There is considerable interest in the role of neuroimmune processes in neuropsychiatric presentations among young people seeking mental health, neurological, paediatric and rheumatological services. The increasing availability of new immunotherapies, particularly monoclonal antibodies, introduces challenges in effectively and appropriately selecting candidates for immunotherapies. Neuroimmune-mediated neuropsychiatric syndromes (NIMNPS) typically include two broad types: i) ‘autoimmune encephalitis’, characterised by acute or subacute onset, neurological signs such as seizures, delirium or motor features and severe psychotic or major mood phenomena. Anti-N-methyl-D-aspartate receptor encephalitis was a pioneering clinical example, but various other autoantibodies have since been associated with this phenotype; and ii) atypical mood or psychotic syndromes with sub-acute or insidious onset, moderately severe atypical mood or psychotic symptoms, autonomic dysregulation, narcolepsy-like features, poor response to conventional treatments and adverse (notably motor) effects from psychotropic medications. Diagnosis of NIMNPS requires clinical or laboratory evidence of direct brain involvement, though autoantibodies are not always detectable. Given the broad and controversial diagnostic criteria for NIMNPS, we propose standardised clinical criteria for identifying ‘possible cases’, followed by laboratory, neuropsychological and brain imaging tests to confirm ‘probable’ cases suitable for immunotherapy. We emphasise rapid clinical and informed co-decision-making with young people and their families and loved ones. While immunotherapy holds promise for symptom alleviation, highly-personalised approaches and long-term management are essential. Future research should validate our proposed criteria, establish optimal, standardised yet personalised immunotherapy strategies that balance between clinical benefit and risks, and identify predictive markers of treatment response.

Migrants and refugees face elevated risks for mental health problems but have limited access to services. This study compared two strategies for training and supervising nonspecialists to deliver a scalable psychological intervention, Group Problem Management Plus (gPM+), in northern Colombia. Adult women who reported elevated psychological distress and functional impairment were randomized to receive gPM+ delivered by nonspecialists who received training and supervision by: 1) a psychologist (specialized technical support); or 2) a nonspecialist who had been trained as a trainer/supervisor (nonspecialized technical support). We examined effectiveness and implementation outcomes using a mixed-methods approach. Thirteen nonspecialists were trained as gPM+ facilitators and three were trained-as-trainers. We enrolled 128 women to participate in gPM+ across the two conditions. Intervention attendance was higher in the specialized technical support condition. The nonspecialized technical support condition demonstrated higher fidelity to gPM+ and lower cost of implementation. Other indicators of effectiveness, adoption and implementation were comparable between the two implementation strategies. These results suggest it is feasible to implement mental health interventions, like gPM+, using lower-resource, community-embedded task sharing models, while maintaining safety and fidelity. Further evidence from fully powered trials is needed to make definitive conclusions about the relative cost of these implementation strategies.

Accelerating COVID-19 Treatment Interventions and Vaccines (ACTIV) was initiated by the US government to rapidly develop and test vaccines and therapeutics against COVID-19 in 2020. The ACTIV Therapeutics-Clinical Working Group selected ACTIV trial teams and clinical networks to expeditiously develop and launch master protocols based on therapeutic targets and patient populations. The suite of clinical trials was designed to collectively inform therapeutic care for COVID-19 outpatient, inpatient, and intensive care populations globally. In this report, we highlight challenges, strategies, and solutions around clinical protocol development and regulatory approval to document our experience and propose plans for future similar healthcare emergencies.

In many regions of Canada, knowledge of the distribution of insect species is far from complete. This knowledge gap, known as the Wallacean Shortfall, is often manifest by species records separated by large, often remote areas with no records. Paradoxically, these difficult-to-access areas offer the best opportunity to study unaltered native community assemblages. Such gaps in knowledge are exemplified by ground beetles, a well-known group, yet with record gaps in many unstudied areas of Canada, including Akimiski Island, Nunavut. This postglacial rebound island, located in James Bay, has no permanently occupied human dwellings and almost no human-altered habitat. Using a combination of pitfall-malaise traps, pitfall traps, and hand captures during 2008–2014, we collected 1368 ground beetles (Coleoptera: Carabidae) as part of a larger biodiversity survey. We identified 31 species, 29 of which were first territorial records for Nunavut. Our results almost double the number of Carabidae known from Nunavut and extend the known range of eight other species. Seventeen of the species that we caught cannot fly, evidence for colonists arriving on Akimiski on floating debris. Our study fills substantial range gaps and serves as baseline information to detect future change.

The provision of pensions for Civil Servants and other employees in public office, such as the police, as well as in large private businesses, became more widespread in the second half of the nineteenth century. Such pensions, and other non-pay benefits, including sick pay, not only helped with recruitment but also provided a means of managing the retirement of workers who were deemed to be incapable of performing their roles. The rules governing eligibility to receive a pension in the Metropolitan Police in London were closely linked to the certification of poor health. Police doctors restricted the certification of sickness as a reason for retirement because it impacted the size of the force, resulted in the loss of more experienced men, and added to the cost of the pension fund. This strategy generated conflict with the workforce, resulting in industrial unrest. Piecemeal reforms failed to address workers’ concerns until 1890, when the rights to receive a pension were improved. These reforms, rather than stricter vigilance by police doctors, were an effective way of retaining experienced officers in the police force.

This study suggests that there may be considerable difficulties in providing accurate calendar age estimates in the Roman period in Europe, between ca. AD 60 and ca. AD 230, using the radiocarbon calibration datasets that are currently available. Incorporating the potential for systematic offsets between the measured data and the calibration curve using the ΔR approach suggested by Hogg et al. (2019), only marginally mitigates the biases in calendar date estimates observed. At present, it clearly behoves researchers in this period to “caveat emptor” and validate the accuracy of their calibrated radiocarbon dates and chronological models against other sources of dating information.

Lynchets, often the defining component of historic agricultural landscapes in northern Europe, are generally associated with soft-limestone geologies and are particularly well developed on loess-mantled landscapes. To understand their formation and chronology, the authors present their geoarchaeological analyses of lynchet soils and loess deposits at Blick Mead and Charlton Forest in southern England, and Sint Martens-Voeren in Belgium. The lynchets date from the late prehistoric to the medieval periods and were constructed by plough action at the English sites, and by both cut-and-fill and ploughing in Belgium. This has resulted in the preservation of highly fertile loessic soils across chalk slopes, lost elsewhere. Although each example is associated with local/regional agricultural histories, the lynchets’ effective soil-retention capacities allowed them to survive as important heritage features with environmental benefits over millennia.

To investigate the symptoms of SARS-CoV-2 infection, their dynamics and their discriminatory power for the disease using longitudinally, prospectively collected information reported at the time of their occurrence. We have analysed data from a large phase 3 clinical UK COVID-19 vaccine trial. The alpha variant was the predominant strain. Participants were assessed for SARS-CoV-2 infection via nasal/throat PCR at recruitment, vaccination appointments, and when symptomatic. Statistical techniques were implemented to infer estimates representative of the UK population, accounting for multiple symptomatic episodes associated with one individual. An optimal diagnostic model for SARS-CoV-2 infection was derived. The 4-month prevalence of SARS-CoV-2 was 2.1%; increasing to 19.4% (16.0%–22.7%) in participants reporting loss of appetite and 31.9% (27.1%–36.8%) in those with anosmia/ageusia. The model identified anosmia and/or ageusia, fever, congestion, and cough to be significantly associated with SARS-CoV-2 infection. Symptoms’ dynamics were vastly different in the two groups; after a slow start peaking later and lasting longer in PCR+ participants, whilst exhibiting a consistent decline in PCR- participants, with, on average, fewer than 3 days of symptoms reported. Anosmia/ageusia peaked late in confirmed SARS-CoV-2 infection (day 12), indicating a low discrimination power for early disease diagnosis.

Glowacki offers many new directions for understanding and even eliminating the problem of war, especially creating positive interdependencies with out-group members. We develop Glowacki's intriguing proposition that in-group dynamics provide a route to peace by describing a prosocial motivational system, the caregiving system, that aligns individual interests and eliminates the need to use coercion to achieve mutually beneficial outcomes.

Female fertility is a complex trait with age-specific changes in spontaneous dizygotic (DZ) twinning and fertility. To elucidate factors regulating female fertility and infertility, we conducted a genome-wide association study (GWAS) on mothers of spontaneous DZ twins (MoDZT) versus controls (3273 cases, 24,009 controls). This is a follow-up study to the Australia/New Zealand (ANZ) component of that previously reported (Mbarek et al., 2016), with a sample size almost twice that of the entire discovery sample meta-analysed in the previous article (and five times the ANZ contribution to that), resulting from newly available additional genotyping and representing a significant increase in power. We compare analyses with and without male controls and show unequivocally that it is better to include male controls who have been screened for recent family history, than to use only female controls. Results from the SNP based GWAS identified four genomewide significant signals, including one novel region, ZFPM1 (Zinc Finger Protein, FOG Family Member 1), on chromosome 16. Previous signals near FSHB (Follicle Stimulating Hormone beta subunit) and SMAD3 (SMAD Family Member 3) were also replicated (Mbarek et al., 2016). We also ran the GWAS with a dominance model that identified a further locus ADRB2 on chr 5. These results have been contributed to the International Twinning Genetics Consortium for inclusion in the next GWAS meta-analysis (Mbarek et al., in press).