Association of Cardiometabolic Multimorbidity With Mortality.

IMPORTANCE: The prevalence of cardiometabolic multimorbidity is increasing. OBJECTIVE: To estimate reductions in life expectancy associated with cardiometabolic multimorbidity. DESIGN, SETTING, AND PARTICIPANTS: Age- and sex-adjusted mortality rates and hazard ratios (HRs) were calculated using individual participant data from the Emerging Risk Factors Collaboration (689,300 participants; 91 cohorts; years of baseline surveys: 1960-2007; latest mortality follow-up: April 2013; 128,843 deaths). The HRs from the Emerging Risk Factors Collaboration were compared with those from the UK Biobank (499,808 participants; years of baseline surveys: 2006-2010; latest mortality follow-up: November 2013; 7995 deaths). Cumulative survival was estimated by applying calculated age-specific HRs for mortality to contemporary US age-specific death rates. EXPOSURES: A history of 2 or more of the following: diabetes mellitus, stroke, myocardial infarction (MI). MAIN OUTCOMES AND MEASURES: All-cause mortality and estimated reductions in life expectancy. RESULTS: In participants in the Emerging Risk Factors Collaboration without a history of diabetes, stroke, or MI at baseline (reference group), the all-cause mortality rate adjusted to the age of 60 years was 6.8 per 1000 person-years. Mortality rates per 1000 person-years were 15.6 in participants with a history of diabetes, 16.1 in those with stroke, 16.8 in those with MI, 32.0 in those with both diabetes and MI, 32.5 in those with both diabetes and stroke, 32.8 in those with both stroke and MI, and 59.5 in those with diabetes, stroke, and MI. Compared with the reference group, the HRs for all-cause mortality were 1.9 (95% CI, 1.8-2.0) in participants with a history of diabetes, 2.1 (95% CI, 2.0-2.2) in those with stroke, 2.0 (95% CI, 1.9-2.2) in those with MI, 3.7 (95% CI, 3.3-4.1) in those with both diabetes and MI, 3.8 (95% CI, 3.5-4.2) in those with both diabetes and stroke, 3.5 (95% CI, 3.1-4.0) in those with both stroke and MI, and 6.9 (95% CI, 5.7-8.3) in those with diabetes, stroke, and MI. The HRs from the Emerging Risk Factors Collaboration were similar to those from the more recently recruited UK Biobank. The HRs were little changed after further adjustment for markers of established intermediate pathways (eg, levels of lipids and blood pressure) and lifestyle factors (eg, smoking, diet). At the age of 60 years, a history of any 2 of these conditions was associated with 12 years of reduced life expectancy and a history of all 3 of these conditions was associated with 15 years of reduced life expectancy. CONCLUSIONS AND RELEVANCE: Mortality associated with a history of diabetes, stroke, or MI was similar for each condition. Because any combination of these conditions was associated with multiplicative mortality risk, life expectancy was substantially lower in people with multimorbidity

Association of Cardiometabolic Multimorbidity With Mortality.

IMPORTANCE: The prevalence of cardiometabolic multimorbidity is increasing. OBJECTIVE: To estimate reductions in life expectancy associated with cardiometabolic multimorbidity. DESIGN, SETTING, AND PARTICIPANTS: Age- and sex-adjusted mortality rates and hazard ratios (HRs) were calculated using individual participant data from the Emerging Risk Factors Collaboration (689,300 participants; 91 cohorts; years of baseline surveys: 1960-2007; latest mortality follow-up: April 2013; 128,843 deaths). The HRs from the Emerging Risk Factors Collaboration were compared with those from the UK Biobank (499,808 participants; years of baseline surveys: 2006-2010; latest mortality follow-up: November 2013; 7995 deaths). Cumulative survival was estimated by applying calculated age-specific HRs for mortality to contemporary US age-specific death rates. EXPOSURES: A history of 2 or more of the following: diabetes mellitus, stroke, myocardial infarction (MI). MAIN OUTCOMES AND MEASURES: All-cause mortality and estimated reductions in life expectancy. RESULTS: In participants in the Emerging Risk Factors Collaboration without a history of diabetes, stroke, or MI at baseline (reference group), the all-cause mortality rate adjusted to the age of 60 years was 6.8 per 1000 person-years. Mortality rates per 1000 person-years were 15.6 in participants with a history of diabetes, 16.1 in those with stroke, 16.8 in those with MI, 32.0 in those with both diabetes and MI, 32.5 in those with both diabetes and stroke, 32.8 in those with both stroke and MI, and 59.5 in those with diabetes, stroke, and MI. Compared with the reference group, the HRs for all-cause mortality were 1.9 (95% CI, 1.8-2.0) in participants with a history of diabetes, 2.1 (95% CI, 2.0-2.2) in those with stroke, 2.0 (95% CI, 1.9-2.2) in those with MI, 3.7 (95% CI, 3.3-4.1) in those with both diabetes and MI, 3.8 (95% CI, 3.5-4.2) in those with both diabetes and stroke, 3.5 (95% CI, 3.1-4.0) in those with both stroke and MI, and 6.9 (95% CI, 5.7-8.3) in those with diabetes, stroke, and MI. The HRs from the Emerging Risk Factors Collaboration were similar to those from the more recently recruited UK Biobank. The HRs were little changed after further adjustment for markers of established intermediate pathways (eg, levels of lipids and blood pressure) and lifestyle factors (eg, smoking, diet). At the age of 60 years, a history of any 2 of these conditions was associated with 12 years of reduced life expectancy and a history of all 3 of these conditions was associated with 15 years of reduced life expectancy. CONCLUSIONS AND RELEVANCE: Mortality associated with a history of diabetes, stroke, or MI was similar for each condition. Because any combination of these conditions was associated with multiplicative mortality risk, life expectancy was substantially lower in people with multimorbidity

Genome-wide identification of directed gene networks using large-scale population genomics data

Identification of causal drivers behind regulatory gene networks is crucial in understanding gene function. Here, we develop a method for the large-scale inference of gene–gene interactions in observational population genomics data that are both directed (using local genetic instruments as causal anchors, akin to Mendelian Randomization) and specific (by controlling for linkage disequilibrium and pleiotropy). Analysis of genotype and whole-blood RNA-sequencing data from 3072 individuals identified 49 genes as drivers of downstream transcriptional changes (Wald P < 7 × 10−10), among which transcription factors were overrepresented (Fisher’s P = 3.3 × 10−7). Our analysis suggests new gene functions and targets, including for SENP7 (zinc-finger genes involved in retroviral repression) and BCL2A1 (target genes possibly involved in auditory dysfunction). Our work highlights the utility of population genomics data in deriving directed gene expression networks. A resource of trans-effects for all 6600 genes with a genetic instrument can be explored individually using a web-based browser

Effects of various ballast water treatment methods on the survival of phytoplankton and bacteria

Aquatische invasieve soorten zijn een van de grootste bedreigingen voor de biodiversiteit in de oceanen. Een van de transportroutes voor deze invasieve soorten is ballastwater. Om dit tegen te gaan heeft de Internationale Maritieme Organisatie richtlijnen geformuleerd die grenzen stellen aan de hoeveelheid organismen in ballastwater. Om aan deze richtlijnen te voldoen zijn zogenaamde ballastwater behandelingssystemen ontwikkeld door verschillende fabrikanten. Deze behandelingssystemen gebruiken verschillende methoden zoals filtratie, chloor-toevoeging of UV-licht om organismen te verwijderen of doden. In dit proefschrift werd de effectiviteit van deze behandelingsmethoden getest en ook het potentiaal van de organismen om na behandeling te hergroeien. Daarnaast werden verschillende analysemethoden getest om de hergroeiende organismen te identificeren. Alle ballastwater behandelingssystemen die getest werden reduceerden organisme aantallen tot onder de internationale standaarden, maar bij alle behandelingssystemen vond ook hergroei plaats na behandeling. Met een combinatie van flow-cytometrie, mikroskopie en DGGE/sequencing werden de hergroeiende soorten geidentificeerd. De hergroeiende organismen waren vergelijkbaar bij behandelingssystemen die hetzelfde type behandeling gebruikten, maar verschillend voor behandelingssystemen die verschillende typen behandeling gebruikten. hergroei vond vooral plaats bij organismen <10 µm, dit formaat organismen is geen deel van de internationale ballastwater richtlijnen. Dit betekent dat er een omissie is in de internationale richtlijnen wat gecorrigeerd zou moeten worden

A comparison of six different ballast water treatment systems based on UV radiation, electrochlorination and chlorine dioxide

The spread of aquatic invasive species through ballast water is a major ecological and economical threat. Because of this, the International Maritime Organization (IMO) set limits to the concentrations of organisms allowed in ballast water. To meet these limits, ballast water treatment systems (BWTSs) were developed. The main techniques used for ballast water treatment are ultraviolet (UV) radiation and electrochlorination (EC). In this study, phytoplankton regrowth after treatment was followed for six BWTSs. Natural plankton communities were treated and incubated for 20 days. Growth, photosystem II efficiency and species composition were followed. The three UV systems all showed similar patterns of decrease in phytoplankton concentrations followed by regrowth. The two EC and the chlorine dioxide systems showed comparable results. However, UV- and chlorine-based treatment systems showed significantly different responses. Overall, all BWTSs reduced phytoplankton concentrations to below the IMO limits, which represents a reduced risk of aquatic invasions through ballast water

Imaging the human microcirculation during cardiopulmonary resuscitation in a hypothermic victim of submersion trauma

The microcirculation is essential for delivery of oxygen and nutrients to tissue. However, the human microvascular response to cardiopulmonary resuscitation (CPR) is unknown. We report on the first use of sidestream dark field imaging to assess the human microcirculation during CPR with a mechanical chest compression/decompression device (mCPR). mCPR was able to provide microvascular perfusion. Capillary flow persisted even during brief mCPR interruption. However, indices of microvascular perfusion were low and improved vastly after return of spontaneous circulation. Microvascular perfusion was relatively independent from blood pressure. The microcirculation may be a useful monitor for determining the adequacy of CPR. (C) 2009 Elsevier Ireland Ltd. All rights reserve