Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Neutrophil–lymphocyte ratio predicts cardiovascular and all-cause mortality in hemodialysis patients

Neutrophil–lymphocyte ratio (NLR) is a marker of systemic inflammation that has been shown to predict mortality in patients with malignancies, ischemic heart disease and peripheral vascular disease. Its prognostic value in hemodialysis patients is unclear. The aims of this study were to: (i) explore the relationship between NLR and other biochemical parameters and (ii) to examine the value of NLR as a predictor of cardiovascular and all-cause mortality in hemodialysis patients. The study included all the incident hemodialysis patients from a single center between 2007 and 2012. NLR was calculated using samples obtained 3 months after commencing hemodialysis. One hundred seventy hemodialysis patients were included with a median follow-up of 37 months. There were 54 deaths (32%). NLR was positively correlated with C-reactive protein (r=0.24, p=0.0023) and negatively correlated with hemoglobin (r=-0.27, p=0.00048), albumin (r=-0.23, p¼0.0034) and total cholesterol (r=-0.17, p=-0.049) levels. In multivariate Cox regression, NLR was independently associated with both all-cause mortality (adjusted hazard ratio [HR] 1.4; 95% confidence interval [CI], 1.2–1.6; p<=0.0001) and cardiovascular death (HR 1.3, 95% CI 1.1–1.6, p=0.0032). Other predictors of all-cause mortality were age (HR 1.6 per decade; 95% CI, 1.2–2.1; p=0.0017), body mass index (HR 0.93; 95% CI, 0.88–0.98; p=0.0047), albumin (HR 0.91; 95% CI, 0.86–0.97; p=0.0035) and peripheral vascular disease (HR 2.7; 95% CI, 1.4–5.1; p=0.0023). NLR is a practical, cost-efficient and easy to use predictor of cardiovascular and all-cause mortality in incident hemodialysis patients

Neutrophil-lymphocyte ratio as a marker of inflammation and predictor of mortality in patients with end-stage kidney disease

Aim: To examine the value of neutrophil-lymphocyte ratio (NLR) as a marker of inflammation and predictor of all-cause mortality in patients with end-stage kidney disease (ESKD).\ud \ud Background: NLR is a marker of systemic inflammation that has been shown to predict mortality in patients with coronary and peripheral vascular disease. In contrast to albumin, NLR is unlikely to be affected by nutritional status. Its prognostic value in ESKD patients is unclear.\ud \ud Methods: We retrospectively reviewed all consecutive haemodialysis patients between January 2007 and December 2011 at a single centre. We recorded patient's full blood count and other biochemistry three months after commencement of dialysis. Correlations between NLR and other metabolic and inflammatory markers were evaluated using Pearson's r coefficient. The prognostic value of NLR was tested using Kaplan Meier, univariate and multivariate Cox analyses adjusted for Australian and New Zealand Dialysis and Transplant Registry data.\ud \ud Results: 140 haemodialysis patients were included with median follow-up of 36 months and overall mortality of 41% (58 patients). Neutrophil-lymphocyte ratio was positively correlated with C-reactive protein (r = 0.48, P < 0.01) and negatively correlated with haemoglobin (r = -0.32, P < 0.01) and albumin (r = -0.40, P < 0.01). In Kaplan Meier analysis, NLR (stratified into tertiles) was associated with all-cause mortality (log-rank, P = 0.01). In multivariate Cox analysis, NLR was independently associated with all-cause mortality (HR 1.09, 95% CI 1.01– 1.17 P = 0.03). Other predictors of all-cause mortality in multivariate analysis were low albumin (HR 0.89, 95% CI 0.89–0.94 P < 0.01) and history of cardiovascular disease (HR 2.29, 95% CI 1.25–4.48 P = 0.01).\ud \ud Conclusions: Neutrophil-lymphocyte ratio correlates with other markers of systemic inflammation in ESKD patients and is associated with poor survival. The extent to which other confounding factors affect these results is unknown

Waveform Modelling for the Laser Interferometer Space Antenna

International audienceLISA, the Laser Interferometer Space Antenna, will usher in a new era in gravitational-wave astronomy. As the first anticipated space-based gravitational-wave detector, it will expand our view to the millihertz gravitational-wave sky, where a spectacular variety of interesting new sources abound: from millions of ultra-compact binaries in our Galaxy, to mergers of massive black holes at cosmological distances; from the beginnings of inspirals that will venture into the ground-based detectors' view to the death spiral of compact objects into massive black holes, and many sources in between. Central to realising LISA's discovery potential are waveform models, the theoretical and phenomenological predictions of the pattern of gravitational waves that these sources emit. This white paper is presented on behalf of the Waveform Working Group for the LISA Consortium. It provides a review of the current state of waveform models for LISA sources, and describes the significant challenges that must yet be overcome

Waveform Modelling for the Laser Interferometer Space Antenna

International audienceLISA, the Laser Interferometer Space Antenna, will usher in a new era in gravitational-wave astronomy. As the first anticipated space-based gravitational-wave detector, it will expand our view to the millihertz gravitational-wave sky, where a spectacular variety of interesting new sources abound: from millions of ultra-compact binaries in our Galaxy, to mergers of massive black holes at cosmological distances; from the beginnings of inspirals that will venture into the ground-based detectors' view to the death spiral of compact objects into massive black holes, and many sources in between. Central to realising LISA's discovery potential are waveform models, the theoretical and phenomenological predictions of the pattern of gravitational waves that these sources emit. This white paper is presented on behalf of the Waveform Working Group for the LISA Consortium. It provides a review of the current state of waveform models for LISA sources, and describes the significant challenges that must yet be overcome

Waveform Modelling for the Laser Interferometer Space Antenna

International audienceLISA, the Laser Interferometer Space Antenna, will usher in a new era in gravitational-wave astronomy. As the first anticipated space-based gravitational-wave detector, it will expand our view to the millihertz gravitational-wave sky, where a spectacular variety of interesting new sources abound: from millions of ultra-compact binaries in our Galaxy, to mergers of massive black holes at cosmological distances; from the beginnings of inspirals that will venture into the ground-based detectors' view to the death spiral of compact objects into massive black holes, and many sources in between. Central to realising LISA's discovery potential are waveform models, the theoretical and phenomenological predictions of the pattern of gravitational waves that these sources emit. This white paper is presented on behalf of the Waveform Working Group for the LISA Consortium. It provides a review of the current state of waveform models for LISA sources, and describes the significant challenges that must yet be overcome