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.
Recent changes to US research funding are having far-reaching consequences that imperil the integrity of science and the provision of care to vulnerable populations. Resisting these changes, the BJPsych Portfolio reaffirms its commitment to publishing mental science and advancing psychiatric knowledge that improves the mental health of one and all.
An online survey was distributed to South Dakota stakeholders to understand how noxious weeds are currently being managed. The response rate was 26%; 129 stakeholders completed the survey of the 491 stakeholders who opened the survey. Eighty percent of respondents stated noxious weeds were a problem. Canada thistle [Cirsium arvense (L.) Scop.], leafy spurge (Euphorbia esula L.), and absinth wormwood (Artemisia absinthium L.) were the most common and troublesome, but all statewide noxious weeds were reported. The most common singular response to manage noxious weeds was herbicides alone (25%), but respondents utilized two (27%) to three (24%) other tactics as well. Most respondents (47%) were somewhat satisfied with management tactics, while others were completely satisfied (9%), neither satisfied nor dissatisfied (20%), somewhat unsatisfied (11%), or very unsatisfied (15%). A covariate analysis showed that the more management tactics individual stakeholders utilized, the less satisfied they were with control (P < 0.0001). The most common barrier of adopting new tactics was effectiveness (26%) followed by a combination of effectiveness + current production practices + cost + labor (13%). An additional covariate analysis showed that the increase in management tactics increased the barriers of adoption (P = 0.04) and increasing the number of barriers of adoption resulted in stakeholders being dissatisfied with control (P = 0.0003). Overall, the results of the survey suggest that statewide noxious weeds remain a problem, and multiple tactics are used to manage these weeds. However, Cooperative extension efforts need to address how to use current management and implement new management strategies to increase effectiveness.
Vaccines have revolutionised the field of medicine, eradicating and controlling many diseases. Recent pandemic vaccine successes have highlighted the accelerated pace of vaccine development and deployment. Leveraging this momentum, attention has shifted to cancer vaccines and personalised cancer vaccines, aimed at targeting individual tumour-specific abnormalities. The UK, now regarded for its vaccine capabilities, is an ideal nation for pioneering cancer vaccine trials. This article convened experts to share insights and approaches to navigate the challenges of cancer vaccine development with personalised or precision cancer vaccines, as well as fixed vaccines. Emphasising partnership and proactive strategies, this article outlines the ambition to harness national and local system capabilities in the UK; to work in collaboration with potential pharmaceutic partners; and to seize the opportunity to deliver the pace for rapid advances in cancer vaccine technology.
Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).
Aims
We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.
Method
Based on individual genotypes from case–control cohorts of BPD and MDD shared through the Psychiatric Genomics Consortium, we compile case–case–control cohorts, applying a careful quality control procedure. In a resulting cohort of 51 149 individuals (15 532 BPD patients, 12 920 MDD patients and 22 697 controls), we perform a variety of GWAS and PRS analyses.
Results
Although our GWAS is not well powered to identify genome-wide significant loci, we find significant chip heritability and demonstrate the ability of the resulting PRS to distinguish BPD from MDD, including BPD cases with depressive onset (BPD-D). We replicate our PRS findings in an independent Danish cohort (iPSYCH 2015, N = 25 966). We observe strong genetic correlation between our case–case GWAS and that of case–control BPD.
Conclusions
We find that MDD and BPD, including BPD-D are genetically distinct. Our findings support that controls, MDD and BPD patients primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BPD and, importantly, BPD-D from MDD.
A liquefied natural gas (LNG) facility often incorporates replicate liquefaction trains. The performance of equivalent units across trains, designed using common numerical models, might be expected to be similar. In this article, we discuss statistical analysis of real plant data to validate this assumption. Analysis of operational data for end flash vessels from a pair of replicate trains at an LNG facility indicates that one train produces 2.8%–6.4% more end flash gas than the other. We then develop statistical models for train operation, facilitating reduced flaring and hence a reduction of up to 45% in CO2 equivalent flaring emissions, noting that flaring emissions for a typical LNG facility account for ~4%–8% of the overall facility emissions. We recommend that operational data-driven models be considered generally to improve the performance of LNG facilities and reduce their CO2 footprint, particularly when replica units are present.
Many foodborne illness outbreaks originate in food service establishments. We tested two behavioural interventions designed to improve the duration and quality of handwashing. We ran a three-armed parallel trial in a laboratory kitchen, from 7 March to 27 May 2022. Participants were n = 195 workers who handle food. We randomly allocated participants to three groups: Timer – tap-mounted timer that counted seconds while participants washed their hands; Precommitment – agreed to five statements on good hand hygiene before attending the kitchen; and Control. Participants completed a food preparation task under time pressure. Cameras focused on the sink captured handwashing. Outcome measures were number of times participants washed their hands; number of times they washed their hands using soap; number of times they washed using soap and washed the backs of their hands; and mean duration of handwashing attempts using soap. Participants in Timer washed their hands for 1.9 s longer on average than Control (β = 2.20, 95% CI = 0.34-4.06, p = 0.021). Participants in Precommitment washed their hands for 2.5 s longer on average than Control (β = 2.30, 95% CI = 0.33-4.27, p = 0.022). We found no statistically significant differences on any other outcome measure.
OBJECTIVES/GOALS: We have designed an analogue of the Vitamin E tocotrienols called tocoflexol, which improves their pharmacokinetic limitations to make it an effective radiation medical countermeasure. Our goal is to demonstrate that tocoflexol is an effective radiomitigator in vivo when administered after exposure to lethal doses of total body irradiation. METHODS/STUDY POPULATION: Tocoflexol was designed using computational techniques to improve binding to ATTP, the key transporter that reduces the rate of elimination of tocols. In vitro studies compared the antioxidant and cell uptake properties to conventional tocotrienols. Next, we used a mouse model of lethal total body irradiation to evaluate its radioprotection efficacy (treating before radiation). To determine the optimal administration route for radiomitigation (treating after radiation), we will test oral and subcutaneous dosing. Mouse survival will be monitored for 30 days after irradiation. Sample tissues will be taken to evaluate the ability of tocoflexol to protect key organs from acute radiation syndrome. The bioavailability of tocoflexol will be evaluated in a rodent model. RESULTS/ANTICIPATED RESULTS: Known Results: Results show that tocoflexol has potent antioxidant properties and high cell uptake. When tocoflexol was administered 24 hours before exposure to lethal doses of radiation, tocoflexol-treated mice showed 100% survival. Anticipated Results: Because of its improved bioavailability and pharmacokinetic properties, we expect that tocoflexol will show radiomitigation efficacy when administered 24 hours after radiation, improving survival and protecting key organ systems from acute radiation syndrome. DISCUSSION/SIGNIFICANCE: There is an unmet need for safe and effective radiomitigators that can offer multi-organ protection and be rapidly administered in the event of nuclear emergencies. Demonstration of radiomitigation efficacy will position tocoflexol as a prime candidate to be developed into a nuclear medical countermeasure and stockpiled for emergencies.
Preclinical evidence has identified the trace amine-associated receptor 1 (TAAR1) as a novel regulator of metabolic control. Ulotaront is a TAAR1 and 5-HT1A agonist currently in Phase 3 clinical trials for the treatment of schizophrenia. Here we summarize preclinical results assessing the effects of ulotaront on weight and metabolic parameters.
Methods
Effects of ulotaront administration were evaluated on oral glucose tolerance (oGTT), gastric emptying, and in rodent models of weight gain (high-fat diet [HFD]-, corticosterone-, and olanzapine-induced).
Results
Following 15-day oral administration of ulotaront, rats on HFD showed dose-dependent reduction in body weight, food intake, and liver triglyceride content compared to controls. In addition, a more rapid reversal of olanzapine-induced weight gain and food intake was observed in rats switched to ulotaront (vs. vehicle). Consistent with weight-lowering effects in rats, chronic ulotaront treatment normalized corticosterone-induced weight gain in mice. Assessment of oGTT showed a dose-dependent reduction of glucose excursion in response to acute ulotaront administration in naive and diabetic db/db mice. Ulotaront administration also delayed gastric emptying in mice—a likely mechanism driving reductions in glucose excursions during the oGTT. Whole-brain c-fos imaging of ulotaront-treated mice revealed increased neuronal activity in several brain regions associated with regulation of food intake and metabolic signals.
Conclusions
The data indicate that ulotaront not only lacks metabolic liabilities typically associated with antipsychotics but can reduce body weight and improve glucose tolerance in rodent models. The underlying mechanisms may include TAAR1-mediated peripheral effects on glucose homeostasis and/or direct modulation of homeostatic and hedonic neurocircuits regulating energy balance. The beneficial metabolic effects of ulotaront may suggest a substantially improved risk-benefit profile compared to established antipsychotics.
Funding
Sunovion Pharmaceuticals Inc. and Otsuka Pharmaceutical Development & Commercialization, Inc.
This review presents a summary of the Buzdujeni I report, which is only available in Russian, alongside recent publications in English concerning both this site and other cave sites that were included in an extensive programme of research into the later Palaeolithic of Moldova, Ukraine, and Russia.
This chapter synthesises insights from the Deep Decarbonisation Pathways Project (DDPP), which provided detailed analysis of how 16 countries representing three-quarters of global emissions can transition to very low-carbon economies. The four ‘pillars’ of decarbonisation are identified as: achieving low or zero-carbon electricity supply; electrification and fuel switching in transport, industry and housing; ambitious energy efficiency improvements; and reducing non-energy emissions. The chapter focuses on decarbonisation scenarios for Australia. It shows that electricity supply can be readily decarbonised and greatly expanded to cater for electrification of transport, industry and buildings. There would be remaining emissions principally from industry and agriculture, these could be fully compensated through land-based carbon sequestration. The analysis shows that such decarbonisation would be consistent with continued growth in GDP and trade, and would require very little change in economic structure of Australia’s economy. Australia is rich in renewable energy potential, which could re-enable new industries such as energy-intensive manufacturing for export
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
Aims
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Method
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Results
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
Conclusions
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
There has been an increasing focus in the UK on the support provided to the Armed Forces community, with the publication of the Armed Forces Covenant (2011), the Strategy for our Veterans (2018) and the first ever Office for Veterans’ Affairs (2019). There is also an important body of research – including longitudinal research – focusing on transitions from military to civilian life, much of which is quantitative. At the same time, the UK has witnessed a period of unprecedented welfare reform. However, research focused on veterans’ interactions with the social security system has been largely absent. This article draws on the authors’ experiences of undertaking qualitative longitudinal research (QLR) to address this knowledge gap. We reflect on how QLR was essential in engaging policy makers enabling the research to bridge the two parallel policy worlds of veterans’ support and welfare reform, leading to significant policy and practice impact.
A significant number of people with autism require in-patient psychiatric care. Although the requirement to adequately meet the needs of people with autism in these settings is enshrined in UK law and supported by national guidelines, little information is available on current practice.
Aims
To describe characteristics of UK in-patient psychiatric settings admitting people with autism. Also to examine psychiatric units for their suitability, and the resultant impact on admission length and restrictive interventions.
Method
Multiple-choice questions about in-patient settings and their ability to meet the needs of people with autism and the impact on their outcomes were developed as a cross-sectional study co-designed with a national autism charity. The survey was distributed nationally, using an exponential and non-discriminatory snowballing technique, to in-patient unit clinicians to provide a current practice snapshot.
Results
Eighty responses were analysed after excluding duplications, from across the UK. Significant variation between units across all enquired parameters exist. Lack of autism-related training and skills across staff groups was identified, this becoming disproportionate when comparing intellectual disability units with general mental health units particularly regarding psychiatrists working in these units (psychiatrists: 94% specialist skills in intellectual disability units versus 6% specialist skills in general mental health units). In total, 28% of survey respondents felt people with autism are more likely to be subject to seclusion and 40% believed in-patients with autism are likely to end in segregation.
Conclusions
There is no systematic approach to supporting people with autism who are admitted to in-patient psychiatric units. Significant concerns are highlighted of lack of professional training and skill sets resulting in variable clinical practice and care delivery underpinned by policy deficiency. This could account for the reported in-patient outcomes of longer stay and segregation experienced by people with autism.
Diets varying in SFA and MUFA content can impact glycaemic control; however, whether underlying differences in genetic make-up can influence blood glucose responses to these dietary fatty acids is unknown. We examined the impact of dietary oils varying in SFA/MUFA content on changes in blood glucose levels (primary outcome) and whether these changes were modified by variants in the stearoyl-CoA desaturase (SCD) gene (secondary outcome). Obese men and women participating in the randomised, crossover, isoenergetic, controlled-feeding Canola Oil Multicenter Intervention Trial II consumed three dietary oils for 6 weeks, with washout periods of ˜6 weeks between each treatment. Diets studied included a high SFA/low MUFA Control oil (36·6 % SFA/28·2 % MUFA), a conventional canola oil (6·2 % SFA/63·1 % MUFA) and a high-oleic acid canola oil (5·8 % SFA/74·7 % MUFA). No differences in fasting blood glucose were observed following the consumption of the dietary oils. However, when stratified by SCD genotypes, significant SNP-by-treatment interactions on blood glucose response were found with additive models for rs1502593 (P = 0·01), rs3071 (P = 0·02) and rs522951 (P = 0·03). The interaction for rs3071 remained significant (P = 0·005) when analysed with a recessive model, where individuals carrying the CC genotype showed an increase (0·14 (sem 0·09) mmol/l) in blood glucose levels with the Control oil diet, but reductions in blood glucose with both MUFA oil diets. Individuals carrying the AA and AC genotypes experienced reductions in blood glucose in response to all three oils. These findings identify a potential new target for personalised nutrition approaches aimed at improving glycaemic control.
There is a wide-ranging belief that people with severe mental illnesses (SMI) are violent or dangerous. Most patients with schizophrenia are not chronically aggressive or violent; among patients with schizophrenia, there is a small increase in violence and violent offending on average compared with general population standards in the USA and Europe. However, violence on the part of people with SMI has several features that differentiate it from violence in the general population. First, it is less likely to be motivated by financial reasons. Second, it can be unpredictable and directed toward strangers. Not being financially motivated, it is more challenging for the general public to avoid.
Year-round monitoring of Erebus volcano (Ross Island) has proved challenging due to the difficulties of maintaining continuous power for scientific instruments, especially through the Antarctic winter. We sought a potential solution involving the harvesting of thermal energy dissipated close to the summit crater of the volcano in a zone of diffuse hot gas emissions. We designed, constructed and tested a power generator based on the Seebeck effect, converting thermal energy to electrical power, which could, in principle, be used to run monitoring devices year round. We report here on the design of the generator and the results of an 11 day trial deployment on Erebus volcano in December 2014. The generator produced a mean output power of 270 mW, although we identified some technical issues that had impaired its efficiency. Nevertheless, this is already sufficient power for some monitoring equipment and, with design improvements, such a generator could provide a viable solution to powering a larger suite of instrumentation.
Background: Sink drainage systems are a potential reservoir for the dissemination of gram-negative bacilli but are not amenable to standard methods of cleaning and disinfection. Pouring liquid disinfectants down drains has only a limited and transient effect on drain colonization, presumably due to inadequate disinfectant contact time and suboptimal penetration into areas harboring biofilm-associated organisms. Methods: We compared the antimicrobial efficacy of 2 novel sink disinfection methods intended to enhance disinfectant contact time and penetration. Healthcare facility sinks were randomly assigned to disinfection with 300 mL hydrogen peroxide-based disinfectant applied either as a foam (N = 13 sinks) or instilled for 30 minutes behind a temporary obstruction created by an inflated urinary catheter balloon (N = 12 sinks). Swabs were used to collect quantitative cultures from the proximal sink drain to depth of 2.5 cm (1 inch) below the strainer before treatment and at 15 minutes and 1, 2, 3, 5, and 7 days after treatment. Repeated measures analysis of variance was performed to compare the efficacy of the 2 treatments. Results: As shown in Fig. 1, both methods yielded an initial reduction of >3 log10 CFU of gram-negative bacilli. Over the 7-day follow-up period, disinfectant instillation resulted in significantly greater reduction than the foam application (P < .01). Recovery of sink colonization to >2 log per swab occurred at day 3 for both treatments, whereas recovery to >3 log per swab occurred on day 3 for the foam treatment versus day 7 for disinfectant instillation. Conclusions: Two novel disinfection methods were effective in reducing sink drain colonization for several days. The instillation method was more effective than the foam method in maintaining reductions over 7 days.
Emerging data suggest that recovery from mild traumatic brain injury (mTBI) takes longer than previously thought. This paper examines trajectories for cognitive recovery up to 48 months post-mTBI, presenting these visually using a Sankey diagram and growth curve analysis.
Methods:
This sample (n = 301) represents adults (≥16 years) from a population-based Brain Injury Outcomes in the New Zealand Community study over a 4-year follow-up on the CNS-Vital Signs neuropsychological test. Data were collected within 2 weeks of injury, and then at 1, 6, 12 and 48 months post-injury.
Results:
Significant improvement in cognitive functioning was seen up to 6 months post-injury. Using growth curve modelling, we found significant improvements in overall neurocognition from baseline to 6 months, on average participants improved one point per month (0.9; 95% CI 0.42–1.39) p < 0.001. No change in neurocognition was found within the time periods 6–12 months or 12–48 months. The Sankey highlighted that at each time point, a small proportion of participants remained unchanged or declined. Proportionally, few show any improvement after the first 6 months.
Conclusion:
Most individuals remained stable or improved over time to 6 months post-injury. Summary statistics are informative regarding overall trends, but can mask differing trajectories for recovery. The Sankey diagram indicates that not all improve, as well as the potential impact of individuals moving in and out of the study. The Sankey diagram also indicated the level of functioning of those most likely to withdraw, allowing targeting of retention strategies.
Rapid diagnosis of dementia is essential to ensure optimum patient care. This study used real-world data to quantify the dementia diagnostic pathway in Australia.
Design:
A real-world, cross-sectional survey of physicians and patients.
Setting:
Clinical practice.
Participants:
Primary care or specialist physicians managing patients with cognitive impairment (CI).
Measurements:
Descriptive analyses focused on key events in the diagnostic pathway. Regression modeling compared the duration between first consultation and formal diagnosis with various factors.
Results:
Data for 600 patients were provided by 60 physicians. Mean time from initial symptoms to first consultation was 6.1 ± 4.4 months; 20% of patients had moderate or severe CI at first consultation. Mean time from first consultation to formal diagnosis was 4.0 ± 7.4 months (1.2 ± 3.6 months if not referred to a secondary physician, and 5.3 ± 8.3 months if referred). Time from first consultation to diagnosis was significantly associated with CI severity at first consultation; time was shorter with more severe CI. There was no association of disease severity and referral to a secondary physician; 69.5% of patients were referred, the majority (57.1%) to a geriatrician. The highest proportion of patients were diagnosed by geriatricians (47.4%). Some form of test or scale was used to aid diagnosis in 98.8% of patients.
Conclusions:
A substantial number of Australians experience cognitive decline and behavioral changes some time before consulting a physician or being diagnosed with dementia. Increasing public awareness of the importance of early diagnosis is essential to improve the proportion of patients receiving comprehensive support prior to disease progression.
Alexander Neville (1544–1614) was an English humanist, scholar, author and translator who made his reputation as a Latinist and worked as a secretary for Matthew Parker, Archbishop of Canterbury. This book offers the Latin text and modern translations of Neville's De furoribus Norfolciensium Ketto Duce, Norwicus, and Ad Walliae proceres apologia.