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Studies of schizophrenia with functional MRI showed hyper- and hypoactivations in various brain regions including the prefrontal cortex. Functional abnormalities have also been reported in first-degree relatives of schizophrenic patients. The aim of this study was to examine working memory related brain functions in healthy subjects, schizophrenic patients and unaffected relatives and to determine the influence of psychopathology on these processes.
A parametric n-back working memory task and functional MRI were used to examine 61 schizophrenic patients on antipsychotic medication, 11 nonpsychotic relatives of schizophrenic patients and a comparison group of 61 healthy subjects. The task difficulty was incrementally increased using a parametric task (0-back, 1-back, 2-back, and 3-back) to examine the relationship between working memory load, performance, and brain activity.
The results indicated that during the attention task (0-back) behavioral responses of patients and healthy subjects hardly differed but BOLD responses were considerably enhanced in schizophrenic patients. With increasing task difficulty differences between groups in BOLD responses diminished whereas behavioral deficits of patients increased. The examination of attention-independent working memory-functions (2- vs. 0-back) produced hypoactivations in patients, especially in frontal, temporal and subcortical brain regions. Behavioral performance and neural responses of unaffected relatives of schizophrenic patients were intermediate between schizophrenic patients and controls indicating slight brain dysfunctions. In addition, compensatory strategies were demonstrated.
These findings suggest that the genetic risk for schizophrenia is accompanied by neural inefficiency which is associated with cognitive deficits, especially in difficult tasks.
Collecting prospective data on medication adherence, course of illness, course of treatment, cost effectiveness and quality of life among patients with schizophrenia under the German health system.
The ELAN study was conducted as a multi-centre, non-interventional observation study. 374 patients with a diagnosis of schizophrenia or schizoaffective disorder (ICD-10 F2) who had been discharged with a medication of quetiapine (N=183), olanzapine (N=91) or risperidone (N=100) were included. Follow-up interviews were conducted after 6,12,18 and 24 months. Applied instruments comprised PANSS, MARS-S, EPS-M, AIMS-S, GAF, ZST and a questionnaire for quality of life.
For each follow-up, at least 80% of the original sample could be included. After two years, between 39% and 43% of patients continued to take the drug prescribed at discharge. Only between 4% and 7% of patients received no neuroleptic treatment in the last 6 months, respectively. The variety of drugs used increased during the course. Only small differences could be found regarding the defined outcome measures (PANSS, GAF, rehospitalisation rate) and side effects. Changes in medication were mostly due to insufficient efficacy or side effects. Doctor's recommendations had an important influence on patients’ decisions.
Under conditions of routine treatment, medication adherence was much greater and differences between drugs were smaller than reported in randomised controlled clinical trials. Taking into account the low sample selection bias and the small percentage of lost-to-follow-up subjects, this study provides some new insight into routine clinical treatment and outcomes in patients with schizophrenia.
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.
To examine the predictive validity of early improvement in a naturalistic sample of inpatients and to identify the criterion that best defines early improvement.
Two hundred and forty-seven inpatients who fulfilled ICD-10 criteria for schizophrenia were assessed with the Positive And Negative Syndrome Scale (PANSS) at admission and at biweekly intervals until discharge from hospital. Remission was defined according to the recently proposed consensus criteria, response as a reduction of at least 40% in the PANNS total score from admission to discharge.
Receiver operating characteristic (ROC) analyses showed that early improvement (reduction of the PANSS total score within the first 2 weeks of treatment) predicts remission (AUC = 0.659) and response (AUC = 0.737) at discharge. A 20% reduction in the PANSS total score within the first 2 weeks was the most accurate cut-off for the prediction of remission (total accuracy: 65%; sensitivity: 53%; specificity: 76%), and a 30% reduction the most accurate cut-off for the prediction of response (total accuracy: 76%; sensitivity: 47%; specificity: 90%).
The findings of clinical drug trials that early improvement is a predictor of subsequent treatment response were replicated in a naturalistic sample. Further studies should examine whether patients without early improvement benefit from an early change of antipsychotic medication.
Aim was to examine depressive symptoms in acutely ill schizophrenia patients on a single symptom basis and to evaluate their relationship with positive, negative and general psychopathological symptoms.
Two hundred and seventy-eight patients suffering from a schizophrenia spectrum disorder were analysed within a naturalistic study by the German Research Network on Schizophrenia. Using the Calgary Depression Scale for Schizophrenia (CDSS) depressive symptoms were examined and the Positive and Negative Syndrome Scale (PANSS) was applied to assess positive, negative and general symptoms. Correlation and factor analyses were calculated to detect the underlying structure and relationship of the patient’s symptoms.
The most prevalent depressive symptoms identified were depressed mood (80%), observed depression (62%) and hopelessness (54%). Thirty-nine percent of the patients suffered from depressive symptoms when applying the recommended cut-off of a CDSS total score of > 6 points at admission. Negligible correlations were found between depressive and positive symptoms as well as most PANSS negative and global symptoms despite items on depression, guilt and social withdrawal. The factor analysis revealed that the factor loading with the PANSS negative items accounted for most of the data variance followed by a factor with positive symptoms and three depression-associated factors.
The naturalistic study design does not allow a sufficient control of study results for the effect of different pharmacological treatments possibly influencing the appearance of depressive symptoms.
Results suggest that depressive symptoms measured with the CDSS are a discrete symptom domain with only partial overlap with positive or negative symptoms.
The role of H2 in forming interstellar complex organics is still not clear due to the high activation energies required for “non-energetic” association reactions. In this work, we investigated the potential contribution of H2 to the hydrogenated species (HnNCO) formation on dust grains when the “energetic” processing is involved. The goal is to test whether an additional hydrogenation pathway is possible upon UV irradiation of a CO:H2 ice mixture. It is proposed that the electronically excited carbon monoxide (CO*) induced by UV-photons can react with a ground-state H2 to form HCO, ultimately enhancing the production of COMs in ice mantle.
Breast-feeding is thought to facilitate young children’s acceptance of new foods, including vegetables, but the evidence for this relationship appears inconsistent across studies. Increasing children’s vegetable intake remains challenging; therefore the present study aimed to investigate whether breast-feeding duration predicts vegetable intake in 2–6-year-old children.
Actual vegetable intake was measured in studies across three European countries. General linear model analyses with breast-feeding duration, sex and age of the child and maternal education as variables were used to predict children’s vegetable intake per country. Additionally, the relationships between child eating behaviour characteristics (asked through the Child Eating Behaviour Questionnaire) and vegetable intake were investigated via Pearson correlations.
Daycare centres, schools and home settings in Denmark, Greece and the Netherlands.
Children aged 2–6 years (n 750).
Breast-feeding duration was positively associated with children’s vegetable intake at 2–6 years old in Denmark (P<0·01) and the Netherlands (P<0·05), but not in Greece (P=0·17). Age of the child, maternal education and sex of the child did not predict vegetable intake in our sample. All countries showed an inverse relationship between food neophobia and children’s vegetable intake and a positive relationship between vegetable liking and intake.
The present study found that breast-feeding duration is a predictor of later vegetable intake, but that current child eating behaviour characteristics, such as vegetable liking, food neophobia and enjoyment of food, also influence vegetable intake. Besides encouragement of breast-feeding duration, strategies that support vegetable liking and food enjoyment and decrease food neophobia are needed to support young children’s vegetable intake.
We study the geometric and topological properties of strange non-chaotic attractors created in non-smooth saddle-node bifurcations of quasiperiodically forced interval maps. By interpreting the attractors as limit objects of the iterates of a continuous curve and controlling the geometry of the latter, we determine their Hausdorff and box-counting dimension and show that these take distinct values. Moreover, the same approach allows us to describe the topological structure of the attractors and to prove their minimality.
Measles, mumps, rubella (MMR) and varicella zoster virus (VZV) infection can cause serious diseases and complications in the HIV-positive population. Due to successful vaccination programmes measles, mumps and congenital rubella syndrome has become neglected in Germany. However, recent outbreaks of measles have occurred from import-associated cases. In this cross-sectional study the serostatus for MMR and VZV in 2013 HIV-positive adults from three different university outpatient clinics in Bonn (n = 544), Cologne (n = 995) and Munich (n = 474) was analysed. Sera were tested for MMR- and VZV-specific immunglobulin G antibodies using commercial immunoassays. Seronegativity was found in 3% for measles, 26% for mumps, 11% for rubella and 2% for VZV. Regarding MMR, 35% of patients lacked seropositivity against at least one infectious agent. In multivariable analysis younger age was strongly associated with seronegativity against all four viruses, measles, mumps, rubella (P < 0·001, P < 0·001 and P = 0·001, respectively) and VZV (P = 0·001). In conclusion, there is high need for MMR and VZV vaccination in people living with HIV in Germany born in 1970 or later. Thus, systematic MMR and VZV antibody screening and vaccination should be implemented in the HIV-positive population to prevent serious disease and complications of vaccine-preventable diseases.
Approximately half of the variation in wellbeing measures overlaps with variation in personality traits. Studies of non-human primate pedigrees and human twins suggest that this is due to common genetic influences. We tested whether personality polygenic scores for the NEO Five-Factor Inventory (NEO-FFI) domains and for item response theory (IRT) derived extraversion and neuroticism scores predict variance in wellbeing measures. Polygenic scores were based on published genome-wide association (GWA) results in over 17,000 individuals for the NEO-FFI and in over 63,000 for the IRT extraversion and neuroticism traits. The NEO-FFI polygenic scores were used to predict life satisfaction in 7 cohorts, positive affect in 12 cohorts, and general wellbeing in 1 cohort (maximal N = 46,508). Meta-analysis of these results showed no significant association between NEO-FFI personality polygenic scores and the wellbeing measures. IRT extraversion and neuroticism polygenic scores were used to predict life satisfaction and positive affect in almost 37,000 individuals from UK Biobank. Significant positive associations (effect sizes <0.05%) were observed between the extraversion polygenic score and wellbeing measures, and a negative association was observed between the polygenic neuroticism score and life satisfaction. Furthermore, using GWA data, genetic correlations of -0.49 and -0.55 were estimated between neuroticism with life satisfaction and positive affect, respectively. The moderate genetic correlation between neuroticism and wellbeing is in line with twin research showing that genetic influences on wellbeing are also shared with other independent personality domains.
The aim of this study was to evaluate the quality of life in patients with vascular chronic Q fever at time of diagnosis and during follow-up. Based upon the SF-36 questionnaire, the mean physical and mental health of each patient were assessed at 3-month intervals for up to 18 months. A total of 26 patients were included in the study. At time of diagnosis, the mean physical health and mental health score was 50·6 [95% confidence interval (CI) 46·7–54·4] and 44·6 (95% CI 41·6–47·5), respectively. During treatment, the mean physical health score declined significantly by 1·7 points each 3 months (P < 0·001) to 40·8 (95% CI 34·4–45·1). The mean mental health score significantly and steadily increased towards 51·2 (95% CI 46·9–54·3) during follow-up (P = 0·026). A total of 23% of patients were cured after 18 months of follow-up. In conclusion, quality of life at time of diagnosis for patients with vascular chronic Q fever is lower compared to a similar group of patients, matched for age and gender, with an aortic abdominal aneurysmal disease, and physical health decreases further after starting treatment. Considering the low percentage of cure, the current treatment of vascular chronic Q fever patients may require a separate strategy from that of endocarditis in order to increase survival.
Polycyclic aromatic hydrocarbon (PAH) molecules have been long considered promising candidates for the carriers of the diffuse interstellar bands (DIBs). The PAH-DIB hypothesis, however, raises two major issues. First, the number of interstellar PAH species is potentially orders of magnitude larger than the number of DIBs. Second, the absorption spectrum of a PAH is in general dominated by bands found at UV wavelengths while, conversely, DIBs are absent from the UV wavelength domain and arise at visible and near IR wavelengths. These issues do not necessarily weaken the PAH-DIB hypothesis and can actually allow us to refine it. In that context, we analyze the UV/vis absorption spectra of PAH molecules isolated in Ne matrices and propose that polyynyl-substituted PAHs, or similar species, are valid candidates for the carriers of the DIBs. Finally, a possible lifecycle for DIB-carrying PAHs is presented.
The electronic spectroscopy of various polycyclic aromatic hydrocarbon (PAH) molecules has been studied in the laboratory at low temperatures using both molecular beam and matrix isolation spectroscopy techniques. While molecular beam spectra can be readily compared to astronomical observations, the band positions measured in Ne and Ar matrices are extrapolated to obtain rather good estimates for the same transitions in the gas phase. Absolute absorption cross sections are determined for gas-phase and matrix spectra by comparing them with calibrated solution spectra. All laboratory results are analyzed and discussed in view of the role that PAHs can play as carriers of the diffuse interstellar bands (DIBs). Our studies suggest that regular neutral PAHs are not responsible for any of the known strong DIBs.
This study examines historical variation in individual trajectories of heavy drinking and marijuana use from age 18 to 22. Unlike most studies that have examined cohort differences in drug use, it focuses on differences in both level of use and rates of change (growth). Nearly 39,000 youths from the high school classes of 1976–2004 were surveyed at biennial intervals between the ages of 18 and 22 as part of the national Monitoring the Future study. Between 1976 and 2004, adolescent heavy drinking decreased substantially. However, because the age 18–22 heavy drinking growth rate increased threefold for males and sixfold for females during this period, heavy drinking among 21- to 22-year-olds remained largely stable. The growth rate for marijuana use was more stable across cohorts, and historical declines in use were sizable across the entire 18–22 age band. Generally, historical variation in use was unrelated to college status and living arrangements as well as to historical changes in the distribution of young adult social roles. Findings suggest that historical fluctuations in use were less the result of proximal young adult factors and more the result of historical variation in distal adolescent factors, the effect of which diminished with age, especially for heavy drinking.
To analyse insight of illness during the course of inpatient treatment, and to identify influencing factors and predictors of insight.
Insight into illness was examined in 399 patients using the item G12 of the Positive and Negative Syndrome Scale (“lack of insight and judgement”). Ratings of the PANSS, HAMD, UKU, GAF, SOFAS, SWN-K and Kemp's compliance scale were performed and examined regarding their potential association with insight. The item G12 was kept as an ordinal variable to compare insight between subgroups of patients.
Almost 70% of patients had deficits in their insight into illness at admission. A significant improvement of impairments of insight during the treatment (p<0.0001) was observed. At admission more severe positive and negative symptoms, worse functioning and worse adherence were significantly associated with poorer insight. Less depressive symptoms (p = 0.0004), less suicidality (p = 0.0218), suffering from multiple illness-episodes (p<0.0001) and worse adherence (p = 0.0012) at admission were identified to be significant predictors of poor insight at discharge.
The revealed predictors might function as treatment targets in order to improve insight and with it outcome of schizophrenia.
The main reason for recreational use of cannabis is the ‘high’, the primary psychotropic effect of Δ9-tetrahydrocannabinol (THC). This psychoactive compound of cannabis induces a range of subjective, physical and mental reactions. The effect on heart rate is pronounced and complicates bloodflow-based neuroimaging of psychotropic effects of THC. In this study we investigated the effects of THC on baseline brain perfusion and activity in association with the induction of ‘feeling high’. Twenty-three subjects participated in a pharmacological MRI study, where we applied arterial spin labelling (ASL) to measure perfusion, and resting-state functional MRI to assess blood oxygen level-dependent signal fluctuation as a measure of baseline brain activity. Feeling high was assessed with a visual analogue scale and was compared to the imaging measures. THC increased perfusion in the anterior cingulate cortex, superior frontal cortex, and insula, and reduced perfusion in the post-central and occipital gyrus. Baseline brain activity was altered, indicated by increased amplitude of fluctuations in resting-state functional MRI signal after THC administration in the insula, substantia nigra and cerebellum. Perfusion changes in frontal cortex were negatively correlated with ratings of feeling high, suggesting an interaction between cognitive control and subjective effects of THC. In conclusion, an acute THC challenge altered baseline brain perfusion and activity, especially in frontal brain areas involved in cognitive and emotional processes, and the insula, associated with interoceptive awareness. These changes may represent the THC-induced neurophysiological correlates of feeling high. The alterations in baseline brain perfusion and activity also have relevance for studies on task-related effects of THC on brain function.
Of eight acute infections in German tourists caused by sandfly fever virus, serotype Toscana (TOS). and diagnosed clinically and serologically, seven were acquired during visits to Tuscany, Italy, and one to Coimbra, Portugal. An indirect immunofluorescence assay (IFA) using infected cells, and a newly developed enzyme-immunoassay (EIA) using crude virus antigen prepared from infected Vero-E6 cells was used to detect anti-TOS IgM and IgG. In a seroepidemiological survey of 859 health care workers and medical students, anti-TOS IgG was detected in 1·0% by IFA, and in 0·7% by EIA. In 2034 German patients hospitalized for various diseases, 1·6% were positive for anti-TOS IgG by IFA, and 0·8% by EIA. Anti-TOS IgG was detected in 43 samples of commercial immunoglobulins at titres of 10–1000 by EIA. Although the seroprevalence of antibodies to TOS is low in Germany, TOS infection should be considered in patients returning from endemic areas who complain of fever, and headaches, and have symptoms of meningitis.
Effective infection control measures during norovirus outbreaks are urgently needed in places where vulnerable individuals gather. In the present study, the effect of a number of measures was investigated in daily practice. Forty-nine Dutch nursing homes were monitored prospectively for norovirus outbreaks during two winter seasons. A total of 37 norovirus outbreaks were registered. Control measures were most effective when implemented within 3 days after onset of disease of the first patient. Measures targeted at reduced transmission between persons, via aerosols, and via contaminated surfaces reduced illness in staff and in residents. Reducing illness in staff results in fewer costs for sick leave and substitution of staff and less disruption in the care of residents. The effect of control measures on outbreak duration was limited. This is the first intervention study examining the effect of control measures. Further research is needed to extend and refine the conclusions.
The aim of the investigation was to study the influence of indenter tip geometry on the conventionally obtained indentation modulus of enamel by nanoindentation. Indentation tests on bovine enamel using three different diamond pyramidal indenters with half face angles 65.27°, 45°, and 35.26° were conducted to evaluate the indentation modulus using the Oliver–Pharr method [W.C. Oliver and G.M. Pharr, J. Mater. Res.7, 1564 (1992)]. In addition, three different dehydration conditions were studied: wet under Hank's balanced salt solution, laboratory dried, and vacuum dehydrated. For the Berkovich indenter (65.27°) and 45° pyramidal indenters, there was only a small difference between indentation modulus values, whereas for the cube-corner indenter (35.26°) a ratio of 2.4 between laboratory dry and wet samples was found. A detailed evaluation, including indentation creep and recovery as well as pileup, resulted in a reduction of this latter ratio to 1.7. This still large difference was rationalized on the basis of the different deformation mechanisms generated by indenters of different face angles.