally were drastically reduced after pulsing through the reconnected wetland. Fish response to the reconnection was equally striking. High-resolution sonar revealed extensive bidirectional movement of fish through the structure on a daily and seasonal basis. There also were significant increases in both the catch per unit effort (CPUE) and the species richness of all sites in Pool 2B from 2010 to 2011. Reconnecting the diked pool to the larger Crane Creek wetland complex, and therefore Lake Erie, has opened up rich new habitat for many fish species. Thirteen species of fish not previously found in the pool entered through the structure and actively used the reconnected wetland. We also found that the wetland functions as a productive spawning ground and nursery area with notable shifts in the predominant age-class of several species of fish, especially northern pike. We observed no negative effects of reconnection on the avian or vegetative communities. All sites within the connected pool had increases in diversity and abundance in the avian community and decreases in the species richness and Floristic Quality Assessment Index values for vegetative communities. After one year of study, data suggest that maintaining a hydrologic connection between diked and coastal wetlands in Lake Erie allows fishes to use vegetated habitats regularly, reduces the concentration of nutrients in coastal waters, and maintains productive habitats for birds and other biota.  It will be important to continue to monitor the status of the reconnected wetland to determine the effect of long-term connection to Crane Creek and Lake Erie.  If conditions degrade, periodic management actions involving hydrologic isolation of the rehabilitated coastal wetland could be used to mimic intermediate levels of disturbance and maintain wetland vegetation.

Short time dynamics of water coalescence on a flat water pool

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lim, Su Jin; Gim, Bopil; Fezzaa, Kamel

2016-12-01

Coalescence is an important hydrodynamic event that frequently takes place in nature as well as in industry. Here we provide an experimental study on short time dynamics of water coalescence, particularly when a water droplet comes in contact with a flat water surface, by utilizing high-resolution high-penetration ultrafast X-ray microscopy. Our results demonstrate a possibility that an extreme curvature difference between a drop and a flat surface can significantly modify the hydrodynamics of water coalescence, which is unexpected in the existing theory. We suggest a plausible explanation for why coalescence can be modified by an extreme curvature difference.

The Onset of the 1997-1998 El Nino and its Impact on the Phytoplankton Community of the Central Equatorial Pacific

NASA Technical Reports Server (NTRS)

Chavez, F. P.; Strutton, P. G.; McPhaden, M. J.

1996-01-01

Using physical and bio-optical data from moorings in the central equatorial Pacific, the perturbations to phytoplankton biomass and productivity associated with the onset of the 1997-98 El Nino event were investigated. The data presented depict the physical progression of El Nino onset, from reversal of the trade winds in the western equatorial Pacific, through eastward propagation of equatorially trapped Kelvin waves and advection of waters from the nutrient-poor western equatorial warm pool. The physical perturbations led to fluctuations in phytoplankton biomass, quantum yield of fluorescence and a 50% reduction in primary productivity.

Tracking the establishment of local endemic populations of an emergent enteric pathogen

PubMed Central

Holt, Kathryn E.; Thieu Nga, Tran Vu; Thanh, Duy Pham; Vinh, Ha; Kim, Dong Wook; Vu Tra, My Phan; Campbell, James I.; Hoang, Nguyen Van Minh; Vinh, Nguyen Thanh; Minh, Pham Van; Thuy, Cao Thu; Nga, Tran Thi Thu; Thompson, Corinne; Dung, Tran Thi Ngoc; Nhu, Nguyen Thi Khanh; Vinh, Phat Voong; Tuyet, Pham Thi Ngoc; Phuc, Hoang Le; Lien, Nguyen Thi Nam; Phu, Bui Duc; Ai, Nguyen Thi Thuy; Tien, Nguyen Manh; Dong, Nguyen; Parry, Christopher M.; Hien, Tran Tinh; Farrar, Jeremy J.; Parkhill, Julian; Dougan, Gordon; Thomson, Nicholas R.; Baker, Stephen

2013-01-01

Shigella sonnei is a human-adapted pathogen that is emerging globally as the dominant agent of bacterial dysentery. To investigate local establishment, we sequenced the genomes of 263 Vietnamese S. sonnei isolated over 15 y. Our data show that S. sonnei was introduced into Vietnam in the 1980s and has undergone localized clonal expansion, punctuated by genomic fixation events through periodic selective sweeps. We uncover geographical spread, spatially restricted frontier populations, and convergent evolution through local gene pool sampling. This work provides a unique, high-resolution insight into the microevolution of a pioneering human pathogen during its establishment in a new host population. PMID:24082120

10 CFR 36.53 - Operating and emergency procedures.

Code of Federal Regulations, 2011 CFR

2011-01-01

... pool, or another alarmed area; (9) Natural phenomena, including an earthquake, a tornado, flooding, or...) Monitoring pool water for contamination while the water is in the pool and before release of pool water to... or pool monitor; (4) Detection of leaking sources, pool contamination, or alarm caused by...

75 FR 56597 - University of Wisconsin; University of Wisconsin Nuclear Reactor Environmental Assessment and...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-16

...,000 gallons being typical. The licensee maintains a pool leak surveillance program. The pool water leak surveillance program continues to monitor the pool water evaporation rate, the pool water make-up volume, and pool water radioactivity. The pool leak surveillance program indicated that approximately 2...

Swimming Pools.

ERIC Educational Resources Information Center

Ministry of Housing and Local Government, London (England).

Technical and engineering data are set forth on the design and construction of swimming pools. Consideration is given to site selection, pool construction, the comparative merits of combining open air and enclosed pools, and alternative uses of the pool. Guidelines are presented regarding--(1) pool size and use, (2) locker and changing rooms, (3)…

Swimming Pools. A Guide to Their Planning, Design and Operation.

ERIC Educational Resources Information Center

Gabrielsen, M. Alexander, Ed.

Information is presented regarding all phases of swimming pool development and operation from earliest planning considerations to final programing. This comprehensive book covers--(1) the steps involved in planning a pool, (2) designing the pool, (3) water circulation, filtration, and treatment, (4) community pools, school and agency pools, and…

13 CFR 120.1709 - Transfers of Pool Certificates.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 13 Business Credit and Assistance 1 2012-01-01 2012-01-01 false Transfers of Pool Certificates... Transfers of Pool Certificates. (a) Transfer of Pool Certificates. A Pool Certificate is transferable. A transfer of a Pool Certificate must comply with Article 8 of the Uniform Commercial Code of the State of...

13 CFR 120.1709 - Transfers of Pool Certificates.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Transfers of Pool Certificates... Transfers of Pool Certificates. (a) Transfer of Pool Certificates. A Pool Certificate is transferable. A transfer of a Pool Certificate must comply with Article 8 of the Uniform Commercial Code of the State of...

13 CFR 120.1709 - Transfers of Pool Certificates.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 13 Business Credit and Assistance 1 2014-01-01 2014-01-01 false Transfers of Pool Certificates... Transfers of Pool Certificates. (a) Transfer of Pool Certificates. A Pool Certificate is transferable. A transfer of a Pool Certificate must comply with Article 8 of the Uniform Commercial Code of the State of...

13 CFR 120.1709 - Transfers of Pool Certificates.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 13 Business Credit and Assistance 1 2011-01-01 2011-01-01 false Transfers of Pool Certificates... Transfers of Pool Certificates. (a) Transfer of Pool Certificates. A Pool Certificate is transferable. A transfer of a Pool Certificate must comply with Article 8 of the Uniform Commercial Code of the State of...