Clinical impact of additional findings detected by genome-wide non-invasive prenatal testing:Follow-up results of the TRIDENT-2 study

In the TRIDENT-2 study, all pregnant women in the Netherlands are offered genome-wide non-invasive prenatal testing (GW-NIPT) with a choice of receiving either full screening or screening solely for common trisomies. Previous data showed that GW-NIPT can reliably detect common trisomies in the general obstetric population and that this test can also detect other chromosomal abnormalities (additional findings). However, evidence regarding the clinical impact of screening for additional findings is lacking. Therefore, we present follow-up results of the TRIDENT-2 study to determine this clinical impact based on the laboratory and perinatal outcomes of cases with additional findings. Between April 2017 and April 2019, additional findings were detected in 402/110,739 pregnancies (0.36%). For 358 cases, the origin was proven to be either fetal (n = 79; 22.1%), (assumed) confined placental mosaicism (CPM) (n = 189; 52.8%), or maternal (n = 90; 25.1%). For the remaining 44 (10.9%), the origin of the aberration could not be determined. Most fetal chromosomal aberrations were pathogenic and associated with severe clinical phenotypes (61/79; 77.2%). For CPM cases, occurrence of pre-eclampsia (8.5% [16/189] vs 0.5% [754/159,924]; RR 18.5), and birth weigh

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Correction:How the COVID-19 pandemic highlights the necessity of animal research (vol 30, pg R1014, 2020)

(Current Biology 30, R1014–R1018; September 21, 2020) As a result of an author oversight in the originally published version of this article, a number of errors were introduced in the author list and affiliations. First, the middle initials were omitted from the names of several authors. Second, the surname of Dr. van Dam was mistakenly written as “Dam.” Third, the first name of author Bernhard Englitz was misspelled as “Bernard” and the surname of author B.J.A. Pollux was misspelled as “Pullox.” Finally, Dr. Keijer's first name was abbreviated rather than written in full. These errors, as well as various errors in the author affiliations, have now been corrected online

Antibodies against ARHGDIB are associated with long-term kidney graft loss

The clinical significance of non‐HLA antibodies on renal allograft survival is a matter of debate, due to differences in reported results and lack of large‐scale studies incorporating analysis of multiple non‐HLA antibodies simultaneously. We developed a multiplex non‐HLA antibody assay against 14 proteins highly expressed in the kidney. In this study, the presence of pretransplant non‐HLA antibodies was corre

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Activation of Proteinase 3 Contributes to Nonalcoholic Fatty Liver Disease and Insulin Resistance

Abstract Activation of inflammatory pathways is known to accompany development of obesity-induced nonalcoholic fatty liver disease (NAFLD), insulin resistance and type 2 diabetes. In addition to caspase-1, the neutrophil serine proteases proteinase 3, neutrophil elastase and cathepsin G are able to process the inactive proinflammatory mediators interleukin (IL)-1β and IL-18 to their bioactive forms, thereby regulating inflammatory responses. In this study, we investigated whether proteinase 3 is involved in obesity-induced development of insulin resistance and NAFLD. We investigated the development of NAFLD and insulin resistance in mice deficient for neutrophil elastase/proteinase 3 and neutrophil elastase/cathepsin G and in wild-type mice treated with the neutrophil serine proteinase inhibitor human α-1 antitrypsin. Expression profiling of metabolically relevant tissues obtained from insulin-resistant mice showed that expression of proteinase 3 was specifically upregulated in the liver, whereas neutrophil elastase, cathepsin G and caspase-1 were not. Neutrophil elastase/proteinase 3-deficient mice showed strongly reduced levels of lipids in the liver after being fed a high-fat diet. Moreover, these mice were resistant to high-fat-diet-induced weight gain, inflammation and insulin resistance. Injection of proteinase 3 exacerbated insulin resistance in caspase-1−/− mice, indicating that proteinase 3 acts independently of caspase-1. Treatment with α-1 antitrypsin during the last 10 d of a 16-wk high-fat diet reduced hepatic lipid content and decreased fasting glucose levels. We conclude that proteinase 3 is involved in NAFLD and insulin resistance and that inhibition of proteinase 3 may have therapeutic potential

Rewetting does not return drained fen peatlands to their old selves

Peatlands, in particular groundwater-fed fens of the temperate zone, have been drained for agriculture, forestry and peat extraction for a long time and on a large scale. Drainage turns peatlands from a carbon and nutrient sink into a respective source, diminishes water regulation capacity at the landscape scale, causes continuous surface height loss and destroys their typical biodiversity. Over the last decades, drained peatlands have been rewetted for biodiversity restoration and, as it strongly decreases greenhouse gas emissions, also for climate protection. With the dataset published here, we quantified restoration success by comparing 320 rewetted fen peatland sites to 243 near-natural peatland sites of similar origin across temperate Europe with regards to biodiversity (vegetation), ecosystem functioning (hydrology, geochemistry) and land cover characteristics based on remote sensing. Vegetation data comes as species-specific cover values. Hydrology data covers on average 2.3 years and minimally one full year and comes as median, minimum, and maximum water table depth. Geochemistry consists of pH and electrical conductivity of the pore water (0-60 cm), bulk density and organic matter content of the top soil layer (0-30 cm), all sampled in summer for all sites included here alongside the vegetation data sampling. Land cover characteristics contain 208 spectral-temporal metrics for a full annual time series of Copernicus Sentinel-2 A/B data for 2018.Several taxa included in this dataset are at risk from a harmful human activity, in accordance to Chapman 2008 (https://docs.gbif.org/sensitive-species-best-practices/master/en/) we therefore report the georeferences denatured to 0.1 degrees (~10 km). Data may be supplied at finer scales on request under the conditions of a written data agreement. Missing values are coded as NA, zeros are true and measured values. Funding provided by: European Social FundCrossref Funder Registry ID: http://dx.doi.org/10.13039/501100004895Award Number: ESF/14-BM-A55-0027/16 to ESF/14-BM-A55-0035/16Funding provided by: BiodivERsA*Crossref Funder Registry ID: Award Number: DFG JO 332/15-1Funding provided by: BiodivERsA*Crossref Funder Registry ID: Award Number: BELSPO BR/175/A1Funding provided by: BiodivERsA*Crossref Funder Registry ID: Award Number: NCN 2016/22/Z/NZ8/00001Funding provided by: Ministerium für Bildung, Wissenschaft und Kultur Mecklenburg-VorpommernCrossref Funder Registry ID: http://dx.doi.org/10.13039/501100014848Award Number: ESF/14-BM-A55-0027/16 to ESF/14-BM-A55-0035/16Funding provided by: BiodivERsACrossref Funder Registry ID: Award Number: DFG JO 332/15-1See methods section of the accompanying paper for details about data collection and processing; see ReadMe-file for parameter explanation. Potential sites were found through literature search and contacting the respective authors. All such authors providing data were included as co-authors and we included all data from fen ecosystems of temperate Europe which were drained and had a dateable rewetting action and all sites without direct drainage history as confirmed by local experts and remote sensing. We included all sites that provided data for at least two of the following four response clusters in order to obtain comparable datasets for these clusters: (1) vegetation, (2) hydrology, (3) geochemistry, (4) land cover characteristics. We included all available datasets fitting to the definitions laid out above. Sampling for vegetation and geochemistry occurred in summer for all sites. Vegetation sampling consisted of complete lists of vascular plants and bryophytes (539 species in total) based on 16 m² (median, ranging between 12 and 25 m²) with estimates of individual plant species cover. All vegetation data collections included in this study aimed at full species lists and used comparable methodologies, i.e. estimating species-specific cover values. Studies focusing on specific taxa or just reporting the dominant species were excluded from the analyses. Geochemical sampling quantified pH and electrical conductivity of the pore water (0-60 cm) and bulk density and organic matter content of the top soil layer (0-30 cm). Hydrological data relied on on continuous are at least monthly manual sampling for on average, 2.3 years, and a minimum of at least one full year. Land cover characteristics were sampled after the fact for all sites for which the required remote sensing prodcuts were available in the year 2018. Data was collected for different purposes over different years. The data owners are included as co-authors. Vegetation data is the estimated aboveground cover of all vascular plants and bryophytes (539 species in total) within a 16 m² (median, ranging between 12 and 25 m²) plot noted down by experts with pen on paper. Hydrological data is based on 269 piezometers with dataloggers, 91 piezometers related to a datalogger in a transect, 216 piezometers with manual measurements of at least one year and biweekly or monthly readings of the water table depth relative to the peat surface. Geochemical data consisted of pH and electric conductivity of the pore water extracted in the field and measured directly with portable pH-sensors and conductivity sensors. Bulk density was quantfied based on volumetric field samples (0-30cm depth) in relation to their dry weight after drying to constant weight in a drying cabinet. Organic matter was quantified as the loss on ignition of these dry samples. Land cover characteristics: spectral-temporal metrics for a full annual time series of Copernicus Sentinel-2 A/B data for 2018. The Sentinel-2 A/B constellation provides optical imagery of the Earth's surface between ~0.49 - ~2.2 µm in ten spectral bands and at 10 – 20 m ground sampling distance at a theoretical acquisition frequency of 2.5 – 5 days. We here acquired all available Sentinel-2 A/B imagery for 2018 with cloud cover <70% from the ESA API Hub. We used all valid observations to derive spectral-temporal metrics from the time series. Spectral temporal metrics are statistical measures (e.g. average, minimum, maximum, quartiles, …) per spectral band or index (e.g. MNDWI = (green - short wave infrared)/(green + short wave infrared)) using all available cloud- and shadow-free observations over time. The median count of clear-sky-observations per pixel across the sites is 45, while 90% of all sites featured 27 clear-sky observations or more. Both data processing to Analysis Ready Data as well as calculating spectral-temporal metrics was performed through the Framework for Operational Radiometric Correction for Environmental monitoring. Our analysis included data averaged over 3x3 pixels around the center plot location of the site. Different spatial aggregations (e.g. single pixels, 5x5 pixels around the center plot) led to highly similar results, implying that the intra-site variability was robust around locations of the vegetation survey. The inclusion of an annual series of Sentinel-1 synthetic aperture radar data (temporal metrics for VV and VH polarization, IW swath at 10 m resolution) for the same year did not affect the results. Spatial scale: temperate fen ecosystems of Europe. Timing: Data was collected between 1994 and 2019 with sampling for vegetation and geochemistry occurring once per site with known year and time since rewetting for the rewetted sites but different years between sites. Hydrology was monitored for >1 year at each site (see above for details and rationale), again with known time periods per site and different timing for different sites. Land cover characteristics were sampled for all sites for the year 2018 as decribed above