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To assess the prevalence of prediabetes and metabolic abnormalities among overweight or obese clozapine- or olanzapine-treated schizophrenia patients, and to identify characteristics of the schizophrenia group with prediabetes.
A cross-sectional study assessing the presence of prediabetes and metabolic abnormalities in schizophrenia clozapine- or olanzapine-treated patients with a body mass index (BMI) ≥27 kg/m2. Procedures were part of the screening process for a randomized, placebo-controlled trial evaluating liraglutide vs placebo for improving glucose tolerance. For comparison, an age-, sex-, and BMI-matched healthy control group without psychiatric illness and prediabetes was included. Prediabetes was defined as elevated fasting plasma glucose and/or impaired glucose tolerance and/or elevated glycated hemoglobin A1c.
Among 145 schizophrenia patients (age = 42.1 years; males = 59.3%) on clozapine or olanzapine (clozapine/olanzapine/both: 73.8%/24.1%/2.1%), prediabetes was present in 69.7% (101 out of 145). While schizophrenia patients with and without prediabetes did not differ regarding demographic, illness, or antipsychotic treatment variables, metabolic abnormalities (waist circumference: 116.7±13.7 vs 110.1±13.6 cm, P = 0.007; triglycerides: 2.3±1.4 vs 1.6±0.9 mmol/L, P = 0.0004) and metabolic syndrome (76.2% vs 40.9%, P<0.0001) were significantly more pronounced in schizophrenia patients with vs without prediabetes. The age-, sex-, and BMI-matched healthy controls had significantly better glucose tolerance compared to both groups of patients with schizophrenia. The healthy controls also had higher levels of high-density lipoprotein compared to patients with schizophrenia and prediabetes.
Prediabetes and metabolic abnormalities were highly prevalent among the clozapine- and olanzapine-treated patients with schizophrenia, putting these patients at great risk for later type 2 diabetes and cardiovascular disease. These results stress the importance of identifying and adequately treating prediabetes and metabolic abnormalities among clozapine- and olanzapine-treated patients with schizophrenia.
To assess variability in antimicrobial use and associations with infection testing in pediatric ventilator-associated events (VAEs).
Descriptive retrospective cohort with nested case-control study.
Pediatric intensive care units (PICUs), cardiac intensive care units (CICUs), and neonatal intensive care units (NICUs) in 6 US hospitals.
Children≤18 years ventilated for≥1 calendar day.
We identified patients with pediatric ventilator-associated conditions (VACs), pediatric VACs with antimicrobial use for≥4 days (AVACs), and possible ventilator-associated pneumonia (PVAP, defined as pediatric AVAC with a positive respiratory diagnostic test) according to previously proposed criteria.
Among 9,025 ventilated children, we identified 192 VAC cases, 43 in CICUs, 70 in PICUs, and 79 in NICUs. AVAC criteria were met in 79 VAC cases (41%) (58% CICU; 51% PICU; and 23% NICU), and varied by hospital (CICU, 20–67%; PICU, 0–70%; and NICU, 0–43%). Type and duration of AVAC antimicrobials varied by ICU type. AVAC cases in CICUs and PICUs received broad-spectrum antimicrobials more often than those in NICUs. Among AVAC cases, 39% had respiratory infection diagnostic testing performed; PVAP was identified in 15 VAC cases. Also, among AVAC cases, 73% had no associated positive respiratory or nonrespiratory diagnostic test.
Antimicrobial use is common in pediatric VAC, with variability in spectrum and duration of antimicrobials within hospitals and across ICU types, while PVAP is uncommon. Prolonged antimicrobial use despite low rates of PVAP or positive laboratory testing for infection suggests that AVAC may provide a lever for antimicrobial stewardship programs to improve utilization.
Avian influenza virus (AIV) subtypes H5 and H7 can infect poultry causing low pathogenicity (LP) AI, but these LPAIVs may mutate to highly pathogenic AIV in chickens or turkeys causing high mortality, hence H5/H7 subtypes demand statutory intervention. Serological surveillance in the European Union provides evidence of H5/H7 AIV exposure in apparently healthy poultry. To identify the most sensitive screening method as the first step in an algorithm to provide evidence of H5/H7 AIV infection, the standard approach of H5/H7 antibody testing by haemagglutination inhibition (HI) was compared with an ELISA, which detects antibodies to all subtypes. Sera (n = 1055) from 74 commercial chicken flocks were tested by both methods. A Bayesian approach served to estimate diagnostic test sensitivities and specificities, without assuming any ‘gold standard’. Sensitivity and specificity of the ELISA was 97% and 99.8%, and for H5/H7 HI 43% and 99.8%, respectively, although H5/H7 HI sensitivity varied considerably between infected flocks. ELISA therefore provides superior sensitivity for the screening of chicken flocks as part of an algorithm, which subsequently utilises H5/H7 HI to identify infection by these two subtypes. With the calculated sensitivity and specificity, testing nine sera per flock is sufficient to detect a flock seroprevalence of 30% with 95% probability.
We performed spectroscopy of globular clusters associated with NGC 1399 and measured radial velocities of about 450 clusters, the largest sample ever obtained for dynamical studies. In this progress report, we present the sample and the first preliminary results. Red and blue clusters have slightly different velocity dispersions in accordance with their different density profiles in the case of a spherical and isotropic model. We then measure a constant circular velocity of 422 ± 20 km/s, which agrees well with that of the inner luminous component.
Maternal exposures to fever and infections in pregnancy have been linked to subsequent psychiatric morbidity in the child. This study examined whether fever and common infections in pregnancy were associated with psychosis-like experiences (PLEs) in the child.
A longitudinal study of 46 184 children who participated in the 11-year follow-up of the Danish National Birth Cohort was conducted. Pregnant women were enrolled between 1996 and 2002 and information on fever, genitourinary infections, respiratory tract infection, and influenza-like illness during pregnancy was prospectively collected in two interviews during pregnancy. PLEs were assessed using the seven-item Adolescent Psychotic-Like Symptom Screener in a web-based questionnaire completed by the children themselves at age 11.
PLEs were reported among 11% of the children. Multinomial logistic regression models with probability weights to adjust for potential selection bias due to attrition suggested that maternal fever, genitourinary infections and influenza-like illness were associated with a weak to moderate increased risk of subclinical psychosis-like symptoms in the offspring, whereas respiratory tract infections were not. No clear pattern was observed between the strengths of the associations and the timing of exposure, or the type of psychosis-like symptom.
In this study, maternal exposures to fevers and common infections in pregnancy were generally associated with a subtle excess risk of PLEs in the child. A more pronounced association was found for influenza-like illness under an a priori definition, leaving open the possibility that certain kinds of infections may constitute important risk factors.
A transverse profile of velocity was measured across Ice Stream B, West Antarctica, in order to determine the role of the margins in the force balance of an active ice stream. The profile extended from near the ice-stream center line, through a marginal shear zone and on to the slow-moving ice sheet. The velocity profile exhibits a high degree of shear deformation within a marginal zone, where intense, chaotic crevassing occurs. Detailed analysis of the profile, using analytical and numerical models of ice flow, leads to the following conclusions regarding the roles of the bed and the margins in ice-stream dynamics:
(i)The overall resistive drag on the ice stream is partitioned nearly equally between the margins and the bed and, thus, both are important in the force balance of the ice stream.
(ii)The ice within the chaotic zone must be about 10 times softer than the ice in the central part of the ice stream.
(iii)The average basal shear stress is 0.06 × 105 Pa. This implies that the entire bed cannot be blanketed by the weak, deformable till observed by Engelhardt and others (1990) near the center of the ice stream — there must be regions of increased basal drag.
(iv)High strain rates and shear stresses in the marginal zones indicate that strain heating in the margins may be significant.
While the exact quantitative values leading to these conclusions are somewhat model and location-dependent, the overall conclusions are robust. As such, they are likely to have importance for ice-stream dynamics in general.
Adult ventilator-associated event (VAE) definitions include ventilator-associated conditions (VAC) and subcategories for infection-related ventilator-associated complications (IVAC) and possible ventilator-associated pneumonia (PVAP). We explored these definitions for children.
Pediatric, cardiac, or neonatal intensive care units (ICUs) in 6 US hospitals
Patients ≤18 years old ventilated for ≥1 day
We identified patients with pediatric VAC based on previously proposed criteria. We applied adult temperature, white blood cell count, antibiotic, and culture criteria for IVAC and PVAP to these patients. We matched pediatric VAC patients with controls and evaluated associations with adverse outcomes using Cox proportional hazards models.
In total, 233 pediatric VACs (12,167 ventilation episodes) were identified. In the cardiac ICU (CICU), 62.5% of VACs met adult IVAC criteria; in the pediatric ICU (PICU), 54.2% of VACs met adult IVAC criteria; and in the neonatal ICU (NICU), 20.2% of VACs met adult IVAC criteria. Most patients had abnormal white blood cell counts and temperatures; we therefore recommend simplifying surveillance by focusing on “pediatric VAC with antimicrobial use” (pediatric AVAC). Pediatric AVAC with a positive respiratory diagnostic test (“pediatric PVAP”) occurred in 8.9% of VACs in the CICU, 13.3% of VACs in the PICU, and 4.3% of VACs in the NICU. Hospital mortality was increased, and hospital and ICU length of stay and duration of ventilation were prolonged among all pediatric VAE subsets compared with controls.
We propose pediatric AVAC for surveillance related to antimicrobial use, with pediatric PVAP as a subset of AVAC. Studies on generalizability and responsiveness of these metrics to quality improvement initiatives are needed, as are studies to determine whether lower pediatric VAE rates are associated with improvements in other outcomes.
Psychosocial therapy after deliberate self-harm might be associated with reduced risk of specific causes of death.
In this matched cohort study, we included patients, who after an episode of deliberate self-harm received psychosocial therapy at a Suicide Prevention Clinic in Denmark between 1992 and 2010. We used propensity score matching in a 1:3 ratio to select a comparison group from 59 046 individuals who received standard care. National Danish registers supplied data on specific causes of death over a 20-year follow-up period.
At the end of follow-up, 391 (6.9%) of 5678 patients in the psychosocial therapy group had died, compared with 1736 (10.2%) of 17 034 patients in the matched comparison group. Lower odds ratios of dying by mental or behavioural disorders [0.54, 95% confidence interval (CI) 0.37–0.79], alcohol-related causes (0.63, 95% CI 0.50–0.80) and other diseases and medical conditions (0.61, 95% CI 0.49–0.77) were noted in the psychosocial therapy group. Also, we found a reduced risk of dying by suicide as well as other external causes, however, not by neoplasms and circulatory system diseases. Numbers needed to treat were 212.9 (95% CI 139.5–448.4) for mental or behavioural disorders as a cause of death, 111.1 (95% CI 79.2–210.5) for alcohol-related causes and 96.8 (95% CI 69.1–161.8) for other diseases and medical conditions.
Our findings indicate that psychosocial therapy after deliberate self-harm might reduce long-term risk of death from select medical conditions and external causes. These promising results should be tested in a randomized design.
Auditory verbal hallucinations (AVH) are common during development and may arise due to dysregulation in top-down processing of sensory input. This study was designed to examine the frequency and correlates of speech illusions measured using the White Noise (WN) task in children from the general population. Associations between speech illusions and putative risk factors for psychotic disorder and negative affect were examined.
A total of 1486 children aged 11–12 years of the Copenhagen Child Cohort 2000 were examined with the WN task. Psychotic experiences and negative affect were determined using the Kiddie-SADS-PL. Register data described family history of mental disorders. Exaggerated Theory of Mind functioning (hyper-ToM) was measured by the ToM Storybook Frederik.
A total of 145 (10%) children experienced speech illusions (hearing speech in the absence of speech stimuli), of which 102 (70%) experienced illusions perceived by the child as positive or negative (affectively salient). Experiencing hallucinations during the last month was associated with affectively salient speech illusions in the WN task [general cognitive ability: adjusted odds ratio (aOR) 2.01, 95% confidence interval (CI) 1.03–3.93]. Negative affect, both last month and lifetime, was also associated with affectively salient speech illusions (aOR 2.01, 95% CI 1.05–3.83 and aOR 1.79, 95% CI 1.11–2.89, respectively). Speech illusions were not associated with delusions, hyper-ToM or family history of mental disorders.
Speech illusions were elicited in typically developing children in a WN-test paradigm, and point to an affective pathway to AVH mediated by dysregulation in top-down processing of sensory input.
Layers of volcanic ash, or tephra form widespread chronostratigraphic marker horizons which are important because of their distinctive characteristics and rapid deposition over large areas. Absolute dating of prehistoric layers effectively depends upon 14C analysis. We focus here on Icelandic tephra layers at both proximal and distal sites and consider three strategies to obtain age estimates: 1) the conventional dating of individual profiles; 2) high-precision multisample techniques or “wiggle-matching” using stratigraphic sequences of peat; and 3) a combination of routine analyses from multiple sites. The first approach is illustrated by the dating of a peat profile in Scotland containing tephra from the ad 1510 eruption of Hekla. This produced a 14C age compatible with ad 1510, independently derived by geochemical correlation with historically dated Icelandic deposits. In addition, the ca. 2100 bp date for the Glen Garry tephra in Scotland, determined by a series of dates on a peat profile in Caithness, is supported by its stratigraphic position within 14C dated profiles in Sutherland, and may be applied over a very large area of Scotland. More precise dates for individual tephras may be produced by “wiggle-matching”, although this approach could be biased by changes in peat-bog stratigraphy close to the position of the tephra fall. As appropriate sites for “wiggle-match” exercises may be found only for a few Icelandic tephras, we also consider the results of a spatial approach to 14C dating tephra layers. We combined dates on peat underlying the same layer at several sites to estimate the age of the tephra: 3826 ± 12 bp for the Hekla-4 tephra and 2879 ± 34 bp for the Hekla-3 tephra. This approach is effective in terms of cost, the need for widespread applicability to Icelandic tephra stratigraphy and the production of ages of a useful resolution. We stress the need for accurate identification of tephra deposits without which the conclusions drawn from subsequent 14C dating will be fundamentally flawed.
The objective of the current experiment was to compare the effects of supplementing mid-lactation dairy cows with all-rac-α-tocopheryl acetate (SyntvE), RRR-α-tocopheryl acetate (NatvE) or seaweed meal (Seaweed) in the presence of a Control group (no supplemental vitamin E or seaweed) on the concentration of α-tocopherol in plasma and milk, and antibody response following immunization. The hypothesis was that supplementation of dairy cows with vitamin E, regardless of its form, would increase plasma and milk α-tocopherol compared to the control diet and this incremental response would be bigger with NatvE than SyntvE. Furthermore, it was hypothesized that vitamin E, regardless of its form, will provide an improved adaptive immune response to immunization than the Control diet, and cows supplemented with Seaweed meal would produce better adaptive immune response following immunization than cows in the Control group. Twenty-four Norwegian Red (NR) dairy cows in their mid-lactation were allocated randomly to the four treatments in a replicated Latin square design. The cows were fed on a basal diet of silage and concentrate on top of which the experimental supplements were provided. Plasma and milk α-tocopherol concentrations were higher in NatvE and SyntvE groups than in the other two groups. The RRR-α-tocopherol stereoisomer was the predominant form (>0·86), in both plasma and milk, whereas the remaining part was largely made up of the other three 2R stereoisomers (RRS, RSR and RSS). In cows fed the Control, Seaweed and NatvE, the proportion of the RRR-α-tocopherol stereoisomer in plasma and milk constituted >0·97 of the total α-tocopherol. Mid-lactation NR dairy cows had higher than adequate levels of plasma α-tocopherol (9·99 mg/l) even when not supplemented with external source of vitamin E, suggesting that with a good quality silage these cows may not be at risk of vitamin E deficiency. Furthermore, the present study shows that dairy cows in mid to late lactation have preferential uptake of RRR stereoisomer of α-tocopherol compared with other stereoisomers. All cows responded well to immunization with different antigens, but there were no significant group effects of the diet on the immune response measured.
There is an increasing interest in pasture-based dairy systems in Europe, mainly because of increasing production costs for intensive dairying. Milk is a matrix of compounds that influence nutritional and manufacturing properties, many dependent on husbandry linked to pasture-based systems (increase in pasture intake, forage : concentrate ratio, clover inclusion in swards/silages and use of alternative dairy breeds). The present study investigated the impact of three grazing-based dairy systems with contrasting feeding intensity or reliance on pasture intakes (conventional high-intensity, low pasture intake [CH], organic medium-intensity, medium pasture intake [OM], conventional low-intensity, high pasture intake [CL]) on milk fatty acid (FA) profiles, protein composition and α-tocopherol and antioxidants concentrations. The proportion of animals of alternative breeds (e.g. Jersey) and crossbred cows in the herd increased with decreasing production intensity (CH < OM < CL). Milk constituents known to be beneficial for human health, such as vaccenic acid, rumenic acid, monounsaturated FA, polyunsaturated FA, antioxidants and caseins, were elevated with decreasing production intensity (CH < OM < CL), while less desirable saturated FA were lower, although not all differences between OM and CL were significant. Omega-3 FA were maximized under OM practices, primarily as a result of higher clover intake. Increases in pasture intake may explain the higher concentrations of desirable FA while increased use of crossbreed cows is likely to be responsible for higher total protein and casein content of milk; a combination of these two factors may explain increased antioxidant levels. The higher concentrations of vaccenic acid, rumenic acid, omega-3 FA, lutein, zeaxanthin, protein and casein in OM and CL milk were found over most sampling months and in both years, reinforcing the higher nutritional quality and manufacturing properties associated with milk from these systems. A switch to pasture-based dairy products would increase the intake of milk's beneficial compounds and reduce consumption of less desirable saturated FA.
Dairy products have previously been reported to be associated with beneficial effects on body weight and metabolic risk markers. Moreover, primary data from the Diet, Obesity and Genes (DiOGenes) study indicate a weight-maintaining effect of a high-protein–low-glycaemic index diet. The objective of the present study was to examine putative associations between consumption of dairy proteins and changes in body weight and metabolic risk markers after weight loss in obese and overweight adults. Results were based on secondary analyses of data obtained from overweight and obese adults who completed the DiOGenes study. The study consisted of an 8-week weight-loss phase and a 6-month weight-maintenance (WM) phase, where the subjects were given five different diets varying in protein content and glycaemic index. In the present study, data obtained from all the subjects were pooled. Dairy protein intake was estimated from 3 d dietary records at two time points (week 4 and week 26) during the WM phase. Body weight and metabolic risk markers were determined at baseline (week − 9 to − 11) and before and at the end of the WM phase (week 0 and week 26). Overall, no significant associations were found between consumption of dairy proteins and changes in body weight and metabolic risk markers. However, dairy protein intake tended to be negatively associated with body weight gain (P= 0·08; β = − 0·17), but this was not persistent when controlled for total protein intake, which indicates that dairy protein adds no additional effect to the effect of total protein. Therefore, the present study does not report that dairy proteins are more favourable than other proteins for body weight regulation.
Biohydrogenation of C18 fatty acids in the rumen of cows, from polyunsaturated and monounsaturated to saturated fatty acids, is lower on clover than on grass-based diets, which might result in increased levels of polyunsaturated fatty acids in the milk from clover-based diets affecting its nutritional properties. The effect of forage type on ruminal hydrogenation was investigated by in vitro incubation of feed samples in rumen fluid. Silages of red clover, white clover and perennial ryegrass harvested in spring growth and in third regrowth were used, resulting in six silages. Fatty acid content was analysed after 0, 2, 4, 6, 8 and 24 h of incubation to study the rate of hydrogenation of unsaturated C18 fatty acids. A dynamic mechanistic model was constructed and used to estimate the rate constants (k, h) of the hydrogenation assuming mass action-driven fluxes between the following pools of C18 fatty acids: C18:3 (linolenic acid), C18:2 (linoleic acid), C18:1 (mainly vaccenic acid) and C18:0 (stearic acid) as the end point. For kC18:1,C18:2 the estimated rate constants were 0.0685 (red clover), 0.0706 (white clover) and 0.0868 (ryegrass), and for kC18:1,C18:3 it was 0.0805 (red clover), 0.0765 (white clover) and 0.1022 (ryegrass). Type of forage had a significant effect on kC18:1,C18:2 (P < 0.05) and a tendency to effect kC18:1,C18:3 (P < 0.10), whereas growth had no effect on kC18:1,C18:2 or kC18:1,C18:3 (P > 0.10). Neither forage nor growth significantly affected kC18:0,C18:1, which was estimated to be 0.0504. Similar, but slightly higher, results were observed when calculating the rate of disappearance for linolenic and linoleic acid. This effect persists regardless of the harvest time and may be because of the presence of plant secondary metabolites that are able to inhibit lipolysis, which is required before hydrogenation of polyunsaturated fatty acids can begin.
The effective use of model-based formal methods in the development of complex embedded systems requires the integration of discrete-event models of controllers with continuous-time models of their environments. This paper proposes a new approach to the development of such combined models (co-models), in which an initial discrete-event model may include approximations of continuous-time behaviour that can subsequently be replaced by couplings to continuous-time models. An operational semantics of co-simulation allows the discrete and continuous models to run on their respective simulators and managed by a coordinating co-simulation engine. This permits the exploration of the composite co-model's behaviour in a range of operational scenarios. The approach has been realised using the Vienna Development Method (VDM) as the discrete-event formalism, and 20-sim as the continuous-time framework, and has been applied successfully to a case study based on the distributed controller for a personal transporter device.
Blood lipid response to a given dietary intervention could be determined by the effect of diet, gene variants or gene–diet interactions. The objective of the present study was to investigate whether variants in presumed nutrient-sensitive genes involved in lipid metabolism modified lipid profile after weight loss and in response to a given diet, among overweight European adults participating in the Diet Obesity and Genes study. By multiple linear regressions, 240 SNPs in twenty-four candidate genes were investigated for SNP main and SNP–diet interaction effects on total cholesterol, LDL-cholesterol, HDL-cholesterol and TAG after an 8-week low-energy diet (only main effect), and a 6-month ad libitum weight maintenance diet, with different contents of dietary protein or glycaemic index. After adjusting for multiple testing, a SNP–dietary protein interaction effect on TAG was identified for lipin 1 (LPIN1) rs4315495, with a decrease in TAG of − 0·26 mmol/l per A-allele/protein unit (95 % CI − 0·38, − 0·14, P= 0·000043). In conclusion, we investigated SNP–diet interactions for blood lipid profiles for 240 SNPs in twenty-four candidate genes, selected for their involvement in lipid metabolism pathways, and identified one significant interaction between LPIN1 rs4315495 and dietary protein for TAG concentration.
Numerous studies have shown that people adjust their intake directly to that of their eating companions. A potential explanation for this modelling effect is that the eating behaviour of others operates as an external eating cue that stimulates food intake. The present study explored whether this cue-reactive mechanism can account for modelling effects on intake. It was investigated whether attentional bias towards dynamic eating cues and impulsivity would influence the degree of modelling. Participants completed one individual session and one session in which an experimental confederate accompanied them. In the first session, eye movements were recorded as an index of attentional bias to dynamic eating cues. In addition, self-reported impulsivity and response inhibition were assessed. The second session employed a between-participants design with three experimental conditions in which participants were exposed to a same-sex confederate instructed to eat nothing, a low or a large amount of M&Ms. A total of eighty-five young women participated. The participants' self-reported impulsivity determined the occurrence of modelling; only low-impulsive women adjusted their intake to that of their eating companion. Attention towards eating cues and response inhibition, however, did not moderate modelling of food intake. The present study suggests that cue-reactive mechanisms may not underlie modelling of food intake. Instead, the results emphasise the importance of social norms in explaining modelling effects, whereas it is suggested that the degree of impulsivity may play a role in whether or not women adhere to the intake norms set by their eating companion.