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We study direct numerical simulations of turbulence arising from the interaction of an initial background shear, a linear background stratification and an external body force. In each simulation the turbulence produced is spatially intermittent, with dissipation rates varying over orders of magnitude in the vertical. We focus analysis on the statistically quasi-steady states achieved by applying large-scale body forcing to the domain, and compare flows forced by internal gravity waves with those forced by vertically uniform vortical modes. By considering the turbulent energy budgets for each simulation, we find that the injection of potential energy from the wave forcing permits a reversal in the sign of the mean buoyancy flux. This change in the sign of the buoyancy flux is associated with large, convective density overturnings, which in turn lead to more efficient mixing in the wave-forced simulations. The inhomogeneous dissipation in each simulation allows us to investigate localised correlations between the kinetic and potential energy dissipation rates. These correlations lead us to the conclusion that an appropriate definition of an instantaneous mixing efficiency,
are the volume-averaged turbulent viscous dissipation rate and fluctuation density variance destruction rate respectively) in the wave-forced cases is independent of an appropriately defined local turbulent Froude number, consistent with scalings proposed for low Froude number stratified turbulence.
At present, analysis of diet and bladder cancer (BC) is mostly based on the intake of individual foods. The examination of food combinations provides a scope to deal with the complexity and unpredictability of the diet and aims to overcome the limitations of the study of nutrients and foods in isolation. This article aims to demonstrate the usability of supervised data mining methods to extract the food groups related to BC. In order to derive key food groups associated with BC risk, we applied the data mining technique C5.0 with 10-fold cross-validation in the BLadder cancer Epidemiology and Nutritional Determinants study, including data from eighteen case–control and one nested case–cohort study, compromising 8320 BC cases out of 31 551 participants. Dietary data, on the eleven main food groups of the Eurocode 2 Core classification codebook, and relevant non-diet data (i.e. sex, age and smoking status) were available. Primarily, five key food groups were extracted; in order of importance, beverages (non-milk); grains and grain products; vegetables and vegetable products; fats, oils and their products; meats and meat products were associated with BC risk. Since these food groups are corresponded with previously proposed BC-related dietary factors, data mining seems to be a promising technique in the field of nutritional epidemiology and deserves further examination.
The volume of evidence from scientific research and wider observation is greater than ever before, but much is inconsistent and scattered in fragments over increasingly diverse sources, making it hard for decision-makers to find, access and interpret all the relevant information on a particular topic, resolve seemingly contradictory results or simply identify where there is a lack of evidence. Evidence synthesis is the process of searching for and summarising a body of research on a specific topic in order to inform decisions, but is often poorly conducted and susceptible to bias. In response to these problems, more rigorous methodologies have been developed and subsequently made available to the conservation and environmental management community by the Collaboration for Environmental Evidence. We explain when and why these methods are appropriate, and how evidence can be synthesised, shared, used as a public good and benefit wider society. We discuss new developments with potential to address barriers to evidence synthesis and communication and how these practices might be mainstreamed in the process of decision-making in conservation.
Non-epileptic seizures (NES) are a diverse group of disorders, whose paroxysmal events can be mistaken for epilepsy, although they are caused by a mental or psychogenic process rather than a neurological cause.
We present a case of a 45-year-old female patient with history of generalized seizures prior to Meningioma resection in August 2015, referred to the Liaison Psychiatry outpatient follow up clinic at the Royal London Hospital after has gone several times to emergency department complaining about flush and hot sensation that proceeded to corners of mouth turning down, teeth chattering, shaking of left arm and torso at first and then legs. During the episodes, she was awake with no consciousness loss. Her mood was low, with clinical evidence of depression and she had very high levels of health anxiety.
A diagnosis of non-epileptic attacks was made in the sequence of those episodes. A holistic and multidisciplinary approach was made, including pharmacotherapy, cognitive-behavioral therapy and domiciliary support. The clinical response was good regarding both mood, anxiety levels and NES.
Approximately 25% of patients who have a previous diagnosis of epilepsy and are not responding to drug therapy are found to be misdiagnosed and it is common that epileptic patients have both epileptic and non-epileptic seizures. Although distinguishing epileptic and non-epileptic seizures is not easy, there are some clinical clues that the physicians should look for, like age of onset, time of the day that episodes occur and presence or absence of postictal confusion.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
In the UK, mental illness is a major source of disease burden costing in the region of £105 billion pounds. mHealth is a novel and emerging field in psychiatric and psychological care for the treatment of mental health difficulties such as psychosis.
To develop an intelligent real-time therapy (iRTT) mobile intervention (TechCare) which assesses participant's symptoms in real-time and responds with a personalised self-help based psychological intervention, with the aim of reducing participant's symptoms. The system will utilise intelligence at two levels:
– intelligently increasing the frequency of assessment notifications if low mood/paranoia is detected;
– an intelligent machine learning algorithm which provides interventions in real-time and also provides recommendations on the most popular selected interventions.
The aim of the current project is to develop a mobile phone intervention for people with psychosis, and to conduct a feasibility study of the TechCare App.
The study consists of both qualitative and quantitative components. The study will be run across three strands:
– qualitative work;
– test run and intervention refinement;
– feasibility trial.
Preliminary analysis of qualitative data from Strand 2 (test run and intervention refinement) in-depth interviews with service users (n = 2) and focus group with health professionals (n = 1), highlighted main themes around security of the device, multimedia and the acceptability of psychological interventions being delivered via the TechCare App.
Research in this area can be potentially helpful in addressing the demand on mental health services globally, particularly improving access to psychological interventions.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
There are often substantial delays before diagnosis and initiation of treatment in people bipolar disorder. Increased delays are a source of considerable morbidity among affected individuals.
To investigate the factors associated with delays to diagnosis and treatment in people with bipolar disorder.
Retrospective cohort study using electronic health record data from the South London and Maudsley NHS Foundation Trust (SLaM) from 1364 adults diagnosed with bipolar disorder. The following predictor variables were analysed in a multivariable Cox regression analysis on diagnostic delay and treatment delay from first presentation to SLaM: age, gender, ethnicity, compulsory admission to hospital under the UK Mental Health Act, marital status and other diagnoses prior to bipolar disorder.
The median diagnostic delay was 62 days (interquartile range: 17–243) and median treatment delay was 31 days (4–122). Compulsory hospital admission was associated with a significant reduction in both diagnostic delay (hazard ratio 2.58, 95% CI 2.18–3.06) and treatment delay (4.40, 3.63–5.62). Prior diagnoses of other psychiatric disorders were associated with increased diagnostic delay, particularly alcohol (0.48, 0.33–0.41) and substance misuse disorders (0.44, 0.31–0.61). Prior diagnosis of schizophrenia and psychotic depression were associated with reduced treatment delay.
Some individuals experience a significant delay in diagnosis and treatment of bipolar disorder, particularly those with alcohol/substance misuse disorders. These findings highlight a need to better identify the symptoms of bipolar disorder and offer appropriate treatment sooner in order to facilitate improved clinical outcomes. This may include the development of specialist early intervention services.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
The mechanism through which developmental programming of offspring overweight/obesity following in utero exposure to maternal overweight/obesity operates is unknown but may operate through biologic pathways involving offspring anthropometry at birth. Thus, we sought to examine to what extent the association between in utero exposure to maternal overweight/obesity and childhood overweight/obesity is mediated by birth anthropometry. Analyses were conducted on a retrospective cohort with data obtained from one hospital system. A natural effects model framework was used to estimate the natural direct effect and natural indirect effect of birth anthropometry (weight, length, head circumference, ponderal index, and small-for-gestational age [SGA] or large-for-gestational age [LGA]) for the association between pre-pregnancy maternal body mass index (BMI) category (overweight/obese vs normal weight) and offspring overweight/obesity in childhood. Models were adjusted for maternal and child socio-demographics. Three thousand nine hundred and fifty mother–child dyads were included in analyses (1467 [57.8%] of mothers and 913 [34.4%] of children were overweight/obese). Results suggest that a small percentage of the effect of maternal pre-pregnancy BMI overweight/obesity on offspring overweight/obesity operated through offspring anthropometry at birth (weight: 15.5%, length: 5.2%, head circumference: 8.5%, ponderal index: 2.2%, SGA: 2.9%, and LGA: 4.2%). There was a small increase in the percentage mediated when gestational diabetes or hypertensive disorders were added to the models. Our study suggests that some measures of birth anthropometry mediate the association between maternal pre-pregnancy overweight/obesity and offspring overweight/obesity in childhood and that the size of this mediated effect is small.
Transoral laser microsurgery for glottic squamous cell carcinoma is the standard of care at many institutions. Repeat transoral laser microsurgery for recurrence may avoid the need for radiotherapy and total laryngectomy. This study aimed to identify oncological and functional outcomes in a cohort of patients who had undergone repeat transoral laser microsurgery procedures.
A retrospective review of prospectively collected data of patients treated with transoral laser microsurgery for carcinoma in situ or tumour stages T1 or T2 glottic cancer, from 2003 to 2018.
Twenty patients were identified. Additional treatment was not needed in 45 per cent of patients. The five-year overall survival rate was 90 per cent. The disease-specific survival rate was 100 per cent. The laryngeal preservation rate was 85 per cent. There was improvement in mean Voice Handicap Index-10 scores following repeat transoral laser microsurgery treatment, when comparing the pre- and post-operative periods (mean scores = 15.5 vs 11.5, p = 0.373).
Repeat transoral laser microsurgery can be an oncologically safe alternative to other salvage therapies for glottic squamous cell carcinoma recurrence, without sacrificing functional outcomes.
True Colours is an automated symptom monitoring programme used by National Health Service psychiatric services. This study explored whether patients with unipolar treatment-resistant depression (TRD) found this a useful addition to their treatment regimes. Semi-structured qualitative interviews were conducted with 21 patients with TRD, who had engaged in True Colours monitoring as part of the Lithium versus Quetiapine in Depression study. A thematic analysis was used to assess participant experiences of the system.
Six main themes emerged from the data, the most notable indicating that mood monitoring increased patients' insight into their disorder, but that subsequent behaviour change was absent.
Patients with TRD can benefit from mood monitoring via True Colours, making it a worthwhile addition to treatment. Further development of such systems and additional support may be required for patients with TRD to experience further benefits as reported by other patient groups.
Gut microbiota data obtained by DNA sequencing are not only complex because of the number of taxa that may be detected within human cohorts, but also compositional because characteristics of the microbiota are described in relative terms (e.g., “relative abundance” of particular bacterial taxa expressed as a proportion of the total abundance of taxa). Nutrition researchers often use standard principal component analysis (PCA) to derive dietary patterns from complex food data, enabling each participant's diet to be described in terms of the extent to which it fits their cohort's dietary patterns. However, compositional PCA methods are not commonly used to describe patterns of microbiota in the way that dietary patterns are used to describe diets. This approach would be useful for identifying microbiota patterns that are associated with diet and body composition. The aim of this study is to use compositional PCA to describe gut microbiota profiles in 5 year old children and explore associations between microbiota profiles, diet, body mass index (BMI) z-score, and fat mass index (FMI) z-score. This study uses a cross-sectional data for 319 children who provided a faecal sample at 5 year of age. Their primary caregiver completed a 123-item quantitative food frequency questionnaire validated for foods of relevance to the gut microbiota. Body composition was determined using dual-energy x-ray absorptiometry, and BMI and FMI z-scores calculated. Compositional PCA identified and described gut microbiota profiles at the genus level, and profiles were examined in relation to diet and body size. Three gut microbiota profiles were found. Profile 1 (positive loadings on Blautia and Bifidobacterium; negative loadings on Bacteroides) was not related to diet or body size. Profile 2 (positive loadings on Bacteroides; negative loadings on uncultured Christensenellaceae and Ruminococcaceae) was associated with a lower BMI z-score (r = -0.16, P = 0.003). Profile 3 (positive loadings on Faecalibacterium, Eubacterium and Roseburia) was associated with higher intakes of fibre (r = 0.15, P = 0.007); total (r = 0.15, P = 0.009), and insoluble (r = 0.13, P = 0.021) non-starch polysaccharides; protein (r = 0.12, P = 0.036); meat (r = 0.15, P = 0.010); and nuts, seeds and legumes (r = 0.11, P = 0.047). Further regression analyses found that profile 2 and profile 3 were independently associated with BMI z-score and diet respectively. We encourage fellow researchers to use compositional PCA as a method for identifying further links between the gut, diet and obesity, and for developing the next generation of research in which the impact on body composition of dietary interventions that modify the gut microbiota is determined.
The Vietnam Era Twin Study of Aging (VETSA) is a longitudinal behavioral genetic study with a primary focus on cognitive and brain aging in men, particularly early identification of risk for mild cognitive impairment (MCI) and Alzheimer’s disease (AD). It comprises a subset of over 1600 twins from the Vietnam Era Twin Registry. Twins live all over the USA. Assessments began when participants were in their 50s. Follow-ups were conducted every 5–6 years, and wave 3 has been completed as of this writing. The age range of participants is narrow (about 10 years). An extensive neurocognitive test battery has added precision in assessing differences in middle-aged adults, and predicting progression to MCI. Young adult cognitive test data (at an average age of 20 years) provide a means of disentangling aging effects from longstanding differences. Genome wide genotyping and plasma assays of AD biomarkers from waves 1 and 3 were conducted in wave 3. These features make the VETSA ideal for studying the heterogeneity of within-individual trajectories from midlife to old age, and for early detection of risk factors for cognitive decline.
The Minnesota Center for Twin and Family Research (MCTFR) comprises multiple longitudinal, community-representative investigations of twin and adoptive families that focus on psychological adjustment, personality, cognitive ability and brain function, with a special emphasis on substance use and related psychopathology. The MCTFR includes the Minnesota Twin Registry (MTR), a cohort of twins who have completed assessments in middle and older adulthood; the Minnesota Twin Family Study (MTFS) of twins assessed from childhood and adolescence into middle adulthood; the Enrichment Study (ES) of twins oversampled for high risk for substance-use disorders assessed from childhood into young adulthood; the Adolescent Brain (AdBrain) study, a neuroimaging study of adolescent twins; and the Siblings Interaction and Behavior Study (SIBS), a study of adoptive and nonadoptive families assessed from adolescence into young adulthood. Here we provide a brief overview of key features of these established studies and describe new MCTFR investigations that follow up and expand upon existing studies or recruit and assess new samples, including the MTR Study of Relationships, Personality, and Health (MTR-RPH); the Colorado-Minnesota (COMN) Marijuana Study; the Adolescent Brain Cognitive Development (ABCD) study; the Colorado Online Twins (CoTwins) study and the Children of Twins (CoT) study.
Here we provide an update of the 2013 report on the Nigerian Twin and Sibling Registry (NTSR). The major aim of the NTSR is to understand genetic and environmental influences and their interplay in psychological and mental health development in Nigerian children and adolescents. Africans have the highest twin birth rates among all human populations, and Nigeria is the most populous country in Africa. Due to its combination of large population and high twin birth rates, Nigeria has one of the largest twin populations in the world. In this article, we provide current updates on the NTSR samples recruited, recruitment procedures, zygosity assessment and findings emerging from the NTSR.
The purpose of this review is to provide a detailed and updated description of the FinnTwin16 (FT16) study and its future directions. The Finnish Twin Cohort comprises three different cohorts: the Older Twin Cohort established in the 1970s and the FinnTwin12 and FT16 initiated in the 1990s. FT16 was initiated in 1991 to identify the genetic and environmental precursors of alcoholism, but later the scope of the project expanded to studying the determinants of various health-related behaviors and diseases in different stages of life. The main areas addressed are alcohol use and its consequences, smoking, physical activity, overall physical health, eating behaviors and eating disorders, weight development, obesity, life satisfaction and personality. To date, five waves of data collection have been completed and the sixth is now planned. Data from the FT16 cohort have contributed to several hundred studies and many substudies, with more detailed phenotyping and collection of omics data completed or underway. FT16 has also contributed to many national and international collaborations.
Twins Research Australia (TRA) is a community of twins and researchers working on health research to benefit everyone, including twins. TRA leads multidisciplinary research through the application of twin and family study designs, with the aim of sustaining long-term twin research that, both now and in the future, gives back to the community. This article summarizes TRA’s recent achievements and future directions, including new methodologies addressing causation, linkage to health, economic and educational administrative datasets and to geospatial data to provide insight into health and disease. We also explain how TRA’s knowledge translation and exchange activities are key to communicating the impact of twin studies to twins and the wider community. Building researcher capability, providing registry resources and partnering with all key stakeholders, particularly the participants, are important for how TRA is advancing twin research to improve health outcomes for society. TRA provides researchers with open access to its vibrant volunteer membership of twins, higher order multiples (multiples) and families who are willing to consider participation in research. Established four decades ago, this resource facilitates and supports research across multiple stages and a breadth of health domains.
The Colorado Twin Registry (CTR) is a population-based registry formed from birth and school records including twins born between 1968 and the present. Two previous reports on the CTR [Rhea et al., (2006). Twin Research and Human Genetics, 9, 941–949; Rhea et al., (2013).Twin Research and Human Genetics, 16, 351–357] covered developments in the CTR through 2012. This report briefly summarizes previously presented material on ascertainment and recruitment and the relationships between samples and studies, discusses developments since 2012 for four previously described twin samples, describes two new samples and their complementary studies and expands on two subjects briefly mentioned in the last report: a history of genotyping efforts involving CTR samples, and a survey of collaborations and consortia in which CTR twins have been included. The CTR remains an active resource for both ongoing, longitudinal research and the recruitment of new twin samples for newly identified research opportunities.
Smoking prevalence is higher amongst individuals with schizophrenia and depression compared with the general population. Mendelian randomisation (MR) can examine whether this association is causal using genetic variants identified in genome-wide association studies (GWAS).
We conducted two-sample MR to explore the bi-directional effects of smoking on schizophrenia and depression. For smoking behaviour, we used (1) smoking initiation GWAS from the GSCAN consortium and (2) we conducted our own GWAS of lifetime smoking behaviour (which captures smoking duration, heaviness and cessation) in a sample of 462690 individuals from the UK Biobank. We validated this instrument using positive control outcomes (e.g. lung cancer). For schizophrenia and depression we used GWAS from the PGC consortium.
There was strong evidence to suggest smoking is a risk factor for both schizophrenia (odds ratio (OR) 2.27, 95% confidence interval (CI) 1.67–3.08, p < 0.001) and depression (OR 1.99, 95% CI 1.71–2.32, p < 0.001). Results were consistent across both lifetime smoking and smoking initiation. We found some evidence that genetic liability to depression increases smoking (β = 0.091, 95% CI 0.027–0.155, p = 0.005) but evidence was mixed for schizophrenia (β = 0.022, 95% CI 0.005–0.038, p = 0.009) with very weak evidence for an effect on smoking initiation.
These findings suggest that the association between smoking, schizophrenia and depression is due, at least in part, to a causal effect of smoking, providing further evidence for the detrimental consequences of smoking on mental health.
The aim of the Avera Twin Register (ATR) is to establish a prospective longitudinal repository of twins, multiples, siblings and family members’ biological samples to study environmental and genetic influences on health and disease. Also, it is our intention to contribute to international genome-wide association study (GWAS) twin consortia when appropriate sample size is achieved within the ATR. The ATR is young compared with existing registers and continues to collect a longitudinal repository of biological specimens, survey data and health information. Data and biological specimens were originally collected via face-to-face appointments or the postal department and consisted of paper-informed consents and questionnaires. Enrollment of the ATR began on May 18, 2016 and is located in Sioux Falls, South Dakota, a rural and frontier area in the Central United States with a regional population of approximately 880,000. The original target area for the ATR was South Dakota and the four surrounding states: Minnesota, Iowa, North Dakota and Nebraska. The ATR has found a need to expand that area based on twin and multiple siblings who live in various areas surrounding these states. A description of the state of the ATR today and its transition to online data collection and informed consent will be presented. The ATR collects longitudinal data on lifestyle, including diet and activity levels, aging, plus complex traits and diseases. All twins and multiples participating in the ATR are genotyped on the Illumina Global Screening Array and receive zygosity results.