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The introduction of American mink (Neovison vison; hereafter mink) into Europe has had severe impacts on many native wildlife species, including the water vole (Arvicola amphibius) in mainland Britain. Although trapping has been widely used to attempt to control mink, managers have little direct evidence of its effect on mink density or distribution, particularly where immigration of mink from nearby areas is inevitable. Such evidence is needed to justify the use of lethal methods in conservation policy. During 2006—2010 we removed mink from the River Monnow Catchment in western Britain, using track-recording rafts to monitor continuously for mink presence, guiding a strategic trapping effort. The area monitored and trapped was increased in stages, from a core sub-catchment with 109 km of water-course in 2006, to a 421-km² catchment with 203 km of water-course in 2009. In each successive sub-catchment, mink detection and capture rates declined rapidly to near-zero levels after trapping began. Detections and captures showed seasonal peaks in every year corresponding to known dispersal periods, but also declined steadily from year to year, with increasing periods in which we did not detect mink. These results suggested that each sub-catchment was cleared of mink within a few months, with subsequent captures attributable to immigration. On average, we detected each mink 5.1 times before capture (daily probability of detection = 0.059 per mink and raft), and trapped them 3.4 days after deploying traps in response. On average, mink entering the area were likely to have been present for less than 13 days before capture. Water voles had been extinct in the Monnow Catchment since the 1980s. During 2006—2008 (starting 6 months after mink trapping commenced), we released 700 captive-bred water voles into the treatment area to re-establish a wild population. Persistence of this population through the 4 years of the project was considered indicative of effective mink control. This study demonstrates that, even in a mainland context, a systematic trapping strategy can have a substantial impact on the density and distribution of a damaging species, in this case allowing the restoration of a native prey species.

Pregnancy loss and perinatal death are devastating events for families. We assessed ‘genomic autopsy’ as an adjunct to standard autopsy for 200 families who had experienced fetal or newborn death, providing a definitive or candidate genetic diagnosis in 105 families. Our cohort provides evidence of severe atypical in utero presentations of known genetic disorders and identifies novel phenotypes and disease genes. Inheritance of 42% of definitive diagnoses were either autosomal recessive (30.8%), X-linked recessive (3.8%) or autosomal dominant (excluding de novos, 7.7%), with risk of recurrence in future pregnancies. We report that at least ten families (5%) used their diagnosis for preimplantation (5) or prenatal diagnosis (5) of 12 pregnancies. We emphasize the clinical importance of genomic investigations of pregnancy loss and perinatal death, with short turnaround times for diagnostic reporting and followed by systematic research follow-up investigations. This approach has the potential to enable accurate counseling for future pregnancies. In a new study including 200 families who experienced perinatal death, adding genomic analyses to standard autopsies improved the identification of underlying pathogenic causes and informed genetic counseling.

Background Existing treatments for young people with severe depression have limited effectiveness. The aim of the Study of Ketamine for Youth Depression (SKY-D) trial is to determine whether a 4-week course of low-dose subcutaneous ketamine is an effective adjunct to treatment-as-usual in young people with major depressive disorder (MDD). Methods SKY-D is a double-masked, randomised controlled trial funded by the Australian Government’s National Health and Medical Research Council (NHMRC). Participants aged between 16 and 25 years (inclusive) with moderate-to-severe MDD will be randomised to receive either low-dose ketamine (intervention) or midazolam (active control) via subcutaneous injection once per week for 4 weeks. The primary outcome is change in depressive symptoms on the Montgomery-Åsberg Depression Rating Scale (MADRS) after 4 weeks of treatment. Further follow-up assessment will occur at 8 and 26 weeks from treatment commencement to determine whether treatment effects are sustained and to investigate safety outcomes. Discussion Results from this trial will be important in determining whether low-dose subcutaneous ketamine is an effective treatment for young people with moderate-to-severe MDD. This will be the largest randomised trial to investigate the effects of ketamine to treat depression in young people. Trial registration Australian and New Zealand Clinical Trials Registry ID: ACTRN12619000683134. Registered on May 7, 2019. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=377513 .

ObjectiveTo implement complex, PINCER (pharmacist led information technology intervention) prescribing indicators, on a national scale with general practice data to describe the impact of the covid-19 pandemic on safe prescribing.DesignPopulation based, retrospective cohort study using federated analytics.SettingElectronic general practice health record data from 56.8 million NHS patients by use of the OpenSAFELY platform, with the approval of the National Health Service (NHS) England.ParticipantsNHS patients (aged 18-120 years) who were alive and registered at a general practice that used TPP or EMIS computer systems and were recorded as at risk of at least one potentially hazardous PINCER indicator.Main outcome measureBetween 1 September 2019 and 1 September 2021, monthly trends and between practice variation for compliance with 13 PINCER indicators, as calculated on the first of every month, were reported. Prescriptions that do not adhere to these indicators are potentially hazardous and can cause gastrointestinal bleeds; are cautioned against in specific conditions (specifically heart failure, asthma, and chronic renal failure); or require blood test monitoring. The percentage for each indicator is formed of a numerator of patients deemed to be at risk of a potentially hazardous prescribing event and the denominator is of patients for which assessment of the indicator is clinically meaningful. Higher indicator percentages represent potentially poorer performance on medication safety.ResultsThe PINCER indicators were successfully implemented across general practice data for 56.8 million patient records from 6367 practices in OpenSAFELY. Hazardous prescribing remained largely unchanged during the covid-19 pandemic, with no evidence of increases in indicators of harm as captured by the PINCER indicators. The percentage of patients at risk of potentially hazardous prescribing, as defined by each PINCER indicator, at mean quarter 1 (Q1) 2020 (representing before the pandemic) ranged from 1.11% (age ≥65 years and non-steroidal anti-inflammatory drugs) to 36.20% (amiodarone and no thyroid function test), while Q1 2021 (representing after the pandemic) percentages ranged from 0.75% (age ≥65 years and non-steroidal anti-inflammatory drugs) to 39.23% (amiodarone and no thyroid function test). Transient delays occurred in blood test monitoring for some medications, particularly angiotensin-converting enzyme inhibitors (where blood monitoring worsened from a mean of 5.16% in Q1 2020 to 12.14% in Q1 2021, and began to recover in June 2021). All indicators substantially recovered by September 2021. We identified 1 813 058 patients (3.1%) at risk of at least one potentially hazardous prescribing event.ConclusionNHS data from general practices can be analysed at national scale to generate insights into service delivery. Potentially hazardous prescribing was largely unaffected by the covid-19 pandemic in primary care health records in England.

Somatic, cognitive and mental health issues have been identified in three-quarters of people 5 months after hospitalisation for severe acute SARS-CoV-2 (COVID-19) infection. The underlying neuroanatomical basis of these symptoms remains unclear, but recent studies suggest a role for altered brainstem physiology. We aimed to test the hypothesis that brainstem neurochemical profiles differ in patients who had been hospitalised for COVID-19 compared to matched controls using 7T magnetic resonance spectroscopy (MRS). This prospective case-control study recruited 34 individuals who were hospitalised for COVID-19 and 15 healthy controls with no history of COVID-19 infection from two major UK hospitals before vaccines became available. The participants underwent 7T semi-adiabatic localization by adiabatic selective refocusing (sLASER) H-MRS at the ponto-medullary junction. Water-referenced metabolite concentrations were compared between the patients and controls and correlated with infection severity, as measured by maximum C-reactive protein (CRP ) assay during inpatient admission. Linear mixed modelling was used with a 0.05 significance level. Spectral quality was high/acceptable in 44/49 participants according to the MRS Consensus criteria. The magnitude of inflammation during patient admission (i.e., CRP ) correlated positively with -inositol concentration (  = 0.005,  = 0.035), as did patient-reported symptoms (  = -0.564,  = 0.023). However, metabolite concentrations were not significantly different between the patients and controls. We show the feasibility of assessing brainstem neurochemical profiles using 7T H-MRS in a multi-centre study. Technical limitations at one site's 7T MRI led to variable repetition times, which limited our statistical power and should be avoided in future studies. Our findings highlight the need for further investigation into the role of neuroinflammation in post-acute COVID-19.

Uterine polyps can cause abnormal bleeding in women. Conventional practise is to remove them under general anaesthesia but advances in technology have made it possible to perform polypectomy in the office setting. We conducted a patient-preference study to explore women’s preferences for treatment setting and to evaluate the effectiveness and treatment experience of women undergoing uterine polypectomy. Three hundred ninety-nine women with abnormal uterine bleeding who were found to have uterine polyps at diagnostic hysteroscopy were recruited. Office polypectomies were performed in office hysteroscopy clinics, and inpatient procedures were undertaken in operating theatres. Three hundred twenty-four of 399 (81 %) expressed a preference for office treatment. There was no difference found between office treatment and inpatient treatment in terms of alleviating abnormal uterine bleeding as assessed by patients and in improving disease-specific quality of life. Acceptability was lower and patient pain scores were significantly higher in the office group. When offered a choice of treatment setting for uterine polypectomy, patients have a preference for office over inpatient treatment. Ambulatory gynaecology services should be available within healthcare systems to meet patient demand.

Tuberculosis (TB) is a major cause of morbidity and mortality worldwide despite widespread intradermal (ID) BCG vaccination in newborns. We previously demonstrated that changing the route and dose of BCG vaccination from 5×10 CFU ID to 5×10 CFU intravenous (IV) resulted in prevention of infection and disease in a rigorous, highly susceptible non-human primate model of TB. Identifying the immune mechanisms of protection for IV BCG will facilitate development of more effective vaccines against TB. Here, we depleted select lymphocyte subsets in IV BCG vaccinated macaques prior to Mtb challenge to determine the cell types necessary for that protection. Depletion of CD4 T cells or all CD8α expressing lymphoycytes (both innate and adaptive) resulted in loss of protection in most macaques, concomitant with increased bacterial burdens (~4-5 log thoracic CFU) and dissemination of infection. In contrast, depletion of only adaptive CD8αβ+ T cells did not significantly reduce protection against disease. Our results demonstrate that CD4 T cells and innate CD8α+ lymphocytes are critical for IV BCG-induced protection, supporting investigation of how eliciting these cells and their functions can improve future TB vaccines.

Readers both affirm and criticize the article's main idea that industry is largely liable and therefore responsible for environmental problems. In response, the author asserts that economic growth must be accompanied by concern for the environment.