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This study analyses the experience and response of farmers within a multi-year collaborative research trial focused on the development of forage-based fallows in eight communities in the central Peruvian Andes. Quantitative data from a rural household survey were used to characterize farming household socioeconomic factors, livelihood strategies and soil and crop management practices of community members belonging to four participation groups with respect to the trials: 1) current participants near the end of the trial; 2.) those who participated early on, but dropped the trials after the first year; 3) those who participated in meetings but not directly in experiments; and 4) those who never participated meaningfully in the process. Furthermore, qualitative interviews of farmers in the four groups were used to examine trends and questions arising from the quantitative survey findings. Analysis of this mixed-methods dataset showed that better resource-endowed households (in terms of human and social capital, more livestock assets, higher levels of farm value production and income, and farm inputs) tended to be more likely to participate compared to households with lower levels of these variables. Our findings suggest that the differences in resource endowment among participation group households may be related to household life cycles, where access to resources change over time, reflecting the changing demography of a household. It was established that farm households with intermediate-age children, that is near the middle of a farm life cycle trajectory, are those with the most wherewithal to participate in trials and likely serve as examples and test cases for other farms with younger parents or older farmers with children moved away. Follow-up interviews indicated that farming households at either end of the farm life cycle trajectory may be using a ‘wait-and-see’ approach to the trials carried out by their neighbours who have more labour and other resources to deploy. In light of these findings, we suggest that participatory research should aim to ensure that the voices, challenges and opportunities of Non-participants are represented in the research process and experimental design. Additionally, greater consideration should be placed on understanding management by context issues in order to better target potential farming innovations such as improved fallows, at multiple levels, from the field to the household and to the community and beyond.
Emergency service workers (ESW) are known to be at increased risk of mental disorders but population-level and longitudinal data regarding their risk of suicide are lacking.
Suicide data for 2001–2017 were extracted from the Australian National Coronial Information Service (NCIS) for two occupational groups: ESW (ambulance personnel, fire-fighters and emergency workers, police officers) and individuals employed in all other occupations. Age-standardised suicide rates were calculated and risk of suicide compared using negative binomial regression modelling.
13 800 suicide cases were identified among employed adults (20–69 years) over the study period. The age-standardised suicide rate across all ESW was 14.3 per 100 000 (95% CI 11.0–17.7) compared to 9.8 per 100 000 (95% CI 9.6–9.9) for other occupations. Significant occupational differences in the method of suicide were identified (p < 0.001). There was no evidence for increased risk of suicide among ESW compared to other occupations once age, gender and year of death were accounted for (RR = 0.99, 95% CI 0.84–1.17; p = 0.95). In contrast, there was a trend for ambulance personnel to be at elevated risk of suicide (RR = 1.41, 95% CI 1.00–2.00, p = 0.053).
Whilst age-standardised suicide rates among ESW are higher than other occupations, emergency service work was not independently associated with an increased risk of suicide, with the exception of an observed trend in ambulance personnel. Despite an increased focus on ESW mental health and wellbeing over the last two decades, there was no evidence that rates of suicide among ESW are changing over time.
Coronavirus disease 2019 (COVID-19) spread globally, including across Europe, resulting in different morbidity and mortality outcomes. The aim of this study was to explore the progression of the COVID-19 pandemic over 18 mo in relation to the effect of COVID-19 vaccination at a population level across 35 nations in Europe, while evaluating the data for cross-border epidemiological trends to identify any pertinent lessons that can be implemented in the future.
Epidemiological data were obtained from European Centre for Disease Prevention and Control and Our World in Data databases while Ministry of Health websites of each respective country and local newspapers were used for COVID-19-related vaccination strategies. Case, mortality, and vaccination incidence comparative analyses were made across neighboring countries.
Similar morbidity and mortality outcomes were evident across neighboring countries over 18 mo, with a bidirectional relationship evident between cumulative fully vaccinated population and case fatality rates.
Countries’ COVID-19 outcome is related on national mitigative measures, vaccination rollouts, and neighboring countries’ actions and COVID-19 situations. Mass population vaccination appeared to be effective in reducing COVID-19 case severity and mortality rates. Vaccination equity and pan-European commitment for cross-border governance appear to be the way forward to ensure populations’ return to “normality.”
Early in the COVID-19 pandemic, the World Health Organization stressed the importance of daily clinical assessments of infected patients, yet current approaches frequently consider cross-sectional timepoints, cumulative summary measures, or time-to-event analyses. Statistical methods are available that make use of the rich information content of longitudinal assessments. We demonstrate the use of a multistate transition model to assess the dynamic nature of COVID-19-associated critical illness using daily evaluations of COVID-19 patients from 9 academic hospitals. We describe the accessibility and utility of methods that consider the clinical trajectory of critically ill COVID-19 patients.
Monoclonal antibody therapeutics to treat coronavirus disease (COVID-19) have been authorized by the US Food and Drug Administration under Emergency Use Authorization (EUA). Many barriers exist when deploying a novel therapeutic during an ongoing pandemic, and it is critical to assess the needs of incorporating monoclonal antibody infusions into pandemic response activities. We examined the monoclonal antibody infusion site process during the COVID-19 pandemic and conducted a descriptive analysis using data from 3 sites at medical centers in the United States supported by the National Disaster Medical System. Monoclonal antibody implementation success factors included engagement with local medical providers, therapy batch preparation, placing the infusion center in proximity to emergency services, and creating procedures resilient to EUA changes. Infusion process challenges included confirming patient severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positivity, strained staff, scheduling, and pharmacy coordination. Infusion sites are effective when integrated into pre-existing pandemic response ecosystems and can be implemented with limited staff and physical resources.
In the First-HD pivotal trial, the maximum deutetrabenazine dose evaluated to treat chorea associated with Huntington’s disease (HD chorea) was 48 mg/d, which is the approved maximum dose for this population. In ARC-HD, an open-label extension study evaluating the long-term efficacy and safety of deutetrabenazine to treat HD chorea, dosage ranged from 6 mg/d to 72 mg/d, with doses ≥12 mg/d administered twice daily. Doses in ARC-HD were increased by 6 mg/d per week in a response-driven manner based on efficacy and tolerability until 48 mg/d (Week 8). At the investigator’s discretion, further increases were permitted by 12 mg/d per week to a maximum of 72 mg/d. This post-hoc analysis evaluates the safety and tolerability of deutetrabenazine >48 mg/d compared to ≤48 mg/d to treat HD chorea in ARC-HD.
Patient counts and safety assessments were attributed to patients when they received a dose of either ≤48 mg/d or >48 mg/d. For 9 selected adverse events (AEs), we compared AE rates adjusted for duration of drug exposure (as number of AEs/year) at ≤48 mg/d or >48 mg/d. The AE rates were determined after titration when participants were on stable doses of deutetrabenazine.
All 113 patients were exposed to doses ≤48 mg/d (177.1 patient-years) and 49 patients were ever exposed to doses >48 mg/d (74.1 patient-years). In patients taking deutetrabenazine >48 mg/d compared to ≤48 mg/d after the titration period, there were no apparent differences in exposure-adjusted AE rates.
Based on clinical experience, some patients with HD may benefit from doses higher than 48 mg/d to adequately control chorea. These doses were tolerated without apparent increase in the exposure-adjusted rates of selected AEs after titration. This analysis does not address the occurrence of other AEs or whether adequate efficacy was achieved at lower doses, factors that may have influenced dose increases.
Teva Pharmaceutical Industries Ltd., Petach Tikva, Israel
Chorea is a prominent motor dysfunction in Huntington’s disease (HD). Deutetrabenazine, a vesicular monoamine transporter 2 (VMAT2) inhibitor, is FDA-approved for the treatment of chorea in HD. In the pivotal, 12-week First-HD trial, deutetrabenazine treatment reduced the Unified Huntington’s Disease Rating Scale (UHDRS) total maximal chorea (TMC) score versus placebo. ARC-HD, an open-label extension study, evaluated long-term safety and efficacy of deutetrabenazine dosed in a response-driven manner for treatment of HD chorea.
Patients who completed First-HD (Rollover) and patients who converted overnight from a stable dose of tetrabenazine (Switch) were included. Safety was assessed over the entire treatment period; exposure-adjusted incidence rates (EAIRs; adverse events [AEs] per person-year) were calculated. A stable, post-titration time point of 8 weeks was chosen for efficacy analyses.
Of 119 patients enrolled (Rollover, n=82; Switch, n=37), 100 (84%) completed ≥1 year of treatment (mean [SD] follow-up, 119  weeks). End of study EAIRs for patients in the Rollover and Switch cohorts, respectively, were: any AE, 2.6 and 4.3; serious AEs, 0.13 and 0.14; AEs leading to dose suspension, 0.05 and 0.04. Overall, 68% and 73% of patients in Rollover and Switch, respectively, experienced a study drug–related AE. Most common AEs possibly related to study drug were somnolence (17% Rollover; 27% Switch), depression (23%; 19%), anxiety (9%; 11%), insomnia (10%; 8%), and akathisia (9%; 14%). Rates of AEs of interest include suicidality (9%; 3%) and parkinsonism (6%; 11%). In both cohorts, mean UHDRS TMC score and total motor score (TMS) decreased from baseline to Week 8; mean (SD) change in TMC score (units) was –4.4 (3.1) and –2.1 (3.3) and change in TMS was –7.1 (7.3) and –2.4 (8.7) in Rollover and Switch, respectively. While receiving stable dosing from Week 8 to 132 (or end of treatment), patients showed minimal change in TMC score (0.9 [5.0]), but TMS increased compared to Week 8 (9.0 [11.3]). Upon drug withdrawal, there were no remarkable AEs and TMC scores increased 4.4 (3.7) units compared to end of treatment.
The type and severity of AEs observed in long-term deutetrabenazine exposure are consistent with the previous study. Efficacy in reducing chorea persisted over time. There was no unexpected worsening of HD or chorea associated with HD upon deutetrabenazine withdrawal.
Teva Pharmaceutical Industries Ltd., Petach Tikva, Israel
The dynamics of initially truncated and bent line solitons for the Kadomtsev–Petviashvili (KPII) equation modelling internal and surface gravity waves is analysed using modulation theory. In contrast to previous studies on obliquely interacting solitons that develop from acute incidence angles, this work focuses on initial value problems for the obtuse incidence of two or three partial line solitons, which propagate away from one another. Despite counterpropagation, significant residual soliton interactions are observed with novel physical consequences. The initial value problem for a truncated line soliton – describing the emergence of a quasi-one-dimensional soliton from a wide channel – is shown to be related to the interaction of oblique solitons. Analytical descriptions for the development of weak and strong interactions are obtained in terms of interacting simple wave solutions of modulation equations for the local soliton amplitude and slope. In the weak interaction case, the long-time evolution of truncated and large obtuse angle solitons exhibits a decaying, parabolic wave profile with temporally increasing focal length that asymptotes to a cylindrical Korteweg–de Vries soliton. In contrast, the strong interaction case of slightly obtuse interacting solitons evolves into a steady, one-dimensional line soliton with amplitude reduced by an amount proportional to the incidence slope. This strong interaction is identified with the ‘Mach expansion’ of a soliton with an expansive corner, contrasting with the well-known Mach reflection of a soliton with a compressive corner. Interestingly, the critical angles for Mach expansion and reflection are the same. Numerical simulations of the KPII equation quantitatively support the analytical findings.
This is the first report on the association between trauma exposure and depression from the Advancing Understanding of RecOvery afteR traumA(AURORA) multisite longitudinal study of adverse post-traumatic neuropsychiatric sequelae (APNS) among participants seeking emergency department (ED) treatment in the aftermath of a traumatic life experience.
We focus on participants presenting at EDs after a motor vehicle collision (MVC), which characterizes most AURORA participants, and examine associations of participant socio-demographics and MVC characteristics with 8-week depression as mediated through peritraumatic symptoms and 2-week depression.
Eight-week depression prevalence was relatively high (27.8%) and associated with several MVC characteristics (being passenger v. driver; injuries to other people). Peritraumatic distress was associated with 2-week but not 8-week depression. Most of these associations held when controlling for peritraumatic symptoms and, to a lesser degree, depressive symptoms at 2-weeks post-trauma.
These observations, coupled with substantial variation in the relative strength of the mediating pathways across predictors, raises the possibility of diverse and potentially complex underlying biological and psychological processes that remain to be elucidated in more in-depth analyses of the rich and evolving AURORA database to find new targets for intervention and new tools for risk-based stratification following trauma exposure.
There is evidence that depression can be prevented; however, traditional approaches face significant scalability issues. Digital technologies provide a potential solution, although this has not been adequately tested. The aim of this study was to evaluate the effectiveness of a new smartphone app designed to reduce depression symptoms and subsequent incident depression amongst a large group of Australian workers.
A randomized controlled trial was conducted with follow-up assessments at 5 weeks and 3 and 12 months post-baseline. Participants were employed Australians reporting no clinically significant depression. The intervention group (N = 1128) was allocated to use HeadGear, a smartphone app which included a 30-day behavioural activation and mindfulness intervention. The attention-control group (N = 1143) used an app which included a 30-day mood monitoring component. The primary outcome was the level of depressive symptomatology (PHQ-9) at 3-month follow-up. Analyses were conducted within an intention-to-treat framework using mixed modelling.
Those assigned to the HeadGear arm had fewer depressive symptoms over the course of the trial compared to those assigned to the control (F3,734.7 = 2.98, p = 0.031). Prevalence of depression over the 12-month period was 8.0% and 3.5% for controls and HeadGear recipients, respectively, with odds of depression caseness amongst the intervention group of 0.43 (p = 0.001, 95% CI 0.26–0.70).
This trial demonstrates that a smartphone app can reduce depression symptoms and potentially prevent incident depression caseness and such interventions may have a role in improving working population mental health. Some caution in interpretation is needed regarding the clinical significance due to small effect size and trial attrition.
Trial Registration Australian and New Zealand Clinical Trials Registry (www.anzctr.org.au/) ACTRN12617000548336
An early rescue excavation in 1900 revealed part of a medieval building of the Dominican friary of Black Friars, London. Further archaeological work in the twentieth century revealed other parts of the building. Here, the authors consider the archaeological and architectural evidence, including a preserved in situ window and two relocated ex situ architectural features. Alfred Clapham suggested in a 1912 article in Archaeologia that the building was the Dominican provincial prior’s house; the present authors instead identify the ground-floor chamber as the late thirteenth-century chapter house. Construction of the friary (the second London Black Friars) began in 1278 or 1279 and the chapter house, funded by a will of 1281, was probably built later in the 1280s. The lower chamber was a well-lit, five-bay undercroft with a quadripartite vault rising from Reigate stone responds and Purbeck marble columns: this was probably the chapter house chamber. The hall-like chamber over was approximately 57ft by 28ft (17.3m × 8.5m) and may have been the library. The building may be the work of Robert of Beverley, the king’s master mason from 1260, perhaps in conjunction with Michael of Canterbury. French royal works of the thirteenth century (such as the lower chapel of the Sainte-Chapelle, Paris) may have served as inspiration.
New U–Pb radioisotopic ages on early Cambrian volcanic zircons condition a high-resolution Bayesian age model that constrains the first occurrences and zonations of West Gondwanan archaeocyaths and trilobites in southern Morocco. The oldest archaeocyaths in the Tiout Member of the Igoudine Formation (519.71 + 0.26/− 0.35 Ma) are c. 6 Ma younger than the oldest Siberian archaeocyaths. The oldest Moroccan trilobite fragments, from the lower member of the Igoudine, are constrained to 519.95 + 0.43/− 0.40 Ma. The succeeding Issendalenian Stage (i.e. Hupetina antique – Eofallotaspis tioutensis – Fallotaspis plana – Choubertella – Daguinaspis trilobite zones) spans c. 1.5 Ma (519.78 + 0.26/− 0.37 Ma to 518.43 + 0.25/− 0.69 Ma). Identifiable Moroccan fallotaspidids and bigotinids, among Earth’s oldest trilobites, occur above a positive δ13C excursion dated with our age model at 520.27 + 0.59/− 0.57 Ma, and correlated with the IV excursion peak within the lower range of Siberian Atdabanian Stage trilobites (Repinaella Zone). This excursion is the best standard for a Cambrian Series 2 base. The oldest West Gondwana trilobite fragments are c. 1 Ma younger than those in Siberia and c. 0.5 Ma older than the oldest Avalonian trilobites (Callavia Zone). This diachrony means a trilobite first appearance datum is an inappropriate chronostratigraphic base for Cambrian Series 2. Taxonomic differences in the oldest trilobites between Cambrian palaeocontinents are in accordance with trace fossil evidence for the group’s appearance possibly as late as c. 530 Ma in the Cambrian Evolutionary Radiation. Coeval 519–517 Ma dates from Avalonia (cool-water siliciclastic shelf) and West Gondwana (tropical carbonate platform) sections with distinct macrofaunas emphasize these successions were latitudinally separate by the late Ediacaran Period.
Studies suggest that alcohol consumption and alcohol use disorders have distinct genetic backgrounds.
We examined whether polygenic risk scores (PRS) for consumption and problem subscales of the Alcohol Use Disorders Identification Test (AUDIT-C, AUDIT-P) in the UK Biobank (UKB; N = 121 630) correlate with alcohol outcomes in four independent samples: an ascertained cohort, the Collaborative Study on the Genetics of Alcoholism (COGA; N = 6850), and population-based cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC; N = 5911), Generation Scotland (GS; N = 17 461), and an independent subset of UKB (N = 245 947). Regression models and survival analyses tested whether the PRS were associated with the alcohol-related outcomes.
In COGA, AUDIT-P PRS was associated with alcohol dependence, AUD symptom count, maximum drinks (R2 = 0.47–0.68%, p = 2.0 × 10−8–1.0 × 10−10), and increased likelihood of onset of alcohol dependence (hazard ratio = 1.15, p = 4.7 × 10−8); AUDIT-C PRS was not an independent predictor of any phenotype. In ALSPAC, the AUDIT-C PRS was associated with alcohol dependence (R2 = 0.96%, p = 4.8 × 10−6). In GS, AUDIT-C PRS was a better predictor of weekly alcohol use (R2 = 0.27%, p = 5.5 × 10−11), while AUDIT-P PRS was more associated with problem drinking (R2 = 0.40%, p = 9.0 × 10−7). Lastly, AUDIT-P PRS was associated with ICD-based alcohol-related disorders in the UKB subset (R2 = 0.18%, p < 2.0 × 10−16).
AUDIT-P PRS was associated with a range of alcohol-related phenotypes across population-based and ascertained cohorts, while AUDIT-C PRS showed less utility in the ascertained cohort. We show that AUDIT-P is genetically correlated with both use and misuse and demonstrate the influence of ascertainment schemes on PRS analyses.
Carbon nanomaterials are consistently providing new excitement over their properties and potential applications, but many of these material have yet to fully live up to their expectations commercially. The barrier to adoption often exists as a result of complex processing, fragility of the as-produced material, or difficulty scaling beyond laboratory quantities. This work provides a new approach for utilizing fibrous carbon nanomaterials to advance the technology toward new applications and industrial utility. This is accomplished by creating tailored device architectures through in-situ integration of activated carbon powder using carbon nanofiber deposition. The resulting hybrid materials and components can serve in diverse applications, with each instance able to be fine-tuned through a combination of processing parameters. The applications of such materials are anticipated to directly serve current carbon-based technology in filtration, energy storage and delivery, and thermal management, but the concepts are not limited to current carbon applications.
Grotesque and vulgar, the masked character Gongoli upends the codes of Mende decorum in his madcap pursuit of laughs. His impropriety goes so far as to allow his mask to fall, comically revealing the identity of his dancer and subverting the anonymity so elemental to his fellow spirits’ vaunted status. Yet despite such transgressions, he stands among the most beloved figures of Sierra Leone's rich performance traditions. Gongoli's popularity hinges on his irreverence towards the fundamental laws of masked dance, laws that also regulate the balance between individual agency and communal responsibility, between internal desire and external restraint. The only quality necessary to play Gongoli is shamelessness (ngufe baa), and the greatest performers are acrobats braving risks that are not physical, but social. This article follows Siloh, an itinerant performer whose celebrity inheres in his uncanny similarity to the Gongoli he often plays. The composite figure Siloh Gongoli exemplifies a comic aesthetic relished throughout Sierra Leone in storytelling, ritual, festivals, videos and radio shows. Although mobilized for different ends, each of these conventions undermines principles of self-effacement, gerontocratic privilege and esoteric power by shamelessly playing with and within the existential tensions between interior and exterior selves.