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Psychiatric disorders are associated with increased risk of ischaemic heart disease (IHD) and stroke, but it is not known whether the associations or the role of sociodemographic factors have changed over time.
To investigate the association between psychiatric disorders and IHD and stroke, by time period and sociodemographic factors.
We used Scottish population-based records from 1991 to 2015 to create retrospective cohorts with a hospital record for psychiatric disorders of interest (schizophrenia, bipolar disorder or depression) or no record of hospital admission for mental illness. We estimated incidence and relative risks of IHD and stroke in people with versus without psychiatric disorders by calendar year, age, gender and area-based deprivation level.
In all cohorts, incidence of IHD (645 393 events) and stroke (276 073 events) decreased over time, but relative risks decreased for depression only. In 2015, at the mean age at event onset, relative risks were 2- to 2.5-fold higher in people with versus without a psychiatric disorder. Age at incidence of outcome differed by cohort, gender and socioeconomic status. Relative but not absolute risks were generally higher in women than men. Increasing deprivation conveys a greater absolute risk of IHD for people with bipolar disorder or depression.
Despite declines in absolute rates of IHD and stroke, relative risks remain high in those with versus without psychiatric disorders. Cardiovascular disease monitoring and prevention approaches may need to be tailored by psychiatric disorder and cardiovascular outcome, and be targeted, for example, by age and deprivation level.
Non-communicable diseases are projected to become the most common causes of death in Africa by 2030. The impact on health of epidemiological and nutritional transitions in sub-Saharan Africa remains unclear. To assess the trends of dietary fatty acids over time in Uganda, we examined fatty acids in serum collected from individuals in rural south-west Uganda, at three time points over two decades. Independent cross-sectional samples of 915 adults and children were selected from the general population cohort in 1990 (n 281), 2000 (n 283) and 2008 (n 351). Serum phospholipid fatty acids were measured by GC. Multivariate regression analyses were performed to compare the geometric means of fatty acids by time period. Serum fatty acid profiling showed high proportions of SFA, cis-MUFA and industrial trans-fatty acids (iTFA), likely to be biomarkers of high consumption of palm oil and hydrogenated fats. In contrast, proportions of n-6 and n-3 PUFA from vegetable oils and fish were low. From 1990 to 2008, serum phospholipids showed increases in absolute amounts of SFA (17·3 % increase in adults and 26·4 % in children), MUFA (16·7 % increase in adults and 16·8 % in children) and n-6:n-3 PUFA (40·1 % increase in adults and 39·8 % in children). The amount of elaidic acid, iTFA from hydrogenated fats, increased in children (60·1 % increase). In this rural Ugandan population, we show evidence of unfavourable trends over time of dietary fatty acids.
Based on the vulnerability–stress model, we aimed to (1) determine new onset of depression in individuals who had not shown evidence of depression at baseline (5 years earlier) and (2) identify social, psychological, behavioral, and somatic predictors.
Longitudinal data of N = 10 036 participants (40–79 years) were evaluated who had no evidence of depression at baseline based on Patient Health Questionnaire (PHQ-9), no history of depression, or intake of antidepressants. Multivariate logistic regression models were used to predict the onset of depression.
Prevalence of new cases of depression was 4.4%. Higher rates of women (5.1%) than men (3.8%) were due to their excess incidence <60 years of age. Regression analyses revealed significant social, psychological, behavioral, and somatic predictors: loneliness [odds ratio (OR) 2.01; 95% confidence interval (CI) 1.48–2.71], generalized anxiety (OR 2.65; 1.79–3.85), social phobia (OR 1.87; 1.34–2.57), panic (OR 1.67; 1.01–2.64), type D personality (OR 1.85; 1.47–2.32), smoking (OR 1.35; 1.05–1.71), and comorbid cancer (OR 1.58; 1.09–2.24). Protective factors were age (OR 0.88; 0.83–0.93) and social support (OR 0.93; 0.90–0.95). Stratified by sex, cancer was predictive for women; for men smoking and life events. Entered additionally, the PHQ-9 baseline score was strongly predictive (OR 1.40; 1.34–1.47), generalized anxiety became only marginally, and panic was no longer predictive. Other predictors remained significant, albeit weaker.
Psychobiological vulnerability, stress, and illness-related factors were predictive of new onset of depression, whereas social support was protective. Baseline subclinical depression was an additional risk weakening the relationship between anxiety and depression by taking their overlap into account. Vulnerability factors differed between men and women.
OBJECTIVES/SPECIFIC AIMS: Despite aggressive chemotherapy, surgical resection, and radiation therapy, glioblastoma remains almost universally fatal. In a pilot, randomized, and blinded clinical trial, we recently demonstrated that administration of RNA-loaded DC vaccines was associated with significantly improved progression-free and overall survival in patients with glioblastoma (Mitchell et al., Nature, 2015). Furthermore, clinical outcomes correlated with DC migration to vaccine-site draining lymph nodes measured by Indium-111 labeling of RNA-loaded DCs and SPECT/CT imaging. Although these studies demonstrated that tracking DC migration may be an important clinical biomarker for response to DC vaccination, the complexity and regulatory requirements associated with nuclear labelling to track DC migration limits widespread application of this technique. We have therefore developed RNA-loaded magnetic nanoparticles (RNA-NPs) to enhance DC migration to LNs and track that migration with a widely available imaging modality (i.e., MRI). METHODS/STUDY POPULATION: Cationic liposomes were loaded with iron oxide nanoparticles with or without cholesterol. The resulting nanoparticles were complexed with RNA and used to transfect DCs ex vivo. RNA-NP-loaded DsRed+ DCs were then injected intradermally into mice and tracked noninvasively with T2-weighted 11T MRI before excision and quantification with flow cytometry. RESULTS/ANTICIPATED RESULTS: In vitro experiments demonstrate that iron oxide loading does not reduce RNA-NP-mediated transfection of DCs. Additionally, replacement of cationic lipids with cholesterol increased RNA-NP transfection of the DC2.4 cell line and enhanced the T cell stimulatory capacity of treated bone marrow-derived dendritic cells (BMDCs). Compared to electroporation, RNA-NPs enhanced DC migration to lymph nodes and reduced T2 MRI intensity in DC-bearing lymph nodes. DISCUSSION/SIGNIFICANCE OF IMPACT: This data suggests that iron oxide-loaded RNA-NPs enable noninvasive cell tracking with MRI and enhance DC migration to lymph nodes. We have further shown that inclusion of cholesterol in RNA-NPs augments the stimulatory capacity of transfected DCs. Future work will consider effects of RNA-NPs on antitumor immune responses and the utility of MRI-detected DC migration as a biomarker of vaccine efficacy.
Background: Recent research has supported the efficacy of schema therapy as a treatment for personality disorders. A group format has been developed (group schema therapy; GST), which has been suggested to improve both the clinical and cost-effectiveness of the treatment. Aims: Efficacy studies of GST need to assess treatment fidelity. The aims of the present study were to improve, describe and evaluate a fidelity measure for GST, the Group Schema Therapy Rating Scale – Revised (GSTRS-R). Method: Following a pilot study on an initial version of the scale (GSTRS), items were revised and guidelines were modified in order to improve the reliability of the scale. Students highly experienced with the scale rated recorded GST therapy sessions using the GSTRS-R in addition to a group cohesion measure, the Harvard Community Health Plan Group Cohesiveness Scale – II (GCS-II). The scores were used to assess internal consistency and inter-rater reliability. Discriminant validity was assessed by comparing the scores on the GSTRS-R with the GCS-II. Results: The GSTRS-R displayed substantial internal consistency and inter-rater reliability, and adequate discriminate validity, evidenced by a weak positive correlation with the GCS-II. Conclusions: Overall, the GSTRS-R is a reliable tool that may be useful for evaluating therapist fidelity to GST model, and assisting GST training and supervision. Initial validity was supported by a weak association with GCS-II, indicating that although associated with cohesiveness, the instrument also assesses factors specific to GST. Limitations are discussed.
Early finished lambs are able to command a higher premium at slaughter. Improvement in growth rate can increase the profitability of the enterprise. The use of yeast cell wall preparations, in particular the mannan oligosaccharide portion, has been shown to improve intestinal tract health and thus growth rates in other species (Uni & Smirnov, 2006; Rosen, 2006). Farm studies have suggested that the inclusion of mannan oligosaccharides have the greatest effect in young animals prior to weaning. The aim of the current study was to determine the effect of feeding a mannan oligosaccharide on the growth rates of early finished lambs reared indoors on a commercial farm from birth until weaning.
There are many rationing models used commercially for evaluating diets fed to dairy cows. A new model – BioParaMilk – uses a unique protein degradation model to determine microbial protein synthesis, based upon the in vitro gas production technique (IVGPT). Optigen®, a slow release, blended, non-protein nitrogen source, can partially replace soyabean meal (SBM) in a dairy diet. The partial replacement of soyabean meal and rapeseed meal with Optigen® has been shown to increase fibre digestion and may improve volatile fatty acid (VFA) and microbial nitrogen (N) flow in the rumen (Sinclair et al., 2008). The purpose of this study was to evaluate the protein degradation curve from Optigen® compared to SBM for use in this new model, using IVGPT.
Yeasts are the first micro-organism that become active in the silage upon exposure to air, using the residual sugars and lactic acid to produce carbon dioxide. Maize silage is particularly prone to spoilage as maize silage tends to have a larger concentration of water soluble carbohydrates, which was considered to be a better substrate for micro-organisms than volatile fatty acids (Auerbach et al., 1998). The aim of this experiment was to measure the effect of inoculating maize silage with Maize-all GS (inoculant) and Sil-all Fireguard (inoculant and preservative) on aerobic stability.
The pregnant uterus has a requirement for glucose that rises rapidly towards the end of pregnancy (Robinson et al., 1977). Despite this, the dry matter (DM) intake of the ewe is often depressed during this period causing excessive mobilisation of adipose tissue and an increased concentration of plasma ketones. Propylene glycol resists fermentation in the rumen and following absorption is converted to glucose and glycogen (Andrews, 1982). There is little data available on how in feed inclusion of propylene glycol affects the productivity and energy metabolism of late pregnant and lactating ewes.
The use of direct fed microbials has been shown to enhance digestion in the ruminant. One source of microbial live populations is a yeast culture Saccharomyces cerevisae (Yea-Sacc1026, CBS 493.94; Alltech Inc, USA), and its use in ruminants has been associated with a range of benefits including an overall increase in dry matter and fiber digestibility (Wiedmeier and Arambel, 1985), combating heat stress in lactating cows (Huber and Higgenbotham, 1985) and increased performance (Fallon and Harte, 1987). Glade and Biesik (1982) working with yearling horses, demonstrated increased DM and N digestibility when S. cerevisae was added to the diet. It was suggested that S. cerevisae enhanced cellulolytic activity, triggering microbial metabolism changes in the horse’s large intestine that enhance hemicellulose fermentation. They also reported that the addition of S. cerevisae results in smaller percentages of absorbed nitrogen excreted in the urine, indicating that the biological value of the S. cerevisae -supplemented diets may be more than the direct contribution of the nitrogen within the yeast itself. The aim of this review is to determine the effects of S. cerevisae on performance parameters of bulls.
Major depression and anxiety disorders are known to negatively influence cognitive performance. Moreover, there is evidence for greater cognitive decline in older adults with generalized anxiety disorder. Except for clinical studies, complex executive planning functions and subclinical levels of anxiety have not been examined in a population-based sample with a broad age range.
Planning performance was assessed using the Tower of London task in a population-based sample of 4240 participants aged 40–80 years from the Gutenberg Health Study (GHS) and related to self-reported anxiety and depression by means of multiple linear regression analysis.
Higher anxiety ratings were associated with lower planning performance (β = −0.20; p < 0.0001) independent of age (β = 0.03; p = 0.47). When directly comparing the predictive value of depression and anxiety on cognition, only anxiety attained significance (β = −0.19; p = 0.0047), whereas depression did not (β = −0.01; p = 0.71).
Subclinical levels of anxiety but not of depression showed negative associations with cognitive functioning independent of age. Our results demonstrate that associations observed in clinical groups might differ from those in population-based samples, also with regard to the trajectory across the life span. Further studies are needed to uncover causal interrelations of anxiety and cognition, which have been proposed in the literature, in order to develop interventions aimed at reducing this negative affective state and to improve executive functioning.
Tidal flexure in ice shelf grounding zones has been used extensively in the past to determine grounding line position and ice properties. Although the rheology of ice is viscoelastic at tidal loading frequencies, most modelling studies have assumed some form of linear elastic beam approximation to match observed flexure profiles. Here we use density, radar and DInSAR measurements in combination with full-Stokes viscoelastic modelling to investigate a range of additional controls on the flexure of the Southern McMurdo Ice Shelf. We find that inclusion of observed basal crevasses and density dependent ice stiffness can greatly alter the flexure profile and yet fitting a simple elastic beam model to that profile will still produce an excellent fit. Estimates of the effective Young's modulus derived by fitting flexure profiles are shown to vary by over 200% depending on whether these factors are included, even when the local thickness is well constrained. Conversely, estimates of the grounding line position are relatively insensitive to these considerations for the case of a steep bed slope in our study region. By fitting tidal amplitudes only, and ignoring phase information, elastic beam theory can provide a good fit to observations in a wide variety of situations. This should, however, not be taken as an indication that the underlying rheological assumptions are correct.
Grounding zones are vital to ice-sheet mass balance and its coupling to the global ocean circulation. Processes here determine the mass discharge from the grounded ice sheet, to the floating ice shelves. The response of this transition zone to tidal forcing has been described by both elastic and viscoelastic models. Here we examine the validity of these models for grounding zone flexure over tidal timescales using field data from the Southern McMurdo Ice Shelf (78° 15′S, 167° 7′E). Observations of tidal movement were carried out by simultaneous tiltmeter and GPS measurements along a profile across the grounding zone. Finite-element simulations covering a 64 d period reveal that the viscoelastic model fits best the observations using a Young's modulus of 1.6 GPa and a viscosity of 1013.7 Pa s (≈ 50.1 TPa s). We conclude that the elastic model is only well-constrained for tidal displacements >35% of the spring-tidal amplitude using a Young's modulus of 1.62 ± 0.69 GPa, but that a viscoelastic model is necessary to adequately capture tidal bending at amplitudes below this threshold. In grounding zones where bending stresses are greater than at the Southern McMurdo Ice Shelf or ice viscosity is lower, the threshold would be even higher.
The aim of this article is to investigate the argument that choice and competition will unleash entrepreneurial innovation in free schools. Free schools were introduced as a subset of the Academies by the Conservative–Liberal Democrat Coalition government, following the general election in 2010. The government made it possible for non-state providers to set up their own independent, state-funded schools in order to create more choice, competition and innovation. We conclude that a higher level of substantive innovation is taking place in regards to management practices than in respect of curriculum and pedagogical practices. Innovation in curriculum and pedagogical practices is very limited. Creating a free school offer that seems to differ from other schools appears to be done through marketing and branding rather than innovation. We argue that parents, OFSTED, and the relative isolation of free schools constrain innovation from taking place.
There is, indeed, a difficulty about part and whole … whether the part and the whole are one or more than one, and how they can be one or many, and, if they are more than one, in what sense they are more than one.
Aristotle (First Book of Physics) (384–322 BC)
The system concept was the very first one introduced in Chapter 1. We argued that using the word “design” instead of “system” allows us to make use of the extensive work done on studying systems. In this chapter, we take up the system discussion again and assert that every design is a system.What is the exact “system” is a matter of subjective perspective and focus of the design effort. Following the discussion in Section 1.2, our working concept of a system is that the system comprises elements, probably interacting with each other, that function together. A system can be partitioned into its elements (system partitioning), and its overall function is achieved through properly tracking how the elements function together (system coordination). The elements can be physical parts (object partitioning) or function disciplines (aspect partitioning).
System optimization acknowledges this partitioning and coordination character and follows the basic principle of decomposition: break the problem into simpler problem pieces (subproblems), solve each subproblem separately, and coordinate the subproblem solutions so that you obtain the solution to the original problem. This decomposition-based optimization strategy is useful if: (i) the effort for partitioning, subproblem solution, and coordination is less than the effort required to solve the original problem; or (ii) the original problem is simply not solvable without decomposition; and (iii) the decomposition-based solution is indeed the same as the solution to the original nonpartitioned problem. The first two cases are a practical matter for when to use decomposition strategies. The third one is both practical and theoretical; it requires a mathematical convergence proof that the decomposition strategy will yield solutions within the solution set of the original problem. This mathematical requirement turns out to be quite demanding, as many strategies developed for solving practical system design problems tend to be heuristic with no convergence proofs. Still, getting a good answer for a complex problem is better than no answer.