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Treatment-resistant schizophrenia, affecting approximately 20–30% of patients with schizophrenia, has a high burden both for patients and healthcare services. There is a need to identify treatment resistance earlier in the course of the illness, in order that effective treatment, such as clozapine, can be offered promptly. We conducted a systemic literature review of prospective longitudinal studies with the aim of identifying predictors of treatment-resistant schizophrenia from the first episode. From the 545 results screened, we identified 12 published studies where data at the first episode was used to predict treatment resistance. Younger age of onset was the most consistent predictor of treatment resistance. We discuss the gaps in the literature and how future prediction models can identify predictors of treatment response more robustly.
Pelvic internal organs change in volume and position during radiotherapy. This may compromise the efficacy of treatment or worsen its toxicity. There may be limitations to fully correcting these changes using online image guidance; therefore, effective and consistent patient preparation and positioning remain important. This review aims to provide an overview of the extent of pelvic organ motion and strategies to manage this motion.
Methods and Materials:
Given the breadth of this topic, a systematic review was not undertaken. Instead, existing systematic reviews and individual high-quality studies addressing strategies to manage pelvic organ motion have been discussed. Suggested levels of evidence and grades of recommendation for each strategy have been applied.
Various strategies to manage rectal changes have been investigated including diet and laxatives, enemas and rectal emptying tubes and rectal displacement with endorectal balloons (ERBs) and rectal spacers. Bladder-filling protocols and bladder ultrasound have been used to try to standardise bladder volume. Positioning the patient supine, using a full bladder and positioning prone with or without a belly board, has been examined in an attempt to reduce the volume of irradiated small bowel. Some randomised trials have been performed, with evidence to support the use of ERBs, rectal spacers, bladder-filling protocols and the supine over prone position in prostate radiotherapy. However, there was a lack of consistent high-quality evidence that would be applicable to different disease sites within the pelvis. Many studies included small numbers of patients were non-randomised, used less conformal radiotherapy techniques or did not report clinical outcomes such as toxicity.
There is uncertainty as to the clinical benefit of many of the commonly adopted interventions to minimise pelvic organ motion. Given this and the limitations in online image guidance compensation, further investigation of adaptive radiotherapy strategies is required.
We apply two methods to estimate the 21-cm bispectrum from data taken within the Epoch of Reionisation (EoR) project of the Murchison Widefield Array (MWA). Using data acquired with the Phase II compact array allows a direct bispectrum estimate to be undertaken on the multiple redundantly spaced triangles of antenna tiles, as well as an estimate based on data gridded to the uv-plane. The direct and gridded bispectrum estimators are applied to 21 h of high-band (167–197 MHz; z = 6.2–7.5) data from the 2016 and 2017 observing seasons. Analytic predictions for the bispectrum bias and variance for point-source foregrounds are derived. We compare the output of these approaches, the foreground contribution to the signal, and future prospects for measuring the bispectra with redundant and non-redundant arrays. We find that some triangle configurations yield bispectrum estimates that are consistent with the expected noise level after 10 h, while equilateral configurations are strongly foreground-dominated. Careful choice of triangle configurations may be made to reduce foreground bias that hinders power spectrum estimators, and the 21-cm bispectrum may be accessible in less time than the 21-cm power spectrum for some wave modes, with detections in hundreds of hours.
Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
The current review aimed to synthesise the literature on food literacy interventions among adolescents in secondary schools, the attitudes and perceptions of food literacy interventions in secondary schools, and their effects on dietary outcomes.
The systematic review searched five electronic databases from the earliest record to present.
The studies selected for the review were from sixteen countries: Australia (n 10), Canada (n 1), China (n 1), France (n 1), Greece (n 2), Iran (n 1), South Africa (n 1), South India (n 1), Kenya (n 1), Norway (n 2), Portugal (n 1), Denmark (n 1), Northern Ireland (n 1), USA (n 17), UK (n 1) and Sweden (n 2).
Adolescents aged 10–19 years.
Forty-four studies were eligible for inclusion. Adolescents with greater nutritional knowledge and food skills showed healthier dietary practices. Studies found a mixed association between food literacy and long-term healthy dietary behaviour. Two studies showed an improvement in adolescents’ cooking skills and food safety knowledge; six studies showed an improvement in overall food safety knowledge; six studies showed an improvement in overall food and nutritional knowledge; and two studies showed an improvement in short-term healthy dietary behaviour.
Food literacy interventions conducted in a secondary-school setting have demonstrated a positive impact on healthy food and nutritional knowledge. However, there appears to be limited evidence supporting food literacy interventions and long-term dietary behaviours in adolescents. More evidence-based research is required to adequately measure all domains of food literacy and more age-specific food literacy interventions.
Background: The classic ketogenic diet is the main non-pharmacological treatment for refractory epilepsy; however, adherence is often challenging. The low glycemic index diet (LGID) is less strict, almost equally effective, and associated with improved adherence. Little is known about the quality of life of children treated with LGID. The objective of this study was to explore changes in the quality of life of children with epilepsy transitioning to the LGID. Methods: Patients on LGID and their parents filled out Pediatric Quality of Life Epilepsy Module questionnaires; one while being on the LGID, and one retrospectively for the time prior to starting the LGID. Results: Data was collected from five children ages 3-13 and their parents. Complete seizure control was seen in two children, >50% seizure reduction in one, and no change in two children. Parental reported quality of life while on the LGID increased with two participants but decreased in all child self reports. Conclusions: Although the LGID led to improved seizure control in three out of five patients, the child-reported quality of life decreased in all children. Larger prospective studies are warranted to reliably assess the impact of the LGID on the quality of life in children with epilepsy.
Background: Spinal muscular atrophy (SMA) is a children’s neuromuscular disorder. Although motor neuron loss is a major feature of the disease, we have identified fatty acid abnormalities in SMA patients and in preclinical animal models, suggesting metabolic perturbation is also an important component of SMA. Methods: Biochemical, histological, proteomic, and high resolution respirometry were used. Results: SMA patients are more susceptible to dyslipidemia than the average population as determined by a standard lipid profile in a cohort of 72 pediatric patients. As well, we observed a non-alcoholic liver disease phenotype in apreclinical mouse model. Denervation alone was not sufficient to induce liver steatosis, as a mouse model of ALS, did not develop fatty liver. Hyperglucagonemia in Smn2B/-mice could explain the hepatic steatosis by increasing plasma substrate availability via glycogen depletion and peripheral lipolysis. Proteomic analysis identified mitochondrion and lipid metabolism as major clusters. Alterations in mitochondrial function were revealed by high-resolution respirometry. Finally, low-fat diets led to increased survival in Smn2B/-mice. Conclusions: These results provide strong evidence for lipid metabolism defects in SMA. Further investigation will be required to establish the primary mechanism of these alterations and understand how they lead to additional co-morbidities in SMA patients.
Agriculture is one of the major sources of methane in the UK and the major contribution is that from the ruminant animal. Most current inventories include evaluations of emission rates determined from ammals in respiration chambers. Methodolgy has been developed at IGER, North Wyke which enables measurements to be made with grazing animals (tunnel system). Preliminary measurements have indicated that methane emissions from grazing sheep in the tunnel system were lower than reported values for zero-grazed grass determined in chambers. The objective was to determine if these observed differences were a result of methodological differences.
Different diagnostic interviews are used as reference standards for major depression classification in research. Semi-structured interviews involve clinical judgement, whereas fully structured interviews are completely scripted. The Mini International Neuropsychiatric Interview (MINI), a brief fully structured interview, is also sometimes used. It is not known whether interview method is associated with probability of major depression classification.
To evaluate the association between interview method and odds of major depression classification, controlling for depressive symptom scores and participant characteristics.
Data collected for an individual participant data meta-analysis of Patient Health Questionnaire-9 (PHQ-9) diagnostic accuracy were analysed and binomial generalised linear mixed models were fit.
A total of 17 158 participants (2287 with major depression) from 57 primary studies were analysed. Among fully structured interviews, odds of major depression were higher for the MINI compared with the Composite International Diagnostic Interview (CIDI) (odds ratio (OR) = 2.10; 95% CI = 1.15–3.87). Compared with semi-structured interviews, fully structured interviews (MINI excluded) were non-significantly more likely to classify participants with low-level depressive symptoms (PHQ-9 scores ≤6) as having major depression (OR = 3.13; 95% CI = 0.98–10.00), similarly likely for moderate-level symptoms (PHQ-9 scores 7–15) (OR = 0.96; 95% CI = 0.56–1.66) and significantly less likely for high-level symptoms (PHQ-9 scores ≥16) (OR = 0.50; 95% CI = 0.26–0.97).
The MINI may identify more people as depressed than the CIDI, and semi-structured and fully structured interviews may not be interchangeable methods, but these results should be replicated.
Declaration of interest
Drs Jetté and Patten declare that they received a grant, outside the submitted work, from the Hotchkiss Brain Institute, which was jointly funded by the Institute and Pfizer. Pfizer was the original sponsor of the development of the PHQ-9, which is now in the public domain. Dr Chan is a steering committee member or consultant of Astra Zeneca, Bayer, Lilly, MSD and Pfizer. She has received sponsorships and honorarium for giving lectures and providing consultancy and her affiliated institution has received research grants from these companies. Dr Hegerl declares that within the past 3 years, he was an advisory board member for Lundbeck, Servier and Otsuka Pharma; a consultant for Bayer Pharma; and a speaker for Medice Arzneimittel, Novartis, and Roche Pharma, all outside the submitted work. Dr Inagaki declares that he has received grants from Novartis Pharma, lecture fees from Pfizer, Mochida, Shionogi, Sumitomo Dainippon Pharma, Daiichi-Sankyo, Meiji Seika and Takeda, and royalties from Nippon Hyoron Sha, Nanzando, Seiwa Shoten, Igaku-shoin and Technomics, all outside of the submitted work. Dr Yamada reports personal fees from Meiji Seika Pharma Co., Ltd., MSD K.K., Asahi Kasei Pharma Corporation, Seishin Shobo, Seiwa Shoten Co., Ltd., Igaku-shoin Ltd., Chugai Igakusha and Sentan Igakusha, all outside the submitted work. All other authors declare no competing interests. No funder had any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.
For livestock production systems to play a positive role in global food security, the balance between their benefits and disbenefits to society must be appropriately managed. Based on the evidence provided by field-scale randomised controlled trials around the world, this debate has traditionally centred on the concept of economic-environmental trade-offs, of which existence is theoretically assured when resource allocation is perfect on the farm. Recent research conducted on commercial farms indicates, however, that the economic-environmental nexus is not nearly as straightforward in the real world, with environmental performances of enterprises often positively correlated with their economic profitability. Using high-resolution primary data from the North Wyke Farm Platform, an intensively instrumented farm-scale ruminant research facility located in southwest United Kingdom, this paper proposes a novel, information-driven approach to carry out comprehensive assessments of economic-environmental trade-offs inherent within pasture-based cattle and sheep production systems. The results of a data-mining exercise suggest that a potentially systematic interaction exists between ‘soil health’, ecological surroundings and livestock grazing, whereby a higher level of soil organic carbon (SOC) stock is associated with a better animal performance and less nutrient losses into watercourses, and a higher stocking density with greater botanical diversity and elevated SOC. We contend that a combination of farming system-wide trials and environmental instrumentation provides an ideal setting for enrolling scientifically sound and biologically informative metrics for agricultural sustainability, through which agricultural producers could obtain guidance to manage soils, water, pasture and livestock in an economically and environmentally acceptable manner. Priority areas for future farm-scale research to ensure long-term sustainability are also discussed.
In the proceedings of this, and of several recent close binary conferences, there have been several contributions describing smoothed particle hydrodynamics simulations of accretion disks. It is opposite therefore to review the numerical scheme itself with emphasis on its advantages for disk modelling, and the methods used for modelling viscous processes.
Partisan identification is a fundamental force in individual and mass political behavior around the world. Informed by scholarship on human sociality, coalitional psychology, and group behavior, this research argues that partisan identification, like many other group-based behaviors, is influenced by forces of evolution. If correct, then party identifiers should exhibit adaptive behaviors when making group-related political decisions. The authors test this assertion with citizen assessments of the relative physical formidability of competing leaders, an important adaptive factor in leader evaluations. Using original and novel data collected during the contextually different 2008 and 2012 U.S. presidential elections, as well as two distinct measures obtained during both elections, this article presents evidence that partisans overestimate the physical stature of the presidential candidate of their own party compared with the stature of the candidate of the opposition party. These findings suggest that the power of party identification on political behavior may be attributable to the fact that modern political parties address problems similar to the problems groups faced in human ancestral times.
Enteric pathogens are commonly known to be transmitted through food or water; however, contact with animals is another important transmission route. This study estimated the annual burden of illness attributable to animal contact for eight enteric pathogens in Canada. Using data from a Canadian expert elicitation on transmission routes, the proportion of enteric illnesses attributable to animal contact was estimated for each pathogen to estimate the annual number of illnesses, hospitalizations and deaths in Canada. For each estimate, a mean and probability intervals were generated. Of all illnesses caused by these eight pathogens, 16% were estimated attributable to animal contact. This estimate translates to 86 000 (31 000–166 000) illnesses, 488 (186–890) hospitalizations and 12 (2–28) deaths annually for the eight pathogens combined. Campylobacter spp. is the leading cause of illnesses annually, with an estimated 38 000 (14 000–71 000) illnesses occurring each year, followed by non-typhoidal Salmonella spp. (17 000, 6000–32 000). The majority of hospitalizations were attributable to non-typhoidal Salmonella spp. (36%) and Campylobacter spp. (31%). Non-typhoidal Salmonella spp. (28%) and Listeria monocytogenes (31%) were responsible for the majority of the estimated deaths. These results identify farm animal and pet/pet food exposure as key pathways of transmission for several pathogens. The estimated burden of illness associated with animal contact is substantial.
Clover based silages offer an opportunity for both conventional and organic upland producers to add value and improve the marketability pattern of organic hill and upland lambs. The objective of this study was to examine the performance of weaned hill lambs finished on contrasting clover based silages (SIL) supplemented with organic concentrates (CONC) containing varying ratios of wheat and beans.
Assessment of the quality characteristics of meat is time consuming and, due to the heterogeneity of muscle tissue, is subject to considerable variability. A cheap, fast, accurate and non-destructive method of assessment of meat with the potential to predict subsequent quality, would be useful to the meat industry. Near infra red spectroscopy (NIRS) offers this potential for rapid quality assessment and has been shown to be a valuble tool in the evaluation of a variety of meats (Cozzolino et al 1996)
Twenty beef bulls were selected from a commercial herd. Ten bulls (group US) were fed a standard barley-based ration consisting of (g kg–1 DM) barley, 900; GFS Beef 34 protein pellets, 100. Ten bulls (group S) were fed an identical ration supplemented with α-tocopherol acetate (ATA). The average daily intake of these diets was 10 kg DM head-1 d-1 over 100 days prior to slaughter.
A range of endophenotypes characterise psychosis, however there has been limited work understanding if and how they are inter-related.
This multi-centre study includes 8754 participants: 2212 people with a psychotic disorder, 1487 unaffected relatives of probands, and 5055 healthy controls. We investigated cognition [digit span (N = 3127), block design (N = 5491), and the Rey Auditory Verbal Learning Test (N = 3543)], electrophysiology [P300 amplitude and latency (N = 1102)], and neuroanatomy [lateral ventricular volume (N = 1721)]. We used linear regression to assess the interrelationships between endophenotypes.
The P300 amplitude and latency were not associated (regression coef. −0.06, 95% CI −0.12 to 0.01, p = 0.060), and P300 amplitude was positively associated with block design (coef. 0.19, 95% CI 0.10–0.28, p < 0.001). There was no evidence of associations between lateral ventricular volume and the other measures (all p > 0.38). All the cognitive endophenotypes were associated with each other in the expected directions (all p < 0.001). Lastly, the relationships between pairs of endophenotypes were consistent in all three participant groups, differing for some of the cognitive pairings only in the strengths of the relationships.
The P300 amplitude and latency are independent endophenotypes; the former indexing spatial visualisation and working memory, and the latter is hypothesised to index basic processing speed. Individuals with psychotic illnesses, their unaffected relatives, and healthy controls all show similar patterns of associations between endophenotypes, endorsing the theory of a continuum of psychosis liability across the population.
We have developed a new numerical technique for simulating dusty-gas flows. Our code incorporates gas hydrodynamics, self-gravity and dust drag to follow the dynamical evolution of a dusty-gas medium. We have incorporated several descriptions for the drag between gas and dust phases and can model flows with submillimetre, centimetre and metre size “dust”. We present calculations run on the APAC1 supercomputer following the evolution of the dust distribution in the pre-solar nebula.
The association between cigarette smoking and psychosis remains unexplained, but could relate to causal effects in both directions, confounding by socioeconomic factors, such as ethnicity, or use of other substances, including cannabis. Few studies have evaluated the association between cigarettes and psychotic experiences (PEs) in diverse, inner-city populations, or relationships with number of cigarettes consumed.
We assessed associations and dose–response relationships between cigarette smoking and PEs in a cross-sectional survey of household residents (n = 1680) in South East London, using logistic regression to adjust for cannabis use, other illicit substances, and socioeconomic factors, including ethnicity.
We found association between any PEs and daily cigarette smoking, which remained following adjustment for age, gender, ethnicity, cannabis and use of illicit stimulant drugs (fully adjusted odds ratio 1.47, 95% confidence interval 1.01–2.15). Fully adjusted estimates for the association, and with number of PEs, increased with number of cigarettes smoked daily, implying a dose–response effect (p = 0.001 and <0.001, respectively). Odds of reporting any PEs in ex-smokers were similar to never-smokers.
In this diverse epidemiological sample, association between smoking and PEs was not explained by confounders such as cannabis or illicit drugs. Daily cigarette consumption showed a dose–response relationship with the odds of reporting PEs, and of reporting a greater number of PEs. There was no difference in odds of reporting PEs between ex-smokers and never-smokers, raising the possibility that the increase in PEs associated with smoking may be reversible.