Lessons for conservation management: Monitoring temporal changes in genetic diversity of Cape mountain zebra (Equus zebra zebra)

The Cape mountain zebra (Equus zebra zebra) is a subspecies of mountain zebra endemic to South Africa. The Cape mountain zebra experienced near extinction in the early 1900's and their numbers have since recovered to more than 4,800 individuals. However, there are still threats to their long-term persistence. A previous study reported that Cape mountain zebra had low genetic diversity in three relict populations and that urgent conservation management actions were needed to mitigate the risk of further loss. As these suggestions went largely unheeded, we undertook the present study, fifteen years later to determine the impact of management on genetic diversity in three key populations. Our results show a substantial loss of heterozygosity across the Cape mountain zebra populations studied. The most severe losses occurred at De Hoop Nature Reserve where expected heterozygosity reduced by 22.85% from 0.385 to 0.297. This is alarming, as the De Hoop Nature Reserve was previously identified as the most genetically diverse population owing to its founders originating from two of the three remaining relict stocks. Furthermore, we observed a complete loss of multiple private alleles from all populations, and a related reduction in genetic structure across the subspecies. These losses could lead to inbreeding depression and reduce the evolutionary potential of the Cape mountain zebra. We recommend immediate implementation of evidence-based genetic management and monitoring to prevent further losses, which could jeopardise the long term survival of Cape mountain zebra, especially in the face of habitat and climate change and emerging diseases

One step forward and two steps back? The ‘20 Principles’ for questioning vulnerable witnesses and the lack of an evidence-based approach

It is a widely held belief that questioning vulnerable witnesses is a specialist skill. In England and Wales vulnerable witness advocacy training built around ‘20 Principles’ has been developed and is being delivered. The 20 Principles do not cite a tested theoretical framework(s) or empirical evidence in support. This paper considers whether the 20 Principles are underpinned by research evidence. It is submitted that advocacy training and the approach to questioning witnesses in the courtroom should take into account the already available research evidence. The authors make recommendations for revision of the training and for a wider review of the approach taken to the handling of witness evidence

Environmental Exposure and Leptospirosis, Peru

Human infection by leptospires has highly variable clinical manifestations, which range from subclinical infection to fulminant disease. We conducted a population-based, cross-sectional seroepidemiologic study in Peru to determine potential relationships of environmental context to human exposure to Leptospira and disease associated with seroconversion. Three areas were studied: a flooded, urban slum in the Peruvian Amazon city of Iquitos; rural, peri-Iquitos villages; and a desert shantytown near Lima. Seroprevalence in Belen was 28% (182/650); in rural areas, 17% (52/316); and in a desert shantytown, 0.7% (1/150). Leptospira-infected peridomestic rats were found in all locales. In Belen, 20 (12.4%) of 161 patients seroconverted between dry and wet seasons (an incidence rate of 288/1,000). Seroconversion was associated with history of febrile illness; severe leptospirosis was not seen. Human exposure to Leptospira in the Iquitos region is high, likely related both to the ubiquity of leptospires in the environment and human behavior conducive to transmission from infected zoonotic sources

Levetiracetam versus phenytoin for second-line treatment of paediatric convulsive status epilepticus (EcLiPSE): a multicentre, open-label, randomised trial

Background Phenytoin is the recommended second-line intravenous anticonvulsant for treatment of paediatric convulsive status epilepticus in the UK; however, some evidence suggests that levetiracetam could be an effective and safer alternative. This trial compared the efficacy and safety of phenytoin and levetiracetam for second-line management of paediatric convulsive status epilepticus.Methods This open-label, randomised clinical trial was undertaken at 30 UK emergency departments at secondary and tertiary care centres. Participants aged 6 months to under 18 years, with convulsive status epilepticus requiring second-line treatment, were randomly assigned (1:1) using a computer-generated randomisation schedule to receive levetiracetam (40 mg/kg over 5 min) or phenytoin (20 mg/kg over at least 20 min), stratified by centre. The primary outcome was time from randomisation to cessation of convulsive status epilepticus, analysed in the modified intention-to-treat population (excluding those who did not require second-line treatment after randomisation and those who did not provide consent). This trial is registered with ISRCTN, number ISRCTN22567894.Findings Between July 17, 2015, and April 7, 2018, 1432 patients were assessed for eligibility. After exclusion of ineligible patients, 404 patients were randomly assigned. After exclusion of those who did not require second-line treatment and those who did not consent, 286 randomised participants were treated and had available data: 152 allocated to levetiracetam, and 134 to phenytoin. Convulsive status epilepticus was terminated in 106 (70%) children in the levetiracetam group and in 86 (64%) in the phenytoin group. Median time from randomisation to cessation of convulsive status epilepticus was 35 min (IQR 20 to not assessable) in the levetiracetam group and 45 min (24 to not assessable) in the phenytoin group (hazard ratio 1·20, 95% CI 0·91–1·60; p=0·20). One participant who received levetiracetam followed by phenytoin died as a result of catastrophic cerebral oedema unrelated to either treatment. One participant who received phenytoin had serious adverse reactions related to study treatment (hypotension considered to be immediately life-threatening [a serious adverse reaction] and increased focal seizures and decreased consciousness considered to be medically significant [a suspected unexpected serious adverse reaction]). Interpretation Although levetiracetam was not significantly superior to phenytoin, the results, together with previously reported safety profiles and comparative ease of administration of levetiracetam, suggest it could be an appropriate alternative to phenytoin as the first-choice, second-line anticonvulsant in the treatment of paediatric convulsive status epilepticus

The effect on cardiovascular risk factors of migration from rural to urban areas in Peru: PERU MIGRANT Study

BACKGROUND: Mass-migration observed in Peru from the 1970s occurred because of the need to escape from politically motivated violence and work related reasons. The majority of the migrant population, mostly Andean peasants from the mountainous areas, tends to settle in clusters in certain parts of the capital and their rural environment could not be more different than the urban one. Because the key driver for migration was not the usual economic and work-related reasons, the selection effects whereby migrants differ from non-migrants are likely to be less prominent in Peru. Thus the Peruvian context offers a unique opportunity to test the effects of migration. METHODS/DESIGN: The PERU MIGRANT (PEru's Rural to Urban MIGRANTs) study was designed to investigate the magnitude of differences between rural-to-urban migrant and non-migrant groups in specific CVD risk factors. For this, three groups were selected: Rural, people who have always have lived in a rural environment; Rural-urban, people who migrated from rural to urban areas; and, Urban, people who have always lived in a urban environment. DISCUSSION: Overall response rate at enrolment was 73.2% and overall response rate at completion of the study was 61.6%. A rejection form was obtained in 282/323 people who refused to take part in the study (87.3%). Refusals did not differ by sex in rural and migrant groups, but 70% of refusals in the urban group were males. In terms of age, most refusals were observed in the oldest age-group (>60 years old) in all study groups. The final total sample size achieved was 98.9% of the target sample size (989/1000). Of these, 52.8% (522/989) were females. Final size of the rural, migrant and urban study groups were 201, 589 and 199 urban people, respectively. Migrant's average age at first migration and years lived in an urban environment were 14.4 years (IQR 10-17) and 32 years (IQR 25-39), respectively. This paper describes the PERU MIGRANT study design together with a critical analysis of the potential for bias and confounding in migrant studies, and strategies for reducing these problems. A discussion of the potential advantages provided by the case of migration in Peru to the field of migration and health is also presented

Uncovering the complex genetics of human temperament

Experimental studies of learning suggest that human temperament may depend on the molecular mechanisms for associative conditioning, which are highly conserved in animals. The main genetic pathways for associative conditioning are known in experimental animals, but have not been identified in prior genome-wide association studies (GWAS) of human temperament. We used a data-driven machine learning method for GWAS to uncover the complex genotypic-phenotypic networks and environmental interactions related to human temperament. In a discovery sample of 2149 healthy Finns, we identified sets of single-nucleotide polymorphisms (SNPs) that cluster within particular individuals (i.e., SNP sets) regardless of phenotype. Second, we identified 3 clusters of people with distinct temperament profiles measured by the Temperament and Character Inventory regardless of genotype. Third, we found 51 SNP sets that identified 736 gene loci and were significantly associated with temperament. The identified genes were enriched in pathways activated by associative conditioning in animals, including the ERK, PI3K, and PKC pathways. 74% of the identified genes were unique to a specific temperament profile. Environmental influences measured in childhood and adulthood had small but significant effects. We confirmed the replicability of the 51 Finnish SNP sets in healthy Korean (90%) and German samples (89%), as well as their associations with temperament. The identified SNPs explained nearly all the heritability expected in each sample (37-53%) despite variable cultures and environments. We conclude that human temperament is strongly influenced by more than 700 genes that modulate associative conditioning by molecular processes for synaptic plasticity and long-term memory.Peer reviewe

Discovery of common and rare genetic risk variants for colorectal cancer.

To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P < 5 × 10-8, bringing the number of known independent signals for CRC to ~100. New signals implicate lower-frequency variants, Krüppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development.Goncalo R Abecasis has received compensation from 23andMe and Helix. He is currently an employee of Regeneron Pharmaceuticals. Heather Hampel performs collaborative research with Ambry Genetics, InVitae Genetics, and Myriad Genetic Laboratories, Inc., is on the scientific advisory board for InVitae Genetics and Genome Medical, and has stock in Genome Medical. Rachel Pearlman has participated in collaborative funded research with Myriad Genetics Laboratories and Invitae Genetics but has no financial competitive interest

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

What Works in Conservation 2018

This book provides an assessment of the effectiveness of 1277 conservation interventions based on summarized scientific evidence. The 2018 edition contains new chapters covering practical global conservation of primates, peatlands, shrublands and heathlands, management of captive animals as well as an extended chapter on control of freshwater invasive species. Other chapters cover global conservation of amphibians, bats, birds and forests, conservation of European farmland biodiversity and some aspects of enhancing natural pest control, enhancing soil fertility and control of freshwater invasive species. It contains key results from the summarized evidence for each conservation intervention and an assessment of the effectiveness of each by international expert panels. The accompanying website www.conservationevidence.com describes each of the studies individually, and provides full references