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\"Rather than continue to focus on discrete, geographically bounded bodies of water, ocean advocate and marine-policy researcher Deborah Wright urges a Plan Sea, which reimagines the oceans as the continuous ecosystem it is, not disconnected buckets of salt and plankton. This book proposes that the global marine environment be protected under the precautionary principle. It argues that the policy framework for such protection already exists -- it just needs to be enforced. In a series of case studies, with first-person vignettes woven throughout, Wright encourages us to begin every conversation about ocean policy with the assumption that any extractive or polluting activities in the world's oceans should require special permission. Her argument invokes the Public Trust Doctrine already embedded in many constitutions, and hinges on the Law of the Sea, which was established by the U.N. in 1982 to protect the \"high seas,\" or the remote parts of the ocean considered international waters. To some, Wright's plan may seem idealistic, but its audacity might also be seen as a welcome nudge to our collective imagination. Many scientists are convinced that ocean ecosystems are on the brink of collapse -- there's something to be said, then, for a book that's radical enough to unlock new thinking about what might be possible, and maybe necessary, in terms of their protection\"-- Provided by publisher.

In early 2022, a cluster of monkeypox virus (MPXV) infection (mpox) cases were identified within the UK with no prior travel history to MPXV-endemic regions. Subsequently, case numbers exceeding 80,000 were reported worldwide, primarily affecting gay, bisexual, and other men who have sex with men (GBMSM). Public health agencies worldwide have offered the IMVANEX Smallpox vaccination to these individuals at high-risk to provide protection and limit the spread of MPXV. We have developed a comprehensive array of ELISAs to study poxvirus-induced antibodies, utilising 24 MPXV and 3 Vaccinia virus (VACV) recombinant antigens. Panels of serum samples from individuals with differing Smallpox-vaccine doses and those with prior MPXV infection were tested on these assays, where we observed that one dose of Smallpox vaccination induces a low number of antibodies to a limited number of MPXV antigens but increasing with further vaccination doses. MPXV infection induced similar antibody responses to diverse poxvirus antigens observed in Smallpox-vaccinated individuals. We identify MPXV A27 as a serological marker of MPXV-infection, whilst MPXV M1 (VACV L1) is likely IMVANEX-specific. Here, we demonstrate analogous humoral antigen recognition between both MPXV-infected or Smallpox-vaccinated individuals, with binding to diverse yet core set of poxvirus antigens, providing opportunities for future vaccine (e.g., mRNA) and therapeutic (e.g., mAbs) design. In this work, Otter et al. compared the humoral immune responses induced by MPXV infection and Smallpox vaccination. Although comparable responses were observed, infection- or vaccination specific serological markers were identified enabling discrimination between vaccinated and infected individuals.

Objective This study examined the prevalence and severity of burnout and depression in first-year medical students at different points in the academic year. Methods U.S. first-year allopathic medical students with a pass/fail preclinical curriculum were emailed through the school’s email list with four rounds of surveys consisting of the full set of questions from the Copenhagen Burnout Inventory and the Patient Health Questionnaire-9, with the question order randomized. The surveys were sent before winter break, during block final exams, the subsequent block’s midpoint, and after the subsequent block’s midterm examinations. Results A total of 147 students completed the questionnaire (29.4%; n = 147/500). Most participants (73.5%) reported experiencing symptoms of work-related burnout, and 44.2% reported symptoms of depression. Client-related burnout and PHQ-9 scores were strongly correlated (Spearman r = 0.645, p < 0.001). Work-related burnout was also strongly related to client-related burnout (r = 0.739, p < 0.001) and PHQ-9 scores (r = 0.786, p < 0.001). No statistically significant differences in depression or burnout were noted throughout all four survey rounds. Conclusions Burnout and depression severity in first-year medical students remain statistically similar throughout the academic year despite significant events such as exams or breaks. This may indicate that scheduling exams after breaks reduces any protective effect it may have on burnout/depression. It may also suggest that institutional changes such as a pass-fail preclinical curriculum meant to improve medical students’ mental health have not had the intended positive effect.

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IntroductionPostoperative pain is common and frequently addressed through opioid analgesia. This practice must balance the benefits of achieving adequate pain relief against the harms of adverse effects such as opioid-induced ventilatory impairment and opioid use disorder. This student and trainee-led collaborative study aims to investigate and compare the prescription versus consumption of opioids at 7 days postdischarge after common surgical procedures and their impact on patient-reported outcomes regarding postoperative pain.Methods and analysisThis is a prospective multicentre observational cohort study of surgical patients in Australia, Aotearoa New Zealand and select international sites, conducted by networks of students, trainees and consultants. Consecutive adult patients undergoing common elective and emergency general, orthopaedic, gynaecological and urological surgical procedures are eligible for inclusion, with follow-up 7 days after hospital discharge. The primary outcome will be the proportion of prescribed opioids consumed by patients at 7 days postdischarge. Secondary outcomes will include patient-reported quality of life and satisfaction scores, rate of non-opioid analgesic use, rate of continuing use of opioids at follow-up, rates of opioid prescription from other sources and hospital readmissions at 7 days postdischarge for opioid related side-effects or surgery-related pain. Descriptive and multivariate analyses will be conducted to investigate factors associated with opioid requirements and prescription-consumption discrepancies.Ethics and disseminationOPERAS has been approved in Australia by the Hunter New England Human Research Ethics Committee (Protocol 2021/ETH11508) and by the Southern Health and Disability Ethics Committee (2021 EXP 11199) in Aotearoa New Zealand. Results will be submitted for conference presentation and peer-reviewed publication. Centre-level data will be distributed to participating sites for internal audit.Trial registration numberANZCTR (ID: ACTRN12621001451897p)

False images and videos can induce people to believe in and remember events that never happened. Using a novel method, we examined whether the timing of false evidence would influence its effect (Experiment 1 ) and determined the relationship between timing and repetition (Experiment 2 ). Subjects completed a hazard perception driving test and were falsely accused of cheating. Some subjects were shown a fake video or photograph of the cheating either after a 9-min delay (Experiment 1 ) or more than once with or without a delay (Experiment 2 ). Subjects were more likely to falsely believe that they had cheated and to provide details about how the cheating happened when the false evidence was delayed or repeated—especially when repeated over time—relative to controls. The results show that even a strikingly short delay between an event and when false evidence is disclosed can distort people’s beliefs and that repeating false evidence over a brief delay fosters false beliefs more so than without a delay. These findings have theoretical implications for metacognitive models of autobiographical memory and practical implications for police interrogations.

Background Hartmann’s procedure (sigmoid resection with end colostomy) is a commonly performed emergency procedure for diseases of the sigmoid colon. Aim To determine the proportion of patients undergoing Hartmann’s reversal (restoration of GI continuity) following Hartmann’s procedure, the clinical and demographic factors associated with reversal, and the reasons for non-reversal. Method This is a single center, retrospective audit of patients undergoing Hartmann’s procedure between June 2011 and May 2020. Age, sex, American Society of Anesthesiologists classification (ASA), indication for Hartmann’s, surgical approach, specialty of responsible surgeon (General or Colorectal), 30-day reoperation, requirement for radiologically-guided drain, and reason for non-reversal were recorded. The association between these factors and reversal was determined with Fischer’s exact test and logistic regression. Cumulative reversal proportions were calculated with the Kaplan–Meier method. Results Data was obtained for 114/117 patients, of whom 31% (35/114) underwent Hartmann’s reversal. The median (IQR) time to reversal was 372 (188–500) days. Patients with restoration of GI continuity were younger (median 67 versus 73 years, P  < 0.001) with fewer co-morbidities, (ASA ≤ 2 34% versus 9% P  = 0.002). The estimated cumulative 24-month reversal incidence was 37%. Patients who had a Hartmann’s procedure performed for diverticulitis had an increased odds of being reversed (OR 4.1 (95% CI 1.6, 10.5) P  = 0.001); Hartmann’s for malignancy was associated with decreased odds of reversal (OR 0.37 (95% CI 0.12, 1) P  = 0.035). Conclusion Of patients who underwent Hartmann’s procedure, the majority retained a permanent stoma. Older patients, those with high ASA, and those who underwent index procedures for malignancy had lower rates of reversal.

BackgroundChimeric antigen receptor (CAR) T cell therapy has shown outstanding benefit in hematological malignancies with three autologous CAR-T therapies commercially available and several in clinical development. The use of autologous T cells to manufacture CAR therapies has several disadvantages including production time, cost, lengthy time to treatment and dependence on patient T cell functionality. An allogeneic off the shelf CAR product can overcome these issues. We use invariant natural killer T (iNKT) cells as basis for our allogeneic cell therapy platform. Invariant NKT cells are innate-like lymphocytes that bridge innate and adaptative immune response to promote anti-cancer immunity. iNKT cells share characteristics of T cells and Natural Killer (NK) cells, expressing both an invariant T Cell Receptor (iTCR) and canonical NK receptors. They can be activated by recognition of lipid antigens through the iTCR, pro-inflammatory cytokines and recognition of stress ligands. Moreover, iNKT do not cause Graft versus Host Disease making them an ideal platform for allogeneic CAR cell therapy. Here we describe a novel allogeneic iNKT-CAR product targeting BCMA designed to promote effective anti-cancer immunityMethodsOur proprietary CARDIS TM platform is a 2-stage discovery process where screening of highly diverse scFv libraries via phage display is followed by selection of potent CARs using mammalian display platform. Using this high throughput approach, we can interrogate large cell-based CAR libraries for specific binding and activation simultaneously, as well as eliminate tonic signaling at an early stage. This novel platform enabled rapid identification of a candidate CAR (agenT-F6) for the targeting of BCMA. Anti-cancer efficacy of stably expressed BCMA CAR in expanded iNKT cells has been testedResultsAgent-F6 expressed at high levels in iNKT cells. Functional characterization demonstrated potent cytotoxic activity of agent-F6 expressing iNKT cells against human hematologic tumor cell lines expressing BCMA in vitro. Activated agenT-F6 iNKT cells display a pro-inflammatory phenotype when challenged with tumor cell lines. Furthermore, using a multiple myeloma in vivo xenograft model, infusion of agenT-F6 iNKT cells showed comparable tumor control to a clinical-stage BCMA CAR reference.ConclusionsMiNK therapeutics is developing the next generation allogeneic CAR-iNKT therapies by using 1) a CAR discovery platform that allows more rapid and efficient identification of antigen-specific and biologically potent CAR candidates and 2) an iNKT cell platform naturally lacking alloreactivity that allows rapid engineering and expansion of an off-the-shelf CAR product.Ethics ApprovalAll procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards

Describes their experience enabling large-scale collaborative studies within trainee-led surgical research networks, to highlight systemic barriers to the use of this methodology and to propose solutions that will facilitate trainee-led collaborative research in New Zealand. Source: National Library of New Zealand Te Puna Matauranga o Aotearoa, licensed by the Department of Internal Affairs for re-use under the Creative Commons Attribution 3.0 New Zealand Licence.