We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.
To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure no-reply@cambridge.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Trace amine-associated receptor 1 (TAAR1) agonists offer a new approach, but there is uncertainty regarding their effects, exact mechanism of action and potential role in treating psychosis.
Aims
To evaluate the available evidence on TAAR1 agonists in psychosis, using triangulation of the output of living systematic reviews (LSRs) of animal and human studies, and provide recommendations for future research prioritisation.
Method
This study is part of GALENOS (Global Alliance for Living Evidence on aNxiety, depressiOn and pSychosis). In the triangulation process, a multidisciplinary group of experts, including those with lived experience, met and appraised the first co-produced living systematic reviews from GALENOS, on TAAR1 agonists.
Results
The animal data suggested a potential antipsychotic effect, as TAAR1 agonists reduced locomotor activity induced by pro-psychotic drug treatment. Human studies showed few differences for ulotaront and ralmitaront compared with placebo in improving overall symptoms in adults with acute schizophrenia (four studies, n = 1291 participants, standardised mean difference (SMD) 0.15, 95% CI −0.05 to 0.34). Large placebo responses were seen in ulotaront phase three trials. Ralmitaront was less efficacious than risperidone (one study, n = 156 participants, SMD = −0.53, 95% CI −0.86 to −0.20). The side-effect profile of TAAR1 agonists was favourable compared with existing antipsychotics. Priorities for future studies included (a) using different animal models of psychosis with greater translational validity; (b) animal and human studies with wider outcomes including cognitive and affective symptoms and (c) mechanistic studies and investigations of other potential applications, such as adjunctive treatments and long-term outcomes. Recommendations for future iterations of the LSRs included (a) meta-analysis of individual human participant data, (b) including studies that used different methodologies and (c) assessing other disorders and symptoms.
Conclusions
This co-produced, international triangulation examined the available evidence and developed recommendations for future research and clinical applications for TAAR1 agonists in psychosis. Broader challenges included difficulties in assessing the risk of bias, reproducibility, translation and interpretability of animal models to clinical outcomes, and a lack of individual and clinical characteristics in the human data. The research will inform a separate, independent prioritisation process, led by lived experience experts, to prioritise directions for future research.
Suicidal behaviors are prevalent among college students; however, students remain reluctant to seek support. We developed a predictive algorithm to identify students at risk of suicidal behavior and used telehealth to reduce subsequent risk.
Methods
Data come from several waves of a prospective cohort study (2016–2022) of college students (n = 5454). All first-year students were invited to participate as volunteers. (Response rates range: 16.00–19.93%). A stepped-care approach was implemented: (i) all students received a comprehensive list of services; (ii) those reporting past 12-month suicidal ideation were directed to a safety planning application; (iii) those identified as high risk of suicidal behavior by the algorithm or reporting 12-month suicide attempt were contacted via telephone within 24-h of survey completion. Intervention focused on support/safety-planning, and referral to services for this high-risk group.
Results
5454 students ranging in age from 17–36 (s.d. = 5.346) participated; 65% female. The algorithm identified 77% of students reporting subsequent suicidal behavior in the top 15% of predicted probabilities (Sensitivity = 26.26 [95% CI 17.93–36.07]; Specificity = 97.46 [95% CI 96.21–98.38], PPV = 53.06 [95% CI 40.16–65.56]; AUC range: 0.895 [95% CIs 0.872–0.917] to 0.966 [95% CIs 0.939–0.994]). High-risk students in the Intervention Cohort showed a 41.7% reduction in probability of suicidal behavior at 12-month follow-up compared to high-risk students in the Control Cohort.
Conclusions
Predictive risk algorithms embedded into universal screening, coupled with telehealth intervention, offer significant potential as a suicide prevention approach for students.
Glyphosate’s efficacy is influenced by the amount absorbed and translocated throughout the plant to inhibit 5-enolpyruvyl shikimate-3-phosphate synthase (EPSPS). Glyphosate resistance can be due to target-site (TS) or non–target site (NTS) resistance mechanisms. TS resistance includes an altered target site and gene overexpression, while NTS resistance includes reduced absorption, reduced translocation, enhanced metabolism, and exclusion/sequestration. The goal of this research was to elucidate the mechanism(s) of glyphosate resistance in common ragweed (Ambrosia artemisiifolia L.) from Ontario, Canada. The resistance factor for this glyphosate-resistant (GR) A. artemisiifolia biotype is 5.1. No amino acid substitutions were found at positions 102 or 106 of the EPSPS enzyme in this A. artemisiifolia biotype. Based on [14C]glyphosate studies, there was no difference in glyphosate absorption or translocation between glyphosate-susceptible (GS) and GR A. artemisiifolia biotypes. Radio-labeled glyphosate metabolites were similar for GS and GR A. artemisiifolia 96 h after application. Glyphosate resistance in this A. artemisiifolia biotype is not due to an altered target site due to amino acid substitutions at positions 102 and 106 in the EPSPS and is not due to the NTS mechanisms of reduced absorption, reduced translocation, or enhanced metabolism.
In April 2019, the U.S. Fish and Wildlife Service (USFWS) released its recovery plan for the jaguar Panthera onca after several decades of discussion, litigation and controversy about the status of the species in the USA. The USFWS estimated that potential habitat, south of the Interstate-10 highway in Arizona and New Mexico, had a carrying capacity of c. six jaguars, and so focused its recovery programme on areas south of the USA–Mexico border. Here we present a systematic review of the modelling and assessment efforts over the last 25 years, with a focus on areas north of Interstate-10 in Arizona and New Mexico, outside the recovery unit considered by the USFWS. Despite differences in data inputs, methods, and analytical extent, the nine previous studies found support for potential suitable jaguar habitat in the central mountain ranges of Arizona and New Mexico. Applying slightly modified versions of the USFWS model and recalculating an Arizona-focused model over both states provided additional confirmation. Extending the area of consideration also substantially raised the carrying capacity of habitats in Arizona and New Mexico, from six to 90 or 151 adult jaguars, using the modified USFWS models. This review demonstrates the crucial ways in which choosing the extent of analysis influences the conclusions of a conservation plan. More importantly, it opens a new opportunity for jaguar conservation in North America that could help address threats from habitat losses, climate change and border infrastructure.
Few studies have derived data-driven dietary patterns in youth in the USA. This study examined data-driven dietary patterns and their associations with BMI measures in predominantly low-income, racial/ethnic minority US youth. Data were from baseline assessments of the four Childhood Obesity Prevention and Treatment Research (COPTR) Consortium trials: NET-Works (534 2–4-year-olds), GROW (610 3–5-year-olds), GOALS (241 7–11-year-olds) and IMPACT (360 10–13-year-olds). Weight and height were measured. Children/adult proxies completed three 24-h dietary recalls. Dietary patterns were derived for each site from twenty-four food/beverage groups using k-means cluster analysis. Multivariable linear regression models examined associations of dietary patterns with BMI and percentage of the 95th BMI percentile. Healthy (produce and whole grains) and Unhealthy (fried food, savoury snacks and desserts) patterns were found in NET-Works and GROW. GROW additionally had a dairy- and sugar-sweetened beverage-based pattern. GOALS had a similar Healthy pattern and a pattern resembling a traditional Mexican diet. Associations between dietary patterns and BMI were only observed in IMPACT. In IMPACT, youth in the Sandwich (cold cuts, refined grains, cheese and miscellaneous) compared with Mixed (whole grains and desserts) cluster had significantly higher BMI (β = 0·99 (95 % CI 0·01, 1·97)) and percentage of the 95th BMI percentile (β = 4·17 (95 % CI 0·11, 8·24)). Healthy and Unhealthy patterns were the most common dietary patterns in COPTR youth, but diets may differ according to age, race/ethnicity or geographic location. Public health messages focused on healthy dietary substitutions may help youth mimic a dietary pattern associated with lower BMI.
Poultry production is an important way of enhancing the livelihoods of rural populations, especially in low- and middle-income countries (LMICs). As poultry production in LMICs remains dominated by backyard systems with low inputs and low outputs, considerable yield gaps exist. Intensification can increase poultry productivity, production and income. This process is relatively recent in LMICs compared to high-income countries. The management practices and the constraints faced by smallholders trying to scale-up their production, in the early stages of intensification, are poorly understood and described. We thus investigated the features of the small-scale commercial chicken sector in a rural area distant from major production centres. We surveyed 111 commercial chicken farms in Kenya in 2016. We targeted farms that sell the majority of their production, owning at least 50 chickens, partly or wholly confined and provided with feeds. We developed a typology of semi-intensive farms. Farms were found mainly to raise dual-purpose chickens of local and improved breeds, in association with crops and were not specialized in any single product or market. We identified four types of semi-intensive farms that were characterized based on two groups of variables related to intensification and accessibility: (i) remote, small-scale old farms, with small flocks, growing a lot of their own feed; (ii) medium-scale, old farms with a larger flock and well located in relation to markets and (iii) large-scale recently established farms, with large flocks, (iii-a) well located and buying chicks from third-party providers and (iii-b) remotely located and hatching their own chicks. The semi-intensive farms we surveyed were highly heterogeneous in terms of size, age, accessibility, management, opportunities and challenges. Farm location affects market access and influences the opportunities available to farmers, resulting in further diversity in farm profiles. The future of these semi-intensive farms could be compromised by several factors, including the competition with large-scale intensive farmers and with importations. Our study suggests that intensification trajectories in rural areas of LMICs are potentially complex, diverse and non-linear. A better understanding of intensification trajectories should, however, be based on longitudinal data. This could, in turn, help designing interventions to support small-scale farmers.
Examine impact of audit and feedback on antipsychotic prescribing in schizophrenia over 4.5-years.
Methods:
Clinical files in three outpatient psychiatric services in Auckland, New Zealand were reviewed at two time-points (March-2000;October-2004). After the first audit, feedback was provided to all three services. Baseline prescribing variations between services were found for antipsychotic combinations and atypical prescribing, in particular clozapine. In two services audit and feedback continued with two interim reviews (October-2001;March-2003). Specific feedback and interventions targeting clozapine use were introduced in both services. No further audit or feedback occurred in the third service until the final audit. Data were collected (patient characteristics, diagnosis, antipsychotic treatment) and analysed at each audit.
Results:
Three prescribing variables (antipsychotic monotherapy, atypical and clozapine use) were consistent with practice recommendations at the final audit (85.7%, 82.7% and 34.5% respectively) and had changed in the desired direction for all three services over 4.5-years. At baseline there were differences between the three services. One service had baseline prescribing variables closest to recommendations, was actively involved in audit, and improved further. The second service, also actively involved in audit had baseline prescribing variables further from recommendations but improved the most. The service not involved in continuing audit and feedback made smaller changes, and atypical and clozapine use at endpoint were significantly lower despite at baseline being comparable to the service which improved the most.
Conclusions:
We found high intensity audit and feedback was an effective intervention in closing the gap between recommended and clinical practice for antipsychotic prescribing.
Objectives: This study investigated the relationship between close proximity to detonated blast munitions and cognitive functioning in OEF/OIF/OND Veterans. Methods: A total of 333 participants completed a comprehensive evaluation that included assessment of neuropsychological functions, psychiatric diagnoses and history of military and non-military brain injury. Participants were assigned to a Close-Range Blast Exposure (CBE) or Non-Close-Range Blast Exposure (nonCBE) group based on whether they had reported being exposed to at least one blast within 10 meters. Results: Groups were compared on principal component scores representing the domains of memory, verbal fluency, and complex attention (empirically derived from a battery of standardized cognitive tests), after adjusting for age, education, PTSD diagnosis, sleep quality, substance abuse disorder, and pain. The CBE group showed poorer performance on the memory component. Rates of clinical impairment were significantly higher in the CBE group on select CVLT-II indices. Exploratory analyses examined the effects of concussion and multiple blasts on test performance and revealed that number of lifetime concussions did not contribute to memory performance. However, accumulating blast exposures at distances greater than 10 meters did contribute to poorer performance. Conclusions: Close proximity to detonated blast munitions may impact memory, and Veterans exposed to close-range blast are more likely to demonstrate clinically meaningful deficits. These findings were observed after statistically adjusting for comorbid factors. Results suggest that proximity to blast should be considered when assessing for memory deficits in returning Veterans. Comorbid psychiatric factors may not entirely account for cognitive difficulties. (JINS, 2018, 24, 466–475)
Two studies consisting of six field experiments each were conducted at three locations in southwestern Ontario, Canada, in 2014 and 2015 to evaluate the possible antagonism when dicamba was added to quizalofop-p-ethyl or clethodim for the control of volunteer glyphosate-resistant (GR) corn. At 4 wk after application (WAA), quizalofop-p-ethyl at 24, 30, or 36 g ai ha−1 provided 88, 94, and 95% control of volunteer GR corn, respectively. The addition of dicamba at 300 or 600 g ae ha−1 to quizalofop-p-ethyl (24 g ha−1) reduced the activity of quizalofop-p-ethyl on volunteer GR corn by 12 and 20%. At 4 WAA, clethodim at 30, 37.5, and 45 g ai ha−1 provided 85, 91, and 95% control of volunteer GR corn, respectively. The addition of dicamba at 300 or 600 g ha−1 to clethodim (30 g ha−1) resulted in antagonism, causing a reduction in volunteer GR corn by 12 and 11%, respectively. In general, there was greater antagonism when the high rate of dicamba was tank-mixed with the lower rate of the graminicide. There was no antagonistic effect on soybean yield by tank-mixing dicamba with either graminicide at all rates evaluated. Based on these results, volunteer GR corn can be controlled effectively by increasing the rate of the graminicide when tankmixed with dicamba.
Glyphosate-resistant (GR) giant ragweed has been confirmed in Ontario, Canada. Giant ragweed is an extremely competitive weed and lack of control in soybean will lead to significant yield losses. Seed companies have developed new herbicide-resistant (HR) crop cultivars and hybrids that stack multiple HR traits. The objective of this research was to evaluate the efficacy of glyphosate and glyphosate plus dicamba tank mixes for the control of GR giant ragweed under Ontario environmental conditions in dicamba-tolerant (DT) soybean. Three field trials were established over a 2-yr period (2010 and 2011) on farms near Windsor and Belle River, ON. Treatments included glyphosate (900 g ae ha−1), dicamba (300 g ae ha−1), and dicamba (600 g ha−1) applied preplant (PP), POST, or sequentially in various combinations. Glyphosate applied PP, POST, or sequentially provided 22 to 68%, 40 to 47%, and 59 to 95% control of GR giant ragweed and reduced shoot dry weight 26 to 80%, 16 to 50%, and 72 to 98%, respectively. Glyphosate plus dicamba applied PP followed by glyphosate plus dicamba applied POST consistently provided 100% control of GR giant ragweed. DT soybean yield correlated with GR giant ragweed control. This is the first report in Canada of weed control in DT soybean, specifically for the control of GR giant ragweed. Results indicate that the use of dicamba in DT soybean will provide an effective option for the control of GR giant ragweed in Ontario.
Herbicide-resistant crops, such as glyphosate-resistant (GR) soybean, allow for broad-spectrum, flexible weed control with minimal crop injury; however, the development of GR weeds, such as horseweed, has forced reliance on alternative herbicides for control of these weeds. While preplant (PP) herbicides provide excellent control of GR-horseweed, there are currently no POST herbicide control options within soybean. The objective of this study was to evaluate the efficacy of dicamba for the control of GR-horseweed when applied PP, POST, and sequentially in dicamba-resistant soybean. Dicamba applied PP at 600 g a.e. ha−1 provided 90 to 100% control of GR-horseweed 8 wk after application (WAA) across three field trials conducted in Ontario in 2011 and 2012. Similarly, sequential applications provided 91 to 100% control. This technology provides a much-needed POST option of dicamba to be applied as a rescue treatment to control weed escapes caused by late emergence or poor initial control following a PP herbicide application.
The aims of this study were to identify Staphylococcus aureus nasal colonization prevalence, behavioural risk factors, and to determine staphylococcal protein A (spa) types in community-based injection drug users (IDUs). Nasal swabs were collected and methicillin susceptibility testing and spa/SCCmec typing were performed on S. aureus isolates. Generalized estimating equations were used to report adjusted odds ratios and 95% confidence intervals. Of the 440 participants, 24·1% were colonized and 5·7% had methicillin-resistant S. aureus (MRSA). Colonization was associated with age, employment/marital status, and the presence of scabs but not with sexually transmitted disease co-infection, HIV status, antibiotic use, hospitalization, or drug treatment programme participation. The USA300 MRSA clone spa types were most common, but 15/49 spa types were new to one of the international databases. Community-based IDUs appear to have different risk factors compared to IDUs from clinical studies. In addition, the number of newly identified spa types indicates a diverse, understudied population.