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Precise instrumental calibration is of crucial importance to 21-cm cosmology experiments. The Murchison Widefield Array’s (MWA) Phase II compact configuration offers us opportunities for both redundant calibration and sky-based calibration algorithms; using the two in tandem is a potential approach to mitigate calibration errors caused by inaccurate sky models. The MWA Epoch of Reionization (EoR) experiment targets three patches of the sky (dubbed EoR0, EoR1, and EoR2) with deep observations. Previous work in Li et al. (2018) and (2019) studied the effect of tandem calibration on the EoR0 field and found that it yielded no significant improvement in the power spectrum (PS) over sky-based calibration alone. In this work, we apply similar techniques to the EoR1 field and find a distinct result: the improvements in the PS from tandem calibration are significant. To understand this result, we analyse both the calibration solutions themselves and the effects on the PS over three nights of EoR1 observations. We conclude that the presence of the bright radio galaxy Fornax A in EoR1 degrades the performance of sky-based calibration, which in turn enables redundant calibration to have a larger impact. These results suggest that redundant calibration can indeed mitigate some level of model incompleteness error.
This study estimates the maximum price at which mesenchymal stem cell (MSC) therapy is deemed cost-effective for septic shock patients and identifies parameters that are most important in making treatment decisions.
We developed a probabilistic Markov model according to the sepsis care trajectory to simulate costs and quality-adjusted life years (QALYs) of septic shock patients receiving either MSC therapy or usual care over their lifetime. We calculated the therapeutic headroom by multiplying the gains attributable to MSCs with willingness-to-pay (WTP) threshold and derived the maximum reimbursable price (MRP) from the expected net monetary benefit and savings attributable to MSCs. We performed scenario analyses to assess the impact of changes to assumptions on the study findings. A value of information analysis is performed to identify parameters with greatest impact on the uncertainty around the cost-effectiveness of MSC therapy.
At a WTP threshold of $50,000 per QALY, the therapeutic headroom and MRP of MSC therapy were $20,941 and $16,748, respectively; these estimates increased with the larger WTP values and the greater impact of MSCs on in-hospital mortality and hospital discharge rates. The parameters with greatest information value were MSC's impact on in-hospital mortality and the baseline septic shock in-hospital mortality.
At a common WTP of $50,000/QALY, MSC therapy is deemed to be economically attractive if its unit cost does not exceed $16,748. This ceiling price can be increased to $101,450 if the therapy significantly reduces both in-hospital mortality and increases hospital discharge rates.
A growing body of research suggests that childhood adversities are associated with later psychosis, broadly defined. However, there remain several gaps and unanswered questions. Most studies are of low-level psychotic experiences and findings cannot necessarily be extrapolated to psychotic disorders. Further, few studies have examined the effects of more fine-grained dimensions of adversity such as type, timing and severity.
Using detailed data from the Childhood Adversity and Psychosis (CAPsy) study, we sought to address these gaps and examine in detail associations between a range of childhood adversities and psychotic disorder.
CAPsy is population-based first-episode psychosis case–control study in the UK. In a sample of 374 cases and 301 controls, we collected extensive data on childhood adversities, in particular household discord, various forms of abuse and bullying, and putative confounders, including family history of psychotic disorder, using validated, semi-structured instruments.
We found strong evidence that all forms of childhood adversity were associated with around a two- to fourfold increased odds of psychotic disorder and that exposure to multiple adversities was associated with a linear increase in odds. We further found that severe forms of adversity, i.e. involving threat, hostility and violence, were most strongly associated with increased odds of disorder. More tentatively, we found that some adversities (e.g. bullying, sexual abuse) were more strongly associated with psychotic disorder if first occurrence was in adolescence.
Our findings extend previous research on childhood adversity and suggest a degree of specificity for severe adversities involving threat, hostility and violence.
To disrupt cycles of health inequity, traceable to dietary inequities in the earliest stages of life, public health interventions should target improving nutritional wellbeing in preconception/pregnancy environments. This requires a deep engagement with pregnant/postpartum people (PPP) and their communities (including their health and social care providers, HSCP). We sought to understand the factors that influence diet during pregnancy from the perspectives of PPP and HSCP, and to outline intervention priorities.
We carried out thematic network analyses of transcripts from ten focus group discussions (FGD) and one stakeholder engagement meeting with PPP and HSCP in a Canadian city. Identified themes were developed into conceptual maps, highlighting local priorities for pregnancy nutrition and intervention development.
FGD and the stakeholder meeting were run in predominantly lower socioeconomic position (SEP) neighbourhoods in the sociodemographically diverse city of Hamilton, Canada.
All local, comprising twenty-two lower SEP PPP and forty-three HSCP.
Salient themes were resilience, resources, relationships and the embodied experience of pregnancy. Both PPP and HSCP underscored that socioeconomic-political forces operating at multiple levels largely determined the availability of individual and relational resources constraining diet during pregnancy. Intervention proposals focused on cultivating individual and community resilience to improve early-life nutritional environments. Participants called for better-integrated services, greater income supports and strengthened support programmes.
Hamilton stakeholders foregrounded social determinants of inequity as main factors influencing pregnancy diet. They further indicated a need to develop interventions that build resilience and redistribute resources at multiple levels, from the household to the state.
There is a need to develop feeding strategies to prevent the adverse effect of concentrate feeding in high-performance horses fed energy-dense diets aiming to maintain their health and welfare. The objective of this study is to determine the effect of a VistaEQ product containing 4% live yeast Saccharomyces cerevisiae (S. cerevisiae), with activity 5 × 108 colony-forming unit/g and fed 2 g/pony per day, on faecal microbial populations when supplemented with high-starch and high-fibre diets using Illumina next generation sequencing of the V3-V4 region of the 16S ribosomal RNA gene. The four treatments were allocated to eight mature Welsh section A pony geldings enrolled in a 4-period × 8 animal crossover design. Each 19-day experimental period consisted of an 18-day adaptation phase and a single collection day, followed by a 7-day wash out period. After DNA extraction from faeces and library preparation, α-diversity and linear discriminant analysis effect size were performed using 16S metagenomics pipeline in Quantitative Insights Into Microbial Ecology (QIIME™) and Galaxy/Hutlab. Differences between the groups were considered significant when linear discriminant analysis score was >2 corresponding to P < 0.05. The present study showed that S. cerevisiae used was able to induce positive changes in the equine microbiota when supplemented to a high-fibre diet: it increased relative abundance (RA) of Lachnospiraceae and Dehalobacteriaceae family members associated with a healthy core microbiome. Yeast supplementation also increased the RA of fibrolytic bacteria (Ruminococcus) when fed with a high-fibre diet and reduced the RA of lactate producing bacteria (Streptococcus) when a high-starch diet was fed. In addition, yeast increased the RA of acetic, succinic acid producing bacterial family (Succinivibrionaceae) and butyrate producing bacterial genus (Roseburia) when fed with high-starch and high-fibre diets, respectively. VistaEQ supplementation to equine diets can be potentially used to prevent acidosis and increase fibre digestibility. It may help to meet the energy requirements of performance horses while maintaining gut health.
Fibre is essential to maintain healthy gut; however, energy demands of performance horses can be too high to be met by forages alone. Yeast may support the function of cellulolytic bacteria to digest fibre. The aim of this work was to determine the effect of an oral supplement (VistaEQ) containing 4% live yeast on the in vitro and in vivo digestibility of high-starch (HS) and high-fibre diets (HF). Eight ponies were used in a 4 × 4 Latin square design consisting of 4- × 19-day periods and four diets: HF, HF + yeast (HFY), HS and HS + yeast (HSY). In vivo apparent digestibility (AD) was estimated using total collection technique, and faecal particle size was measured using NASCO digestive analyser. Faeces from the ponies were subsequently used as an inoculum in ANKOM RF gas production system to assess fermentation kinetics in vitro. Each module contained 1 g of feed substrate DM in the following combinations: 50% grass hay and 50% alfalfa (HF_50 : 50) or concentrate (HS_50 : 50), and 75% grass hay and 25% alfalfa (HF_75 : 25) or concentrate (HS_75 : 25) with or without yeast. Yeast was able to induce more gas production from HF_75 : 25, HS_75 : 25 and HF_50 : 50 feed substrates incubated with respective faecal inoculum base. Yeast did not affect pH in vitro when the substrates were incubated in 50 : 50 ratio, while the pH was higher for HF_75 : 25 incubated with correspondent faecal inoculum compared to HS_75 : 25 and HSY_75 : 25. Yeast had no effects on ADF and CP AD of either diet. Yeast addition increased DM (HF: 0.2%, HS: 0.4%), organic matter (HF: 0.7%, HS: 1.3%), NDF (HF: 0.5%, HS: 1.5%), total detergent fibre (HF: 0.7%; HS: 0.4%) (P < 0.05) and also tended to increase hemicellulose AD (HF: 0.9%, HS: 1.2%) (P < 0.10). Faecal pH in vivo was higher for both HF diets compared to HS diet without yeast supplementation (P < 0.001, HF and HFY: 6.8; HS: 6.6, HSY: 6.7). However, no difference was observed in faecal pH when HSY was compared to both HF diets. Yeast had no effect on the size of the faecal particles (P > 0.05). Yeast increased in vitro gas production, suggesting more energy could be extracted from the feed, and the in vivo AD of some of the nutrients when HF and HS diets were fed.
There is a great deal of information about the management of the airway during many different scenarios, but very little of that information addresses the management of the airway during a mass casualty event following a disaster.
Following a major disaster from which a large number of casualties result, a community’s ability to rescue, triage, transport, evaluate, and treat these casualties quickly and effectively leads to the best possible outcome. The best outcomes occur if treatment is judiciously applied within the “golden hour,” the 60 minutes following the injury to the patient.
Unit cohesion may protect service member mental health by mitigating effects of combat exposure; however, questions remain about the origins of potential stress-buffering effects. We examined buffering effects associated with two forms of unit cohesion (peer-oriented horizontal cohesion and subordinate-leader vertical cohesion) defined as either individual-level or aggregated unit-level variables.
Longitudinal survey data from US Army soldiers who deployed to Afghanistan in 2012 were analyzed using mixed-effects regression. Models evaluated individual- and unit-level interaction effects of combat exposure and cohesion during deployment on symptoms of post-traumatic stress disorder (PTSD), depression, and suicidal ideation reported at 3 months post-deployment (model n's = 6684 to 6826). Given the small effective sample size (k = 89), the significance of unit-level interactions was evaluated at a 90% confidence level.
At the individual-level, buffering effects of horizontal cohesion were found for PTSD symptoms [B = −0.11, 95% CI (−0.18 to −0.04), p < 0.01] and depressive symptoms [B = −0.06, 95% CI (−0.10 to −0.01), p < 0.05]; while a buffering effect of vertical cohesion was observed for PTSD symptoms only [B = −0.03, 95% CI (−0.06 to −0.0001), p < 0.05]. At the unit-level, buffering effects of horizontal (but not vertical) cohesion were observed for PTSD symptoms [B = −0.91, 90% CI (−1.70 to −0.11), p = 0.06], depressive symptoms [B = −0.83, 90% CI (−1.24 to −0.41), p < 0.01], and suicidal ideation [B = −0.32, 90% CI (−0.62 to −0.01), p = 0.08].
Policies and interventions that enhance horizontal cohesion may protect combat-exposed units against post-deployment mental health problems. Efforts to support individual soldiers who report low levels of horizontal or vertical cohesion may also yield mental health benefits.
It remains poorly understood how negative symptoms are experienced in the daily lives of individuals in the early stages of psychosis. We aimed to investigate whether altered affective experience, anhedonia, social anhedonia, and asociality were more pronounced in individuals with an at-risk mental state for psychosis (ARMS) and individuals with first-episode psychosis (FEP) than in controls.
We used the experience sampling methodology (ESM) to assess negative symptoms, as they occurred in the daily life of 51 individuals with FEP and 46 ARMS, compared with 53 controls.
Multilevel linear regression analyses showed no overall evidence for a blunting of affective experience. There was some evidence for anhedonia in FEP but not in ARMS, as shown by a smaller increase of positive affect (BΔat−risk v. FEP = 0.08, p = 0.006) as the pleasantness of activities increased. Against our expectations, no evidence was found for greater social anhedonia in any group. FEP were more often alone (57%) than ARMS (38%) and controls (35%) but appraisals of the social situation did not point to asociality.
Overall, altered affective experience, anhedonia, social anhedonia and asociality seem to play less of a role in the daily life of individuals in the early stages of psychosis than previously assumed. With the experience of affect and pleasure in daily life being largely intact, changing social situations and appraisals thereof should be further investigated to prevent development or deterioration of negative symptoms.
We examined demographic, clinical, and psychological characteristics of a large cohort (n = 368) of adults with dissociative seizures (DS) recruited to the CODES randomised controlled trial (RCT) and explored differences associated with age at onset of DS, gender, and DS semiology.
Prior to randomisation within the CODES RCT, we collected demographic and clinical data on 368 participants. We assessed psychiatric comorbidity using the Mini-International Neuropsychiatric Interview (M.I.N.I.) and a screening measure of personality disorder and measured anxiety, depression, psychological distress, somatic symptom burden, emotional expression, functional impact of DS, avoidance behaviour, and quality of life. We undertook comparisons based on reported age at DS onset (<40 v. ⩾40), gender (male v. female), and DS semiology (predominantly hyperkinetic v. hypokinetic).
Our cohort was predominantly female (72%) and characterised by high levels of socio-economic deprivation. Two-thirds had predominantly hyperkinetic DS. Of the total, 69% had ⩾1 comorbid M.I.N.I. diagnosis (median number = 2), with agoraphobia being the most common concurrent diagnosis. Clinical levels of distress were reported by 86% and characteristics associated with maladaptive personality traits by 60%. Moderate-to-severe functional impairment, high levels of somatic symptoms, and impaired quality of life were also reported. Women had a younger age at DS onset than men.
Our study highlights the burden of psychopathology and socio-economic deprivation in a large, heterogeneous cohort of patients with DS. The lack of clear differences based on gender, DS semiology and age at onset suggests these factors do not add substantially to the heterogeneity of the cohort.
Tuberculosis (TB) in children is a critical public health issue. In Bohol, Philippines, we found a high tuberculin skin test (TST)-positive prevalence (weighted prevalence = 6.4%) among 5476 children (<15 years) from 184 villages, with geographically isolated communities having prevalence as high as 29%. Therefore, we conducted a geospatial and hot spot analysis to examine the association between villages with high TST-positive prevalence (⩾6.5%) and access to medical care (distance (in kilometres and minutes of travel time) to the municipal Rural Health Units (RHU)), access to healthcare resources (distance to Provincial Health Office (PHO)) and socioeconomic determinants of health. Hot spot analysis revealed significant clusters of TST-positive prevalence in villages farthest from the PHO. Based on univariate analysis, the following variables associated with high prevalence were included in the multivariate model: minutes of travel time to the PHO, distance to the PHO, island villages and total deprivation based on socioeconomic indicators. In the final model, only distance to PHO in minutes was significant (P = 0.005). When evaluated further, greater than 1-hour drive significantly increased risk for TST-positivity (P = 0.003). Distance to healthcare resources likely increases the risk of TB transmission within the community. Expanding TB control efforts to geographically isolated areas is critical.
Recent studies have identified DAAO as a probable susceptibility gene for schizophrenia and bipolar disorder. However, little is known about how this gene may affect brain function to increase vulnerability to these disorders.
The present investigation examined the impact of DAAO genotype on brain function in patients with schizophrenia, patients with bipolar I disorder and healthy volunteers.
We tested the hypotheses that the high-risk variant of DAAO would be associated with altered prefrontal function and functional connectivity in schizophrenic and bipolar patients.
We used functional magnetic resonance imaging to measure brain responses during a verbal fluency task in a total of 121 subjects comprising 40 patients with schizophrenia, 33 patients with bipolar I disorder and 48 healthy volunteers. We then used statistical parametric mapping (SPM) and psycho-physiological interaction (PPI) analyses to estimate the main effects of diagnostic group, the main effect of genotype and their interaction on brain activation and functional connectivity.
In schizophrenic patients relative to bipolar patients and controls, the high-risk variant of DAAO was associated with lower deactivation in the left precuneus and greater activation in the right calcarine and posterior cingulate gyrus during task performance. In addiction, these areas expressed altered functional connectivity with the rest of the brain in schizophrenic patients relative to bipolar patients and controls.
Our results suggest that genetic variation in DAAO has a significant impact on brain function and provide preliminary evidence for a disease-specific pattern of gene action in specific brain regions.
To describe symptom expression and functional outcome in psychotic disorders in relation with temperament traits assessed with the Temperament and Character Inventory (TCI) in a population-based sample.
As part of the 31-year follow-up survey of the Northern Finland 1966 Birth Cohort, TCI temperament items were filled in by 4349 members of the cohort. In individuals with psychotic disorders, also positive and negative symptoms and outcome variables were assessed in a 35-year follow-up. Information of TCI and outcomes were available for altogether 41 individuals with psychosis.
Reward dependence (RD) (rho = −0.45) and Persistence (P) (rho = −0.52) were significantly correlated with Positive and Negative Syndrome Scale (PANSS) negative symptoms. Higher P scores predicted higher social and occupational functioning (as measured by Social and Occupational Functioning Assessment Scale [SOFAS]), and higher Harm avoidance (HA) predicted a higher likelihood of being on a disability pension.
Results indicate that understanding of personality dimensions support better understanding of outcome and symptom expressions in psychotic disorders.
We sought to explore whether obstetric complications (OCs) are more likely to occur in the presence of familial/genetic susceptibility for schizophrenia or whether they themselves represent an independent environmental risk factor for schizophrenia.
The presence of OCs was assessed through maternal interview on 216 subjects, comprising 36 patients with schizophrenia from multiply affected families, 38 of their unaffected siblings, 31 schizophrenic patients with no family history of psychosis, 51 of their unaffected siblings and 60 normal comparison subjects. We examined the familiality of OCs and whether OCs were commoner in the patient and sibling groups than in the control group.
OCs tended to cluster within families, especially in multiply affected families. Patients with schizophrenia, especially those from multiply affected families, had a significantly higher rate of OCs compared to normal comparison subjects, but there was no evidence for an elevated rate of OCs in unaffected siblings.
Our data provides little evidence for a link between OCs and genetic susceptibility to schizophrenia. If high rates of OCs are related to schizophrenia genes, this relationship is weak and will only be detected by very large sample sizes.
Follow-up studies of schizophrenia have reported divergent rates of outcomes. In addition to definition and measurement challenges, one reason for divergence may be due to sampling biases. Our aim was to report clinical and social outcomes of schizophrenia in the longitudinal, unselected, population-based Northern Finland 1966 Birth Cohort, and describe associated factors.
Subjects with DSM-III-R schizophrenia (N=109) were followed prospectively from mid-pregnancy up to age 35 years. Used outcome measures were positive and negative symptoms, global clinical impression, use of antipsychotics, psychiatric hospitalisations, social and occupational functioning. Several definitions of good and poor outcomes were explored, and predictors of outcomes were analysed.
In a subsample of 59 cases with complete information of outcomes, good clinical outcome varied from 10% to 59%, and good social outcome 15-46%, depending on definition of outcomes. Poor clinical outcome varied 41-77% and poor social 37-54%. Two subjects recovered fully using the most stringent definition of outcome. Lack of friends in childhood, father's high social class, lower school performance and earlier age of illness onset predicted poor outcomes. When the whole sample was considered, early infant development around the age of 1 year was associated with worse course of illness.
Outcomes were heterogeneous and relatively poor in this sample of relatively young schizophrenia subjects. The results were influenced by the definitions and measurements of outcomes. Persons having a sub-optimal developmental trajectory with poor social contacts, poor school performance, and early age of illness onset seem to have the worst outcome.
There are lacking prospective studies in general population of adolescents about symptoms predicting the onset of first episode psychosis.
Members (N= 9,215) of the Northern Finland 1986 Birth Cohort, an unselected general population cohort, were invited to participate in a field survey during 2001, at ages of 15-16 years. The study included a 21-item PROD-screen questionnaire screening prodromal symptoms for psychosis for last six months (Heinimaa et al. 2003). PROD-screen included nine questions for positive and five questions for negative features. The Finnish Hospital Discharge Register was used to find out new cases of hospital treated mental disorders during 2002-2005.
Of the subjects 17 (0.3%) were treated due to first episode psychosis and 95 (1.5%) due to non-psychotic disorder during the follow-up period. Positive symptoms did not associate with the onset of psychosis, but negative symptoms did. 94% of subjects who got psychosis reported negative symptoms. Respective figure for those who were treated for non-psychotic disorder was 48%, and for those ‘healthy’ without psychiatric hospital treatment 46% (Fisher's exact test: psychosis vs. healthy p<0.001, psychosis vs. non-psychosis p<0.001, and non-psychosis vs. healthy p=0.61).
This study may be the only one exploring prospectively in general population features predicting onset of first episode psychosis. The findings emphasize the importance of negative symptoms in the development of neuropsychiatric disorder of first episode psychosis (Weinberger 1995).
The Academy of Finland, the Signe and Ane Gyllenberg Foundation, the Sigrid Juselius Foundation and the Thule Institute, Finland.