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Executive dysfunction is prevalent in early stroke and can predict long-term outcomes. Impairments can be subtle and undetected in cognitive stroke screens. To better assess executive functions, this study introduced a novel sentence completion test, which assesses multiple executive processes in <5 minutes (Brief Executive Language Screen – Sentence Completion; BELS-SC). The aim was to determine construct, convergent and divergent validity, sensitivity and specificity of the BELS-SC, and to explore differences between left and right hemisphere stroke patients (LHS and RHS, respectively) on the BELS-SC and standard executive function tests.
Method:
Eighty-eight acute/early sub-acute stroke patients and 116 age-matched healthy controls were included.
Results:
Principal Component Analysis (PCA) suggested four to five factors of the BELS-SC: Initiation, Selection, Inhibition (with strategy loading on Inhibition), Inhibition Response Time, and Semantic Retrieval Response Time. The BELS-SC had good sensitivity (.84) but poorer specificity (.66) differentiating controls and stroke, and good sensitivity (.83) and specificity (.80) differentiating executive function impaired versus executive function intact groups. BELS-SC Initiation and Inhibition subtests demonstrated convergent and divergent validity with corresponding Hayling subtests. LHS and RHS showed impairment across initiation, selection, inhibition and strategy; however, greatest deficits were shown by RHS on Inhibition items requiring suppression of one dominant response. More patients were impaired on BELS-SC than other executive function tests.
Conclusions:
The BELS-SC demonstrated convergent, divergent, and construct validity, good sensitivity and specificity, taps multiple executive processes, and provides insight into strategy. Use in early stroke may aid in targeted and timely cognitive rehabilitation.
Increasing daylight exposure might be a simple way to improve mental health. However, little is known about daylight-symptom associations in depressive disorders.
Methods
In a subset of the Australian Genetics of Depression Study (N = 13,480; 75% female), we explored associations between self-reported number of hours spent in daylight on a typical workday and free day and seven symptom dimensions: depressive (overall, somatic, psychological); hypo-manic-like; psychotic-like; insomnia; and daytime sleepiness. Polygenic scores for major depressive disorder (MDD); bipolar disorder (BD); and schizophrenia (SCZ) were calculated. Models were adjusted for age, sex, shift work status, employment status, season, and educational attainment. Exploratory analyses examined age-stratified associations (18–24 years; 25–34 years; 35–64 years; 65 and older). Bonferroni-corrected associations (p < 0.004) are discussed.
Results
Adults with depression reported spending a median of one hour in daylight on workdays and three hours on free days. More daylight exposure on workdays and free days was associated with lower depressive (overall, psychological, somatic) and insomnia symptoms (p’s<0.001), but higher hypo-manic-like symptoms (p’s<0.002). Genetic loading for MDD and SCZ were associated with less daylight exposure in unadjusted correlational analyses (effect sizes were not meaningful). Exploratory analyses revealed age-related heterogeneity. Among 18–24-year-olds, no symptom dimensions were associated with daylight. By contrast, for the older age groups, there was a pattern of more daylight exposure and lower insomnia symptoms (p < 0.003) (except for 25–34-year-olds on free days, p = 0.019); and lower depressive symptoms with more daylight on free days, and to some extent workdays (depending on the age-group).
Conclusions
Exploration of the causal status of daylight in depression is warranted.
Involving participants in the design of clinical trials should improve the overall success of a study. For this to occur, streamlined mechanisms are needed to connect the populations potentially impacted by a given study or health topic with research teams in order to inform trial design in a meaningful and timely manner. To address this need, we developed an innovative mechanism called the “ResearchMatch Expert Advice Tool” that quickly obtains volunteer perspectives from populations with specific health conditions or lived experiences using the national recruitment registry, ResearchMatch. This tool does not ask volunteers to participate in the trial but allows for wider community feedback to be gathered and translated into actionable recommendations used to inform the study’s design. We describe early use cases that shaped the current Expert Advice Tool workflow, how results from this tool were incorporated and implemented by studies, and feedback from volunteers and study teams regarding the tool’s usefulness. Additionally, we present a set of lessons learned during the development of the Expert Advice Tool that can be used by other recruitment registries seeking to obtain volunteer feedback on study design and operations.
Given increased survival for adults with CHD, we aim to determine outcome differences of infective endocarditis compared to patients with structurally normal hearts in the general population.
Methods:
We conducted a retrospective cross-sectional study identifying infective endocarditis hospitalisations in patients 18 years and older from the National Inpatient Sample database between 2001 and 2016 using International Classification of Disease diagnosis and procedure codes. Weighting was used to create national annual estimates indexed to the United States population, and multivariable logistic regression analysis determined variable associations. Outcome variables were mortality and surgery. The primary predictor variable was the presence or absence of CHD.
Results:
We identified 1,096,858 estimated infective endocarditis hospitalisations, of which 17,729 (1.6%) were adults with CHD. A 125% increase in infective endocarditis hospitalisations occurred for adult CHD patients during the studied time period (p < 0.001). Adults with CHD were significantly less likely to experience mortality (5.4% vs. 9.5%, OR 0.54, CI 0.47–0.63, p < 0.001) and more likely to undergo in-hospital surgery (31.6% vs. 6.7%, OR 6.49, CI 6.03–6.98, p < 0.001) compared to the general population. CHD severity was not associated with increased mortality (p = 0.53). Microbiologic aetiology of infective endocarditis varied between groups (p < 0.001) with Streptococcus identified more commonly in adults with CHD compared to patients with structurally normal hearts (36.2% vs. 14.4%).
Conclusions:
Adults with CHD hospitalised for infective endocarditis are less likely to experience mortality and more likely to undergo surgery than the general population.
Diagnostic criteria for major depressive disorder allow for heterogeneous symptom profiles but genetic analysis of major depressive symptoms has the potential to identify clinical and etiological subtypes. There are several challenges to integrating symptom data from genetically informative cohorts, such as sample size differences between clinical and community cohorts and various patterns of missing data.
Methods
We conducted genome-wide association studies of major depressive symptoms in three cohorts that were enriched for participants with a diagnosis of depression (Psychiatric Genomics Consortium, Australian Genetics of Depression Study, Generation Scotland) and three community cohorts who were not recruited on the basis of diagnosis (Avon Longitudinal Study of Parents and Children, Estonian Biobank, and UK Biobank). We fit a series of confirmatory factor models with factors that accounted for how symptom data was sampled and then compared alternative models with different symptom factors.
Results
The best fitting model had a distinct factor for Appetite/Weight symptoms and an additional measurement factor that accounted for the skip-structure in community cohorts (use of Depression and Anhedonia as gating symptoms).
Conclusion
The results show the importance of assessing the directionality of symptoms (such as hypersomnia versus insomnia) and of accounting for study and measurement design when meta-analyzing genetic association data.
Food cravings are one of several important complexities between psychological and physiological triggers for food consumption. Cravings are commonly cited as contributing to over-consumption of hyperpalatable foods (sugary, salty, and fatty foods) and may be causal in obesity(1). The Mediterranean dietary pattern (MedDiet) is linked to reduced disease risk and improved health and wellbeing(2). Despite a lower intake of sugary and salty foods compared to a Western diet, free-living adults switching to the MedDiet find it satiating and achieve high adherence in Western countries. The MedDiet is known to improve mood and wellbeing, is high in fibre, monounsaturated fat and low in added sugar, and has a low glycaemic load, which could separately and synergistically reduce food cravings. The relationship between adherence to the MedDiet and food cravings has never been investigated. In the MedLey randomised controlled trial, we investigated the effects of a MedDiet on food cravings, compared with a habitual Australian diet (HabDiet)(3). Adherence to the MedDiet was scored out of 15 (maximum adherence). Participants completed three food cravings questionnaires at baseline and 6-months. The State questionnaire measures momentary cravings and has a maximum score of 75, indicating maximum food cravings. The Trait-reduced questionnaire measures general cravings and has a maximum score of score of 126, indicating more frequent and intense cravings for foods. The Food Cravings Inventory (FCI) measures cravings for four food domains: fatty foods, fast foods, sugary foods, and high carbohydrate (CHO) foods. MedDiet group (n = 58) responses were compared with the HabDiet group (n = 53) across visits using linear mixed effects modelling. Predicted differences were obtained for adherence scores of ≤8 (median adherence) and ≥9. Means ± SD or CIs are presented. Mean adherence increased from 7.1 ± 1.8 to 10.7 ± 1.48 in the MedDiet group (P<0.01), with no change in the HabDiet group (P = 1.00). Trait-reduced scores were not significantly different between groups at 6-months (P = 0.11), although there was a 5.57-point reduction within the MedDiet group (CI −12.56, −1.96, P = 0.04). State score was significantly lower in the MedDiet group than the HabDiet at 6-months (−4.4 (CI −7.53, −0.39), P = 0.03), and was significantly lower than at baseline (−5.9 (CI −9.33, −0.24,) P = 0.04). There were no differences between groups for the four domains of the FCI (P>0.05). Cravings for sugary foods was significantly reduced within the MedDiet group (−0.26 (CI −0.46, −0.05) P = 0.01). The predictive modelling suggested moving from an adherence score of 8 to 9 was associated with lower cravings for sugar (−0.03 ± 0.01, P = 0.03), fast food (−0.04 ± 0.02, P = 0.02) and CHO foods (−0.05 ± 0.02, P = 0.02). These results are suggestive that higher adherence to a MedDiet could reduce cravings compared to the Australian diet and suggest that the MedDiet may specifically reduce sugar cravings. Further investigation is warranted, through observational and intervention trials.
A total of 140 trout were examined from four lakes in north west Ireland, Loughs Craghy, Waskel, Meela and Owennamarve. Eleven species of metazoan parasite were recorded, ten of which were of freshwater origin and Anisakissp. was the only marine species. No acanthocephalan species were found. Diphyllobothrium ditremum, D. dendriticum and Anisakissp. were the only allogenic species. Lough Owennamarve had the largest component community with nine species recorded. Lough Meela, the only brackish water lake had the smallest component community with six species recorded. Lough Waskel and Craghy had intermediate component community values. Lough Meela showed the lowest levels of similarity to any of the other lakes. Values for the Shannon-Wiener diversity index were highest for Lough Owennamarve and lowest for Lough Meela and intermediate for the other two lakes. Lough Meela had the highest values for the Simpson's dominance index and the Berger-Parker index. Lough Owennamarve had the highest Brillouin's index and Lough Meela had the lowest. The use of multiple regression techniques to control for the potentially confounding effect of geographical distance as a predictor of community similarity was discussed. No parasite species found could be considered as regionally and locally abundant and therefore described as a core species. The helminth community appears to have some degree of predictability, but chance colonization events are also important.
New technologies and disruptions related to Coronavirus disease-2019 have led to expansion of decentralized approaches to clinical trials. Remote tools and methods hold promise for increasing trial efficiency and reducing burdens and barriers by facilitating participation outside of traditional clinical settings and taking studies directly to participants. The Trial Innovation Network, established in 2016 by the National Center for Advancing Clinical and Translational Science to address critical roadblocks in clinical research and accelerate the translational research process, has consulted on over 400 research study proposals to date. Its recommendations for decentralized approaches have included eConsent, participant-informed study design, remote intervention, study task reminders, social media recruitment, and return of results for participants. Some clinical trial elements have worked well when decentralized, while others, including remote recruitment and patient monitoring, need further refinement and assessment to determine their value. Partially decentralized, or “hybrid” trials, offer a first step to optimizing remote methods. Decentralized processes demonstrate potential to improve urban-rural diversity, but their impact on inclusion of racially and ethnically marginalized populations requires further study. To optimize inclusive participation in decentralized clinical trials, efforts must be made to build trust among marginalized communities, and to ensure access to remote technology.
The stressful effects that environments have on farm and laboratory animal welfare are likely to depend on how much animals understand of the behaviour and intentions of their conspecifics as well as on their understanding of their physical environment. However, studies on animal social cognition have primarily focused on primates. Here, we report on our work on social cognition in domestic pigs. It focuses on the ability of domestic pigs to assess and use to their advantage the behaviour of conspecifics, and uses approaches pioneered in studies on primates. Our work has shown that dominant pigs use the privileged knowledge of a subordinate to their own advantage in a competitive foraging situation. While such exploitative behaviour is likely to be based on rapid learning about the subordinate ‘s behaviour, it is also possible that ‘higher’ cognitive abilities such as visual perspective taking could be involved. Ongoing work uses an adaptation of the Guesser-Knower paradigm to test whether pigs are indeed capable of visual perspective taking.
In November 2019, an outbreak of Shiga toxin-producing Escherichia coli O157:H7 was detected in South Yorkshire, England. Initial investigations established consumption of milk from a local dairy as a common exposure. A sample of pasteurised milk tested the next day failed the phosphatase test, indicating contamination of the pasteurised milk by unpasteurised (raw) milk. The dairy owner agreed to immediately cease production and initiate a recall. Inspection of the pasteuriser revealed a damaged seal on the flow divert valve. Ultimately, there were 21 confirmed cases linked to the outbreak, of which 11 (52%) were female, and 12/21 (57%) were either <15 or >65 years of age. Twelve (57%) patients were treated in hospital, and three cases developed haemolytic uraemic syndrome. Although the outbreak strain was not detected in the milk samples, it was detected in faecal samples from the cattle on the farm. Outbreaks of gastrointestinal disease caused by milk pasteurisation failures are rare in the UK. However, such outbreaks are a major public health concern as, unlike unpasteurised milk, pasteurised milk is marketed as ‘safe to drink’ and sold to a larger, and more dispersed, population. The rapid, co-ordinated multi-agency investigation initiated in response to this outbreak undoubtedly prevented further cases.
Informal carers play an essential role in the care of individuals with Parkinson’s disease (PD). This role, however, is often fraught with difficulties, including emotional, physical, and financial. Coping styles and relationship quality have been hypothesized to influence the impact of stressors. The aim of this study is to examine the relationship between carers’ coping style, relationship quality, and carer burden.
Design:
Cross-sectional.
Participants:
Thirty-nine PD patient carer dyads were included in the study.
Measurements:
Participants completed self-rated questionnaires including the Dyadic Adjustment Scale, Zarit Burden Interview, and Brief Coping Orientation to Problems Experienced Inventory.
Results:
Correlational analyses found significant and positive correlation between carer burden and all three coping styles (problem-focused, emotion-focused, and dysfunctional). There was also a moderate association between carers’ perceived relationship quality and satisfaction and carer burden. Regression analyses found that carer’s gender, severity of PD, relationship quality, emotion-focused, and dysfunctional coping styles did not predict carer burden. Conversely, problem-focused coping style predicted carer burden.
Conclusion:
The results highlight that there is no perfect way to react and care for a loved one and serves as important information for practitioners who design and implement interventions.
Young people with social disability and severe and complex mental health problems have poor outcomes, frequently struggling with treatment access and engagement. Outcomes may be improved by enhancing care and providing targeted psychological or psychosocial intervention.
Aims
We aimed to test the hypothesis that adding social recovery therapy (SRT) to enhanced standard care (ESC) would improve social recovery compared with ESC alone.
Method
A pragmatic, assessor-masked, randomised controlled trial (PRODIGY: ISRCTN47998710) was conducted in three UK centres. Participants (n = 270) were aged 16–25 years, with persistent social disability, defined as under 30 hours of structured activity per week, social impairment for at least 6 months and severe and complex mental health problems. Participants were randomised to ESC alone or SRT plus ESC. SRT was an individual psychosocial therapy delivered over 9 months. The primary outcome was time spent in structured activity 15 months post-randomisation.
Results
We randomised 132 participants to SRT plus ESC and 138 to ESC alone. Mean weekly hours in structured activity at 15 months increased by 11.1 h for SRT plus ESC (mean 22.4, s.d. = 21.4) and 16.6 h for ESC alone (mean 27.7, s.d. = 26.5). There was no significant difference between arms; treatment effect was −4.44 (95% CI −10.19 to 1.31, P = 0.13). Missingness was consistently greater in the ESC alone arm.
Conclusions
We found no evidence for the superiority of SRT as an adjunct to ESC. Participants in both arms made large, clinically significant improvements on all outcomes. When providing comprehensive evidence-based standard care, there are no additional gains by providing specialised SRT. Optimising standard care to ensure targeted delivery of existing interventions may further improve outcomes.
Clinical trials continue to face significant challenges in participant recruitment and retention. The Recruitment Innovation Center (RIC), part of the Trial Innovation Network (TIN), has been funded by the National Center for Advancing Translational Sciences of the National Institutes of Health to develop innovative strategies and technologies to enhance participant engagement in all stages of multicenter clinical trials. In collaboration with investigator teams and liaisons at Clinical and Translational Science Award institutions, the RIC is charged with the mission to design, field-test, and refine novel resources in the context of individual clinical trials. These innovations are disseminated via newsletters, publications, a virtual toolbox on the TIN website, and RIC-hosted collaboration webinars. The RIC has designed, implemented, and promised customized recruitment support for 173 studies across many diverse disease areas. This support has incorporated site feasibility assessments, community input sessions, recruitment materials recommendations, social media campaigns, and an array of study-specific suggestions. The RIC’s goal is to evaluate the efficacy of these resources and provide access to all investigating teams, so that more trials can be completed on time, within budget, with diverse participation, and with enough accrual to power statistical analyses and make substantive contributions to the advancement of healthcare.
In October 2019, public health surveillance systems in Scotland identified an increase in the number of reported infections of Shiga toxin-producing Escherichia coli (STEC) O26:H11 involving bloody diarrhoea. Ultimately, across the United Kingdom (UK) 32 cases of STEC O26:H11 stx1a were identified, with the median age of 27 years and 64% were male; six cases were hospitalised. Among food exposures there was an association with consuming pre-packed sandwiches purchased at outlets belonging to a national food chain franchise (food outlet A) [odds ratio (OR) = 183.89, P < 0.001]. The common ingredient identified as a component of the majority of the sandwiches sold at food outlet A was a mixed salad of Apollo and Iceberg lettuce and spinach leaves. Microbiological testing of food and environmental samples were negative for STEC O26:H11, although STEC O36:H19 was isolated from a mixed salad sample taken from premises owned by food outlet A. Contamination of fresh produce is often due to a transient event and detection of the aetiological agent in food that has a short-shelf life is challenging. Robust, statistically significant epidemiological analysis should be sufficient evidence to direct timely and targeted on-farm investigations. A shift in focus from testing the microbiological quality of the produce to investigating the processes and practices through the supply chain and sampling the farm environment is recommended.
Sublabial gland biopsy is the ‘gold standard’ in establishing the diagnosis of primary Sjögren's syndrome. Bleeding and nerve damage are complications. Our centre has adopted the use of the chalazion clamp to provide a dry surgical field to address these challenges. This study aimed to assess the accuracy of minor salivary gland harvest rate using this technique.
Method
A retrospective review of all minor salivary gland biopsies was carried out in a single tertiary referral centre over a five-year period.
Results
Forty-one biopsy patients were identified, with a mean age of 56.1 years. There was 100 per cent accuracy in harvest rate in our series. Twelve patients (29 per cent) were positive for primary Sjögren's syndrome. No patients had a complication immediately or at one month follow up.
Conclusion
Dry surgical field sublabial gland biopsy is a safe and highly effective technique in the diagnosis of primary Sjögren's syndrome. Initial results indicate it may provide a higher harvest rate with fewer complications than traditional non-ischaemic techniques.
The schizophrenia polygenic risk score (SCZ-PRS) is an emerging tool in psychiatry.
Aims
We aimed to evaluate the utility of SCZ-PRS in a young, transdiagnostic, clinical cohort.
Method
SCZ-PRSs were calculated for young people who presented to early-intervention youth mental health clinics, including 158 patients of European ancestry, 113 of whom had longitudinal outcome data. We examined associations between SCZ-PRS and diagnosis, clinical stage and functioning at initial assessment, and new-onset psychotic disorder, clinical stage transition and functional course over time in contact with services.
Results
Compared with a control group, patients had elevated PRSs for schizophrenia, bipolar disorder and depression, but not for any non-psychiatric phenotype (for example cardiovascular disease). Higher SCZ-PRSs were elevated in participants with psychotic, bipolar, depressive, anxiety and other disorders. At initial assessment, overall SCZ-PRSs were associated with psychotic disorder (odds ratio (OR) per s.d. increase in SCZ-PRS was 1.68, 95% CI 1.08–2.59, P = 0.020), but not assignment as clinical stage 2+ (i.e. discrete, persistent or recurrent disorder) (OR = 0.90, 95% CI 0.64–1.26, P = 0.53) or functioning (R = 0.03, P = 0.76). Longitudinally, overall SCZ-PRSs were not significantly associated with new-onset psychotic disorder (OR = 0.84, 95% CI 0.34–2.03, P = 0.69), clinical stage transition (OR = 1.02, 95% CI 0.70–1.48, P = 0.92) or persistent functional impairment (OR = 0.84, 95% CI 0.52–1.38, P = 0.50).
Conclusions
In this preliminary study, SCZ-PRSs were associated with psychotic disorder at initial assessment in a young, transdiagnostic, clinical cohort accessing early-intervention services. Larger clinical studies are needed to further evaluate the clinical utility of SCZ-PRSs, especially among individuals with high SCZ-PRS burden.
Biogenic nanoscale vanadium magnetite is produced by converting V(V)-bearing ferrihydrites through reductive transformation using the metal-reducing bacterium Geobacter sulfurreducens. With increasing vanadium in the ferrihydrite, the amount of V-doped magnetite produced decreased due to V-toxicity which interrupted the reduction pathway ferrihydrite–magnetite, resulting in siderite or goethite formation. Fe L2,3 and V L2,3 X-ray absorption spectra and data from X-ray magnetic circular dichroism analysis revealed the magnetite to contain the V in the Fe(III) Oh site, predominately as V(III) but always with a component of V(VI), present a consistent V(IV)/V(III) ratio in the range 0.28 to 0.33. The bacteriogenic production of V-doped magnetite nanoparticles from V-doped ferrihydrite is confirmed and the work reveals that microbial reduction of contaminant V(V) to V(III)/V(IV) in the environment will occur below the Fe-redox boundary where it will be immobilised in biomagnetite nanoparticles.