A virtual postgraduate community of practice

During the COVID-19 lockdown one community of homeworkers at risk of being overlooked in contingency planning is that of postgraduate student researchers, known to suffer from higher levels of mental ill-health than the general population. Physical distance from a supportive network of supervisors, peers and colleagues holds the potential to negatively impact postgraduates' health

Understanding psychotic-like experiences in children in the context of dimensions of psychological problems

Introduction: Although psychotic behaviors can be difficult to assess in children, early identification of children at high risk for the emergence of psychotic symptoms may facilitate the prevention of related disorders. Psychotic-like experiences (PLEs), or subthreshold thought and perceptual disturbances, could be early manifestations of psychosis that may predict a future diagnosis of a psychosis-related disorder or nonspecific correlates of a wide range of psychological problems. Additional research is needed regarding how PLEs map onto dimensions of psychopathology in children. Methods: In the present study, we examined the association between PLEs and general and specific dimensions of psychological problems in a sample of 10,692 children from the Adolescent Brain Cognitive Development Study (ABCD Study). Results: The results of this study showed that self-reported PLEs were associated with a general psychopathology factor and an ADHD factor, which were defined in hierarchical models of parent-rated psychological problems. Discussion: These findings suggest that PLEs are broadly associated with a wide range of psychological problems through the general psychopathology factor even before psychotic disorders typically manifest. This study supports the need for longitudinal analyses of future waves of the ABCD Study to determine if PLEs can detect children at high risk for serious psychological problems in adulthood.</p

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

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Effects of Ultraviolet Light Supplementation on Pekin Duck Production, Behavior, and Welfare

Ducks, like other domestic poultry species, can visualize the ultraviolet (UV) portion of the light spectrum; however, the importance of UV light radiation in artificially lit duck growout facilities remains unknown. The objective of this study was to determine the effects of UV light supplementation on Pekin duck production parameters, eye development, stress, and fear. Pekin ducks were reared with light-emitting diode (LED) lights supplemented with UV light or just LED lights (control). There were no differences in body weight (p = 0.32), feed conversion ratio (p = 0.38), or gait score (p = 0.89). Differences in eye morphology were observed, with ducks reared under UV light having narrower (12.3 &plusmn; 0.06632 mm; p = 0.010) and lighter (1.46 &plusmn; 0.01826 g; p = 0.025) eyes than the control (12.5 &plusmn; 0.05583 mm; 1.53 &plusmn; 0.02386 g). Ducks reared in UV environments had lower acute and chronic stress susceptibility with lower plasma corticosterone (6317 &plusmn; 593.79 pg/mL; p = 0.024), heterophil to lymphocyte ratios (0.43 &plusmn; 0.02889; p = 0.035), and composite asymmetry (0.58 &plusmn; 0.0298; p = 0.002) than control ducks (9242 &plusmn; 1120.7 pg/mL; 0.54 &plusmn; 0.04212; 0.76 &plusmn; 0.03726 mm, respectively). Ultraviolet ducks had a faster latency for the first head movement during tonic immobility (61.28 &plusmn; 9.4863 s, p = 0.026) and required more attempts to induce tonic immobility (1.71 &plusmn; 0.07333, p = 0.018) than control ducks (100.7 &plusmn; 14.846 s and 1.48 &plusmn; 0.06478, respectively). There were no differences in inversion testing (p = 0.91). These results indicate that UV lighting can lower stress and fear responses in Pekin ducks and can therefore increase welfare. Additionally, this study emphasizes the importance of choosing correct artificial lighting for all poultry species

Evaluation of Egg Quality and Performance in Late-Lay Hens Fed Different Combinations of Copper, Manganese, and Zinc Complexed with Sulfate or Amino Acid Ion

Dietary inclusion of copper (Cu), manganese (Mn), and zinc (Zn) can improve egg shell quality through changing the membrane structure. This study aimed to compare the responses of egg shell to different mineral sources. In this study, 60-week-old laying hens (n = 378) were assigned to one of seven treatments with 18 replicates each in an RCBD. Treatments included the following: control (basal + sulfated minerals (CuSO4, MnSO4, and ZnSO4)), and basal + amino acid complexed (AAC) minerals (AAC Cu, AAC Mn, AAC Zn, AAC Cu + Mn, AAC Mn + Zn, AAC Zn + Cu). Trace minerals were added to a basal diet containing 20 ppm MnSO4 and 20 ppm ZnSO4 to achieve overall target concentrations of 20 ppm Cu, 60 ppm Mn, and 60 ppm Zn. The hens were fed the treatment diet for 15 weeks, and egg production and egg quality were assessed during weeks 5, 10, and 15 of the experiment. Egg shells, egg contents, and excreta were analyzed for Cu, Mn, Zn, Ca, and P during weeks 10 and 15. No treatment differences (p > 0.05) were observed for production or egg quality. Differences between excreta mineral content were observed. The mineral content of egg shells and egg contents did not differ (p > 0.05) at any time point. The mineral source did not affect egg mineral deposition and egg quality measures (p > 0.05). Some AAC trace minerals enhanced retention of zinc, calcium, and manganese, although AAC Cu increased Cu excretion. Taken together, feeding AAC trace minerals does not significantly affect egg production or egg quality during the late-lay period. More research is needed to demonstrate whether Cu excretion is increased when feeding AAC Cu due to increased bioavailability or other factors