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Persons discharged from inpatient psychiatric services are at greatly elevated risk of harming themselves or inflicting violence on others, but no studies have reported gender-specific absolute risks for these two outcomes across the spectrum of psychiatric diagnoses. We aimed to estimate absolute risks for self-harm and interpersonal violence post-discharge according to gender and diagnostic category.
Methods
Danish national registry data were utilized to investigate 62,922 discharged inpatients, born 1967–2000. An age and gender matched cohort study was conducted to examine risks for self-harm and interpersonal violence at 1 year and at 10 years post-discharge. Absolute risks were estimated as cumulative incidence percentage values.
Results
Patients diagnosed with substance misuse disorders were at especially elevated risk, with the absolute risks for either self-harm or interpersonal violence being 15.6% (95% CI 14.9, 16.3%) of males and 16.8% (15.6, 18.1%) of females at 1 year post-discharge, rising to 45.7% (44.5, 46.8%) and 39.0% (37.1, 40.8%), respectively, within 10 years. Diagnoses of personality disorders and early onset behavioral and emotional disorders were also associated with particularly high absolute risks, whilst risks linked with schizophrenia and related disorders, mood disorders, and anxiety/somatoform disorders, were considerably lower.
Conclusions
Patients diagnosed with substance misuse disorders, personality disorders and early onset behavioral and emotional disorders are at especially high risk for internally and externally directed violence. It is crucial, however, that these already marginalized individuals are not further stigmatized. Enhanced care at discharge and during the challenging transition back to life in the community is needed.
To understand the emergence of symptoms in autism spectrum disorder (ASD), we need to identify the mechanisms that underpin the development of core social skills. Mounting evidence indicates that young children with later ASD attend less to other people, which could compromise learning opportunities with cascading effects. Passive looking behaviour does not tell us about engagement with visual information, but measures of physiological arousal can provide information on the depth of engagement. In the current study, we use heart rate (HR) and heart rate variability (HRV) to measure engagement with social dynamic stimuli in ASD.
Methods
Sixty-seven preschoolers with ASD and 65 typical developing preschoolers between 2 and 4 years of age participated in a study where HR was measured during viewing of social and non-social videos. Using latent profile analyses, more homogeneous subgroups of children were created based on phenotype and physiology.
Results
Preschool-aged children with ASD, regardless of their non-verbal, verbal and social competencies, do not differ in overall HR or HRV compared to TD children. However, the ASD group showed a larger increase in HR (more disengagement) than the TD group to later-presented social stimuli. Phenotypic and physiological profiles showed this was primarily the case for children with below average verbal and non-verbal skills, but not necessarily those with more ASD symptoms.
Conclusion
Children with ASD, especially a subgroup showing moderate cognitive delays, show an increase in HR to social stimuli over time; this may reflect difficulties re-engaging with social information when attention is waning.
The first demonstration of laser action in ruby was made in 1960 by T. H. Maiman of Hughes Research Laboratories, USA. Many laboratories worldwide began the search for lasers using different materials, operating at different wavelengths. In the UK, academia, industry and the central laboratories took up the challenge from the earliest days to develop these systems for a broad range of applications. This historical review looks at the contribution the UK has made to the advancement of the technology, the development of systems and components and their exploitation over the last 60 years.
Diagnosis of prodromal Alzheimer's disease and Alzheimer's disease dementia in people with Down syndrome is a major challenge. The Cambridge Examination for Mental Disorders of Older People with Down's Syndrome and Others with Intellectual Disabilities (CAMDEX-DS) has been validated for diagnosing prodromal Alzheimer's disease and Alzheimer's disease dementia, but the diagnostic process lacks guidance.
Aims
To derive CAMDEX-DS informant interview threshold scores to enable accurate diagnosis of prodromal Alzheimer's disease and Alzheimer's disease dementia in adults with Down syndrome.
Method
Psychiatrists classified participants with Down syndrome into no dementia, prodromal Alzheimer's disease and Alzheimer's disease dementia groups. Receiver operating characteristic analyses assessed the diagnostic accuracy of CAMDEX-DS informant interview-derived scores. Spearman partial correlations investigated associations between CAMDEX-DS scores, regional Aβ binding (positron emission tomography) and regional cortical thickness (magnetic resonance imaging).
Results
Diagnostic performance of CAMDEX-DS total scores were high for Alzheimer's disease dementia (area under the curve (AUC), 0.998; 95% CI 0.953–0.999) and prodromal Alzheimer's disease (AUC = 0.954; 95% CI 0.887–0.982) when compared with healthy adults with Down syndrome. When compared with those with mental health conditions but no Alzheimer's disease, CAMDEX-DS Section B scores, denoting memory and orientation ability, accurately diagnosed Alzheimer's disease dementia (AUC = 0.958; 95% CI 0.892–0.984), but were unable to diagnose prodromal Alzheimer's disease. CAMDEX-DS total scores exhibited moderate correlations with cortical Aβ (r ~ 0.4 to 0.6, P ≤ 0.05) and thickness (r ~ −0.4 to −0.44, P ≤ 0.05) in specific regions.
Conclusions
CAMDEX-DS total score accurately diagnoses Alzheimer's disease dementia and prodromal Alzheimer's disease in healthy adults with Down syndrome.
Treatment for major depressive disorder (MDD) is imprecise and often involves trial-and-error to determine the most effective approach. To facilitate optimal treatment selection and inform timely adjustment, the current study investigated whether neurocognitive variables could predict an antidepressant response in a treatment-specific manner.
Methods
In the two-stage Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC) trial, outpatients with non-psychotic recurrent MDD were first randomized to an 8-week course of sertraline selective serotonin reuptake inhibitor or placebo. Behavioral measures of reward responsiveness, cognitive control, verbal fluency, psychomotor, and cognitive processing speeds were collected at baseline and week 1. Treatment responders then continued on another 8-week course of the same medication, whereas non-responders to sertraline or placebo were crossed-over under double-blinded conditions to bupropion noradrenaline/dopamine reuptake inhibitor or sertraline, respectively. Hamilton Rating for Depression scores were also assessed at baseline, weeks 8, and 16.
Results
Greater improvements in psychomotor and cognitive processing speeds within the first week, as well as better pretreatment performance in these domains, were specifically associated with higher likelihood of response to placebo. Moreover, better reward responsiveness, poorer cognitive control and greater verbal fluency were associated with greater likelihood of response to bupropion in patients who previously failed to respond to sertraline.
Conclusion
These exploratory results warrant further scrutiny, but demonstrate that quick and non-invasive behavioral tests may have substantial clinical value in predicting antidepressant treatment response.
Gravitational waves from coalescing neutron stars encode information about nuclear matter at extreme densities, inaccessible by laboratory experiments. The late inspiral is influenced by the presence of tides, which depend on the neutron star equation of state. Neutron star mergers are expected to often produce rapidly rotating remnant neutron stars that emit gravitational waves. These will provide clues to the extremely hot post-merger environment. This signature of nuclear matter in gravitational waves contains most information in the 2–4 kHz frequency band, which is outside of the most sensitive band of current detectors. We present the design concept and science case for a Neutron Star Extreme Matter Observatory (NEMO): a gravitational-wave interferometer optimised to study nuclear physics with merging neutron stars. The concept uses high-circulating laser power, quantum squeezing, and a detector topology specifically designed to achieve the high-frequency sensitivity necessary to probe nuclear matter using gravitational waves. Above 1 kHz, the proposed strain sensitivity is comparable to full third-generation detectors at a fraction of the cost. Such sensitivity changes expected event rates for detection of post-merger remnants from approximately one per few decades with two A+ detectors to a few per year and potentially allow for the first gravitational-wave observations of supernovae, isolated neutron stars, and other exotica.
Polyhalite is a multi-nutrient mineral ore containing potassium (K), calcium (Ca), magnesium (Mg) and sulphur (S). Historically, it has enjoyed minor use as a fertilizer, but the opening of a new mine in the UK will make larger quantities available. Therefore, an examination of the performance of crops fertilized with polyhalite, or selected commercial alternatives, was pertinent and is reported here.
Four field trials were carried out between 2013 and 2016 to investigate the response of winter barley (Hordeum vulgare L.) and forage maize (Zea mays L.) to different application rates of polyhalite, potassium chloride (muriate of potash, MOP) and potassium sulphate (sulphate of potash, SOP) fertilizers. Potassium and S nutrition were the focus of these trials as they limit field production more often than Mg and Ca.
Polyhalite was found to be an effective source of both K and S for crop production. In three out of four trials, application of polyhalite resulted in similar or greater K offtake compared with both MOP and SOP; MOP application resulted in greater K offtake in one trial. In three out of four trials, application of polyhalite resulted in similar or better S offtake compared with both MOP and SOP; SOP application resulted in greater S offtake in one trial. Polyhalite and MOP treatments produced similar total dry weight in all four trials, but were slightly inferior to SOP treatment.
Excessive mobilization of body reserves during the transition from pregnancy to lactation imposes a risk for metabolic diseases on dairy cows. We aimed to establish an experimental model for high v. normal mobilization and herein characterized performance, metabolic and endocrine changes from 7 weeks antepartum (a.p.) to 12 weeks postpartum (p.p.). Fifteen weeks a.p., 38 pregnant multiparous Holstein cows were allocated to two groups that were fed differently to reach either high or normal body condition scores (HBCS: 7.2 NEL MJ/kg dry matter (DM); NBCS: 6.8 NEL MJ/kg DM) at dry-off. Allocation was also based on differences in body condition score (BCS) in the previous and the ongoing lactation that was further promoted by feeding to reach the targeted BCS and back fat thickness (BFT) at dry-off (HBCS: >3.75 and >1.4 cm; NBCS: <3.5 and <1.2 cm). Thereafter, both groups were fed identical diets. Blood samples were drawn weekly from 7 weeks a.p. to 12 weeks p.p. to assess the serum concentrations of metabolites and hormones. The HBCS cows had greater BCS, BFT and BW than the NBCS cows throughout the study and lost more than twice as much BFT during the first 7 weeks p.p. compared with NCBS. Milk yield and composition were not different between groups, except that lactose concentrations were greater in NBSC than in HBCS. Feed intake was also greater in NBCS, and NBCS also reached a positive energy balance earlier than HBCS. The greater reduction in body mass in HBCS was accompanied by greater concentrations of non-esterified fatty acids, and β-hydroxybutyrate in serum after calving than in NBCS, indicating increased lipomobilization and ketogenesis. The mean concentrations of insulin across all time-points were greater in HBCS than in NBCS. In both groups, insulin and IGF-1 concentrations were lower p.p than in a.p. Greater free thyroxine (fT4) concentrations and a lower free 3-3′-5-triiodothyronine (fT3)/fT4 ratio were observed in HBCS than in NBCS a.p., whereas p.p. fT3/fT4 ratio followed a reverse pattern. The variables indicative for oxidative status had characteristic time courses; group differences were limited to greater plasma ferric reducing ability values in NBSC. The results demonstrate that the combination of pre-selection according to BCS and differential feeding before dry-off to promote the difference was successful in obtaining cows that differ in the intensity of mobilizing body reserves. The HBCS cows were metabolically challenged due to intense mobilization of body fat, associated with reduced early lactation dry matter intake and compromised antioxidative capacity.
Major depressive disorder (MDD) is a highly heterogeneous condition in terms of symptom presentation and, likely, underlying pathophysiology. Accordingly, it is possible that only certain individuals with MDD are well-suited to antidepressants. A potentially fruitful approach to parsing this heterogeneity is to focus on promising endophenotypes of depression, such as neuroticism, anhedonia, and cognitive control deficits.
Methods
Within an 8-week multisite trial of sertraline v. placebo for depressed adults (n = 216), we examined whether the combination of machine learning with a Personalized Advantage Index (PAI) can generate individualized treatment recommendations on the basis of endophenotype profiles coupled with clinical and demographic characteristics.
Results
Five pre-treatment variables moderated treatment response. Higher depression severity and neuroticism, older age, less impairment in cognitive control, and being employed were each associated with better outcomes to sertraline than placebo. Across 1000 iterations of a 10-fold cross-validation, the PAI model predicted that 31% of the sample would exhibit a clinically meaningful advantage [post-treatment Hamilton Rating Scale for Depression (HRSD) difference ⩾3] with sertraline relative to placebo. Although there were no overall outcome differences between treatment groups (d = 0.15), those identified as optimally suited to sertraline at pre-treatment had better week 8 HRSD scores if randomized to sertraline (10.7) than placebo (14.7) (d = 0.58).
Conclusions
A subset of MDD patients optimally suited to sertraline can be identified on the basis of pre-treatment characteristics. This model must be tested prospectively before it can be used to inform treatment selection. However, findings demonstrate the potential to improve individual outcomes through algorithm-guided treatment recommendations.
Factors associated with relapse among children who are discharged after reaching a threshold denoted ‘recovered’ from moderate acute malnutrition (MAM) are not well understood. The aim of this study was to identify factors associated with sustained recovery, defined as maintaining a mid-upper-arm circumference≥12·5 cm for 1 year after release from treatment. On the basis of an observational study design, we analysed data from an in-depth household (HH) survey on a sub-sample of participants within a larger cluster randomised controlled trial (cRCT) that followed up children for 1 year after recovery from MAM. Out of 1497 children participating in the cRCT, a subset of 315 children participated in this sub-study. Accounting for other factors, HH with fitted lids on water storage containers (P=0·004) was a significant predictor of sustained recovery. In addition, sustained recovery was better among children whose caregivers were observed to have clean hands (P=0·053) and in HH using an improved sanitation facility (P=0·083). By contrast, socio-economic status and infant and young child feeding practices at the time of discharge and HH food security throughout the follow-up period were not significant. Given these results, we hypothesise that improved water, sanitation and hygiene conditions in tandem with management of MAM through supplemental feeding programmes have the possibility to decrease relapse following recovery from MAM. Furthermore, the absence of associations between relapse and nearly all HH-level factors indicates that the causal factors of relapse may be related mostly to the child’s individual, underlying health and nutrition status.
Subjective reports of insomnia and hypersomnia are common in bipolar disorder (BD). It is unclear to what extent these relate to underlying circadian rhythm disturbance (CRD). In this study we aimed to objectively assess sleep and circadian rhythm in a cohort of patients with BD compared to matched controls.
Method
Forty-six patients with BD and 42 controls had comprehensive sleep/circadian rhythm assessment with respiratory sleep studies, prolonged accelerometry over 3 weeks, sleep questionnaires and diaries, melatonin levels, alongside mood, psychosocial functioning and quality of life (QoL) questionnaires.
Results
Twenty-three (50%) patients with BD had abnormal sleep, of whom 12 (52%) had CRD and 29% had obstructive sleep apnoea. Patients with abnormal sleep had lower 24-h melatonin secretion compared to controls and patients with normal sleep. Abnormal sleep/CRD in BD was associated with impaired functioning and worse QoL.
Conclusions
BD is associated with high rates of abnormal sleep and CRD. The association between these disorders, mood and functioning, and the direction of causality, warrants further investigation.
Stereotypies are used as indicators of poor animal welfare and it is, therefore, important to understand underlying factors mediating their development. In calves, two oral stereotypies, that is, tongue playing and object manipulation, result mostly from insufficient structure in the diet. Three hypotheses were studied: (1) oral stereotypies in calves are one of two alternative strategies, the alternative being hypo-activity; (2) stereotyping and non-stereotyping calves differ in terms of cortisol secretion; (3) oral stereotypy development in calves rests on a gene by environment interaction. Eight-week-old bull calves (n=48) were assigned to one of four solid feed allowances (0, 9, 18 or 27 g dry matter/kg metabolic weight per day) with the following composition: 50% concentrate, 25% maize silage and 25% straw on dry matter basis. The calves received milk replacer in buckets, the provision of which was adjusted to achieve equal growth rates. At 14 to 18 weeks of age, calves were exposed to a challenge, that is, tethering inside cages. Oral stereotypies and inactivity were recorded in the home pens in the 4 weeks before the challenge using instantaneous scan sampling. Salivary cortisol levels were measured at −120, +40, +80, +120 min and +48 h relative to the challenge. Individual differences in behaviour were recorded in the first 30 min after challenge implementation using focal animal sampling and continuous recording, and these elements were entered into a principal component (PC) analysis to extract PCs. Regression analyses were performed to find relationships between stereotypies and inactivity, stereotypies and cortisol, and stereotypies and PCs (individual differences, genes) and solid feed (environment). Relationships between PCs and cortisol were also investigated to help with the interpretation of PCs. Hypotheses 1 and 2 were rejected. Hypothesis 3, however, was supported: calves with a zero solid feed allowance, that is, in the most barren environment, showed links between stereotypies and two of the PCs. Calves that displayed high levels of idle and rapid locomotion and low levels of oral contact with the cage during the challenge also displayed high levels of object manipulation in the home pens. Calves that displayed low levels of stepping and turning attempts during the challenge also displayed high levels of tongue playing in the home pens. This study corroborates the gene by environment interaction on the development of oral stereotypies in calves.
The College of Aeronautics has a considerable interest in composite materials, and in their application in particular to aerospace vehicles, over a number of years, and during this time we have conducted several research programmes on these types of materials.
During recent years, an area of research which has attracted our interest is in the application of composite materials to light aircraft, forming part of a more general study of light aircraft which has resulted in our constructing and testing aircraft in this category on two occasions in recent years.
Some of the work on these programmes has been conducted by students at Cranfield studying for higher degrees, and I acknowledge my indebtedness to them for some of the results presented in this paper.
We investigated whether a higher number of fast-food outlets in an individual’s home neighbourhood is associated with increased prevalence of type 2 diabetes mellitus and related risk factors, including obesity.
Design
Cross-sectional study.
Setting
Three UK-based diabetes screening studies (one general population, two high-risk populations) conducted between 2004 and 2011. The primary outcome was screen-detected type 2 diabetes. Secondary outcomes were risk factors for type 2 diabetes.
Subjects
In total 10 461 participants (mean age 59 years; 53 % male; 21 % non-White ethnicity).
Results
There was a higher number of neighbourhood (500 m radius from home postcode) fast-food outlets among non-White ethnic groups (P<0·001) and in socially deprived areas (P<0·001). After adjustment (social deprivation, urban/rural, ethnicity, age, sex), more fast-food outlets was associated with significantly increased odds for diabetes (OR=1·02; 95 % CI 1·00, 1·04) and obesity (OR=1·02; 95 % CI 1·00, 1·03). This suggests that for every additional two outlets per neighbourhood, we would expect one additional diabetes case, assuming a causal relationship between the fast-food outlets and diabetes.
Conclusions
These results suggest that increased exposure to fast-food outlets is associated with increased risk of type 2 diabetes and obesity, which has implications for diabetes prevention at a public health level and for those granting planning permission to new fast-food outlets.
Self-harm is a common reason for Emergency Department (ED) attendance. We aimed to develop a clinical tool to help identify patients at higher risk of repeat self-harm, or suicide, within 6 months of an ED self-harm presentation.
Method
The tool, the ReACT Self-Harm Rule, was derived using multicentre data from a prospective cohort study. Binary recursive partitioning was applied to data from two centres, and data from a separate centre were used to test the tool. There were 29 571 self-harm presentations to five hospital EDs between January 2003 and June 2007, involving 18 680 adults aged ⩾16 years. We estimated sensitivity, specificity and positive and negative predictive values to measure the performance of the tool.
Results
A self-harm presentation was classified as higher risk if at least one of the following factors was present: recent self-harm (in the past year), living alone or homelessness, cutting as a method of harm and treatment for a current psychiatric disorder. The rule performed with 95% sensitivity [95% confidence interval (CI) 94–95] and 21% specificity (95% CI 21–22), and had a positive predictive value of 30% (95% CI 30–31) and a negative predictive value of 91% (95% CI 90–92) in the derivation centres; it identified 83/92 of all subsequent suicides.
Conclusions
The ReACT Self-Harm Rule might be used as a screening tool to inform the process of assessing self-harm presentations to ED. The four risk factors could also be used as an adjunct to in-depth psychosocial assessment to help guide risk formulation. The use of multicentre data helped to maximize the generalizability of the tool, but we need to further verify its external validity in other localities.
Echocardiography detects a greater prevalence of rheumatic heart disease than heart auscultation. Echocardiographic screening for rheumatic heart disease combined with secondary prophylaxis may potentially prevent severe rheumatic heart disease in high-risk populations. We aimed to determine the prevalence of rheumatic heart disease in children from an urban New Zealand population at high risk for acute rheumatic fever.
Methods and results
To optimise accurate diagnosis of rheumatic heart disease, we utilised a two-step model. Portable echocardiography was conducted on 1142 predominantly Māori and Pacific children aged 10–13 years. Children with an abnormal screening echocardiogram underwent clinical assessment by a paediatric cardiologist together with hospital-based echocardiography. Rheumatic heart disease was then classified as definite, probable, or possible. Portable echocardiography identified changes suggestive of rheumatic heart disease in 95 (8.3%) of 1142 children, which reduced to 59 (5.2%) after cardiology assessment. The prevalence of definite and probable rheumatic heart disease was 26.0 of 1000, with 95% confidence intervals ranging from 12.6 to 39.4. Portable echocardiography overdiagnosed rheumatic heart disease with physiological valve regurgitation diagnosed in 28 children. A total of 30 children (2.6%) had non-rheumatic cardiac abnormalities, 11 of whom had minor congenital mitral valve anomalies.
Conclusions
We found high rates of undetected rheumatic heart disease in this high-risk population. Rheumatic heart disease screening has resource implications with cardiology evaluation required for accurate diagnosis. Echocardiographic screening for rheumatic heart disease may overdiagnose rheumatic heart disease unless congenital mitral valve anomalies and physiological regurgitation are excluded.