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Both blood- and milk-based biomarkers have been analysed for decades in research settings, although often only in one herd, and without focus on the variation in the biomarkers that are specifically related to herd or diet. Biomarkers can be used to detect physiological imbalance and disease risk and may have a role in precision livestock farming (PLF). For use in PLF, it is important to quantify normal variation in specific biomarkers and the source of this variation. The objective of this study was to estimate the between- and within-herd variation in a number of blood metabolites (β-hydroxybutyrate (BHB), non-esterified fatty acids, glucose and serum IGF-1), milk metabolites (free glucose, glucose-6-phosphate, urea, isocitrate, BHB and uric acid), milk enzymes (lactate dehydrogenase and N-acetyl-β-D-glucosaminidase (NAGase)) and composite indicators for metabolic imbalances (Physiological Imbalance-index and energy balance), to help facilitate their adoption within PLF. Blood and milk were sampled from 234 Holstein dairy cows from 6 experimental herds, each in a different European country, and offered a total of 10 different diets. Blood was sampled on 2 occasions at approximately 14 days-in-milk (DIM) and 35 DIM. Milk samples were collected twice weekly (in total 2750 samples) from DIM 1 to 50. Multilevel random regression models were used to estimate the variance components and to calculate the intraclass correlations (ICCs). The ICCs for the milk metabolites, when adjusted for parity and DIM at sampling, demonstrated that between 12% (glucose-6-phosphate) and 46% (urea) of the variation in the metabolites’ levels could be associated with the herd-diet combination. Intraclass Correlations related to the herd-diet combination were generally higher for blood metabolites, from 17% (cholesterol) to approximately 46% (BHB and urea). The high ICCs for urea suggest that this biomarker can be used for monitoring on herd level. The low variance within cow for NAGase indicates that few samples would be needed to describe the status and potentially a general reference value could be used. The low ICC for most of the biomarkers and larger within cow variation emphasises that multiple samples would be needed - most likely on the individual cows - for making the biomarkers useful for monitoring. The majority of biomarkers were influenced by parity and DIM which indicate that these should be accounted for if the biomarker should be used for monitoring.
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.
Unbalanced metabolic status in the weeks after calving predisposes dairy cows to metabolic and infectious diseases. Blood glucose, IGF-I, non-esterified fatty acids (NEFA) and β-hydroxybutyrate (BHB) are used as indicators of the metabolic status of cows. This work aims to (1) evaluate the potential of milk mid-IR spectra to predict these blood components individually and (2) to evaluate the possibility of predicting the metabolic status of cows based on the clustering of these blood components. Blood samples were collected from 241 Holstein cows on six experimental farms, at days 14 and 35 after calving. Blood samples were analyzed by reference analysis and metabolic status was defined by k-means clustering (k=3) based on the four blood components. Milk mid-IR analyses were undertaken on different instruments and the spectra were harmonized into a common standardized format. Quantitative models predicting blood components were developed using partial least squares regression and discriminant models aiming to differentiate the metabolic status were developed with partial least squares discriminant analysis. Cross-validations were performed for both quantitative and discriminant models using four subsets randomly constituted. Blood glucose, IGF-I, NEFA and BHB were predicted with respective R2 of calibration of 0.55, 0.69, 0.49 and 0.77, and R2 of cross-validation of 0.44, 0.61, 0.39 and 0.70. Although these models were not able to provide precise quantitative values, they allow for screening of individual milk samples for high or low values. The clustering methodology led to the sharing out of the data set into three groups of cows representing healthy, moderately impacted and imbalanced metabolic status. The discriminant models allow to fairly classify the three groups, with a global percentage of correct classification up to 74%. When discriminating the cows with imbalanced metabolic status from cows with healthy and moderately impacted metabolic status, the models were able to distinguish imbalanced group with a global percentage of correct classification up to 92%. The performances were satisfactory considering the variables are not present in milk, and consequently predicted indirectly. This work showed the potential of milk mid-IR analysis to provide new metabolic status indicators based on individual blood components or a combination of these variables into a global status. Models have been developed within a standardized spectral format, and although robustness should preferably be improved with additional data integrating different geographic regions, diets and breeds, they constitute rapid, cost-effective and large-scale tools for management and breeding of dairy cows.
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.
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.
Our previous work revealed substantial heterogeneity in the cognitive profile of bipolar disorder (BD) due to the presence of three underlying cognitive subgroups characterized as: globally impaired, selectively impaired, or cognitively intact. In an effort to determine whether these subgroups are differentially related to genetic risk for the illness, we investigated whether cognitive deficits were more pronounced in unaffected siblings (UAS) of BD probands within identified clusters.
Cluster analysis was used to identify cognitive clusters in BD (N = 60). UAS (N = 49) were classified into groups according to their proband sibling's cluster assignment; comparisons were made across all clusters and healthy controls (HCs; N = 71).
Three cognitive clusters in BD emerged: a globally impaired (36.7%), a selectively impaired (30%), and a cognitively intact cluster (33.3%). UAS showed a qualitatively similar pattern to their BD siblings; UAS of the globally impaired BD cluster showed verbal memory and general cognitive impairments relative to HCs. In contrast, UAS of the other two clusters did not differ from HCs.
This study corroborates findings from prior work regarding the presence of cognitive heterogeneity in BD. UAS of subjects in the globally impaired BD cluster presented with a qualitatively similar cognitive profile to their siblings and performed worse than all other BD clusters and UAS groups. This suggests that inherited risk factors may be contributing to cognitive deficits more notably in one subgroup of patients with BD, pointing toward differential causes of cognitive deficits in discrete subgroups of patients with the disorder.
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.
The treatment of traumatic tympanic membrane perforations varies in different investigations, ranging from observation to early surgical repair. The present study aimed to focus on the closure rate and the closure time in a group of patients treated with a watchful waiting policy.
The study comprised 133 consecutive patients with a total of 137 perforations. Data were evaluated in terms of aetiology, location and size of perforation, audiometric findings, closure rate, and closure time.
The overall closure rate was 97 per cent. For patients with a known closure time within three months, the median closure time was between three and four weeks. The probability of spontaneous closure over time was further analysed with Kaplan–Meier plots, for those perforations with known closure times and for all perforations including those with unknown closure times. Perforation size was the only significant determining factor for closure time.
Small perforations had a high probability of spontaneous closure within three to four weeks, justifying a watchful waiting policy. Larger uncomplicated perforations might warrant early surgical repair, depending on the patient's needs and the availability of surgery.
Radiometric ages for undated parts of the volcanic succession and intrusions in West Greenland were obtained by the 40Ar–39Ar incremental heating method. Acceptable crystallization ages were obtained for 27 samples. Combined with published results the new data provide a volcanic stratigraphy correlatable throughout the Nuussuaq Basin. The thick onshore volcanic pile consists of four widespread formations: 62.5–61 Ma picrites (Vaigat Formation), 61–60 Ma depleted basalts (Maligât Formation and the Hellefisk-1 well), 60–58 Ma less-depleted basalts (Svartenhuk Formation) and 56–54 Ma enriched basalts (Naqerloq Formation). Two local successions comprise 53.5 Ma alkali basalts (Erqua Formation) and 38.7 Ma transitional basalts (Talerua Member). A central volcano developed on Ubekendt Ejland, leading to the Sarqâta qáqâ gabbro-granophyre intrusion at 57–55 Ma. Pre-break-up volcanism took place further south as early as 64–63 Ma. The offshore volcanic succession most probably comprises the known onshore succession plus some younger lavas. The change in spreading direction near the Paleocene–Eocene boundary took place west of the Nuussuaq Basin c. 56.2 Ma. Some tectonomagmatic events are correlatable across the entire North Atlantic Igneous Province. A quiescent 58–56 Ma period correlates with similar periods in East Greenland and the Faroes, and the Naqerloq Formation is coeval with the Eocene basalts in East Greenland. The Paleocene and Eocene tholeiitic basalts are distinguishable chemically; in early Eocene time, mantle typical of the Iceland plume seems to have extended beneath the whole West Greenland margin as well as the central East Greenland margin.
Two common approaches to identify subgroups of patients with bipolar disorder are clustering methodology (mixture analysis) based on the age of onset, and a birth cohort analysis. This study investigates if a birth cohort effect will influence the results of clustering on the age of onset, using a large, international database.
The database includes 4037 patients with a diagnosis of bipolar I disorder, previously collected at 36 collection sites in 23 countries. Generalized estimating equations (GEE) were used to adjust the data for country median age, and in some models, birth cohort. Model-based clustering (mixture analysis) was then performed on the age of onset data using the residuals. Clinical variables in subgroups were compared.
There was a strong birth cohort effect. Without adjusting for the birth cohort, three subgroups were found by clustering. After adjusting for the birth cohort or when considering only those born after 1959, two subgroups were found. With results of either two or three subgroups, the youngest subgroup was more likely to have a family history of mood disorders and a first episode with depressed polarity. However, without adjusting for birth cohort (three subgroups), family history and polarity of the first episode could not be distinguished between the middle and oldest subgroups.
These results using international data confirm prior findings using single country data, that there are subgroups of bipolar I disorder based on the age of onset, and that there is a birth cohort effect. Including the birth cohort adjustment altered the number and characteristics of subgroups detected when clustering by age of onset. Further investigation is needed to determine if combining both approaches will identify subgroups that are more useful for research.
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.
A total of 3200 milk samples from Holstein and Jersey cows were analysed for free glucose and glucose-6-phosphate (G6P) by an enzymatic-fluorometric method that requires no pre-treatment. The cows were primiparous as well as multiparous, and samples were taken throughout the entire lactation period. In addition, lactose, protein, fat, citrate and β-hydroxybutyrate were determined and comparisons between these variables were made. Data were analysed using GLM model for the effect of parity, breed, time from last milking and stage of lactation on variations in parameters in milk. Pearson’s correlations were generated between milk variables. P<0.05 was considered significant. Concentration of free glucose and G6P were on average 331 and 81 μM, respectively. Time from last milking (stay in the gland cistern) did not increase the concentration of these monosaccharides, indicating that they are not hydrolysis product from lactose post secretion, but rather reflecting the energy status of the mammary epithelial cells pre-secretion. Wide variation in range of these metabolites, that is, from 90 to 630 μM and 5 to 324 μM, for glucose and G6P, respectively, was observed. During the first 21 weeks in milk, free glucose increased whereas G6P decreased. Concentration of free glucose in milk is greater for primiparous than multiparous cows and greater for Holstein than Jersey cows. Concentration of G6P was not affected by parity or breed. The use of free glucose and G6P as indicators of physiological conditions and risk of disease is warranted for use as potential biomarkers for in-line surveillance systems on-farm.
A congenital heart defect (CHD) can increase the risk of mental health problems in affected children and their parents. The extent to which risk factors for these problems are shared in families or are specific to the individual family member is unclear.
Prospective data from the Norwegian Mother and Child Cohort Study (MoBa; n = 93 009) were linked with a nationwide CHD registry, and 408 children with CHD were identified. Mothers' reports on child internalizing problems and their own distress were assessed by questionnaires at child ages 6, 18 and 36 months. A structural model was applied to distinguish between familial (shared) factors and individual-specific factors for mental health problems.
CHD was a substantial risk factor for problems in children and their mothers at all time points. CHD contributed on average 31% and 39% to the variance in children's and mothers' problems respectively. Both shared familial and individual-specific factors unique to CHD families contributed to risk for mental health problems. Whereas individual-specific risk factors contributed to the stability of problems in mothers, the effect of these factors lasted only a short time in children. Mutual influences over time were found between the mother's and the child's mental health at 18 and 36 months.
The burden of CHD in a child is shared between family members but is also specific to the individual. This study points to a need for both an individual and a family-based approach to provide psychological support to children with CHD and their parents.
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.
The junction formation when Cu(InGa)Se2 is deposited onto ZnO in a superstrate configuration (glass/window/buffer/Cu(InGa)Se2/contact) is investigated by x-ray photoelectron spectroscopy and analysis of device behavior. When Cu(InGa)Se2 is deposited on ZnO, a Ga2O3 layer is formed at the interface. Approaches to avoid the formation of this unfavorable interlayer are investigated. This includes modifications of the process to reduce the thermal load during deposition and improvement of the thermal stability of the ZnO buffer layer. It was demonstrated that both lowering of the substrate deposition temperature and deposition of the ZnO buffer layer at elevated temperature limits the Ga2O3 formation. The presence of Ga2O3 at the junction does affect the device behavior, resulting in a kink in JV curves measured under illumination. This behavior is absent in devices with limited Ga2O3 formation.