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Immune system markers may predict affective disorder treatment response, but whether an overall immune system marker predicts bipolar disorder treatment effect is unclear.
Bipolar CHOICE (N = 482) and LiTMUS (N = 283) were similar comparative effectiveness trials treating patients with bipolar disorder for 24 weeks with four different treatment arms (standard-dose lithium, quetiapine, moderate-dose lithium plus optimised personalised treatment (OPT) and OPT without lithium). We performed secondary mixed effects linear regression analyses adjusted for age, gender, smoking and body mass index to investigate relationships between pre-treatment white blood cell (WBC) levels and clinical global impression scale (CGI) response.
Compared to participants with WBC counts of 4.5–10 × 109/l, participants with WBC < 4.5 or WBC ≥ 10 showed similar improvement within each specific treatment arm and in gender-stratified analyses.
An overall immune system marker did not predict differential treatment response to four different treatment approaches for bipolar disorder all lasting 24 weeks.
Observational associations between cannabis and schizophrenia are well documented, but ascertaining causation is more challenging. We used Mendelian randomization (MR), utilizing publicly available data as a method for ascertaining causation from observational data.
We performed bi-directional two-sample MR using summary-level genome-wide data from the International Cannabis Consortium (ICC) and the Psychiatric Genomics Consortium (PGC2). Single nucleotide polymorphisms (SNPs) associated with cannabis initiation (p < 10−5) and schizophrenia (p < 5 × 10−8) were combined using an inverse-variance-weighted fixed-effects approach. We also used height and education genome-wide association study data, representing negative and positive control analyses.
There was some evidence consistent with a causal effect of cannabis initiation on risk of schizophrenia [odds ratio (OR) 1.04 per doubling odds of cannabis initiation, 95% confidence interval (CI) 1.01–1.07, p = 0.019]. There was strong evidence consistent with a causal effect of schizophrenia risk on likelihood of cannabis initiation (OR 1.10 per doubling of the odds of schizophrenia, 95% CI 1.05–1.14, p = 2.64 × 10−5). Findings were as predicted for the negative control (height: OR 1.00, 95% CI 0.99–1.01, p = 0.90) but weaker than predicted for the positive control (years in education: OR 0.99, 95% CI 0.97–1.00, p = 0.066) analyses.
Our results provide some that cannabis initiation increases the risk of schizophrenia, although the size of the causal estimate is small. We find stronger evidence that schizophrenia risk predicts cannabis initiation, possibly as genetic instruments for schizophrenia are stronger than for cannabis initiation.
Safeguarding threatened species in captivity is a promising management approach, but evaluating the performance of captive programmes is essential to assess reintroduction potential. The eastern population of the Northern Bald Ibis, Geronticus eremita, used to be a locally common migratory bird species, but catastrophic population declines throughout the past century have resulted in a single population in southern Turkey that forages freely during summer but only survives in captivity during winter. We examined whether breeding success of this semi-wild colony was comparable to breeding success of previous wild populations, and to what extent breeding success was influenced by supplementary feeding and wild foraging in habitats near the breeding station. Average productivity from 2009 to 2015 was 1.12 fledglings per nesting pair (range 0.96–1.19). In 2013 and 2014, there was no correlation between attendance at supplementary feeding events and productivity, and breeding birds attended on average only 35% of supplementary feeding events. Birds that were frequently observed at a local tree nursery raised fewer offspring, while birds observed more frequently in poldered cultivation, and in particular in mint crops or in fields covered with manure, raised on average more offspring. Foraging success was highest in meadows and cropland, particularly in mint crops and fields covered in manure, and lowest at the tree nursery. We speculate that selection of highly suitable wild foraging habitat such as mint crops or fields covered in manure allows the Northern Bald Ibis to raise more fledglings than exclusive reliance on supplementary food provided at the breeding station. Establishing a second breeding colony of this species in Turkey will therefore require a careful assessment of the suitability of wild foraging habitat in the vicinity of suitable nesting opportunities.
Twin pairs discordant for disease may help elucidate the epigenetic mechanisms and causal environmental factors in disease development and progression. To obtain the numbers of pairs, especially monozygotic (MZ) twin pairs, necessary for in-depth studies while also allowing for replication, twin studies worldwide need to pool their resources. The Discordant Twin (DISCOTWIN) consortium was established for this goal. Here, we describe the DISCOTWIN Consortium and present an analysis of type 2 diabetes (T2D) data in nearly 35,000 twin pairs. Seven twin cohorts from Europe (Denmark, Finland, Norway, the Netherlands, Spain, Sweden, and the United Kingdom) and one from Australia investigated the rate of discordance for T2D in same-sex twin pairs aged 45 years and older. Data were available for 34,166 same-sex twin pairs, of which 13,970 were MZ, with T2D diagnosis based on self-reported diagnosis and medication use, fasting glucose and insulin measures, or medical records. The prevalence of T2D ranged from 2.6% to 12.3% across the cohorts depending on age, body mass index (BMI), and national diabetes prevalence. T2D discordance rate was lower for MZ (5.1%, range 2.9–11.2%) than for same-sex dizygotic (DZ) (8.0%, range 4.9–13.5%) pairs. Across DISCOTWIN, 720 discordant MZ pairs were identified. Except for the oldest of the Danish cohorts (mean age 79), heritability estimates based on contingency tables were moderate to high (0.47–0.77). From a meta-analysis of all data, the heritability was estimated at 72% (95% confidence interval 61–78%). This study demonstrated high T2D prevalence and high heritability for T2D liability across twin cohorts. Therefore, the number of discordant MZ pairs for T2D is limited. By combining national resources, the DISCOTWIN Consortium maximizes the number of discordant MZ pairs needed for in-depth genotyping, multi-omics, and phenotyping studies, which may provide unique insights into the pathways linking genes to the development of many diseases.
The poor survival rate of immature northern bald ibises Geronticus eremita during their first years spent outside the natal site is driving the last known wild colony of the migratory eastern population to extinction. To inform emergency conservation action for this Critically Endangered species we investigated the distribution range and behaviour of immature birds in passage and wintering areas, and the threats to which they are subject. We integrated recent satellite telemetry data with visual observations spanning 130 years. We assessed threats across the range, using satellite tracking and field surveys. Our results show that during the years before they return to the natal site in Syria, immature northern bald ibises reside away from the recently identified adult wintering site in the central Ethiopian highlands. They occur mainly across the northernmost 70–80% of the adult migratory range. Historical records suggest that immature birds spend more time along the western Arabian Peninsula now than in the past. This range shift exposes them for longer periods to threats, such as hunting and electrocution on power lines, which are absent from the wintering site used by adult birds. We suggest that other threatened and declining bird species sharing the same flyway probably face the same threats during migration.
There have been no previous factor analytic studies of the Hamilton Depression Rating Scale (HDRS) in samples with bipolar I depression, and no investigations of the utility of any derived factors in determining treatment response in this condition. This study aimed to identify and compare factors of a 31-item version of the HDRS (HDRS-31) in large samples of patients with bipolar depression and Major Depressive Disorder (MDD), then examine the responsiveness of such factors to lamotrigine compared with placebo in the bipolar depressed sample.
This multivariate analytical study was performed on 2 large depressed samples (one bipolar and the other MDD) that had been recruited for separate, contemporaneous, double-blind placebo-controlled trials of lamotrigine. The 2 studies had similar designs and assessment tools, the major measures being the Montgomery–Asberg Depression Rating Scale (MADRS) and HDRS-31. To identify the constructs underlying the scale, exploratory factor analyses were conducted using HDRS-31 baseline scores. Treatment responsiveness in the bipolar depressed sample—as indicated by improvement in the total MADRS and HDRS-31, as well as HDRS factors—were examined using both a mixed-effects analysis and individual time-point t-tests.
Seven factors of the HDRS-31 were identified: I—“depressive cognitions,” II—“psychomotor retardation,” III—“insomnia,” IV—“hypersomnia,” V—“appetite and weight change,” VI—“anxiety,” and VII—“anergia.” A significant therapeutic effect of lamotrigine in bipolar depression was found for the “depressive cognitions” factor (from week 3) and “psychomotor retardation” (from week 4).
This study has identified 7 factors of the HDRS in a large sample of patients with bipolar depression. The results suggest that that the clinical benefits of lamotrigine in acute bipolar depression are primarily upon depressive cognitions and psychomotor slowing.
Pathological gambling (PG) is a form of behavioural addiction that has been associated with elevated impulsivity and also cognitive distortions in the processing of chance, probability and skill. We sought to assess the relationship between the level of cognitive distortions and state and trait measures of impulsivity in treatment-seeking pathological gamblers.
Thirty pathological gamblers attending the National Problem Gambling Clinic, the first National Health Service clinic for gambling problems in the UK, were compared with 30 healthy controls in a case-control design. Cognitive distortions were assessed using the Gambling-Related Cognitions Scale (GRCS). Trait impulsivity was assessed using the UPPS-P, which includes scales of urgency, the tendency to be impulsive in positive or negative mood states. Delay discounting rates were taken as a state measure of impulsive choice.
Pathological gamblers had elevated impulsivity on several UPPS-P subscales but effect sizes were largest (Cohen's d>1.4) for positive and negative urgency. The pathological gamblers also displayed higher levels of gambling distortions, and elevated preference for immediate rewards, compared to controls. Within the pathological gamblers, there was a strong relationship between the preference for immediate rewards and the level of cognitive distortions (R2=0.41).
Impulsive choice in the gamblers was correlated with the level of gambling distortions, and we hypothesize that an impulsive decision-making style may increase the acceptance of erroneous beliefs during gambling play.
Staphylococcus aureus is a leading cause of infections in deployed service members. Based on a molecular epidemiological study of 182 MRSA isolates from patients in three U.S. Army combat support hospitals in separate regions in Iraq, USA300 clone was the most predominant (80%) pulsotype. This finding suggested that strain carriage from the home country by military personnel is epidemiologically more important than local acquisition.
A method of micro-titration for cytolytic antibodies is described. Standard drops of diluent are placed on a subdivided siliconed slide and dilutions are made by rotating a wire loop holding 1 drop of serum in each drop sequentially. One drop of a mixture of cells and complement is then added. The slide is incubated in a moist chamber for 90 min at 37° C. after which a small cover-slip is placed on each drop and the amount of cell lysis, judged by phase-contrast microscopy, is graded.
An analysis of variance of the method has been performed and the method has been found to be reliable, accurate and unbiased.
It allows accurate estimates of cytolytic activity in sera using cell concentrations of 104 to 105 cells per ml. Eight ten-dilution titrations can be carried out with 1 ml. of such a suspension.
Gyps vulture populations across the Indian subcontinent collapsed in the 1990s and continue to decline. Repeated population surveys showed that the rate of decline was so rapid that elevated mortality of adult birds must be a key demographic mechanism. Post mortem examination showed that the majority of dead vultures had visceral gout, due to kidney damage. The realisation that diclofenac, a non-steroidal anti-inflammatory drug potentially nephrotoxic to birds, had become a widely used veterinary medicine led to the identification of diclofenac poisoning as the cause of the decline. Surveys of diclofenac contamination of domestic ungulate carcasses, combined with vulture population modelling, show that the level of contamination is sufficient for it to be the sole cause of the decline. Testing on vultures of meloxicam, an alternative NSAID for livestock treatment, showed that it did not harm them at concentrations likely to be encountered by wild birds and would be a safe replacement for diclofenac. The manufacture of diclofenac for veterinary use has been banned, but its sale has not. Consequently, it may be some years before diclofenac is removed from the vultures' food supply. In the meantime, captive populations of three vulture species have been established to provide sources of birds for future reintroduction programmes.
The Northern Bald Ibis or Waldrapp Geronticus eremita is a species of arid semi-deserts and steppes, which was formerly widely distributed as a breeding bird across North Africa, the Middle East and the European Alps. Just over 100 breeding pairs now remain in the wild at two sites in Morocco whilst two further wild pairs remain in Syria. There is also a population in Turkey, which is maintained for part of the year in captivity, and a large captive population in zoos. The species is classified by IUCN as ‘Critically Endangered’, the highest threat category. The wild population has grown during the past decade, which represents the first evidence of population growth in the species' recorded history. Conservation action in Morocco has contributed to this recovery. A large part of the contribution of research to conservation action has been to establish and document the value of simple site and species protection. Quantitative assessments of the importance of sites for breeding, roosting and foraging have helped to prevent disturbance and the loss of sites to mass-tourism development. Wardening by members of the local community have reduced disturbance by local people and others and increased the perceived value of the birds. Monitoring has suggested additional ways to improve the breeding status of the species, including the provision of drinking water and removal and deterrence of predators and competitors. These actions have been evaluated by subsequent testing. Steppe and two-year fallows were shown to be the key feeding habitats, and maintaining such non-intensive land uses in future may present major management challenges. The recovery in the Souss-Massa region remains precarious because the population is concentrated in a few places where adverse changes are possible. However, it could provide opportunities for natural extension of the range to formerly occupied sites further north in Morocco.
We examined the sensitivity of the Rey Auditory Verbal Learning Test (AVLT), California Verbal Learning Test (CVLT), Boston Naming Test (BNT), and Multilingual Aphasia Examination Visual Naming subtest (MAE VN) to lateralized temporal lobe epilepsy (TLE) in patients who subsequently underwent anterior temporal lobectomy. For the AVLT (n = 189), left TLE patients performed more poorly than their right TLE counterparts [left TLE = 42.9 (10.6), right TLE = 47.7 (9.9); p < .002 (Cohen's d = .47)]. Although statistically significant, the CVLT group difference (n = 212) was of a smaller magnitude [left LTE = 40.7 (11.1), right TLE = 43.8 (9.9); (p < .03, Cohen's d = .29)] than the AVLT. Group differences were also present for both measures of confrontation naming ability [BNT: left LTE = 43.1 (8.9), right TLE = 48.1 (8.9); p < .001 (Cohen's d = .56); MAE VN: left TLE = 42.2, right TLE = 45.6, p = .02 (Cohen's d = .36)]. When these data were modeled in independent logistic regression analyses, the AVLT and BNT both significantly predicted side of seizure focus, although the positive likelihood ratios were modest. In the subset of 108 patients receiving both BNT and AVLT, the AVLT was the only significant predictor of seizure laterality, suggesting individual patient variability regarding whether naming or memory testing may be more sensitive to lateralized TLE. (JINS, 2008, 14, 394–400.)
The as-deposited passivation quality of amorphous silicon films on crystalline silicon surfaces is dependent on deposition conditions and resulting hydrogen bonding structure. However the initial surface passivation can be significantly improved by low temperature post-deposition anneal. For example an improvement in effective lifetime from 780 μsec as-deposited to 2080 μsec post-anneal is reported in the present work. This work probes the hydrogen bonding environment using monolayer resolution Brewster angle transmission Fourier transform infrared spectroscopy of 100 Å thick films. It is found that there is significant restructuring at the a-Si:H / c-Si interface upon annealing and a gain of mono-hydride bonding at the c-Si surface is detected. Calculations show an additional 3.56 − 4.50 × 1014 cm−2 mono-hydride bonding at c-Si surface due to annealing. The estimation of the surface hydride oscillator strength in transmission mode is reported for the first time to be 7.2 × 10−18 cm on Si (100) surface and 7.5 × 10−18 cm on Si (111).
To assess the efficacy of lamotrigine combined with either divalproex or lithium for the treatment of bipolar disorder.
Lithium and divalproex seem to be predominantly effective for manic and mixed symptoms of bipolar disorder, whereas lamotrigine may be more effective for bipolar depression than for mania. Combination therapy may provide more efficacious treatment for many patients with bipolar disorder.
Data from charts of adult outpatients with bipolar disorder treated with lamotrigine plus divalproex or lithium during a 3-year period were retrospectively analyzed. The Clinical Global Impressions for Bipolar Disorder scale was used to assess severity of illness at baseline (adjunct-therapy initiation) and improvement after 3 months of treatment. The safety and tolerability of the medication combinations were assessed.
After 3 months of treatment, 26 of 39 patients (67%) receiving lamotrigine plus divalproex had a depression rating of 1 (very much improved) or 2 (much improved) compared with seven of 16 (44%) taking lamotrigine plus lithium. The mania rating was 1 or 2 for 13 of 39 (39%) patients treated with lamotrigine plus divalproex and 7 of 16 (44%) patients receiving lamotrigine plus lithium. For overall illness severity, 26 of 39 (67%) patients given lamotrigine plus divalproex had scores of 1 or 2 compared with 10 of 16 (62%) patients taking lamotrigine plus lithium. Five of 39 patients (13%) taking lamotrigine plus divalproex and 5 of 16 (31%) receiving lamotrigine plus lithium discontinued at least one part of the combination in <3 months due to adverse events.
Combination therapy with lamotrigine plus divalproex or lithium may be a valuable option for managing symptoms of bipolar disorder. The combinations were generally well tolerated and apparently effective in improving depression as well as mania.The percentage of patients showing improvement in depression was somewhat larger. Tolerability was somewhat better for lamotrigine plus divalproex in combination than for lamotrigine plus lithium. Differences in tolerability are consistent with studies indicating poorer tolerability of lithium compared with divalproex.
Sub-syndromal symptoms in bipolar disorder impair functioning and
diminish quality of life.
To examine factors associated with time spent with sub-syndromal symptoms
and to characterise how these symptoms influence outcomes.
In a double-blind randomised maintenance trial, patients received either
olanzapine or lithium monotherapy for 1 year. Stepwise logistic
regression models were used to identify factors that were significant
predictors of percentage time spent with sub-syndromal symptoms. The
presence of sub-syndromal symptoms during the first 8 weeks was examined
as a predictor of subsequent relapse.
Presence of sub-syndromal depressive symptoms during the first 8 weeks
significantly increased the likelihood of depressive relapse (relative
risk 4.67, P<0.001). Patients with psychotic features
and those with a greater number of previous depressive episodes were more
likely to experience sub-syndromal depressive symptoms (RR=2.51,
P<0.001 and RR=2.35, P=0.03
These findings help to identify patients at increased risk of affective
relapse and suggest that appropriate therapeutic interventions should be
considered even when syndromal-level symptoms are absent.
Few controlled studies have examined the use of atypical antipsychotic drugs for prevention of relapse in patients with bipolar I disorder.
To evaluate whether olanzapine plus either lithium or valproate reduces the rate of relapse, compared with lithium or valproate alone.
Patients achieving syndromic remission after 6 weeks'treatment with olanzapine plus either lithium (0.6–1.2 mmol/l) or valproate (50–125 μg/ml) received lithium or valproate plus either olanzapine 5–20 mg/day (combination therapy) or placebo (monotherapy), and were followed in a double-masked trial for 18 months.
The treatment difference in time to relapse into either mania or depression was not significant for syndromic relapse (median time to relapse: combination therapy 94 days, monotherapy40.5 days; P=0.742), but was significant for symptomatic relapse (combination therapy 163 days, monotherapy42 days; P=0.023).
Patients taking olanzapine added to lithium or valproate experienced sustained symptomatic remission, but not syndromic remission, for longer than those receiving lithium or valproate monotherapy.
Eventing is a very expensive sport to organise and run and relies heavily upon sponsorship funding to enable it to remain financially viable. This research is concerned with the challenges that events face in attracting and retaining sponsorship and what can be done to address these problems, resulting in a clearer understanding of what makes a successful sponsorship. Fourteen interviews were conducted with both event organisers and sponsoring companies, as well four people who are considered to be knowledgeable about sponsorship within the equine industry, to ensure that a balanced view of the issues was gained. The research found that the industry suffers from a culture of patronage with some companies sponsoring eventing for altruistic reasons. They see sponsorship as a way of raising public awareness and of building goodwill with their customers by being seen to put something back into a sport that their customers care about. Sponsors commented that sponsorship impresses people and gives them an idea about the values of the company and where it is positioned within the industry. They saw the sponsored event as an opportunity for them to entertain clients, customers, press and other business professionals, often in very beautiful surroundings. As eventing attracts more AB and C1 competitors and spectators than any other sport, it can offer sponsors an opportunity for highly targeted marketing to a sector of the population who are acknowledged to be difficult to reach via traditional advertising. Sponsors are interested in getting value for money from their sponsorship, and they expect to be dealt with in a professional manner. Event organisers need to demonstrate clearly how the sponsorship will benefit the company and ensure that they meet all of the sponsors’ business objectives. Sponsors expect to have name and brand awareness delivered to their target audience at the event, thus organisers must ensure that this happens by providing good branding opportunities. In order to gain the maximum benefit from the sponsorship, the sponsoring company needs to promote and publicise the sponsorship as much as possible by integrating it across their whole marketing strategy. This can be a great advantage to the event organiser as it raises the profile of the event. Events at the top end of the sport were found to have good sponsorship deals in place and the organisers said that they did not need sponsorship to make their events viable. However, the smaller events at grassroots level are only viable if sufficient sponsorship can be found. One interviewee suggested that these small events need to target smaller local companies who could benefit from raising their public profile in the local area. The event organisers interviewed feel undervalued by British Eventing, the sport’s governing body, and think that British Eventing could do more to support event organisers in attracting and retaining sponsorship. This is particularly crucial at grassroots level, because without sponsorship these events are not financially viable.