Is the adiposity-associated FTO gene variant related to all-cause mortality independent of adiposity? Meta-analysis of data from 169,551 Caucasian adults.

Previously, a single nucleotide polymorphism (SNP), rs9939609, in the FTO gene showed a much stronger association with all-cause mortality than expected from its association with body mass index (BMI), body fat mass index (FMI) and waist circumference (WC). This finding implies that the SNP has strong pleiotropic effects on adiposity and adiposity-independent pathological pathways that leads to increased mortality. To investigate this further, we conducted a meta-analysis of similar data from 34 longitudinal studies including 169,551 adult Caucasians among whom 27,100 died during follow-up. Linear regression showed that the minor allele of the FTO SNP was associated with greater BMI (n = 169,551; 0.32 kg m(-2) ; 95% CI 0.28-0.32, P < 1 × 10(-32) ), WC (n = 152,631; 0.76 cm; 0.68-0.84, P < 1 × 10(-32) ) and FMI (n = 48,192; 0.17 kg m(-2) ; 0.13-0.22, P = 1.0 × 10(-13) ). Cox proportional hazard regression analyses for mortality showed that the hazards ratio (HR) for the minor allele of the FTO SNPs was 1.02 (1.00-1.04, P = 0.097), but the apparent excess risk was eliminated after adjustment for BMI and WC (HR: 1.00; 0.98-1.03, P = 0.662) and for FMI (HR: 1.00; 0.96-1.04, P = 0.932). In conclusion, this study does not support that the FTO SNP is associated with all-cause mortality independently of the adiposity phenotypes.

A systematic review of the surgical treatment of large incisional hernia.

PURPOSE: Incisional hernia (IH) is one of the most frequent postoperative complications. Of all patients undergoing IH repair, a vast amount have a hernia which can be defined as a large incisional hernia (LIH). The aim of this study is to identify the preferred technique for LIH repair. METHODS: A systematic review of the literature was performed and studies describing patients with IH with a diameter of 10 cm or a surface of 100 cm2 or more were included. Recurrence hazards per year were calculated for all techniques using a generalized linear model. RESULTS: Fifty-five articles were included, containing 3,945 LIH repairs. Mesh reinforced techniques displayed better recurrence rates and hazards than techniques without mesh reinforcement. Of all the mesh techniques, sublay repair, sandwich technique with sublay mesh and aponeuroplasty with intraperitoneal mesh displayed the best results (recurrence rates of <3.6%, recurrence hazard <0.5% per year). Wound complications were frequent and most often seen after complex LIH repair. CONCLUSIONS: The use of mesh during LIH repair displayed the best recurrence rates and hazards. If possible mesh in sublay position should be used in cases of LIH repair.

Protective effects of social networks on disability among older adults in Spain

The loss of autonomy at advanced ages is not only associated with ageing, but also with the characteristics of the physical and social environment. Recent investigations have shown that social networks, social engagement and participation act like predictors of disability among the elderly. The aim of this study is to determine whether social networks are related to the development and progression of disability in the early years of old age. The source of data is the first wave of the survey "Processes of Vulnerability among Spanish Elderly", carried out in 2005 to a sample of 1 244 individuals. The population object of study is the cohort aged 70 to 74 years in metropolitan areas (Madrid and Barcelona) and not institutionalized. Disability is measured by the development of basic activities of daily life (ADL), and instrumental activities of daily life (IADL). The structural aspects of the social relationships are measured through the diversity of social networks and participation. We used the social network index (SNI). For each point over the SNI, the risk of developing any type of disability decreased by 49% (HR = 0.51, 95%CI = 0.31-0.82). The SNI was a decisive factor in all forecasting models constructed with some hazard ratios (HR) that ranged from 0.29 (95%CI = 0.14-0.59) in the first model to 0.43 (95%CI 0.20-0.90) in the full model. The results of the present study showed a strong association between an active social life, emotional support provided by friends and confidents and disability. These findings suggest a protective effect of social networks on disability. Also, these results indicate that some family and emotional ties have a significant effect on both the prevalence and the incidence of disability.

Using vegetation to characterize the avalanche to Canal del Roc Roig, Vall de Núria (Eastern Pyrenees, Spain)

Avalanche hazard maps of high accuracy are difficult to produce. For land-use planning and management purposes, a good knowledge of extreme run-out zones and frequencies of avalanches is required. In the present work, vegetation recognition (especially focused on Pinus uncinata trees) and dendrochronological techniques are used to characterize avalanches that have occurred in historical times, helping to determine both the extent of large or extreme avalanches and their occurrence in time. Vegetation was studied at the Canal del Roc Roig (eastern Pyrenees, Spain) avalanche path. The avalanches descending this path affect the railway that reaches the Vall de Núria resort and the run-up to the opposite slope. During winter 1996, two important avalanches affecting this path were well documented. These are compared with the results of the vegetation study, consisting of an inventory of flora, the recording of vegetation damages along eight transverse profiles at different altitudes on the path and a dendrochronological sampling campaign. The data obtained contributed to a characterization of the predominant snow accumulation in the starting zone, the 1996 avalanches and the range of frequencies of large avalanches. Also, traces of avalanches that increase the path mapped in the avalanche paths map published by the Institut Cartogràfic de Catalunya in 2000 were identified, improving the initial existing information.

Using vegetation to characterize the avalanche to Canal del Roc Roig, Vall de Núria (Eastern Pyrenees, Spain)

Avalanche hazard maps of high accuracy are difficult to produce. For land-use planning and management purposes, a good knowledge of extreme run-out zones and frequencies of avalanches is required. In the present work, vegetation recognition (especially focused on Pinus uncinata trees) and dendrochronological techniques are used to characterize avalanches that have occurred in historical times, helping to determine both the extent of large or extreme avalanches and their occurrence in time. Vegetation was studied at the Canal del Roc Roig (eastern Pyrenees, Spain) avalanche path. The avalanches descending this path affect the railway that reaches the Vall de Núria resort and the run-up to the opposite slope. During winter 1996, two important avalanches affecting this path were well documented. These are compared with the results of the vegetation study, consisting of an inventory of flora, the recording of vegetation damages along eight transverse profiles at different altitudes on the path and a dendrochronological sampling campaign. The data obtained contributed to a characterization of the predominant snow accumulation in the starting zone, the 1996 avalanches and the range of frequencies of large avalanches. Also, traces of avalanches that increase the path mapped in the avalanche paths map published by the Institut Cartogràfic de Catalunya in 2000 were identified, improving the initial existing information.

Towards an alternative testing strategy for nanomaterials used in nanomedicine: Lessons from NanoTEST.

In spite of recent advances in describing the health outcomes of exposure to nanoparticles (NPs), it still remains unclear how exactly NPs interact with their cellular targets. Size, surface, mass, geometry, and composition may all play a beneficial role as well as causing toxicity. Concerns of scientists, politicians and the public about potential health hazards associated with NPs need to be answered. With the variety of exposure routes available, there is potential for NPs to reach every organ in the body but we know little about the impact this might have. The main objective of the FP7 NanoTEST project ( www.nanotest-fp7.eu ) was a better understanding of mechanisms of interactions of NPs employed in nanomedicine with cells, tissues and organs and to address critical issues relating to toxicity testing especially with respect to alternatives to tests on animals. Here we describe an approach towards alternative testing strategies for hazard and risk assessment of nanomaterials, highlighting the adaptation of standard methods demanded by the special physicochemical features of nanomaterials and bioavailability studies. The work has assessed a broad range of toxicity tests, cell models and NP types and concentrations taking into account the inherent impact of NP properties and the effects of changes in experimental conditions using well-characterized NPs. The results of the studies have been used to generate recommendations for a suitable and robust testing strategy which can be applied to new medical NPs as they are developed.

Quaternary active tectonic structures in the offshore Bajo Segura basin (SE Iberian Peninsula Mediterranean Sea).

The Bajo Segura fault zone (BSFZ) is the northern terminal splay of the Eastern Betic shear zone (EBSZ), a large left-lateral strike-slip fault system of sigmoid geometry stretching more than 450 km from Alicante to Almería. The BSFZ extends from the onshore Bajo Segura basin further into the Mediterranean Sea and shows a moderate instrumental seismic activity characterized by small earthquakes. Nevertheless, the zone was affected by large historical earthquakes of which the largest was the 1829 Torrevieja earthquake (IEMS98 X). The onshore area of the BSFZ is marked by active transpressive structures (faults and folds), whereas the offshore area has been scarcely explored from the tectonic point of view. During the EVENT-SHELF cruise, a total of 10 high-resolution single-channel seismic sparker profiles were obtained along and across the offshore Bajo Segura basin. Analysis of these profiles resulted in (a) the identification of 6 Quaternary seismo-stratigraphic units bounded by five horizons corresponding to regional erosional surfaces related to global sea level lowstands; and (b) the mapping of the active sub-seafloor structures and their correlation with those described onshore. Moreover, the results suggest that the Bajo Segura blind thrust fault or the Torrevieja left-lateral strike-slip fault, with prolongation offshore, could be considered as the source of the 1829 Torrevieja earthquake. These data improve our understanding of present deformation along the BSFZ and provide new insights into the seismic hazard in the area.

Positive Outcomes Influence the Rate and Time to Publication, but Not the Impact Factor of Publications of Clinical Trial Results

Objectives: Publication bias may affect the validity of evidence based medical decisions. The aim of this study is to assess whether research outcomes affect the dissemination of clinical trial findings, in terms of rate, time to publication, and impact factor of journal publications. Methods and Findings: All drug-evaluating clinical trials submitted to and approved by a general hospital ethics committee between 1997 and 2004 were prospectively followed to analyze their fate and publication. Published articles were identified by searching Pubmed and other electronic databases. Clinical study final reports submitted to the ethics committee, final reports synopses available online and meeting abstracts were also considered as sources of study results. Study outcomes were classified as positive (when statistical significance favoring experimental drug was achieved), negative (when no statistical significance was achieved or it favored control drug) and descriptive (for non-controlled studies). Time to publication was defined as time from study closure to publication. A survival analysis was performed using a Cox regression model to analyze time to publication. Journal impact factors of identified publications were recorded. Publication rate was 48·4% (380/785). Study results were identified for 68·9% of all completed clinical trials (541/785). Publication rate was 84·9% (180/212) for studies with results classified as positive and 68·9% (128/186) for studies with results classified as negative (p<0·001). Median time to publication was 2·09 years (IC95 1·61-2·56) for studies with results classified as positive and 3·21 years (IC95 2·69-3·70) for studies with results classified as negative (hazard ratio 1·99 (IC95 1·55-2·55). No differences were found in publication impact factor between positive (median 6·308, interquartile range: 3·141-28·409) and negative result studies (median 8·266, interquartile range: 4·135-17·157). Conclusions: Clinical trials with positive outcomes have significantly higher rates and shorter times to publication than those with negative results. However, no differences have been found in terms of impact factor.

Aspirin and statin use and the subsequent development of depression in men and women: Results from a longitudinal population-based study.

OBJECTIVE: Low-grade chronic inflammation is one potential mechanism underlying the well-established association between major depressive disorder (MDD) and increased cardiovascular morbidity. Both aspirin and statins have anti-inflammatory properties, which may contribute to their preventive effect on cardiovascular diseases. Previous studies on the potentially preventive effect of these drugs on depression have provided inconsistent results. The aim of the present paper was to assess the prospective association between regular aspirin or statin use and the incidence of MDD. METHOD: This prospective cohort study included 1631 subjects (43.6% women, mean age 51.7 years), randomly selected from the general population of an urban area. Subjects underwent a thorough physical evaluation as well as semi-structured interviews investigating DSM-IV mental disorders at baseline and follow-up (mean duration 5.2 years). Analyses were adjusted for a wide array of potential confounders. RESULTS: Our main finding was that regular aspirin or statin use at baseline did not reduce the incidence of MDD during follow-up, regardless of sex or age (hazard ratios, aspirin: 1.19; 95%CI, 0.68-2.08; and statins: 1.25; 95%CI, 0.73-2.14; respectively). LIMITATIONS: Our study is not a randomized clinical trial and could not adjust for all potential confounding factors, information on aspirin or statin use was collected only for the 6 months prior to the evaluations, and the sample was restricted to subjects between 35 and 66 years of age. CONCLUSION: Our data do not support a large scale preventive treatment of depression using aspirin or statins in subjects aged from 35 to 66 years from the community.

Työterveys- ja työturvallisuusjohtamisjärjestelmän (OHSAS 18001) kehittäminen

Yritykset kiinnittävät yhä enemmän huomiota toimintaansa ja sen tasoon. Viime vuosien aikana on keskitytty laatu- ja ympäristöasioiden lisäksi myös yrityksen työturvallisuuteen. Tähän ovat vaikuttaneet muun muassa kansainvälisten markkinoiden vaatimukset ja asiakkaiden kiinnostus. Tämä työ on osa Wärtsilä Finland Oy:n työterveys- ja työturvallisuusjärjestelmän kehittämisprojektia. Työn tavoitteena oli tunnistaa työterveys- ja työturvallisuusjohtamisjärjestelmään liittyvät vaatimukset OHSAS 18001 -spesifikaation mukaisesti. Tarkoituksena oli myös osittain kehittää työterveys- ja työturvallisuusjärjestelmää. Organisaation päämääränä on päästä Nolla tapaturmaa -ohjelman tavoitteeseen. Tämä tapahtuu eri keinoja käyttäen, kuten täyttämällä OHSAS 18001 -vaatimukset. OHSAS -vaatimuksista keskeiseen asemaan tässä työssä nousivat yrityksen riskien arviointi sekä tapaturmien tutkinta ja tilastointi. Riskien arviointi tehtiin pilottitehtaassa OHSAS 18001 -koulutukseen liittyvänä harjoituksena. Saatuja tuloksia voidaan pitää kohtalaisina kun huomioidaan, että kyseessä oli ensimmäinen riskien arviointikerta. Osa riskeistä jäi kuitenkin luultavasti havaitsematta, joten kehitystyötä on jatkettava. Tarkistusta ja kehittämistä vaativia asioita löytyi myös tapaturmien tutkimisen ja tilastoinnin saralta. Työn tuloksista voidaan todeta, että yrityksellä on käytössä joitakin OH&S -menettelyjä, mutta kehitettäviä osa-alueita on havaittavissa. Tulevaisuudessa olisi tärkeää, että yritys kehittäisi käyttöönotettua riskien arviointimenetelmää tai etsisi muita mahdollisia tapoja arvioida riskejä. Tätä kautta yrityksen on mahdollista päästä ennaltaehkäisevään työskentelynäkökulmaan ja edetä kohti Nolla tapaturmaa -ohjelman tavoitetta.

Preface: Extreme events induced by weather and climate change: evaluation, forecasting and proactive planning

This special issue of Natural Hazards and Earth System Sciences (NHESS) contains eight papers presented as oral or poster contributions in the Natural Hazards NH-1.2 session on"Extreme events induced by weather and climate change: evaluation, forecasting and proactive planning", held at the European Geosciences Union (EGU) General Assembly in Vienna, Austria, on 13-18 April 2008. The aim of the session was to provide an international forum for presenting new results and for discussing innovative ideas and concepts on extreme hydro-meteorological events, including: (i) the assessment of the risk posed by the extreme events, (ii) the expected changes in the frequency and intensity of the events driven by a changing climate and by multiple human- induced causes, (iii) new modelling approaches and original forecasting methods to predict extreme events and their consequences, and (iv) strategies for hazard mitigation and risk reduction, and for a improved adaptation to extreme hydro-meteorological events ...

Thrombin-receptor antagonist vorapaxar in acute coronary syndromes

Background: Vorapaxar is a new oral protease-activated-receptor 1 (PAR-1) antagonist that inhibits thrombin-induced platelet activation. Methods: In this multinational, double-blind, randomized trial, we compared vorapaxar with placebo in 12,944 patients who had acute coronary syndromes without ST-segment elevation. The primary end point was a composite of death from cardiovascular causes, myocardial infarction, stroke, recurrent ischemia with rehospitalization, or urgent coronary revascularization. RESULTS: Follow-up in the trial was terminated early after a safety review. After a median follow-up of 502 days (interquartile range, 349 to 667), the primary end point occurred in 1031 of 6473 patients receiving vorapaxar versus 1102 of 6471 patients receiving placebo (Kaplan-Meier 2-year rate, 18.5% vs. 19.9%; hazard ratio, 0.92; 95% confidence interval [CI], 0.85 to 1.01; P = 0.07). A composite of death from cardiovascular causes, myocardial infarction, or stroke occurred in 822 patients in the vorapaxar group versus 910 in the placebo group (14.7% and 16.4%, respectively; hazard ratio, 0.89; 95% CI, 0.81 to 0.98; P = 0.02). Rates of moderate and severe bleeding were 7.2% in the vorapaxar group and 5.2% in the placebo group (hazard ratio, 1.35; 95% CI, 1.16 to 1.58; P<0.001). Intracranial hemorrhage rates were 1.1% and 0.2%, respectively (hazard ratio, 3.39; 95% CI, 1.78 to 6.45; P<0.001). Rates of nonhemorrhagic adverse events were similar in the two groups. Conclusions: In patients with acute coronary syndromes, the addition of vorapaxar to standard therapy did not significantly reduce the primary composite end point but significantly increased the risk of major bleeding, including intracranial hemorrhage. (Funded by Merck; TRACER ClinicalTrials.gov number, NCT00527943.)

Efficacy and safety of once-daily aclidinium in chronic obstructive pulmonary disease

Background: The long-term efficacy and safety of aclidinium bromide, a novel, long-acting muscarinic antagonist, were investigated in patients with moderate to severe chronic obstructive pulmonary disease (COPD). Methods: In two double-blind, 52-week studies, ACCLAIM/COPD I (n = 843) and II (n = 804), patients were randomised to inhaled aclidinium 200 μg or placebo once-daily. Patients were required to have a postbronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity ratio of ≤70% and FEV1 <80% of the predicted value. The primary endpoint was trough FEV1 at 12 and 28 weeks. Secondary endpoints were health status measured by St George"s Respiratory Questionnaire (SGRQ) and time to first moderate or severe COPD exacerbation. Results: At 12 and 28 weeks, aclidinium improved trough FEV1 versus placebo in ACCLAIM/COPD I (by 61 and 67 mL; both p < 0.001) and ACCLAIM/COPD II (by 63 and 59 mL; both p < 0.001). More patients had a SGRQ improvement ≥4 units at 52 weeks with aclidinium versus placebo in ACCLAIM/COPD I (48.1% versus 39.5%; p = 0.025) and ACCLAIM/COPD II (39.0% versus 32.8%; p = 0.074). The time to first exacerbation was significantly delayed by aclidinium in ACCLAIM/COPD II (hazard ratio [HR] 0.7; 95% confidence interval [CI] 0.55 to 0.92; p = 0.01), but not ACCLAIM/COPD I (HR 1.0; 95% CI 0.72 to 1.33; p = 0.9). Adverse events were minor in both studies. Conclusion: Aclidinium is effective and well tolerated in patients with moderate to severe COPD. Trial registration: ClinicalTrials.gov: NCT00363896 ACCLAIM/COPD I) and NCT00358436 (ACCLAIM/COPD II).

Pulmonary metastasectomy in colorectal cancer patients with previously resected liver metastasis: pooled analysis.

BACKGROUND: Data addressing the outcomes and patterns of recurrence after pulmonary metastasectomy (PM) in patients with colorectal cancer (CRC) and previously resected liver metastasis are limited. METHODS: We searched the PubMed database for studies assessing PM in CRC and gathered individual data for patients who had PM and a previous curative liver resection. The influence of potential factors on overall survival (OS) was analyzed through univariate and multivariate analysis. RESULTS: Between 1983 and 2009, 146 patients from five studies underwent PM and had previous liver resection. The median interval from resection of liver metastasis until detection of lung metastasis and the median follow-up from PM were 23 and 48 months, respectively. Five-year OS and recurrence-free survival rates calculated from the date of PM were 54.4 and 29.3 %, respectively. Factors predicting inferior OS in univariate analysis included thoracic lymph node (LN) involvement and size of largest lung nodule ≥2 cm. Adjuvant chemotherapy and whether lung metastasis was detected synchronous or metachronous to liver metastasis had no influence on survival. In multivariate analysis, thoracic LN involvement emerged as the only independent factor (hazard ratio 4.86, 95 % confidence interval 1.56-15.14, p = 0.006). CONCLUSIONS: PM offers a chance for long-term survival in selected patients with CRC and previously resected liver metastasis. Thoracic LN involvement predicted poor prognosis; therefore, significant efforts should be undertaken for adequate staging of the mediastinum before PM. In addition, adequate intraoperative LN sampling allows proper prognostic stratification and enrollment in novel adjuvant therapy trials.

Subclinical thyroid dysfunction and fracture risk: a meta-analysis.

IMPORTANCE: Associations between subclinical thyroid dysfunction and fractures are unclear and clinical trials are lacking. OBJECTIVE: To assess the association of subclinical thyroid dysfunction with hip, nonspine, spine, or any fractures. DATA SOURCES AND STUDY SELECTION: The databases of MEDLINE and EMBASE (inception to March 26, 2015) were searched without language restrictions for prospective cohort studies with thyroid function data and subsequent fractures. DATA EXTRACTION: Individual participant data were obtained from 13 prospective cohorts in the United States, Europe, Australia, and Japan. Levels of thyroid function were defined as euthyroidism (thyroid-stimulating hormone [TSH], 0.45-4.49 mIU/L), subclinical hyperthyroidism (TSH <0.45 mIU/L), and subclinical hypothyroidism (TSH ≥4.50-19.99 mIU/L) with normal thyroxine concentrations. MAIN OUTCOME AND MEASURES: The primary outcome was hip fracture. Any fractures, nonspine fractures, and clinical spine fractures were secondary outcomes. RESULTS: Among 70,298 participants, 4092 (5.8%) had subclinical hypothyroidism and 2219 (3.2%) had subclinical hyperthyroidism. During 762,401 person-years of follow-up, hip fracture occurred in 2975 participants (4.6%; 12 studies), any fracture in 2528 participants (9.0%; 8 studies), nonspine fracture in 2018 participants (8.4%; 8 studies), and spine fracture in 296 participants (1.3%; 6 studies). In age- and sex-adjusted analyses, the hazard ratio (HR) for subclinical hyperthyroidism vs euthyroidism was 1.36 for hip fracture (95% CI, 1.13-1.64; 146 events in 2082 participants vs 2534 in 56,471); for any fracture, HR was 1.28 (95% CI, 1.06-1.53; 121 events in 888 participants vs 2203 in 25,901); for nonspine fracture, HR was 1.16 (95% CI, 0.95-1.41; 107 events in 946 participants vs 1745 in 21,722); and for spine fracture, HR was 1.51 (95% CI, 0.93-2.45; 17 events in 732 participants vs 255 in 20,328). Lower TSH was associated with higher fracture rates: for TSH of less than 0.10 mIU/L, HR was 1.61 for hip fracture (95% CI, 1.21-2.15; 47 events in 510 participants); for any fracture, HR was 1.98 (95% CI, 1.41-2.78; 44 events in 212 participants); for nonspine fracture, HR was 1.61 (95% CI, 0.96-2.71; 32 events in 185 participants); and for spine fracture, HR was 3.57 (95% CI, 1.88-6.78; 8 events in 162 participants). Risks were similar after adjustment for other fracture risk factors. Endogenous subclinical hyperthyroidism (excluding thyroid medication users) was associated with HRs of 1.52 (95% CI, 1.19-1.93) for hip fracture, 1.42 (95% CI, 1.16-1.74) for any fracture, and 1.74 (95% CI, 1.01-2.99) for spine fracture. No association was found between subclinical hypothyroidism and fracture risk. CONCLUSIONS AND RELEVANCE: Subclinical hyperthyroidism was associated with an increased risk of hip and other fractures, particularly among those with TSH levels of less than 0.10 mIU/L and those with endogenous subclinical hyperthyroidism. Further study is needed to determine whether treating subclinical hyperthyroidism can prevent fractures.