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We present an overview of the SkyMapper optical follow-up programme for gravitational-wave event triggers from the LIGO/Virgo observatories, which aims at identifying early GW170817-like kilonovae out to
distance. We describe our robotic facility for rapid transient follow-up, which can target most of the sky at
to a depth of
. We have implemented a new software pipeline to receive LIGO/Virgo alerts, schedule observations and examine the incoming real-time data stream for transient candidates. We adopt a real-bogus classifier using ensemble-based machine learning techniques, attaining high completeness (
) and purity (
) over our whole magnitude range. Applying further filtering to remove common image artefacts and known sources of transients, such as asteroids and variable stars, reduces the number of candidates by a factor of more than 10. We demonstrate the system performance with data obtained for GW190425, a binary neutron star merger detected during the LIGO/Virgo O3 observing campaign. In time for the LIGO/Virgo O4 run, we will have deeper reference images allowing transient detection to
Enforcing Consumer and Capital Markets Law: The Diesel Emissions Scandal is an international and intradisciplinary work. On the example of one topical and global collective damage event with far reaching consequences for both consumers and investors, this work critically analyses the various approaches of public and private law enforcement and their effectiveness across several jurisdictions, namely those of Austria, Denmark, France, Germany, England and Wales, Italy, Lithuania, the Netherlands, Portugal, Australia, Brazil, China and the United States of America. Based on decided and pending cases, the book demonstrates to what extent public authorities, but also private claimants, can take effective steps against the violation of their rights in their respective jurisdictions. The following is examined: law enforcement by public institutions, law enforcement by private parties and overlaps as well as hybrids and connections between both areas. A particular focus is given to collective redress, that is representative actions and model case proceedings. Comments from renowned practitioners sharing their experiences are included throughout the book. Separate concluding comparative chapters have two different aims: A comparative analysis of the legal solutions with a supranational European Union level focus provides invaluable insights into best practices and effectiveness. In addition, an intradisciplinary comparison assesses and evaluates the effectiveness of consumer law vs capital markets law mechanisms. Furthermore mechanisms of competition law and company law are taken into account.
In the mink industry, feed costs are the largest variable expense and breeding for feed efficient animals is warranted. Implementation of selection for feed efficiency must consider the relationships between feed efficiency and the current selection traits BW and litter size. Often, feed intake (FI) is recorded on a cage with a male and a female and there is sexual dimorphism that needs to be accounted for. Study aims were to (1) model group recorded FI accounting for sexual dimorphism, (2) derive genetic residual feed intake (RFI) as a measure of feed efficiency, (3) examine the relationship between feed efficiency and BW in males (BWM) and females (BWF) and litter size at day 21 after whelping (LS21) in Danish brown mink and (4) investigate direct and correlated response to selection on each trait of interest. Feed intake records from 9574 cages, BW records on 16 782 males and 16 875 females and LS21 records on 6446 yearling females were used for analysis. Genetic parameters for FI, BWM, BWF and LS21 were obtained using a multivariate animal model, yielding sex-specific additive genetic variances for FI and BW to account for sexual dimorphism. The analysis was performed in a Bayesian setting using Gibbs sampling, and genetic RFI was obtained from the conditional distribution of FI given BW using genetic regression coefficients. Responses to single trait selection were defined as the posterior distribution of genetic superiority of the top 10% of animals after conditioning on the genetic trends. The heritabilities ranged from 0.13 for RFI in females and LS21 to 0.59 for BWF. Genetic correlations between BW in both sexes and LS21 and FI in both sexes were unfavorable, and single trait selection on BW in either sex showed increased FI in both sexes and reduced litter size. Due to the definition of RFI and high genetic correlation between BWM and BWF, selection on RFI did not significantly alter BW. In addition, selection on RFI in either sex did not affect LS21. Genetic correlation between sexes for FI and BW was high but significantly lower than unity. The high correlations across sex allowed for selection on standardized averages of animals’ breeding values (BVs) for RFI, FI and BW, which yielded selection responses approximately equal to the responses obtained using the sex-specific BVs. The results illustrate the possibility of selecting against RFI in mink with no negative effects on BW and litter size.
Pharmacogenetics in schizophrenia comprises pharmacokinetical and pharmacodynamical aspects as well as an approach to identify candidate genes associated with therapy response or side effects. Firstly focussing on classical drug targets like dopaminergic or serotonergic receptors, currently also developmental and regulatory genes presumably associated with effects of antipsychotic therapy are identified. The aim of this study was to investigate associations between therapy response in schizophrenic patients and different polymorphisms previously been identified within a genome wide array in rodents treated with MK-801 and/or haloperidol combined with some well-known schizophrenia candidate genes. We genotyped for 200 different polymorphisms in 285 schizophrenic patients, who were treated with different antipsychotics within randomized controlled trials. Psychopathology was measured weekly using the PANSS scale. Correlations between psychopathology and genotypes were calculated by using a linear model (ANCOVA).
We found significant associations between some well-known candidate genes (e.g. D2-, 5HT1A-, and α1A-receptors) and different PANSS subscales at baseline and after four weeks of antipsychotic treatment considered as therapy response. Furthermore we also identified several significant associations between some genes introduced from the animal model and psychopathology at baseline and towards therapy response. Some of them were formerly described in the literature (e.g. Homer1, Phospholipase C and Transthyretin), but most of them have not been related to schizophrenia or antipsychotic treatment by now (e.g. PLEKHA6, CLIC6 and SOSTDC1).
This indicates an involvement of genes in the pathophysiology of schizophrenia apart from yet known candidate genes and might further help in detecting differential therapy response in individuals with schizophrenia.
Long-term lithium-treatment has been associated with deficits in several cognitive domains in euthymic bipolar patients. At the same time, long-term lithium treatment is also associated with an increase in parathyroid levels, often without a concomitant increase in calcium levels. Such an isolated increase in parathyroid levels has been linked to depressive symptoms and cognitive deficits in otherwise healthy individuals.
To investigate whether increased parathyroid levels are associated with cognitive deficits in euthymic bipolar patients.
We plan to recruit 30 euthymic bipolar patients on lithium treatment for this study. Patients will take part in several neuropsychological tests, covering executive functioning, memory and attention. In parallel, blood levels of lithium, parathyroid hormone, 25-hydroxyvitamin D, creatinine, calcium and phosphate will be assessed, besides clinical chemistry and blood cell count. In addition, to account for potential confounders, a variety of clinical variables will be recorded, including established mood rating scales and demographic variables as well as further parameters relevant to the course of the illness.
As the study is still ongoing results are not available yet at this moment.
Results will be discussed in the context of previous studies examining the impact of lithium and parathyroid hormone on mood and cognition in healthy individuals and patients with bipolar disorder, respectively. Dependent on the outcome of this study, potential future studies, including intervention trials aiming at lowering increased PTH levels in bipolar patients on lithium will be outlined.
The effectiveness of electroconvulsive therapy (ECT) in pharmacotherapy resistant major depression and schizophrenia has been shown for all age groups. Nevertheless, age specific side effects such as greater cognitive impairment and higher somatic risks due to medical comorbidities and concomitant medication may be limiting factors in geriatric patients.
We retrospectively evaluated 4457 treatments in 380 patients. Clinical variables, treatment modalities, ictal and postictal neurophysiological parameters were analysed. For modelling the influence of age on these varibles of interest, linear regression models, if necessary logistic regression models, were performed (statistical software package R 2.8.1).
We found a considerable clinical improvement over all age groups. Higher severity of disease at admission came up with a better clinical response. In comparison of the whole patient sample versus the elderly over the age of 60, there were no significant differences in need and number of concomitant psychotropic, but in medical co-medication. Ictal and postictal EEG parameters were only in part predictive for clinical outcome, but age had a significant influence on most of them. Cardiovascular side effects and cognitive disturbances were more frequent in the elderly but were only transient, and in most cases there was no need for any specific treatment.
The outcome results show excellent effectiveness and tolerability of ECT in all age groups. The very old are more prone to adverse events, but nonetheless tolerate ECT well and are likely to benefit.
To investigate the association of early improvement and treatment emergent suicidal ideation in a large sample (N=705) of naturalistically treated inpatients with major depressive disorder
In line with previous reports early improvement was defined as a 20% HAMD improvement within the first two weeks of antidepressant treatment. Treatment emergent suicidal ideation was defined by a sudden increase from 0 or 1 to at least 3 on HAM-D item-3 and from 0,1 to at least 4 on MADR item 10 for suicidal ideation. Early improvers were compared with non-early improvers with respect to the occurrence of treatment emergent suicidality during treatment.
Early improvers were 3 (MADRS) to 3.4 (HAMD) times less likely to experience new emergence of suicidal ideation during the treatment course than non-improvers. In addition, early improvement was associated with significantly less pessimistic thoughts.
The analysis is based on secondary analysis of prospectively collected data. No controlled study design.
Early improvement is associated with significantly less treatment emergent suicidal ideation for it my may provide rapid symptom relief and reduce hopelessness.
Atypical features are common among depressed primary care patients, but clinical trials testing the efficacy of psychopharmacological and/or psychotherapeutic treatment are lacking. This paper examines the efficacy of sertraline and cognitive behavioural therapy (CBT) among depressed patients with atypical features.
Analyses involve a double-blind comparison of sertraline versus placebo (N=47) and a single-blind comparison between CBT versus a guided self-help group (GSG) (N=48), with primary efficacy endpoints being the Inventory of Depressive Symptomatology (IDSC) and Hamilton Depression Scale (HAMD-17).
In intent-to-treat (ITT) analyses, the decrease on the IDSC scale (and HAMD-17) was greater after CBT compared to GSG: p=0.01 (HAMD-17: p=0.01). The difference between SSRI versus placebo was not significant: p=0.22 (HAMD-17: p=0.36). At endpoint, the CBT versus GSG difference in mean change from baseline IDSc scores was 7.69 points (HAMD-17: 4.97 points), the sertraline versus placebo difference was 3.07 points (HAMD-17: 0.59 points).
The data provide a preliminary suggestion that the mix of patients with minor or mild major depression with atypical features may not be best treated with an SSRI, but that these conditions might be amenable to CBT. Although SSRI were not superior to placebo, it would be premature to rule out SSRI as efficacious in atypical depression.
Since the introduction of second generation antipsychotics (SGA) extrapyramidal-motor symptoms (EPS) have become a lesser problem in the treatment of schizophrenic patients. Yet, some SGAs display these adverse events and first generation antipsychotics are still widely used. Several genetic polymorphisms have been found to be associated with the occurance of EPS.
In this study we tried to identify genes related to EPS from an animal model and then replicated the findings in schizophrenic patients.
To identify new genes and show their relevance in the treatment of schizophrenic patients.
Rats were treated with haloperidol or saline and differential gene expression was assessed by using microarrays. We genotyped 285 schizophrenic patients for candidate genes and differentially expressed genes derived from the animal model. All patients were treated monotherapeutically with different antipsychotics within randomized controlled trials. EPS were assessed weekly using the ESRS and BAS. We used a linear model (ANCOVA) with PANSS total at baseline, type of medication and premedication as covariates for all investigated SNP's.
We found several SNPs to be associated with the occurance of EPS. The best results were obtained for SNPs within the genes of Phospholipase C epsilon 1 (PLCe1), Methionine Sulfoxide Reductase B3 (MSRB3), Chloride Intracellular Channel 6 (CLIC6), Prolactin Receptor (PRLR) and Dopamine Receptor D4 (DRD4). Effect sizes were between 1.7 and 4.9.
We could replicate some findings of the literature and identified four new genes possibly related to EPS. Some of these genes were recently related to schizophrenia.
People with severe mental illnesses, such as schizophrenia, depression or bipolar disorder, have worse physical health and reduced life expectancy compared to the general population. The excess cardiovascular mortality associated with schizophrenia and bipolar disorder is attributed in part to an increased risk of the modifiable coronary heart disease risk factors; obesity, smoking, diabetes, hypertension and dyslipidaemia. Antipsychotic medication and possibly other psychotropic medication like antidepressants can induce weight gain or worsen other metabolic cardiovascular risk factors. Patients may have limited access to general healthcare with less opportunity for cardiovascular risk screening and prevention than would be expected in a non-psychiatric population. The European Psychiatric Association (EPA), supported by the European Association for the Study of Diabetes (EASD) and the European Society of Cardiology (ESC) published this statement with the aim of improving the care of patients suffering from severe mental illness. The intention is to initiate cooperation and shared care between the different healthcare professionals and to increase the awareness of psychiatrists and primary care physicians caring for patients with severe mental illness to screen and treat cardiovascular risk factors and diabetes.
Purpose of this study was to assess subjective well-being in schizophrenia inpatients and to find variables predictive for response and remission of subjective well-being.
The subjective well-being under neuroleptic treatment scale (SWN-K) was used in 232 schizophrenia patients within a naturalistic multicenter trial. Early response was defined as a SWN-K total score improvement of 20% and by at least 10 points within the first 2 treatment weeks, response as an improvement in SWN-K total score of at least 20% and by at least 10 points from admission to discharge and remission in subjective well-being as a total score of more or equal to 80 points at discharge. Logistic regression and CART analyses were used to determine valid predictors of subjective well-being outcome.
Twenty-nine percent of the patients were detected to be SWN-K early responders, 40% fulfilled criteria for response in subjective well-being and 66% fulfilled criteria for remission concerning subjective well-being. Among the investigated predictors, SWN-K early improvement and the educational status were significantly associated with SWN-K response. The SWN-K total score at baseline showed a significant negative predictive value for response. Baseline SWN-K total score, PANSS global subscore, and side effects as well as the educational status were found to be significantly predictive for remission.
Depressive symptoms should be radically treated and side effects closely monitored to improve the patient's subjective well-being. The important influence of subjective well-being on overall treatment outcome could be underlined.