Camelina sativa is an oilseed with desirable agronomic and oil-quality attributes for a viable industrial oil platform crop. Here we generate the first chromosome-scale high-quality reference genome ...sequence for C. sativa and annotated 89,418 protein-coding genes, representing a whole-genome triplication event relative to the crucifer model Arabidopsis thaliana. C. sativa represents the first crop species to be sequenced from lineage I of the Brassicaceae. The well-preserved hexaploid genome structure of C. sativa surprisingly mirrors those of economically important amphidiploid Brassica crop species from lineage II as well as wheat and cotton. The three genomes of C. sativa show no evidence of fractionation bias and limited expression-level bias, both characteristics commonly associated with polyploid evolution. The highly undifferentiated polyploid genome of C. sativa presents significant consequences for breeding and genetic manipulation of this industrial oil crop.
Tobacco smoking is a leading cause of cardiovascular disease (CVD) morbidity and mortality. Evidence on the relation of smoking to different subtypes of CVD, across fatal and non-fatal outcomes, is ...limited.
A prospective study of 188,167 CVD- and cancer-free individuals aged ≥ 45 years from the Australian general population joining the 45 and Up Study from 2006 to 2009, with linked questionnaire, hospitalisation and death data up to the end of 2015. Hazard ratios (HRs) for hospitalisation with or mortality from CVD among current and past versus never smokers were estimated, including according to intensity and recency of smoking, using Cox regression, adjusting for age, sex, urban/rural residence, alcohol consumption, income and education. Population-attributable fractions were estimated.
During a mean 7.2 years follow-up (1.35 million person-years), 27,511 (crude rate 20.4/1000 person-years) incident fatal and non-fatal major CVD events occurred, including 4548 (3.2) acute myocardial infarction (AMI), 3991 (2.8) cerebrovascular disease, 3874 (2.7) heart failure and 2311 (1.6) peripheral arterial disease (PAD) events. At baseline, 8% of participants were current and 34% were past smokers. Of the 36 most common specific CVD subtypes, event rates for 29 were increased significantly in current smokers. Adjusted HRs in current versus never smokers were as follows: 1.63 (95%CI 1.56-1.71) for any major CVD, 2.45 (2.22-2.70) for AMI, 2.16 (1.93-2.42) for cerebrovascular disease, 2.23 (1.96-2.53) for heart failure, 5.06 (4.47-5.74) for PAD, 1.50 (1.24-1.80) for paroxysmal tachycardia, 1.31 (1.20-1.44) for atrial fibrillation/flutter, 1.41 (1.17-1.70) for pulmonary embolism, 2.79 (2.04-3.80) for AMI mortality, 2.26 (1.65-3.10) for cerebrovascular disease mortality and 2.75 (2.37-3.19) for total CVD mortality. CVD risks were elevated at almost all levels of current smoking intensity examined and increased with smoking intensity, with HRs for total CVD mortality in current versus never smokers of 1.92 (1.11-3.32) and 4.90 (3.79-6.34) for 4-6 and ≥ 25 cigarettes/day, respectively. Risks diminished with quitting, with excess risks largely avoided by quitting before age 45. Over one third of CVD deaths and one quarter of acute coronary syndrome hospitalisations in Australia aged < 65 can be attributed to smoking.
Current smoking increases the risk of virtually all CVD subtypes, at least doubling the risk of many, including AMI, cerebrovascular disease and heart failure. Paroxysmal tachycardia is a newly identified smoking-related risk. Where comparisons are possible, smoking-associated relative risks for fatal and non-fatal outcomes are similar. Quitting reduces the risk substantially. In an established smoking epidemic, with declining and low current smoking prevalence, smoking accounts for a substantial proportion of premature CVD events.
Stem cells persist throughout life by self-renewing in numerous tissues including the central and peripheral nervous systems. This raises the issue of whether there is a conserved mechanism to effect ...self-renewing divisions. Deficiency in the polycomb family transcriptional repressor Bmi-1 leads to progressive postnatal growth retardation and neurological defects. Here we show that Bmi-1 is required for the self-renewal of stem cells in the peripheral and central nervous systems but not for their survival or differentiation. The reduced self-renewal of Bmi-1-deficient neural stem cells leads to their postnatal depletion. In the absence of Bmi-1, the cyclin-dependent kinase inhibitor gene p16Ink4a is upregulated in neural stem cells, reducing the rate of proliferation. p16Ink4a deficiency partially reverses the self-renewal defect in Bmi-1-/- neural stem cells. This conserved requirement for Bmi-1 to promote self-renewal and to repress p16Ink4a expression suggests that a common mechanism regulates the self-renewal and postnatal persistence of diverse types of stem cell. Restricted neural progenitors from the gut and forebrain proliferate normally in the absence of Bmi-1. Thus, Bmi-1 dependence distinguishes stem cell self-renewal from restricted progenitor proliferation in these tissues.
Alluvial fans are depositional systems that develop because of a disparity between the upstream and downstream sediment transport capacity of a system, usually at the base of mountain fronts as ...rivers emerge from the constrained mountain area onto the plain. They are dynamic landforms that are prone to abrupt changes on a geomorphological (decades to centuries) time scale, while also being long-term deposition features that preserve sedimentary strata and are sensitive indictors of environmental change. The complexity of interactions between catchment characteristics, climate, tectonics, internal system feedbacks, and environmental processes on field alluvial fans means that it is difficult to isolate individual variables in a field setting; therefore, the controlled conditions afforded by experimental models has provided a novel technique to overcome some of these complexities. The use of experimental models of alluvial fans has a long history and these have been implemented over a range of different research areas utilising various experimental designs. Using this technique, important advances have been made in determining the primary factors influencing fan slope, understanding of avulsion dynamics, identifying autogenic processes driving change on fan systems independent of any change in external conditions, and the mechanics of flow and flood risk on alluvial fans, to name a few. However, experiments cannot be carried out in isolation. Thus, combining the findings from experimental alluvial fans with field research and numerical modelling is important and, likewise, using these techniques to inform experimental design. If this can be achieved, there is potential for future experimental developments to explore key alluvial fan issues such as stratigraphic preservation potential and simulating extra terrestrial fan systems.
•A review paper examining the role of experimental modelling in alluvial fan research•Long history of using experimental alluvial fans to verify fundamental theory•Experimental fans have improved the understanding of flow processes, avulsion mechanics and autogenic forcing•Potential to use experiments for improved understanding of stratigraphic preservation and extra-terrestrial fans
Summary Background Malaria is a major cause of morbidity and mortality in early childhood, yet its consequences for health and education during the school-age years remain poorly understood. We ...examined the effect of intermittent preventive treatment (IPT) in reducing anaemia and improving classroom attention and educational achievement in semi-immune schoolchildren in an area of high perennial transmission. Methods A stratified, cluster-randomised, double-blind, placebo-controlled trial of IPT was done in 30 primary schools in western Kenya. Schools were randomly assigned to treatment (sulfadoxine-pyrimethamine in combination with amodiaquine or dual placebo) by use of a computer-generated list. Children aged 5–18 years received three treatments at 4-month intervals (IPT n=3535, placebo n=3223). The primary endpoint was the prevalence of anaemia, defined as a haemoglobin concentration below 110 g/L. This outcome was assessed through cross-sectional surveys 12 months post-intervention. Analysis was by both intention to treat, excluding children with missing data, and per protocol. This study is registered with ClinicalTrials.gov , number NCT00142246. Findings 2604 children in the IPT group and 2302 in the placebo group were included in the intention-to-treat analysis of the primary outcome; the main reason for exclusion was loss to follow-up. Prevalence of anaemia at 12 months averaged 6·3% in the IPT group and 12·6% in the placebo group (adjusted risk ratio 0·52, 95% CI 0·29–0·93; p=0·028). Significant improvements were also seen in two of the class-based tests of sustained attention, with a mean increase in code transmission test score of 6·05 (95% CI 2·83–9·27; p=0·0007) and counting sounds test score of 1·80 (0·19–3·41; p=0·03), compared with controls. No effect was shown for inattentive or hyperactive-compulsive behaviours or on educational achievement. The per-protocol analysis yielded similar results. 23 serious adverse events were reported within 28 days of any treatment (19 in the IPT group and four in the placebo group); the main side-effects were problems of balance, dizziness, feeling faint, nausea, and/or vomiting shortly after treatment. Interpretation IPT of malaria improves the health and cognitive ability of semi-immune schoolchildren. Effective malaria interventions could be a valuable addition to school health programmes. Funding Gates Malaria Partnership, the Norwegian Education Trust Fund and multidonor Education Development Programme Fund of the World Bank, DBL Centre for Health Research and Development, and the Wellcome Trust.
The objective of this study was to assess the safety and feasibility of in-bed cycling started within the first 4 days of mechanical ventilation (MV) to inform a future randomized clinical trial.
We ...conducted a 33-patient prospective cohort study in a 21-bed adult academic medical-surgical intensive care unit (ICU) in Hamilton, ON, Canada. We included adult patients (≥ 18 years) receiving MV who walked independently pre-ICU. Our intervention was 30 minutes of in-bed supine cycling 6 days/week in the ICU. Our primary outcome was Safety (termination), measured as events prompting cycling termination; secondary Safety (disconnection or dislodgement) outcomes included catheter/tube dislodgements. Feasibility was measured as consent rate and fidelity to intervention. For our primary outcome, we calculated the binary proportion and 95% confidence interval (CI).
From 10/2013-8/2014, we obtained consent from 34 of 37 patients approached (91.9%), 33 of whom received in-bed cycling. Of those who cycled, 16(48.4%) were female, the mean (SD) age was 65.8(12.2) years, and APACHE II score was 24.3(6.7); 29(87.9%) had medical admitting diagnoses. Cycling termination was infrequent (2.0%, 95% CI: 0.8%-4.9%) and no device dislodgements occurred. Cycling began a median IQR of 3 2, 4 days after ICU admission; patients received 5 3, 8 cycling sessions with a median duration of 30.7 21.6, 30.8 minutes per session. During 205 total cycling sessions, patients were receiving invasive MV (150 73.1%), vasopressors (6 2.9%), sedative or analgesic infusions (77 37.6%) and dialysis (4 2.0%).
Early cycling within the first 4 days of MV among hemodynamically stable patients is safe and feasible. Research to evaluate the effect of early cycling on patient function is warranted.
Clinicaltrials.gov: NCT01885442.
Cleaning practices and hand hygiene are important behaviors to prevent and control the spread of infectious disease, especially in congregate settings. This project explored hygiene- and ...cleaning-related experiences in shelters serving people experiencing homelessness (PEH) during May-June 2020 of the COVID-19 pandemic.
We conducted qualitative, in-depth interviews by phone with 22 staff from six shelters in Atlanta, Georgia. The interview guide included questions about cleaning routines, cleaning barriers and facilitators, cleaning promotion, hand hygiene promotion, and hand hygiene barriers and facilitators. We analyzed interview transcripts using thematic analysis.
Multiple individuals, such as shelter individuals (clients), volunteers, and staff, played a role in shelter cleaning. Staff reported engaging in frequent hand hygiene and cleaning practices. Barriers to cleaning included staffing shortages and access to cleaning supplies. Staff reported barriers (e.g., differing perceptions of cleanliness) for clients who were often involved in cleaning activities. Barriers to hand hygiene included limited time to wash hands, forgetting, and inconvenient handwashing facilities. Specific guidance about when and how to clean, and what supplies to use, were requested.
During the early months of the COVID-19 pandemic, shelters serving PEH in the Atlanta-metro area needed resources and support to ensure sufficient staffing and supplies for cleaning activities. As part of future pandemic planning and outbreak prevention efforts, shelters serving PEH could benefit from specific guidance and training materials on cleaning and hand hygiene practices.
Objective To assess the effectiveness of physiotherapy compared with no intervention in patients with Parkinson’s disease.Design Systematic review and meta-analysis of randomised controlled ...trials.Data sources Literature databases, trial registries, journals, abstract books, and conference proceedings, and reference lists, searched up to the end of January 2012.Review methods Randomised controlled trials comparing physiotherapy with no intervention in patients with Parkinson’s disease were eligible. Two authors independently abstracted data from each trial. Standard meta-analysis methods were used to assess the effectiveness of physiotherapy compared with no intervention. Tests for heterogeneity were used to assess for differences in treatment effect across different physiotherapy interventions used. Outcome measures were gait, functional mobility and balance, falls, clinician rated impairment and disability measures, patient rated quality of life, adverse events, compliance, and economic analysis outcomes.Results 39 trials of 1827 participants met the inclusion criteria, of which 29 trials provided data for the meta-analyses. Significant benefit from physiotherapy was reported for nine of 18 outcomes assessed. Outcomes which may be clinically significant were speed (0.04 m/s, 95% confidence interval 0.02 to 0.06, P<0.001), Berg balance scale (3.71 points, 2.30 to 5.11, P<0.001), and scores on the unified Parkinson’s disease rating scale (total score −6.15 points, −8.57 to −3.73, P<0.001; activities of daily living subscore −1.36, −2.41 to −0.30, P=0.01; motor subscore −5.01, −6.30 to −3.72, P<0.001). Indirect comparisons of the different physiotherapy interventions found no evidence that the treatment effect differed across the interventions for any outcomes assessed, apart from motor subscores on the unified Parkinson’s disease rating scale (in which one trial was found to be the cause of the heterogeneity).Conclusions Physiotherapy has short term benefits in Parkinson’s disease. A wide range of physiotherapy techniques are currently used to treat Parkinson’s disease, with little difference in treatment effects. Large, well designed, randomised controlled trials with improved methodology and reporting are needed to assess the efficacy and cost effectiveness of physiotherapy for treating Parkinson’s disease in the longer term.
To estimate small for gestational age birth prevalence and attributable neonatal mortality in low and middle income countries with the INTERGROWTH-21
birth weight standard.
Secondary analysis of ...data from the Child Health Epidemiology Reference Group (CHERG), including 14 birth cohorts with gestational age, birth weight, and neonatal follow-up. Small for gestational age was defined as infants weighing less than the 10th centile birth weight for gestational age and sex with the multiethnic, INTERGROWTH-21
birth weight standard. Prevalence of small for gestational age and neonatal mortality risk ratios were calculated and pooled among these datasets at the regional level. With available national level data, prevalence of small for gestational age and population attributable fractions of neonatal mortality attributable to small for gestational age were estimated.
CHERG birth cohorts from 14 population based sites in low and middle income countries.
In low and middle income countries in the year 2012, the number and proportion of infants born small for gestational age; number and proportion of neonatal deaths attributable to small for gestational age; the number and proportion of neonatal deaths that could be prevented by reducing the prevalence of small for gestational age to 10%.
In 2012, an estimated 23.3 million infants (uncertainty range 17.6 to 31.9; 19.3% of live births) were born small for gestational age in low and middle income countries. Among these, 11.2 million (0.8 to 15.8) were term and not low birth weight (≥2500 g), 10.7 million (7.6 to 15.0) were term and low birth weight (<2500 g) and 1.5 million (0.9 to 2.6) were preterm. In low and middle income countries, an estimated 606 500 (495 000 to 773 000) neonatal deaths were attributable to infants born small for gestational age, 21.9% of all neonatal deaths. The largest burden was in South Asia, where the prevalence was the highest (34%); about 26% of neonatal deaths were attributable to infants born small for gestational age. Reduction of the prevalence of small for gestational age from 19.3% to 10.0% in these countries could reduce neonatal deaths by 9.2% (254 600 neonatal deaths; 164 800 to 449 700).
In low and middle income countries, about one in five infants are born small for gestational age, and one in four neonatal deaths are among such infants. Increased efforts are required to improve the quality of care for and survival of these high risk infants in low and middle income countries.
The 1000 Genomes Project (1kGP) is the largest fully open resource of whole-genome sequencing (WGS) data consented for public distribution without access or use restrictions. The final, phase 3 ...release of the 1kGP included 2,504 unrelated samples from 26 populations and was based primarily on low-coverage WGS. Here, we present a high-coverage 3,202-sample WGS 1kGP resource, which now includes 602 complete trios, sequenced to a depth of 30X using Illumina. We performed single-nucleotide variant (SNV) and short insertion and deletion (INDEL) discovery and generated a comprehensive set of structural variants (SVs) by integrating multiple analytic methods through a machine learning model. We show gains in sensitivity and precision of variant calls compared to phase 3, especially among rare SNVs as well as INDELs and SVs spanning frequency spectrum. We also generated an improved reference imputation panel, making variants discovered here accessible for association studies.
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