To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure email@example.com
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
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 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.
Trauma and traumatic bereavement have well-known consequences for mental health, but little is known about long-term adjustment, particularly with respect to health-protective factors.
To assess the levels of anxiety/depression and perceived social support among the survivors and the bereaved 26 years after the Scandinavian Star ferry disaster compared with expected levels from the general population.
Anxiety/depression and social support were assessed in face-to-face interviews with the survivors and the bereaved (N = 165, response rate 58%). Expected scores were calculated for each participant based on the means and proportions for each age and gender combination from a general population sample. We computed the ratio between expected and observed scores, standardised mean differences with 95% confidence intervals and standardised effect sizes.
We found an elevated level of anxiety/depression symptoms in the victims (Mdiff = 0.28, 95% CI 0.18, 0.38; effect size 0.43, 95% CI 0.31, 0.55) and a significant excess of individuals with a clinically significant level of symptoms. The observed level of perceived social support was significantly lower than that expected (Mdiff = −0.57, 95% CI −0.70, −0.44; effect size −0.73, 95% CI −0.89, −0.57). This was the case for both survivors and those who were bereaved and for both men and women.
This study reveals that disaster survivors and the bereaved reported elevated levels of anxiety and depression symptoms 26 years after the event. They also reported a markedly reduced level of social support. Traumas and post-traumatic responses may thus cause lasting harm to interpersonal relationships.
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.
The aim of the present study was to investigate the associations between the habitual Ca intake and faecal fat and energy excretion as well as blood lipid profile in free-living normal-weight and overweight individuals. The participants were enrolled for an 8-d period where data from a 7-d diet registration (days 1–7), a 5-d faeces collection (days 3–7), a 2-d urine collection (days 5–7), and anthropometric measurements and a fasting blood sample (day 8) were collected. Analyses showed that dietary Ca intake (g/10 MJ per d) was positively associated with excretion of faecal fat (P = 0·004) and energy (P = 0·031) when adjusted for BMI, age, sex and intake of Ca-containing supplements. However, after adjustment for intake of fibre, the effect of Ca intake disappeared. Nevertheless, total cholesterol (CHOL) and LDL-CHOL concentrations were associated negatively with Ca intake (β −0·62 (95 % CI −0·96, −0·28) mmol/l, P < 0·001, and β −0·49 (95 % CI −0·78, −0·20) mmol/l, P = 0·001, respectively, per 1000 mg/10 MJ per d increase in Ca intake). In conclusion, incorporation of Ca-rich food products in a habitual diet was associated with reduced total CHOL and LDL-CHOL concentrations, which may lower the risk of CVD in the long term.
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.
Angiopoietin-like protein 4 (ANGPTL4) is a lipoprotein lipase inhibitor that is involved in lipid metabolism and angiogenesis. Animal studies have suggested that the ANGPTL4 protein is modulated by the gut microbiota, possibly through increased concentrations of SCFA, such as C4, found in whole-fat milk or as a result of fermentation of inulin. This study investigated whether a standardised diet either high in fat content or supplemented with inulin powder would increase plasma ANGPTL4 in overweight men and whether this increase was mediated through a compositional change of the gut microbiota. The study had a crossover design with three arms, where participants were given a standardised isoenergetic diet supplemented with inulin powder, whole-fat milk or water (control). Plasma and urine samples were collected before and after each intervention period. Faecal samples and adipose tissue biopsies were collected after each intervention period. The study included twenty-one participants of whom eighteen completed the study. The dietary interventions did not change ANGPTL4 plasma concentration, nor was plasma ANGPTL4 associated with plasma lipids, TAG or NEFA concentration. The relative abundance of bifidobacteria following the inulin diet was higher, compared with the control diet. However, the changes in microbiota were not associated with plasma ANGPTL4 and the overall composition of the microbiota did not change between the dietary periods. Although weight was maintained throughout the dietary periods, weight was negatively associated with plasma ANGPTL4 concentration. In the adipose tissue, ANGPTL4 expression was correlated with leptin expression, but not with hypoxia-inducible factor 1α (HIF-1α) expression.
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.