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Negative symptoms of schizophrenia remain a major therapeutic challenge. The progress in the conceptualization and assessment is not yet fully reflected by treatment research. Nevertheless, there is a growing evidence base regarding the effects of biological and psychosocial interventions on negative symptoms. The importance of the distinction between primary and secondary negative symptoms for treatment selection might seem evident, but the currently available evidence remains limited. Good clinical practice is recommended for the treatment of secondary negative symptoms. Antipsychotic treatment should be optimized to avoid secondary negative symptoms due to side effects and due to positive symptoms. For most available interventions, further evidence is needed to formulate sound recommendations for primary, persistent, or predominant negative symptoms.
However, based on currently available evidence recommendations for the treatment of undifferentiated negative symptoms (including both primary and secondary negative symptoms) are provided. Although it has proven difficult to formulate an evidence-based recommendation for the choice of an antipsychotic, a switch to a second-generation antipsychotic should be considered for patients who are treated with a first-generation antipsychotic. Antidepressant add-on to antipsychotic treatment is an option. Social skills training is recommended as well as cognitive remediation for patients who also show cognitive impairment. Exercise interventions also have shown promise. Finally, access to treatment and to psychosocial rehabilitation should be ensured for patients with negative symptoms. Overall, there is definitive progress in the field, but further research is clearly needed to develop specific treatments for negative symptoms.
Improved survival has led to a growing population of adults with congenital heart disease (CHD), followed by numerous reports of late complications. Liver disease is a known complication in some patients, with most studies focusing on Fontan associated liver disease. Whether liver disease also exists in other patients with CHD is not fully investigated. Elevated central venous pressure is considered pivotal in the development of liver disease in Fontan associated liver disease, and other patients with alterations in central venous pressure may also be at risk for developing liver fibrosis. We wanted to see if liver fibrosis is present in patients with tetralogy of Fallot. Many patients with tetralogy of Fallot have severe pulmonary regurgitation, which can lead to elevated central venous pressure. Patients with tetralogy of Fallot may be at risk of developing liver fibrosis.
Materials and methods:
Ten patients (24–56 years) with tetralogy of Fallot and pulmonary regurgitation were investigated for liver fibrosis. All patients were examined with magnetic resonance elastography of liver, hepatobiliary iminodiacetic acid scan, indocyanine green elimination by pulse spectrophotometry, elastography via FibroScan, abdominal ultrasound including liver elastography, and blood samples including liver markers.
Three out of ten patients had findings indicating possible liver fibrosis. Two of these had a liver biopsy performed, which revealed fibrosis stage 1 and 2, respectively. The same three patients had an estimated elevated central venous pressure in previous echocardiograms.
Mild liver fibrosis was present in selected patients with tetralogy of Fallot and may be related to elevated central venous pressure.
During the last decades, a renewed interest for negative symptoms (NS) was brought about by the increased awareness that they interfere severely with real-life functioning, particularly when they are primary and persistent.
In this guidance paper, we provide a systematic review of the evidence and elaborate several recommendations for the conceptualization and assessment of NS in clinical trials and practice.
Expert consensus and systematic reviews have provided guidance for the optimal assessment of primary and persistent negative symptoms; second-generation rating scales, which provide a better assessment of the experiential domains, are available; however, NS are still poorly assessed both in research and clinical settings.
This European Psychiatric Association (EPA) guidance recommends the use of persistent negative symptoms (PNS) construct in the context of clinical trials and highlights the need for further efforts to make the definition of PNS consistent across studies in order to exclude as much as possible secondary negative symptoms. We also encourage clinicians to use second-generation scales, at least to complement first-generation ones.
The EPA guidance further recommends the evidence-based exclusion of several items included in first-generation scales from any NS summary or factor score to improve NS measurement in research and clinical settings. Self-rated instruments are suggested to further complement observer-rated scales in NS assessment.
Several recommendations are provided for the identification of secondary negative symptoms in clinical settings.
The dissemination of this guidance paper may promote the development of national guidelines on negative symptom assessment and ultimately improve the care of people with schizophrenia.
Current sea-level rise partly stems from increased surface melting and meltwater runoff from the Greenland ice sheet. Multi-year snow, also known as firn, covers about 80% of the ice sheet and retains part of the surface meltwater. Since the firn cold content integrates its physical and thermal characteristics, it is a valuable tool for determining the meltwater-retention potential of firn. We use gap-filled climatological data from nine automatic weather stations in the ice-sheet accumulation area to drive a surface-energy-budget and firn model, validated against firn density and temperature observations, over the 1998–2017 period. Our results show a stable top 20 m firn cold content (CC20) at most sites. Only at the lower-elevation Dye-2 site did CC20 decrease, by 24% in 2012, before recovering to its original value by 2017. Heat conduction towards the surface is the main process feeding CC20 at all nine sites, while CC20 reduction occurs through low-cold-content fresh-snow addition at the surface during snowfall and latent-heat release when meltwater refreezes. Our simulations suggest that firn densification, while reducing pore space for meltwater retention, increases the firn cold content, enhances near-surface meltwater refreezing and potentially sets favourable conditions for ice-slab formation.
This paper presents a novel solution for precision draping of prepreg composite fabrics onto double curved molds. Our contributions relate to system design, including hardware and software components, and to system integration. On the hardware side, design and implementation of a drape tool with up to 120 suction cups positioned individually by linear actuators are described. On the software side, design and implementation of the software architecture are presented, along with necessary algorithms within sensor technologies and mathematical modeling. The essential system’s components were verified individually, and the entire integrated system was successfully validated in the Proof-of-Concept experiments, performed on an experimental physical model of the system.
Many new approaches have been developed to treat borderline personality disorder (BPD) by means of psychotherapy. Though there is a clear research trend towards short-interventions, the evidence from randomised controlled trials (RCT) on longer-term programmes still accumulates. On the one hand, well-established treatments like Dialectical Behavior Therapy (DBT) or Mentalisation-Based Treatment (MBT) are now subject to real-world effectiveness studies; on the other hand, new dynamic approaches have been studied, lasting longer than 6 months.
We are currently updating the cochrane Collaboration review on psychological interventions for BPD. First findings on the effects of longer-term psychotherapies will be presented.
We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) according to cochrane collaboration standards. Any randomized comparisons of psychological interventions versus unspecific control interventions, waitlist or specific psychotherapeutic interventions in adult BPD patients were eligible. Primary outcomes were BPD core pathology as depicted by DSM criteria. Secondary outcomes included associated pathology, i.e., depression and anxiety, general psychopathology severity and functioning as well as tolerability and safety. Two researchers selected trials, assessed quality and extracted data independently.
The current evidence of longer-term psychological interventions in general, and the types of interventions for which RCT evidence is available will be evaluated and critically discussed.
Disclosure of interest
The authors declare that they have no competing interest.
The western societies have a rapidly aging population and an increasing number of elderly with alcohol use disorders.
The purpose of the elderly study is to develop and test an outpatient behavior therapy program for people with an alcohol use disorders.
Aim of this abstract
To investigate the association between ages, gender, drinking pattern and psychology distress.
The study is a randomized study expected to enroll and treat 1000 participants aged 60+ years before April 2017; 200 in USA; 400 in Germany and 400 in Denmark. To be included in the study the participants have to fulfil the DSM-5 criteria for alcohol use disorder. All participants are examined at baseline, and at four follow up interviews. After the baseline interview all participants are randomized to Motivational Enhancement Therapy (MET); or MET followed by 8 weeks of counseling based on the Community Reinforcement Approach (CRA) with a module added to address problems relevants to elderly people.
The presentation will include baseline characteristics of the Danish participants including demographics, expectations to treatment, history of drinking in the last 90 days before baseline and their psychological distress. We have now enrolled 259 participants in the Danish database. We expect to present results from 320 patients.
The data will present information about the profile of 60+ years’ individuals seeking treatment for alcohol use disorder, and thereby provide knowledge about which characteristics that may be important when planning treatment for this age group.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Ascarid parasites infect a variety of hosts and regular anthelmintic treatment is recommended for all species. Parascaris spp. is the only ascarid species with widespread anthelmintic resistance, which allows for the study of resistance mechanisms. The purpose of this study was to establish an in vitro drug exposure protocol for adult anthelmintic-naïve Parascaris spp. and report a preliminary transcriptomic analysis in response to drug exposure. Live worms were harvested from foal necropsies and maintained in RPMI-1640 at 37 °C. Serial dilutions of oxibendazole (OBZ) and ivermectin (IVM) were prepared for in vitro drug exposure, and worm viability was monitored over time. In a second drug trial, worms were used for transcriptomic analysis. The final drug concentrations employed were OBZ at 40.1 μm (10 μg mL−1) and IVM at 1.1 μm (1 μg mL−1) for 24 and 3 h, respectively. The RNA-seq analysis revealed numerous differentially expressed genes, with some being potentially related to drug detoxification and regulatory mechanisms. This report provides a method for in vitro drug exposure and the phenotypic responses for Parascaris spp., which could be extrapolated to other ascarid parasites. Finally, it also provides preliminary transcriptomic data following drug exposure as a reference point for future studies of Parascaris spp.
The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
The chemical enrichment of the Universe is considerably affected by the contribution of cool evolved stars. We studied the O-rich star R Peg and the C-rich star V Oph, using respectively the VLTI/GRAVITY and VLTI/MIDI instruments. We interpret the data using grids of 1-D and 3-D dynamic model atmospheres.
Significant increases in excess all-cause mortality, particularly in the elderly, were observed during the winter of 2014/15 in England. With influenza A(H3N2) the dominant circulating influenza A subtype, this paper determines the contribution of influenza to this excess controlling for weather. A standardised multivariable Poisson regression model was employed with weekly all-cause deaths the dependent variable for the period 2008–2015. Adjusting for extreme temperature, a total of 26 542 (95% CI 25 301–27 804) deaths in 65+ and 1942 (95% CI 1834–2052) in 15–64-year-olds were associated with influenza from week 40, 2014 to week 20, 2015. This is compatible with the circulation of influenza A(H3N2). It is the largest estimated number of influenza-related deaths in England since prior to 2008/09. The findings highlight the potential health impact of influenza and the important role of the annual influenza vaccination programme that is required to protect the population including the elderly, who are vulnerable to a severe outcome.
Fluid–structure interactions are ubiquitous in nature and technology. However, the systems are often so complex that numerical simulations or ad hoc assumptions must be used to gain insight into the details of the complex interactions between the fluid and solid mechanics. In this paper, we present experiments and theory on viscous flow in a simple bioinspired soft valve which illustrate essential features of interactions between hydrodynamic and elastic forces at low Reynolds numbers. The set-up comprises a sphere connected to a spring located inside a tapering cylindrical channel. The spring is aligned with the central axis of the channel and a pressure drop is applied across the sphere, thus forcing the liquid through the narrow gap between the sphere and the channel walls. The sphere’s equilibrium position is determined by a balance between spring and hydrodynamic forces. Since the gap thickness changes with the sphere’s position, the system has a pressure-dependent hydraulic resistance. This leads to a nonlinear relation between applied pressure and flow rate: flow initially increases with pressure, but decreases when the pressure exceeds a certain critical value as the gap closes. To rationalize these observations, we propose a mathematical model that reduced the complexity of the flow to a two-dimensional lubrication approximation. A closed-form expression for the pressure drop/flow rate is obtained which reveals that the flow rate
depends on the pressure drop
, sphere radius
, gap thickness
, and viscosity
, where the critical pressure
scales with the spring constant
. These predictions compared favourably to the results of our experiments with no free parameters.
Berseem clover (Trifolium alexandrinum L.) is an important forage legume and is the primary winter forage crop in Pakistan. There are significant gaps in yield potential among varieties of berseem clover, as well as yields obtained at research stations and on-farm. To address this problem a survey of farmers was undertaken in the districts of Kasur and Okara, Punjab, Pakistan to determine the level of knowledge and understanding of berseem forage cultivation and seed production. The study comprised 44% smallholder (<3 ha), 26% medium (3–5 ha) and 30% large farmers (>5 ha) with average age of 42 years. Most farmers had little or no knowledge of the role of seed quality, inoculation with rhizobium, pollination, fertiliser use, irrigation management and the importance of forage nutritional value in improving livestock productivity. Most farmers (56%) had received no input from the government or private sector to improve forage production, relying instead on traditional knowledge. Knowledge of the importance of land preparation (95%), sowing rate (98%) and insect and pest management (75%) was higher than seed selection and fertilisation. Adoption of improved varieties (3%) and production technologies (14%) was low due to various constraints including ignorance, high cost of inputs, lack of availability of inputs in the market and a perceived high level of financial risk. Almost 100% of the respondents agreed that seed of improved varieties was a pre-requisite for higher forage and seed production as well as essential to start village-based forage seed enterprises.
The surveillance of Clostridium difficile (CD) in Denmark consists of laboratory based data from Departments of Clinical Microbiology (DCMs) sent to the National Registry of Enteric Pathogens (NREP). We validated a new surveillance system for CD based on the Danish Microbiology Database (MiBa). MiBa automatically collects microbiological test results from all Danish DCMs. We built an algorithm to identify positive test results for CD recorded in MiBa. A CD case was defined as a person with a positive culture for CD or PCR detection of toxin A and/or B and/or binary toxin. We compared CD cases identified through the MiBa-based surveillance with those reported to NREP and locally in five DCMs representing different Danish regions. During 2010–2014, NREP reported 13 896 CD cases, and the MiBa-based surveillance 21 252 CD cases. There was a 99·9% concordance between the local datasets and the MiBa-based surveillance. Surveillance based on MiBa was superior to the current surveillance system, and the findings show that the number of CD cases in Denmark hitherto has been under-reported. There were only minor differences between local data and the MiBa-based surveillance, showing the completeness and validity of CD data in MiBa. This nationwide electronic system can greatly strengthen surveillance and research in various applications.
Several studies have examined whether use of substances can cause schizophrenia. However, due to methodological limitations in the existing literature (e.g. selection bias and lack of adjustment of co-abuse) uncertainties still remain. We aimed to investigate whether substance abuse increases the risk of developing schizophrenia, addressing some of these limitations.
The longitudinal, nationwide Danish registers were linked to establish a cohort of 3 133 968 individuals (105 178 673 person-years at risk), identifying 204 505 individuals diagnosed with substance abuse and 21 305 diagnosed with schizophrenia. Information regarding substance abuse was extracted from several registers and did not include psychotic symptoms caused by substance abuse in the definition. This resulted in a large, generalizable sample of exposed individuals. The data was analysed using Cox regression analyses, and adjusted for calendar year, gender, urbanicity, co-abuse, other psychiatric diagnosis, parental substance abuse, psychiatric history, immigration and socioeconomic status.
A diagnosis of substance abuse increased the overall risk of developing schizophrenia [hazard ratio (HR) 6.04, 95% confidence interval (CI) 5.84–6.26]. Cannabis (HR 5.20, 95% CI 4.86–5.57) and alcohol (HR 3.38, 95% CI 3.24–3.53) presented the strongest associations. Abuse of hallucinogens (HR 1.86, 95% CI 1.43–2.41), sedatives (HR 1.68, 95% CI 1.49–1.90), and other substances (HR 2.85, 95% CI 2.58–3.15) also increased the risk significantly. The risk was found to be significant even 10–15 years subsequent to a diagnosis of substance abuse.
Our results illustrate robust associations between almost any type of substance abuse and an increased risk of developing schizophrenia later in life.
Adverse psychosocial working environments characterized by job strain (the combination of high demands and low control at work) are associated with an increased risk of depressive symptoms among employees, but evidence on clinically diagnosed depression is scarce. We examined job strain as a risk factor for clinical depression.
We identified published cohort studies from a systematic literature search in PubMed and PsycNET and obtained 14 cohort studies with unpublished individual-level data from the Individual-Participant-Data Meta-analysis in Working Populations (IPD-Work) Consortium. Summary estimates of the association were obtained using random-effects models. Individual-level data analyses were based on a pre-published study protocol.
We included six published studies with a total of 27 461 individuals and 914 incident cases of clinical depression. From unpublished datasets we included 120 221 individuals and 982 first episodes of hospital-treated clinical depression. Job strain was associated with an increased risk of clinical depression in both published [relative risk (RR) = 1.77, 95% confidence interval (CI) 1.47–2.13] and unpublished datasets (RR = 1.27, 95% CI 1.04–1.55). Further individual participant analyses showed a similar association across sociodemographic subgroups and after excluding individuals with baseline somatic disease. The association was unchanged when excluding individuals with baseline depressive symptoms (RR = 1.25, 95% CI 0.94–1.65), but attenuated on adjustment for a continuous depressive symptoms score (RR = 1.03, 95% CI 0.81–1.32).
Job strain may precipitate clinical depression among employees. Future intervention studies should test whether job strain is a modifiable risk factor for depression.
Dietary long-chain n-3 PUFA (n-3 LCPUFA) in infancy may have long-term effects on lifestyle disease risk. The present follow-up study investigated whether maternal fish oil (FO) supplementation during lactation affected growth and blood pressure in adolescents and whether the effects differed between boys and girls. Mother–infant pairs (n 103) completed a randomised controlled trial with FO (1·5 g/d n-3 LCPUFA) or olive oil (OO) supplements during the first 4 months of lactation; forty-seven mother–infant pairs with high fish intake were followed-up for 4 months as the reference group. We also followed-up 100 children with assessment of growth, blood pressure, diet by FFQ and physical activity by 7-d accelerometry at 13·5 (sd 0·4) years of age. Dried whole-blood fatty acid composition was analysed in a subgroup (n 49). At 13 years of age, whole-blood n-3 LCPUFA, diet, physical activity and body composition did not differ between the three groups. The children from the FO group were 3·4 (95 % CI 0·2, 6·6) cm shorter (P=0·035) than those from the OO group, and tended to have less advanced puberty (P=0·068), which explained the difference in height. There was a sex-specific effect on diastolic blood pressure (Psex×group=0·020), which was driven by a 3·9 (95 % CI 0·2, 7·5) mmHg higher diastolic blood pressure in the FO compared with the OO group among boys only (P=0·041). Our results indicate that early n-3 LCPUFA intake may reduce height in early adolescence due to a delay in pubertal maturation and increase blood pressure specifically in boys, thereby tending to counteract existing sex differences.
We analyzed birth order differences in means and variances of height and body mass index (BMI) in monozygotic (MZ) and dizygotic (DZ) twins from infancy to old age. The data were derived from the international CODATwins database. The total number of height and BMI measures from 0.5 to 79.5 years of age was 397,466. As expected, first-born twins had greater birth weight than second-born twins. With respect to height, first-born twins were slightly taller than second-born twins in childhood. After adjusting the results for birth weight, the birth order differences decreased and were no longer statistically significant. First-born twins had greater BMI than the second-born twins over childhood and adolescence. After adjusting the results for birth weight, birth order was still associated with BMI until 12 years of age. No interaction effect between birth order and zygosity was found. Only limited evidence was found that birth order influenced variances of height or BMI. The results were similar among boys and girls and also in MZ and DZ twins. Overall, the differences in height and BMI between first- and second-born twins were modest even in early childhood, while adjustment for birth weight reduced the birth order differences but did not remove them for BMI.
While more and more long-period giant planets are discovered by direct imaging, the distribution of planets at these separations (≳5 AU) has remained largely uncertain, especially compared to planets in the inner regions of solar systems probed by RV and transit techniques. The low frequency, the detection challenges, and heterogeneous samples make determining the mass and orbit distributions of directly imaged planets at the end of a survey difficult. By utilizing Monte Carlo methods that incorporate the age, distance, and spectral type of each target, we can use all stars in the survey, not just those with detected planets, to learn about the underlying population. We have produced upper limits and direct measurements of the frequency of these planets with the most recent generation of direct imaging surveys. The Gemini NICI Planet-Finding Campaign observed 220 young, nearby stars at a median H-band contrast of 14.5 magnitudes at 1”, representing the largest, deepest search for exoplanets by the completion of the survey. The Gemini Planet Imager Exoplanet Survey is in the process of surveying 600 stars, pushing these contrasts to a few tenths of an arcsecond from the star. With the advent of large surveys (many hundreds of stars) using advanced planet-imagers we gain the ability to move beyond measuring the frequency of wide-separation giant planets and to simultaneously determine the distribution as a function of planet mass, semi-major axis, and stellar mass, and so directly test models of planet formation and evolution.
A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m2 in childhood and adolescence and up to 0.2 kg/m2 in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.