New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Effect of deposition, detachment and aggregation processes on nanoparticle transport in porous media using Monte Carlo simulations

A novel off-lattice three-dimensional coarse-grained Monte Carlo model is developed to study engineered nanoparticle (ENP) behavior in porous media. Based on individual particle tracking and on the assumption that different physicochemical processes may occur with different probabilities, our model is used to independently evaluate the influence of homoaggregation, attachment and detachment processes on ENP transport and retention inside porous media made of colloidal collectors. The possibility of straining, i.e. trapping of ENPs or aggregates that are too large to pass pore necks, is also included in the model. The overall probability of ENP retention as a function of the above mentioned processes is quantified using functional tests in the form of a alpha(global)(t(ref)) retention parameter. High alpha(global)(t(ref)) values were obtained for moderate probabilities of homoaggregation between ENPs (alpha(ENP-ENP)) and very small probabilities of attachment between ENPs and collectors (alpha(att)), thus indicating the important role of homoaggregation and attachment in ENP retention. Moreover, attaching ENPs and large aggregates was found to cause pore neck enclosure and thus largely contributed to the straining of unbound ENPs. An analysis of depth distribution of retained ENPs revealed that, depending on the dominating conditions, the number of ENPs was decreasing monotonously or exponentially with depth. The introduction of the ENP detachment probability (alpha(det)) from collectors resulted in an increased ENP occurrence at the porous media matrix outlet. It was also found that different sets of alpha(det) and alpha(att) values, reflecting different ENPs and collector physicochemical properties and inter-particle forces, lead to identical alpha(global)(t(ref)) values. This constitutes an important outcome indicating that alpha(global)(t(ref)) values determined from functional tests are not mechanistic but operationally defined parameters and thus cannot be deemed predictive beyond these tests

Retention and Transport of Nanoplastics with Different Surface Functionalities in a Sand Filtration System

The efficiency of sand filtration was investigated in terms of the behavior of the nanoplastics (NPLs) with different surface functionalities. The initial condition concentrations of NPLs were varied, and their effects on retention and transport were investigated under a constant flow rate in saturated porous media. The behavior of NPLs in this porous system was discussed by considering Z- average size and zeta (ζ) potential measurements of each effluent. The retention efficiencies of NPLs were ranked as functionalized with amidine [A-PS]+ &gt; with sulfate [S-PS]− &gt; with surfactant-coated amidine [SDS-A-PS]−. The reversibility of the adsorption process was revealed by introducing surfactant into the sand filter system containing adsorbed [A-PS]+ at three different initial state concentration conditions. The deposition behavior on sand grain showed that positively charged NPLs were attached to the quartz surface, and negatively charged NPLs were attached to the edge of the clay minerals, which can be caused by electrical heterogeneities. The homoaggregates made of positively charged NPLs were more compact than those made of negatively charged NPLs and surfactant-coated NPLs. An anti-correlation was revealed, suggesting a connection between the fractal dimension (Df) of NPL aggregates and retention efficiencies. Increased Df values are associated with decreased retention efficiencies.The findings underscore the crucial influence of NPL surface properties in terms of retention efficiency and reversible adsorption in the presence of surfactants in sand filtration systems.</p

Towards a better understanding of CeO₂ manufactured nanoparticles adsorption onto sand grains used in drinking water treatment plants

An increased production of CeO2 nanoparticles (NPs) will inevitably lead to their higher emissions into the natural water bodies. As these emissions pose a significant treat in terms of environmental impacts and possible human health risks, it is necessary to carefully evaluate processes responsible for their mobility and bioavailability. An adsorption is considered as one of the most important processes controlling the fate and transport of nanomaterials in the environment and industrial filtration units. However, mechanisms and physical or chemical parameters influencing these processes are still poorly understood, especially in the case of porous materials used in water purification. In this study, mechanisms responsible for deposition and attachment of CeO2 nanoparticles (NPs) onto quartz sand used as a filter medium in the drinking water treatment plant of Geneva (Switzerland) are examined. For that purpose, a combination of theoretical kinetics and thermodynamic models and a variety of complementary experimental techniques are used. Batch experiments were performed using ultrapure water (pH of 3.0; reference case) and filtered raw Geneva Lake water (pH of 8.6). Size and surface charge of CeO2 NPs dispersed in the supernatant after mixing with sand were determined using dynamic light scattering and laser Doppler velocimetry whereas residual CeO2 NPs concentrations were measured by UV-vis spectroscopy. CeO2 NPs were found to adsorb onto sand grains surfaces under acidic conditions due to electrostatic attractive interactions. The kinetics of adsorption followed well both pseudo-first-order and pseudo-second-order model. The adsorption process was successfully described by Langmuir isotherm which indicated the formation of a monolayer, with a maximal adsorption capacity of 0.85 ± 0.20 mg g-1 at grain surfaces. Further scanning electron microscopy (SEM) images showed individual CeO2 NPs or small aggregates attached to the sand surface, thus confirming the adsorption mechanisms and corresponding model. The results obtained from batch studies conducted using Geneva Lake water showed that aggregation, caused by the presence of natural organic matter (NOM) and multivalent ions, and further aggregate sedimentation are the main processes responsible for CeO2 NPs elimination under environmental conditions. Moreover, as CeO2 NPs and sand grains both carried negative charges, electrostatic repulsion was a main factor limiting the adsorption. The SEM images confirmed these observations and revealed only few aggregates in the vicinity of sand surface irregularities

Insights into polystyrene nanoplastics adsorption mechanisms onto quartz sand used in drinking water treatment plants

The widespread production and use of plastics with poor recycling practices have resulted in higher discharge of plastic waste into the aquatic systems. Nanoplastics (NPLs) resulting from the fragmentation of microplastics, are considered as the most hazardous fraction. Adsorption to mineral surfaces is considered as one of the most important processes controlling the fate and transport of nanomaterials both in the natural environment and conventional filtration systems. However, adsorption mechanisms, influencing physicochemical parameters, and adsorption capacities of different porous media are still poorly known. In this study, the adsorption process of polystyrene (PS) NPLs to quartz sand, used as a filter medium in the drinking water treatment plant in Geneva (Switzerland), is investigated. Contrasting conditions are considered: ultrapure water and Geneva Lake water. Results indicate that PS NPLs dispersed in ultrapure water are adsorbed to the sand surface mainly due to the electrostatic interactions and adsorption capacity of the sand grains varies from 0.05 ± 0.01 mg g-1 to 0.10 ± 0.02 mg g-1 for PS NPLs concentrations comprised between 10 and 50 mg L-1. The adsorption process is successfully described by Langmuir isotherm, therefore indicating the formation of a monolayer on the sand grain surfaces. SEM micrography confirms PS NPLs monolayer formation and image analysis indicates a maximum surface coverage ranging from 9 to 12%. Adsorption mechanisms of PS NPLs are significantly modified under environmental conditions (i.e., pH, ionic composition, presence of DOM). The adsorption capacity of sand grains for the removal of PS NPLs increased and varies from 0.05 ± 0.01 mg g-1 to 0.7 ± 0.2 mg g-1 for PS NPLs concentrations ranging from 10 to 50 mg L-1. Increased adsorption capacity is due to heteroaggregation and cation bridging processes. SEM micrography shows aggregates attached to smooth sand surfaces and deposited in the vicinity of surface irregularities. </p

Weaning from mechanical ventilation in intensive care units across 50 countries (WEAN SAFE): a multicentre, prospective, observational cohort study

Background Current management practices and outcomes in weaning from invasive mechanical ventilation are poorly understood. We aimed to describe the epidemiology, management, timings, risk for failure, and outcomes of weaning in patients requiring at least 2 days of invasive mechanical ventilation. Methods WEAN SAFE was an international, multicentre, prospective, observational cohort study done in 481 intensive care units in 50 countries. Eligible participants were older than 16 years, admitted to a participating intensive care unit, and receiving mechanical ventilation for 2 calendar days or longer. We defined weaning initiation as the first attempt to separate a patient from the ventilator, successful weaning as no reintubation or death within 7 days of extubation, and weaning eligibility criteria based on positive end-expiratory pressure, fractional concentration of oxygen in inspired air, and vasopressors. The primary outcome was the proportion of patients successfully weaned at 90 days. Key secondary outcomes included weaning duration, timing of weaning events, factors associated with weaning delay and weaning failure, and hospital outcomes. This study is registered with ClinicalTrials.gov, NCT03255109. Findings Between Oct 4, 2017, and June 25, 2018, 10 232 patients were screened for eligibility, of whom 5869 were enrolled. 4523 (77·1%) patients underwent at least one separation attempt and 3817 (65·0%) patients were successfully weaned from ventilation at day 90. 237 (4·0%) patients were transferred before any separation attempt, 153 (2·6%) were transferred after at least one separation attempt and not successfully weaned, and 1662 (28·3%) died while invasively ventilated. The median time from fulfilling weaning eligibility criteria to first separation attempt was 1 day (IQR 0–4), and 1013 (22·4%) patients had a delay in initiating first separation of 5 or more days. Of the 4523 (77·1%) patients with separation attempts, 2927 (64·7%) had a short wean (≤1 day), 457 (10·1%) had intermediate weaning (2–6 days), 433 (9·6%) required prolonged weaning (≥7 days), and 706 (15·6%) had weaning failure. Higher sedation scores were independently associated with delayed initiation of weaning. Delayed initiation of weaning and higher sedation scores were independently associated with weaning failure. 1742 (31·8%) of 5479 patients died in the intensive care unit and 2095 (38·3%) of 5465 patients died in hospital. Interpretation In critically ill patients receiving at least 2 days of invasive mechanical ventilation, only 65% were weaned at 90 days. A better understanding of factors that delay the weaning process, such as delays in weaning initiation or excessive sedation levels, might improve weaning success rates

Weaning from mechanical ventilation in intensive care units across 50 countries (WEAN SAFE): a multicentre, prospective, observational cohort study

International audienceBackground: Current management practices and outcomes in weaning from invasive mechanical ventilation are poorly understood. We aimed to describe the epidemiology, management, timings, risk for failure, and outcomes of weaning in patients requiring at least 2 days of invasive mechanical ventilation. Methods: WEAN SAFE was an international, multicentre, prospective, observational cohort study done in 481 intensive care units in 50 countries. Eligible participants were older than 16 years, admitted to a participating intensive care unit, and receiving mechanical ventilation for 2 calendar days or longer. We defined weaning initiation as the first attempt to separate a patient from the ventilator, successful weaning as no reintubation or death within 7 days of extubation, and weaning eligibility criteria based on positive end-expiratory pressure, fractional concentration of oxygen in inspired air, and vasopressors. The primary outcome was the proportion of patients successfully weaned at 90 days. Key secondary outcomes included weaning duration, timing of weaning events, factors associated with weaning delay and weaning failure, and hospital outcomes. This study is registered with ClinicalTrials.gov, NCT03255109. Findings: Between Oct 4, 2017, and June 25, 2018, 10 232 patients were screened for eligibility, of whom 5869 were enrolled. 4523 (77·1%) patients underwent at least one separation attempt and 3817 (65·0%) patients were successfully weaned from ventilation at day 90. 237 (4·0%) patients were transferred before any separation attempt, 153 (2·6%) were transferred after at least one separation attempt and not successfully weaned, and 1662 (28·3%) died while invasively ventilated. The median time from fulfilling weaning eligibility criteria to first separation attempt was 1 day (IQR 0–4), and 1013 (22·4%) patients had a delay in initiating first separation of 5 or more days. Of the 4523 (77·1%) patients with separation attempts, 2927 (64·7%) had a short wean (≤1 day), 457 (10·1%) had intermediate weaning (2–6 days), 433 (9·6%) required prolonged weaning (≥7 days), and 706 (15·6%) had weaning failure. Higher sedation scores were independently associated with delayed initiation of weaning. Delayed initiation of weaning and higher sedation scores were independently associated with weaning failure. 1742 (31·8%) of 5479 patients died in the intensive care unit and 2095 (38·3%) of 5465 patients died in hospital. Interpretation: In critically ill patients receiving at least 2 days of invasive mechanical ventilation, only 65% were weaned at 90 days. A better understanding of factors that delay the weaning process, such as delays in weaning initiation or excessive sedation levels, might improve weaning success rates. Funding: European Society of Intensive Care Medicine, European Respiratory Society

Weaning from mechanical ventilation in intensive care units across 50 countries (WEAN SAFE): a multicentre, prospective, observational cohort study

Background: Current management practices and outcomes in weaning from invasive mechanical ventilation are poorly understood. We aimed to describe the epidemiology, management, timings, risk for failure, and outcomes of weaning in patients requiring at least 2 days of invasive mechanical ventilation. Methods: WEAN SAFE was an international, multicentre, prospective, observational cohort study done in 481 intensive care units in 50 countries. Eligible participants were older than 16 years, admitted to a participating intensive care unit, and receiving mechanical ventilation for 2 calendar days or longer. We defined weaning initiation as the first attempt to separate a patient from the ventilator, successful weaning as no reintubation or death within 7 days of extubation, and weaning eligibility criteria based on positive end-expiratory pressure, fractional concentration of oxygen in inspired air, and vasopressors. The primary outcome was the proportion of patients successfully weaned at 90 days. Key secondary outcomes included weaning duration, timing of weaning events, factors associated with weaning delay and weaning failure, and hospital outcomes. This study is registered with ClinicalTrials.gov, NCT03255109. Findings: Between Oct 4, 2017, and June 25, 2018, 10 232 patients were screened for eligibility, of whom 5869 were enrolled. 4523 (77·1%) patients underwent at least one separation attempt and 3817 (65·0%) patients were successfully weaned from ventilation at day 90. 237 (4·0%) patients were transferred before any separation attempt, 153 (2·6%) were transferred after at least one separation attempt and not successfully weaned, and 1662 (28·3%) died while invasively ventilated. The median time from fulfilling weaning eligibility criteria to first separation attempt was 1 day (IQR 0-4), and 1013 (22·4%) patients had a delay in initiating first separation of 5 or more days. Of the 4523 (77·1%) patients with separation attempts, 2927 (64·7%) had a short wean (≤1 day), 457 (10·1%) had intermediate weaning (2-6 days), 433 (9·6%) required prolonged weaning (≥7 days), and 706 (15·6%) had weaning failure. Higher sedation scores were independently associated with delayed initiation of weaning. Delayed initiation of weaning and higher sedation scores were independently associated with weaning failure. 1742 (31·8%) of 5479 patients died in the intensive care unit and 2095 (38·3%) of 5465 patients died in hospital. Interpretation: In critically ill patients receiving at least 2 days of invasive mechanical ventilation, only 65% were weaned at 90 days. A better understanding of factors that delay the weaning process, such as delays in weaning initiation or excessive sedation levels, might improve weaning success rates. Funding: European Society of Intensive Care Medicine, European Respiratory Society