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Sarcosine, which is freely sold as a dietary supplement, has pharmacological activity to boost functioning of the glutamatergic N-methyl-d-aspartate receptor (NMDAR) and hence it is a biologically rational treatment for schizophrenia. The small number of studies carried out to date provide some evidence for its efficacy and psychiatrists could consider suggesting its use to their patients.
Declaration of interest
D.C. is involved in schizophrenia-related genetics research that implicates the same system as is targeted by sarcosine.
We describe the production of photovoltaic modules with high-quality large-grain copper indium gallium selenide (CIGS) thin films obtained with the unique combination of low-cost ink-based precursors and a reactive transfer printing method. The proprietary metal-organic inks contain a variety of soluble Cu-, In- and Ga- multinary selenide materials; they are called metal-organic decomposition (MOD) precursors, as they are designed to decompose into the desired precursors. Reactive transfer is a two-stage process that produces CIGS through the chemical reaction between two separate precursor films, one deposited on the substrate and the other on a printing plate in the first stage. In the second stage, these precursors are rapidly reacted together under pressure in the presence of heat. The use of two independent thin films provides the benefits of independent composition and flexible deposition technique optimization, and eliminates pre-reaction prior to the synthesis of CIGS. In a few minutes, the process produces high quality CIGS films, with large grains on the order of several microns, and preferred crystallographic orientation, as confirmed by compositional and structural analysis by XRF, SIMS, SEM and XRD. Cell efficiencies of 14% and module efficiencies of 12% were achieved using this method. The atmospheric deposition processes include slot die extrusion coating, ultrasonic atomization spraying, pneumatic atomization spraying, inkjet printing, direct writing, and screen printing, and provide low capital equipment cost, low thermal budget, and high throughput.
Schizophrenia and anorexia nervosa were recently added to the list of conditions for which whole genome sequencing might be indicated as part of the 100 000 Genomes Project, reflecting the remarkable recent progress in findings emerging from psychiatric genetics research. Genetic testing methods may offer increased opportunities for diagnosis and estimation of familial risk and could have implications for management and treatment options. They also present ethical and philosophical questions about the role of testing and storage of genetic information. Mental health professionals will need to have a good understanding of this area in order for patients to fully realise the benefits of these advances.
Declaration of Interest
K.S.B. is Editor of the British Journal of Psychiatry.
Community treatment orders (CTOs) have been in used in England and Wales since November 2008; however, their effectiveness has been debated widely, as has the question of which methodology is appropriate to investigate them. This paper uses national data to explore the use of CTOs in England.
About 5500 patients are subject to CTOs at any one time. Each year, ~4500 patients are made subject to a CTO each year and ~2500 are fully discharged, usually by the responsible clinician; fewer than half of CTO patients are recalled, and two-thirds of recalls end in revocation. The low rate of CTO discharges by mental health tribunals (below 5%) suggests that they are not used inappropriately.
The introduction of CTOs in England has coincided with a reduction in psychiatric service provision due to the economic downturn. Pressures on services might be even more severe if patients currently subject to CTOs instead needed to be detained as in-patients.
The Patient Reported Outcomes Burdens and Experiences (PROBE) questionnaire was developed with direct patient involvement in questionnaire design, conduct and analysis using patient-centered outcomes to assess health status in patients with hemophilia (PWH). Phase 1 confirmed robustness of the methodology and feasibility. Phase 2a investigated individual test-retest reliability. Phase 2b will explore population level reproducibility.
PWH and non-PWH individuals who attended a hemophilia-related workshop were asked to complete the PROBE questionnaire 3 times (paper-based survey on 2 consecutive days and then a web-based version). Test-retest reliability was analyzed using the percentage agreement and Kappa statistic. Kappa coefficient interpretation .81-1.00 almost perfect, .61- .80 substantial; .41- .60 moderate; .21 -.40 fair; .00 -.20, slight; and < .00 poor agreement.
Sixty-three participants from twenty-one countries were enrolled with a median age of 50 (range 14–76) years. Of these, thirty (47.6 percent) were PWH or carriers, thirty-three (52.5 percent) were participants with no known bleeding disorders. On general health domain, Kappa coefficients ranged from .69 to .92, indicating substantial to almost perfect agreement, for all items. Reliability of the web-based questionnaire showed moderate to substantial agreement for all except one item. For the hemophilia-related domain, Kappa coefficients ranged from .5-1.0. Of these, five of eleven items were in perfect agreement (Kappa = 1.0). Reliability of web-based questionnaire items were in substantial to almost perfect agreement. For overall health related quality of life, the EuroQol five dimensions questionnaire (EQ-5D) had Kappa coefficients of .62 to .92. Intraclass correlation coefficient of visual analog scale (VAS) was .90 (95 percent Confidence Interval, CI; .83-.94). Test-retest reliability was comparable between hemophilia patients and participants with no known bleed.
Phase 2a demonstrated individual test-retest reliability and suggests PROBE is a reliable tool to assess Patient Reported Outcomes in PWH. The Web-based questionnaire has an acceptable agreement with the standard paper-based version in all domains. PROBE Phase 2b, to demonstrate reproducibility at the population level, is on-going. To date, 1,039 participants have been recruited from 10 countries.
X-ray fluorescence (XRF) has been employed as one of several orthogonal means of screening materials to prevent counterfeit and adulterated products from entering the product stream. We document the use of principal component analysis (PCA) of XRF data on compositionally similar and dissimilar stainless steels for the purpose of testing the feasibility of employing XRF spectra to parse and bin these alloys as the same or significantly different alloy materials. The results indicate that XRF spectra can separate and assign alloys via PCA, but that important corrections for detector drift and scaling must be performed in order to achieve valid results.
Since Beck, Katz, and Tucker (1998), the standard method for modeling time dependence in binary data has been to incorporate time dummies or splined time in logistic regressions. Although we agree with the need for modeling time dependence, we demonstrate that time dummies can induce estimation problems due to separation. Splines do not suffer from these problems. However, the complexity of splines has led substantive researchers (1) to use knot values that may be inappropriate for their data and (2) to ignore any substantive discussion concerning temporal dependence. We propose a relatively simple alternative: including t, t2, and t3 in the regression. This cubic polynomial approximation is trivial to implement—and, therefore, interpret—and it avoids problems such as quasi-complete separation. Monte Carlo analysis demonstrates that, for the types of hazards one often sees in substantive research, the polynomial approximation always outperforms time dummies and generally performs as well as splines or even more flexible autosmoothing procedures. Due to its simplicity, this method also accommodates nonproportional hazards in a straightforward way. We reanalyze Crowley and Skocpol (2001) using nonproportional hazards and find new empirical support for the historical-institutionalist perspective.
We thank Neal Beck for his comments. In general, there is little difference in our theoretical and practical positions. We all agree that in some applications, time dummies can be problematic; controlling for temporal dependence is important for less-biased estimation of the coefficients on our substantive regressors; a smoothed function of time (whether via a cubic polynomial or spline) is a useful way to model temporal dependence in grouped binary data; and viewing the graph of the hazard can be informative.
Recent studies point to overlap between neuropsychiatric disorders in symptomatology and genetic aetiology.
To systematically investigate genomics overlap between childhood and adult attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD) and major depressive disorder (MDD).
Analysis of whole-genome blood gene expression and genetic risk scores of 318 individuals. Participants included individuals affected with adult ADHD (n = 93), childhood ADHD (n = 17), MDD (n = 63), ASD (n = 51), childhood dual diagnosis of ADHD–ASD (n = 16) and healthy controls (n = 78).
Weighted gene co-expression analysis results reveal disorder-specific signatures for childhood ADHD and MDD, and also highlight two immune-related gene co-expression modules correlating inversely with MDD and adult ADHD disease status. We find no significant relationship between polygenic risk scores and gene expression signatures.
Our results reveal disorder overlap and specificity at the genetic and gene expression level. They suggest new pathways contributing to distinct pathophysiology in psychiatric disorders and shed light on potential shared genomic risk factors.
Two recent reports convincingly demonstrate that the risk of schizophrenia is influenced by common variation of C4, which codes for complement component 4, and by rare, disruptive mutations of SETD1A, which codes for a histone methylase. These important results open the way for major advances in our understanding of the fundamental biological processes leading to disease.
The British Artists’ Film and Video Study Collection is a small specialist collection dedicated to the history of artists’ moving images in Britain, which is based at Central Saint Martins College of Art and Design at the University of the Arts London. The Collection services the needs of both academics and curators in this specialist area. Its founders describe its raison d’être and collecting policy, and outline some of the challenges of working in an environment susceptible to changing research priorities and uncertain digital storage standards.
Placebo responses raise significant challenges for the design of clinical trials. We report changes in agitation outcomes in the placebo arm of a recent trial of citalopram for agitation in Alzheimer's disease (CitAD).
In the CitAD study, all participants and caregivers received a psychosocial intervention and 92 were assigned to placebo for nine weeks. Outcomes included Neurobehavioral Rating Scale agitation subscale (NBRS-A), modified AD Cooperative Study-Clinical Global Impression of Change (CGIC), Cohen-Mansfield Agitation Inventory (CMAI), the Neuropsychiatric Inventory (NPI) Agitation/Aggression domain (NPI A/A) and Total (NPI-Total) and ADLs. Continuous outcomes were analyzed with mixed-effects modeling and dichotomous outcomes with logistic regression.
Agitation outcomes improved over nine weeks: NBRS-A mean (SD) decreased from 7.8 (3.0) at baseline to 5.4 (3.2), CMAI from 28.7 (6.7) to 26.7 (7.4), NPI A/A from 8.0 (2.4) to 4.9 (3.8), and NPI-Total from 37.3 (17.7) to 28.4 (22.1). The proportion of CGI-C agitation responders ranged from 21 to 29% and was significantly different from zero. MMSE improved from 14.4 (6.9) to 15.7 (7.2) and ADLs similarly improved. Most of the improvement was observed by three weeks and was sustained through nine weeks. The major predictor of improvement in each agitation measure was a higher baseline score in that measure.
We observed significant placebo response which may be due to regression to the mean, response to a psychosocial intervention, natural course of symptoms, or nonspecific benefits of participation in a trial.
An estimated 20–30% of patients with primary Clostridium difficile infection (CDI) develop recurrent CDI (rCDI) within 2 weeks of completion of therapy. While the actual mechanism of recurrence remains unknown, a variety of risk factors have been suggested and studied. The aim of this systematic review and meta-analysis was to evaluate current evidence on the risk factors for rCDI.
We searched MEDLINE and 5 other databases for subject headings and text related to rCDI. All studies investigating risk factors of rCDI in a multivariate model were eligible. Information on study design, patient population, and assessed risk factors were collected. Data were combined using a random-effects model and pooled relative risk ratios (RRs) were calculated.
A total of 33 studies (n=18,530) met the inclusion criteria. The most frequent independent risk factors associated with rCDI were age≥65 years (risk ratio [RR], 1.63; 95% confidence interval [CI], 1.24–2.14; P=.0005), additional antibiotics during follow-up (RR, 1.76; 95% CI, 1.52–2.05; P<.00001), use of proton-pump inhibitors (PPIs) (RR, 1.58; 95% CI, 1.13–2.21; P=.008), and renal insufficiency (RR, 1.59; 95% CI, 1.14–2.23; P=.007). The risk was also greater in patients previously on fluoroquinolones (RR, 1.42; 95% CI, 1.28–1.57; P<.00001).
Multiple risk factors are associated with the development of rCDI. Identification of modifiable risk factors and judicious use of antibiotics and PPI can play an important role in the prevention of rCDI.
Of 82 patients with methicillin-resistant Staphylococcus aureus (MRSA) colonization, 67 (82%) had positive hand cultures for MRSA. A single application of alcohol gel (2 mL) consistently reduced the burden of MRSA on hands. However, incomplete removal of MRSA was common, particularly in those with a high baseline level of recovery.
This investigation examined the relationship between teachers’ beliefs and their preferences for classroom interventions for behaviours consistent with attention-deficit/hyperactivity disorder (ADHD). Teacher ratings of intervention acceptability, effectiveness, and rate of change were compared across United States and New Zealand samples. Beliefs examined were personal teaching efficacy, general teaching efficacy, and pupil control ideology (PCI). Samples were compared regarding their preferences for the daily report card, response cost technique, classroom lottery, and medication as classroom strategies for managing ADHD-related behavioural concerns. Data were analysed using general linear modelling techniques, and an interaction was demonstrated between ADHD intervention x PCI x nationality. Differences were observed for ADHD interventions across samples based upon pupil control orientations. Implications for educators and their classroom practices are discussed.
To describe pediatric emergency medicine (PEM) physicians' reported pain management practices across Canada and explore factors that facilitate or hinder pain management.
This study was a prospective survey of Canadian pediatric emergency physicians. The Pediatric Emergency Research Canada physician database was used to identify participants, and a modified Dillman's Total Design Survey Method was used for recruitment.
The survey response rate was 68% (139 of 206). Most physicians were 31 to 50 years old (82%) with PEM training (56%) and had been in practice for less than 10 years (55%). Almost all pain screening in emergency departments (EDs) occurred at triage (97%). Twenty-four percent of physicians noted institutionally mandated pain score documentation. Ibuprofen and acetaminophen were commonly prescribed in the ED for mild to moderate pain (88% and 83%, respectively). Over half of urinary catheterizations (60%) and intravenous (53%) starts were performed without any analgesia. The most common nonpharmacologic interventions used for infants and children were pacifiers and distraction, respectively. Training background and gender of physicians affected the likelihood of using nonpharmacologic interventions. Physicians noted time restraints to be the greatest barrier to optimal pain management (55%) and desired improved access to pain medications (32%), better policies and procedures (30%), and further education (25%).
When analgesia was reported as provided, ibuprofen and acetaminophen were most commonly used. Both procedural and presenting pain remained suboptimally managed. There is a substantial evidence practice gap in children's ED pain management, highlighting the need for further knowledge translation strategies and policies to support optimal treatment.