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Less than half of stool samples from people symptomatic with infectious intestinal disease (IID) will identify a causative organism. A secondary data analysis was undertaken to explore whether symptomology alone could be used to make inferences about causative organisms. Data were utilised from the Second Study of Infectious Intestinal Disease in the Community. A total of 844 cases were analysed. Few symptoms differentiated individual pathogens, but grouping pathogens together showed that viral IID was more likely when symptom onset was in winter (odds ratio (OR) 2.08, 95% confidence interval (CI) 1.16–3.75) or spring (OR 1.92, 95% CI 1.11–3.33), the patient was aged under 5 years (OR 3.63, 95% CI 2.24–6.03) and there was loss of appetite (OR 2.19, 95% CI 1.29–3.72). The odds of bacterial IID were higher with diarrhoea in the absence of vomiting (OR 3.54, 95% CI 2.37–5.32), diarrhoea which persisted for >3 days (OR 2.69, 95% CI 1.82–3.99), bloody diarrhoea (OR 4.17, 95% CI 1.63–11.83) and fever (OR 1.67, 95% CI 1.11–2.53). Symptom profiles could be of value to help guide clinicians and public health professionals in the management of IID, in the absence of microbiological confirmation.
Bipolar disorder is less prevalent in older people but accounts for 8–10% of psychiatric admissions. Treating and managing bipolar disorder in older people is challenging because of medical comorbidity. We review the cognitive problems observed in older people, explore why these are important and consider current treatment options. There are very few studies examining the cognitive profiles of older people with bipolar disorder and symptomatic depression and mania, and these show significant impairments in executive function. Most studies have focused on cognitive impairment in euthymic older people: as in euthymic adults of working age, significant impairments are observed in tests of attention, memory and executive function/processing speeds. Screening tests are not always helpful in euthymic older people as the impairment can be relatively subtle, and more in-depth neuropsychological testing may be needed to show impairments. Cognitive impairment may be more pronounced in older people with ‘late-onset’ bipolar disorder than in those with ‘early-onset’ disorder. Strategies to address symptomatic cognitive impairment in older people include assertive treatment of the mood disorder, minimising drugs that can adversely affect cognition, optimising physical healthcare and reducing relapse rates.
After reading this article you will be able to:
•understand that cognitive impairment in euthymic older people with bipolar disorder is similar to that in working-age adults with the disorder, affecting attention, memory and executive function/processing speeds
•recognise that cognitive impairment in older people is likely to be a major determinant of functional outcomes
•Implement approaches to treat cognitive impairment in bipolar disorder.
DECLARATION OF INTEREST
B.J.S. consults for Cambridge Cognition, PEAK (www.peak.net) and Mundipharma.
Current standard-of-care for glioblastoma (GBM) includes surgery, radiation and temozolomide. Most tumors recur within a year from diagnosis and median survival for recurrent GBM (rGBM) is 3-9 months. Unmethylated promoter status for O6-methylguanine-DNA-methyltransferase (MGMT) is a validated biomarker for temozolomide-resistance, exhibited by most GBM patients. VAL-083 is a DNA-targeting agent with a mechanism-of-action that is independent of MGMT. VAL-083 overcomes temozolomide-resistance in GBM cell-lines, cancer stem cells, and in vivo models. VAL-083 readily crosses the blood-brain barrier and accumulates in brain-tumor tissue. We recently completed a VAL-083 dose-escalation trial in temozolomide- and bevacizumab-refractory rGBM and determined that 40mg/m2/day given intravenously on days 1,2,3 of a 21-day cycle is generally well-tolerated. This dosing regimen was selected for subsequent GBM trials, including an ongoing single-arm, biomarker-driven Phase 2 trial (N=48) in temolozomide-refractory, bevacizumab-naïve rGBM , MGMT-unmethylated (Clinicaltrials.gov:NCT02717962). The primary objective of this study is to determine if VAL-083 improves OS compared to a historical control of 7.15 months for MGMT-unmethylated rGBM patients treated with lomustine (EORTC26101). In addition, another single-arm, biomarker-driven, Phase 2 study (N=25) of VAL-083 in combination with radiotherapy in newly diagnosed GBM, MGMT-unmethylated is ongoing (Clinicaltrials.gov:NCT03050736). This trial aims to determine a dose for further study of VAL-083 in combination with radiotherapy and explore if VAL-083 improves PFS and OS compared to historical results in newly diagnosed GBM. Enrollment and safety data updates will be provided at the meeting. The results of these studies, if successful, may support VAL-083 as part of a new chemotherapeutic treatment paradigm for GBM.
To date, Ireland has been a leading light in the provision of youth mental health services. However, cognisant of the efforts of governmental and non-governmental agencies working in youth mental health, there is much to be done. Barriers into care as well as discontinuity of care across the spectrum of services remain key challenges. This editorial provides guidance for the next stage of development in youth mental care and support that will require significant national engagement and resource investment.
Early detection of karyotype abnormalities, including aneuploidy, could aid producers in identifying animals which, for example, would not be suitable candidate parents. Genome-wide genetic marker data in the form of single nucleotide polymorphisms (SNPs) are now being routinely generated on animals. The objective of the present study was to describe the statistics that could be generated from the allele intensity values from such SNP data to diagnose karyotype abnormalities; of particular interest was whether detection of aneuploidy was possible with both commonly used genotyping platforms in agricultural species, namely the Applied BiosystemsTM AxiomTM and the Illumina platform. The hypothesis was tested using a case study of a set of dizygotic X-chromosome monosomy 53,X sheep twins. Genome-wide SNP data were available from the Illumina platform (11 082 autosomal and 191 X-chromosome SNPs) on 1848 male and 8954 female sheep and available from the AxiomTM platform (11 128 autosomal and 68 X-chromosome SNPs) on 383 female sheep. Genotype allele intensity values, either as their original raw values or transformed to logarithm intensity ratio (LRR), were used to accurately diagnose two dizygotic (i.e. fraternal) twin 53,X sheep, both of which received their single X chromosome from their sire. This is the first reported case of 53,X dizygotic twins in any species. Relative to the X-chromosome SNP genotype mean allele intensity values of normal females, the mean allele intensity value of SNP genotypes on the X chromosome of the two females monosomic for the X chromosome was 7.45 to 12.4 standard deviations less, and were easily detectable using either the AxiomTM or Illumina genotype platform; the next lowest mean allele intensity value of a female was 4.71 or 3.3 standard deviations less than the population mean depending on the platform used. Both 53,X females could also be detected based on the genotype LRR although this was more easily detectable when comparing the mean LRR of the X chromosome of each female to the mean LRR of their respective autosomes. On autopsy, the ovaries of the two sheep were small for their age and evidence of prior ovulation was not appreciated. In both sheep, the density of primordial follicles in the ovarian cortex was lower than normally found in ovine ovaries and primary follicle development was not observed. Mammary gland development was very limited. Results substantiate previous studies in other species that aneuploidy can be readily detected using SNP genotype allele intensity values generally already available, and the approach proposed in the present study was agnostic to genotype platform.
Elevated birth weight is linked to glucose intolerance and obesity health-related complications later in life. No studies have examined if infant birth weight is associated with gene expression markers of obesity and inflammation in a tissue that comes directly from the infant following birth. We evaluated the association between birth weight and gene expression on fetal programming of obesity. Foreskin samples were collected following circumcision, and gene expression analyzed comparing the 15% greatest birth weight infants (n=7) v. the remainder of the cohort (n=40). Multivariate linear regression models were fit to relate expression levels on differentially expressed genes to birth weight group with adjustment for variables selected from a list of maternal and infant characteristics. Glucose transporter type 4 (GLUT4), insulin receptor substrate 2 (IRS2), leptin receptor (LEPR), lipoprotein lipase (LPL), low-density lipoprotein receptor-related protein 1 (LRP1), matrix metalloproteinase 2 (MMP2), plasminogen activator inhibitor-1 (PAI-1) and transcription factor 7-like 2 (TCF7L2) were significantly upregulated and histone deacetylase 1 (HDAC1) and thioredoxin (TXN) downregulated in the larger birth weight neonates v. controls. Multivariate modeling revealed that the estimated adjusted birth weight group difference exceeded one standard deviation of the expression level for eight of the 10 genes. Between 25 and 50% of variation in expression level was explained by multivariate modeling for eight of the 10 genes. Gene expression related to glycemic control, appetite/energy balance, obesity and inflammation were altered in tissue from babies with elevated birth weight, and these genes may provide important information regarding fetal programming in macrosomic babies.
Anomalous aortic origin of the coronary arteries is associated with exercise-induced ischaemia, leading some physicians to restrict exercise in patients with this condition. We sought to determine whether exercise restriction was associated with increasing body mass index over time. From 1998 to 2015, 440 patients ⩽30 years old were enrolled into an inception cohort. Exercise-restriction status was documented in 143 patients. Using linear mixed model repeated-measures regression, factors associated with increasing body mass index z-score over time, including exercise restriction and surgical intervention as time-varying covariates, were investigated. The 143 patients attended 558 clinic visits for which exercise-restriction status was recorded. The mean number of clinic visits per patient was 4, and the median duration of follow-up was 1.7 years (interquartile range (IQR) 0.5–4.4). The median age at first clinic visit was 10.3 years (IQR 7.1–13.9), and 71% (101/143) were males. All patients were alive at their most recent follow-up. At the first clinic visit, 54% (78/143) were exercise restricted, and restriction status changed in 34% (48/143) during follow-up. The median baseline body mass index z-score was 0.2 (IQR 0.3–0.9). In repeated-measures analysis, neither time-related exercise restriction nor its interaction with time was associated with increasing body mass index z-score. Surgical intervention and its interaction with time were associated with decreasing body mass index z-score. Although exercise restriction was not associated with increasing body mass index over time, surgical intervention was associated with decreasing body mass index z-score over time in patients with anomalous aortic origin of the coronary arteries.
Calcium is considered important in buffering excess stomach acid in mammals, including horses. Control of stomach acid is important in preventing the development of ulcers within the stomach lining, which, in horses, are considered to be caused by acid splashing. Algae supplements contain various minerals which are in natural form, as seen in all plant and feedstuffs. The current trial was conducted to examine if a high calcium algae supplement had any impact on gastric ulceration in horses, which may be due to buffering stomach acid, reducing the pH in a gradual manner, without resorting to medication. Ten horses, of either thoroughbred, standardbred or sport horse breed, were selected on the basis of the presence of ulcers in their stomach, as ascertained by endoscopy. The average ulceration score before algae supplementation was 2.2 ± 0.75 according to the EGUC scoring system. The horses were then maintained on their normal diet (unchanged from the initial ulcer scoring) by the owner with the addition of 40 g per day of the high calcium, algae based Maxia Complete® (Seahorse Supplements Ltd, Christchurch, NZ) for thirty days (T30). All horses were then re endoscoped to assess any change in ulceration score. All horses showed a significant improvement in ulcer score, with seven having a score of zero (fully healed, no evidence of further ulceration) and two with a score of one (some residual inflammation or keratinosis in areas of healed ulcers). This resulted in a mean score of 0.3 ± 0.48 (P < 0.0001: T0 versus T30) at the end of the study. This trial demonstrated that feeding an organic form of high calcium from algae reduced ulceration in horses.
A radiochemical 71Ga−71 Ge experiment to determine the integral flux of neutrinos from the sun has been constructed at the Baksan Neutrino Observatory in the USSR. Measurements have begun with 30 tonnes of gallium. The experiment is being expanded with the addition of another 30 tonnes. The motivation, experimental procedures, and present status of this experiment are presented.
The variability of CD-24 7599 (V=11.48 mag) was discovered by JCC during observing run XCOV7 of the Whole Earth Telescope (WET, Nather et al. 1990) network in February, 1992. The star was observed as an additional target and 117 hours of high-quality temporal spectroscopic observations were obtained.
Our analysis of these data revealed the presence of 7 independent pulsation modes between 27.0 and 38.1 cycles per day (313 – 441 μHz) with semiamplitudes of 2.1 – 10.2 milli-modulation amplitudes (mma). We showed that peaks at linear combination frequencies detected in the power spectra were not due to eigenmodes excited to visible amplitude by resonant mode coupling.
We examine the roles of actuaries in UK life offices, along with trends, challenges to and opportunities for actuaries. We carry out an analysis of senior roles in life offices, a questionnaire survey and interviews with relevant senior personnel. We find that actuaries occupy many important roles in life offices and are regarded as having good industry knowledge and technical skills, especially in financial modelling. There are fewer executive directors and more non-executive directors of life offices who are actuaries compared with the position in 1990. A higher proportion of reserved roles is outsourced to consultants than was the case in 1990. Only a small number of Actuarial Function Holders are directors. Actuaries are more siloed than was the case in the past, although actuaries are well represented in the finance and risk functions of many offices. Although actuarial work in connection with the preparation for Solvency II will decline, there will be important ongoing requirements for actuaries following Solvency II implementation. We also see opportunities for actuaries in four areas: in risk management, in financial analysis and management based on Solvency II and international financial reporting standards, in connection with “big data”, and in product development and the customer proposition. There are implications for the examination syllabus, continuing professional development and research.
The aims of the study were to determine the prevalence of cardiometabolic risk factors and establish the proportion of people with psychosis meeting criteria for the metabolic syndrome (MetS). The study also aimed to identify the key lifestyle behaviours associated with increased risk of the MetS and to investigate whether the MetS is associated with illness severity and degree of functional impairment.
Baseline data were collected as part of a large randomized controlled trial (IMPaCT RCT). The study took place within community mental health teams in five Mental Health NHS Trusts in urban and rural locations across England. A total of 450 randomly selected out-patients, aged 18–65 years, with an established psychotic illness were recruited. We ascertained the prevalence rates of cardiometabolic risk factors, illness severity and functional impairment and calculated rates of the MetS, using International Diabetes Federation (IDF) and National Cholesterol Education Program Third Adult Treatment Panel criteria.
High rates of cardiometabolic risk factors were found. Nearly all women and most men had waist circumference exceeding the IDF threshold for central obesity. Half the sample was obese (body mass index ≥ 30 kg/m2) and a fifth met the criteria for type 2 diabetes mellitus. Females were more likely to be obese than males (61% v. 42%, p < 0.001). Of the 308 patients with complete laboratory measures, 57% (n = 175) met the IDF criteria for the MetS.
In the UK, the prevalence of cardiometabolic risk factors in individuals with psychotic illnesses is much higher than that observed in national general population studies as well as in most international studies of patients with psychosis.
Stars are tidally disrupted and accreted when they approach massive black holes (MBHs) closely, producing a flare of electromagnetic radiation. The majority of the (approximately two dozen) tidal disruption events (TDEs) identified so far have been discovered by their luminous, transient X-ray emission. Once TDEs are detected in much larger numbers, in future dedicated transient surveys, a wealth of new applications will become possible. Here, we present the proposed Einstein Probe mission, which is a dedicated time-domain soft X-ray all-sky monitor aiming at detecting X-ray transients including TDEs in large numbers. The mission consists of a wide-field micro-pore Lobster-eye imager (60° × 60°), and is designed to carry out an all-sky transient survey at energies of 0.5-4 keV. It will also carry a more sensitive telescope for X-ray follow-ups, and will be capable of issuing public transient alerts rapidly. Einstein Probe is expected to revolutionise the field of TDE research by detecting several tens to hundreds of events per year from the early phase of flares, many with long-term, well sampled lightcurves.