Increased hippocampal engagement during learning as a marker of sensitivity to psychotomimetic effects of delta-9-THC

AbstractBackgroundCannabis and its main psychoactive ingredient δ-9-tetrahydrocannibidiol (THC) can induce transient psychotic symptoms in healthy individuals and exacerbate them in those with established psychosis. However, not everyone experience these effects, suggesting that certain individuals are particularly susceptible. The neural basis of this sensitivity to the psychotomimetic effects of THC is unclear.MethodsWe investigated whether individuals who are sensitive to the psychotomimetic effects of THC (TP) under experimental conditions would show differential hippocampal activation compared with those who are not (NP). We studied 36 healthy males under identical conditions under the influence of placebo or THC (10 mg) given orally, on two separate occasions, in a pseudo-randomized, double-blind, repeated measures, within-subject, cross-over design, using psychopathological assessments and functional MRI while they performed a verbal learning task. They were classified into those who experienced transient psychotic symptoms (TP; n = 14) following THC administration and those who did not (NP; n = 22).ResultsUnder placebo conditions, there was significantly greater engagement of the left hippocampus (p &lt; 0.001) in the TP group compared with the NP group during verbal encoding, which survived leave-one-out analysis. The level of hippocampal activation was directly correlated (Spearman's ρ = 0.44, p = 0.008) with the severity of transient psychotic symptoms induced by THC. This difference was not present when we compared two subgroups from the same sample that were defined by sensitivity to anxiogenic effects of THC.ConclusionsThese results suggest that altered hippocampal activation during verbal encoding may serve as a marker of sensitivity to the acute psychotomimetic effects of THC.</jats:sec

Capacity building for wildlife health professionals: the Wildlife Health Bridge

The Wildlife Health Bridge was established in 2009 with the aim of improving the expertise and knowledge base of wildlife health professionals in biodiverse low- and middle-income countries. The Wildlife Health Bridge centres around partnerships among educational institutions: the Zoological Society of London, the Royal Veterinary College, the University of Edinburgh’s Royal (Dick) School of Veterinary Studies, the Wildlife Institute of India, and the University of Melbourne Veterinary School. The Wildlife Health Bridge provides quality education in wildlife health, ecosystem health, and wildlife biology, facilitates the interchange of students between collaborating countries for research studies and provides a global graduate network of wildlife health professionals. In addition to established Masters’ level wildlife health training programmes run by the partner organisations, the Wildlife Health Bridge has developed a collaborative field-based course, Interventions in Wild Animal Health, provided annually in India since 2016, which has trained 138 veterinarians to date, enhancing local and international capacity in managing emerging wildlife health issues and building global professional linkages. The Wildlife Health Bridge’s Wild Animal Alumni network facilitates networking and exchange between Wildlife Health Bridge institutions and graduates, with over 701 members from 67 countries, half of which are biodiverse low- and middle-income countries. Collaboration between educational institutions has enabled new ideas and ongoing developments in the delivery of materials and learning outcomes. The Wildlife Health Bridge is building global capacity in trained wildlife health professionals, through educational programmes and a synergised network, with the aim of impacting conservation practice to benefit human, domestic animal and wildlife health

Risk of progression from pre‐diabetes to type 2 diabetes in a large UK adult cohort

Aims:  People with pre-diabetes are at high risk of progressing to type 2 diabetes. This progression is not well characterised by ethnicity, deprivation and age, which we describe in a large cohort of individuals with pre-diabetes. Methods:  A retrospective cohort study with The Health Improvement Network (THIN) database was conducted. Patients aged 18 years and over and diagnosed with pre-diabetes (HbA1c 42 mmol/mol (6.0%) to 48 mmol/mol (6.5% were included. Cox proportional hazards regression was used to calculate adjusted hazard rate ratios (aHR) for the risk of progression from pre-diabetes to type 2 diabetes for each of the exposure categories (ethnicity, deprivation (Townsend), age and body mass index (BMI)) separately. Results:  Of the baseline population with pre-diabetes (n=397853), South Asian (aHR 1.31; 95% CI 1.26-1.37) or Mixed-Race individuals (aHR 1.22; 95% CI 1.11-1.33) had an increased risk of progression to type 2 diabetes compared with those of white European ethnicity. Likewise, deprivation (aHR 1.17; 95% CI 1.14-1.20; most vs. least deprived) was associated with an increased risk of progression. Both younger (aHR 0.63; 95% CI 0.58-0.69; 18 to <30 years) and older individuals (aHR 0.85; 95% CI 0.84-0.87; ≥65 years) had a slower risk of progression from pre-diabetes to type 2 diabetes, than middle-aged (40 to <65 years) individuals. Conclusions:  South Asian or Mixed-Race individuals and people with social deprivation had an increased risk of progression from pre-diabetes to type 2 diabetes. Clinicians need to recognise the differing risk across their patient populations to implement appropriate prevention strategies

Reducing publication delay to improve the efficiency and impact of conservation science.

Evidence-based decision-making is most effective with comprehensive access to scientific studies. If studies face significant publication delays or barriers, the useful information they contain may not reach decision-makers in a timely manner. This represents a potential problem for mission-oriented disciplines where access to the latest data is required to ensure effective actions are undertaken. We sought to analyse the severity of publication delay in conservation science-a field that requires urgent action to prevent the loss of biodiversity. We used the Conservation Evidence database to assess the length of publication delay (time from finishing data collection to publication) in the literature that tests the effectiveness of conservation interventions. From 7,447 peer-reviewed and non-peer-reviewed studies of conservation interventions published over eleven decades, we find that the raw mean publication delay was 3.2 years (±2SD = 0.1) and varied by conservation subject. A significantly shorter delay was observed for studies focused on Bee Conservation, Sustainable Aquaculture, Management of Captive Animals, Amphibian Conservation, and Control of Freshwater Invasive Species (Estimated Marginal Mean range from 1.4-1.9 years). Publication delay was significantly shorter for the non-peer-reviewed literature (Estimated Marginal Mean delay of 1.9 years ± 0.2) compared to the peer-reviewed literature (i.e., scientific journals; Estimated Marginal Mean delay of 3.0 years ± 0.1). We found publication delay has significantly increased over time (an increase of ~1.2 years from 1912 (1.4 years ± 0.2) to 2020 (2.6 years ± 0.1)), but this change was much weaker and non-significant post-2000s; we found no evidence for any decline. There was also no evidence that studies on more threatened species were subject to a shorter delay-indeed, the contrary was true for mammals, and to a lesser extent for birds. We suggest a range of possible ways in which scientists, funders, publishers, and practitioners can work together to reduce delays at each stage of the publication process

The optimal second-line therapy for older adults with type 2 diabetes mellitus: protocol for a systematic review and network meta-analysis using individual participant data (IPD)

Background: Due to increasing life expectancy, almost half of people with type 2 diabetes are aged 65 years or over worldwide. When metformin alone does not control blood sugar, the choice of which second-line therapy to prescribe next is not clear from currently available evidence. The existence of frailty and comorbidities in older adults further increases the complexity of medical decision-making. As only a relatively small proportion of trials report results separately for older adults, the relative efficacy and safety of second-line therapies in older adults with type 2 diabetes mellitus are unknown and require further investigation. This individual participant data (IPD) network meta-analysis evaluates the relative efficacy and safety of second-line therapies on their own or in combination in older adults with type 2 diabetes mellitus. Methods: All relevant published and unpublished trials will be identified. Studies published prior to 2015 will be identified from two previous comprehensive aggregate data network meta-analyses. Searches will be conducted in CENTRAL, MEDLINE, and EMBASE from 1st January 2015 onwards, and in clinicaltrials.gov from inception. Randomised controlled trials with at least 100 estimated older adults (≥ 65 years) receiving at least 24 weeks of intervention that assess the effects of glucose-lowering drugs on mortality, glycemia, vascular and other comorbidities outcomes, and quality of life will be eligible. The screening and data extraction process will be conducted independently by two researchers. The quality of studies will be assessed using the Cochrane risk of bias tool 2. Anonymised IPD of all eligible trials will be requested via clinical trial portals or by contacting the principal investigators or sponsors. Received data will be reanalysed where necessary to standardise outcome metrics. Network meta-analyses will be performed to determine the relative effectiveness of therapies. Discussion: With the increasing number of older adults with type 2 diabetes worldwide, an IPD network meta-analysis using data from all eligible trials will provide new insights into the optimal choices of second-line antidiabetic drugs to improve patient management and reduce unnecessary adverse events and the subsequent risk of comorbidities in older adults. Systematic review registration: PROSPERO CRD42021272686

Putting Pluralism in its Place

Pluralism about truth is the view that there are many properties, not just one, in virtue of which things are true. Pluralists hope to dodge the objections that face traditional monistic substantive views of truth, as well as those facing deflationary theories of truth. More specifically, pluralists hope to advance an explanatorily potent understanding of truth that can capture the subtleties of various realist and anti-realist domains of discourse, all while avoiding the scope problem. I offer a new objection to pluralism that challenges its fundamental commitment to there being a set of alethic properties in virtue of which claims are true. In its place I offer an alternative view that merges standard truthmaker theory with a primitivist conception of truth. This combination of views satisfies the theoretical desires that pluralists claim for themselves, but without taking on pluralism's host of challenges and problems

Public health ethics: informing better public health practice

Public health ethics has emerged and grown as an independent discipline over the last decade. It involves using ethical theory and empirical analyses to determine and justify the right thing to do in public health. In this paper, we distinguish public health ethics from clinical ethics, research ethics, public health law and politics. We then discuss issues in public health ethics including: how to weigh up the benefits, harms and costs of intervening; how to ensure that public health interventions produce fair outcomes; the potential for public health to undermine or promote the rights of citizens; and the significance of being transparent and inclusive in public health interventions. We conclude that the explicit and systematic consideration of ethical issues will, and should, become central to every public health worker\u27s daily practice

Bringing Back a Healthy Buzz? Invertebrate Parasites and Reintroductions:A Case Study in Bumblebees

Reintroductions can play a key role in the conservation of endangered species. Parasites may impact reintroductions, both positively and negatively, but few case studies of how to manage parasites during reintroductions exist. Bumblebees are in decline at regional and global scales, and reintroductions can be used to re-establish extinct local populations. Here we report on how the risks associated with parasites are being managed in an ongoing reintroduction of the short-haired bumblebee, Bombus subterraneus, to the UK. Disease risk analysis was conducted and disease risk management plans constructed to design a capture-quarantine-release system that minimised the impacts on both the bumblebees and on their natural parasites. Given that bumblebee parasites are (i) generalists, (ii) geographically ubiquitous, and (iii) show evidence of local adaptation, the disease risk management plan was designed to limit the co-introduction of parasites from the source population in Sweden to the destination site in the UK. Results suggest that this process at best eliminated, or at least severely curtailed the co-introduction of parasites, and ongoing updates of the plan enabled minimization of impacts on natural host-parasite dynamics in the Swedish source population. This study suggests that methods designed for reintroductions of vertebrate species can be successfully applied to invertebrates. Future reintroductions of invertebrates where the parasite fauna is less well known should take advantage of next-generation barcoding and multiple survey years prior to the start of reintroductions, to develop comprehensive disease risk management plans