Objectively measured patterns of sedentary time and physical activity in young adults of the Raine study cohort

Background: To provide a detailed description of young adults' sedentary time and physical activity. Methods: 384 young women and 389 young men aged 22.1±0.6 years, all participants in the 22 year old follow-up of the Raine Study pregnancy cohort, wore Actigraph GT3X+ monitors on the hip for 24 h/day over a one-week period for at least one 'valid' day (=10 h of waking wear time). Each minute epoch was classified as sedentary, light, moderate or vigorous intensity using 100 count and Freedson cut-points. Mixed models assessed hourly and daily variation; t-tests assessed gender differences. Results: The average (mean±SD) waking wear time was 15.0±1.6 h/day, of which 61.4±10.1 % was spent sedentary, 34.6±9.1 % in light-, 3.7±5.3 % in moderate- and, 0.3±0.6 % in vigorous-intensity activity. Average time spent in moderate to vigorous activity (MVPA) was 36.2±27.5 min/day. Relative to men, women had higher sedentary time, but also higher vigorous activity time. The 'usual' bout duration of sedentary time was 11.8±4.5 min in women and 11.7±5.2 min in men. By contrast, other activities were accumulated in shorter bout durations. There was large variation by hour of the day and by day of the week in both sedentary time and MVPA. Evenings and Sundays through Wednesdays tended to be particularly sedentary and/or inactive. Conclusion: For these young adults, much of the waking day was spent sedentary and many participants were physically inactive (low levels of MVPA). We provide novel evidence on the time for which activities were performed and on the time periods when young adults were more sedentary and/or less active. With high sedentary time and low MVPA, young adults may be at risk for the life-course sequelae of these behaviours

Sex-Specific Immunization for Sexually Transmitted Infections Such as Human Papillomavirus: Insights from Mathematical Models

Johannes Bogaards and colleagues use mathematical models to investigate whether vaccinating females only, males only, or both sexes is the best way to achieve the most effective reduction in the population prevalence of sexually-transmitted infection

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

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

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

Inflammatory Bowel Disease: Basic Research, Clinical Implications and Trends in Therapy

W HEN LAPAROSCOPIC cholecystectomy was introduced in the United States many surgeons were reluctant to embrace the technique. It went against many ingrained surgical principles, such as making large incisions to palpate all organs. However, fuelled by public and peer pressure, surgeons were forced to consider laparoscopic surgery. In the United States, training courses quickly appeared and any surgeon who performed cholecystectomies felt he/she had to offer this new approach to remain competitive. Subsequently, laparoscopic cholecystectomy was found to have real advantages over the traditional open technique, which include same-day surgery, 90% full activity in one week, minimal time off work and minimal pain. Thus, laparoscopic technique has quickly become the method of choice for removing most gallbladders in the United States (1-4). Only 50 cases of laparoscopic cholecystectomy were reported in 1989, but it has been estimated that over 500,000 cases were performed in 1993 (5). Enthusiasm for laparoscopic surgery has turned towards other organs including the bowel. Proponents hypothesize that the advantages realized SURGICAL ISSUES IN IBD TL HULL. Laparoscopic techniques: What is the role in inflammatory bowel disease? Can J Gastroenterol 1995;9(1):39-41. Laparoscopic cholecystectomy has quickly become the preferred technique for removing the gallbladder. Real advantages in the area of laparoscopic gallbladder removal have spurred interest towards other areas of laparoscopic surgery. There has been interest in laparoscopic bowel surgery but this approach has not gained popularity as quickly as gallbladder surgery. Reasons surround the fact that the bowel is a continuous organ (versus an end organ like the gallbladder) laden with bacteria and it has a rich blood supply. These differences make laparoscopic bowel surgery more difficult and challenging. If inflammatory bowel disease (IBD) is considered, the indications to approach surgery laparoscopically fall into two categories: current and future indications. The current indications are diagnostic laparoscopy, fecal diversion, limited bowel resections with extracorporeal anastomosis and stoma closures. Future indications include laparoscopic subtotal colectomy and laparoscopic assisted pelvic pouch procedures. As experience is gained and laparoscopic instruments are modified and refined for bowel surgery, intracorporeal anastomosis and more extensive bowel resections will be feasible. Currently laparoscopic bowel surgery can be done in select circumstances for problems associated with IBD. It has yet to be proven if doing the surgery laparoscopically provides advantages for bowel surgery as has been demonstrated with gallbladder surgery. Prospective studies are underway to answer these questions. (Pour résumé, voir page 40