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Schubert was fond of writing four-hand music to be played by two pianists sitting on the same piano bench. His thirty-four compositions in this medium range from the earliest extant composition in his hand (a Fantasy penned in 1810) to his Rondo in A Major finished in the summer of 1828. No composer ever approached the piano duet with the seriousness Schubert did, and his corpus of four-hand pieces stands as the apex of the genre. The four-hand configuration seemed ideally suited to his temperament, as it was a congenial form of music-making that was emblematic in Biedermeier culture as an activity of friendship and sociability. It is thus not surprising that these works were a staple in his Schubertiads and ranked among his most successful publications during his lifetime. But the four-handed configuration was also a critical medium for the transmission and reception of much of his orchestral and chamber music. The many piano transcriptions of Schubert’s instrumental music arranged for four-hands issued by publishers over the course of the nineteenth century allowed any two decently practised amateur pianists a chance to get to know his music by reproducing it in the domestic space of the bourgeois parlour.
Tetralogy of Fallot patients face an elevated risk of developing chylothorax and pleural effusions post-surgery. This patient group exhibits risk factors known to compromise the lymphatic system, such as elevated central venous pressure, pulmonary flow changes, and hypoxia. This study investigates the morphology and function of the lymphatic system in tetralogy of Fallot patients through lymphatic magnetic resonance imaging and near-infrared fluorescence imaging, respectively.
Methods:
Post-repair tetralogy of Fallot patients aged 6–18 years were recruited, along with age and gender-matched controls. Magnetic resonance imaging was used to assess the morphology of the thoracic lymphatic vessels and the thoracic, while near-infrared fluorescence imaging was used to assess lymphatic activity utilising lymph rate, velocity, and pressure.
Results:
Nine patients and 10 controls were included. Echocardiography revealed that 2/3 of the patients had moderate-severe pulmonary regurgitation, while none displayed signs of elevated central venous pressure. Magnetic resonance imaging identified three patients with type 3 (out of 4 types) lymphatic abnormalities, while controls had none. The thoracic ducts showed severe (one patient) and moderate (one patient) tortuosity. Mean thoracic duct diameters were 3.3 mm ±1.1 in patients and 3.0 mm ± 0.8 in controls (p-value = 0.53). Near-infrared fluorescence imaging revealed no anomalous patterns.
Conclusion:
Despite no presence of clinical lymphatic disease, 3/9 of the repaired tetralogy of Fallot patients exhibited lymphatic morphological abnormalities. The significance of these anomalies remains uncertain currently. Further research is needed to determine whether these lymphatic alterations in this patient cohort are a result of congenital malformations, haemodynamic shifts, or prenatal and early-life saturation levels.
Discontinuation of antipsychotic medication may be linked to high risk of relapse, hospitalization and mortality. This study investigated the use and discontinuation of antipsychotics in individuals with first-episode schizophrenia in relation to cohabitation, living with children, employment, hospital admission and death.
Methods
Danish registers were used to establish a nationwide cohort of individuals ⩾18 years with schizophrenia included at the time of diagnosis in1995–2013. Exposure was antipsychotic medication calculated using defined daily dose and redeemed prescriptions year 2–5. Outcomes year 5–6 were analysed using binary logistic, negative binomial and Cox proportional hazard regression.
Results
Among 21 351, 9.3% took antipsychotics continuously year 2–5, 38.6% took no antipsychotics, 3.4% sustained discontinuation and 48.7% discontinued and resumed treatment. At follow-up year 6, living with children or employment was significantly higher in individuals with sustained discontinuation (OR 1.98, 95% CI 1.53–2.56 and OR 2.60, 95% CI 1.91–3.54), non-sustained discontinuation (OR 1.25, 95% CI 1.05–1.48 and 2.04, 95% CI 1.64–2.53) and no antipsychotics (OR 2.00, 95% CI 1.69–2.38 and 5.64, 95% CI 4.56–6.97) compared to continuous users. Individuals with non-sustained discontinuation had more psychiatric hospital admissions (IRR 1.27, 95% CI 1.10–1.47) and longer admissions (IRR 1.68, 95% CI 1.30–2.16) year 5–6 compared to continuous users. Mortality during year 5–6 did not differ between groups.
Conclusion
Most individuals with first-episode schizophrenia discontinued or took no antipsychotics the first years after diagnosis and had better functional outcomes. Non-sustained discontinuers had more, and longer admissions compared to continuous users. However, associations found could be either cause or effect.
UK universities re-opened in September 2020, amidst the coronavirus epidemic. During the first term, various national social distancing measures were introduced, including banning groups of >6 people and the second lockdown in November; however, outbreaks among university students occurred. We aimed to measure the University of Bristol staff and student contact patterns via an online, longitudinal survey capturing self-reported contacts on the previous day. We investigated the change in contacts associated with COVID-19 guidance periods: post-first lockdown (23/06/2020–03/07/2020), relaxed guidance period (04/07/2020–13/09/2020), ‘rule-of-six’ period (14/09/2020–04/11/2020) and the second lockdown (05/11/2020–25/11/2020). In total, 722 staff (4199 responses) and 738 students (1906 responses) were included in the study. For staff, daily contacts were higher in the relaxed guidance and ‘rule-of-six’ periods than the post-first lockdown and second lockdown. Mean student contacts dropped between the ‘rule-of-six’ and second lockdown periods. For both staff and students, the proportion meeting with groups larger than six dropped between the ‘rule-of-six’ period and the second lockdown period, although was higher for students than for staff. Our results suggest university staff and students responded to national guidance by altering their social contacts. Most contacts during the second lockdown were household contacts. The response in staff and students was similar, suggesting that students can adhere to social distancing guidance while at university. The number of contacts recorded for both staff and students were much lower than those recorded by previous surveys in the UK conducted before the COVID-19 pandemic.
Administrators and policymakers are increasingly interested in individual placement and support (IPS) as a way of helping people with severe mental illness (SMI) obtain employment or education. It is thus important to investigate the cost-effectiveness to secure that resources are being used properly.
Methods
In a randomized clinical trial, 720 people diagnosed with SMI were allocated into three groups; (a) IPS, (b) IPS supplemented with cognitive remediation a social skills training (IPSE), and (c) Service as usual (SAU). Health care costs, municipal social care costs, and labor market service costs were extracted from nationwide registers and combined with data on use of IPS services. Cost-utility and cost-effectiveness analyses were conducted with two primary outcomes: quality-adjusted life years (QALY) and hours in employment. Incremental cost-effectiveness ratios (ICER) were computed for both QALY, using participant’s responses to the EQ-5D questionnaire, and for hours in employment.
Results
Both IPS and IPSE were less costly, and more effective than SAU. Overall, there was a statistically significant cost difference of €9,543 when comparing IPS with SAU and €7,288 when comparing IPSE with SAU. ICER’s did generally not render statistically significant results. However, there was a tendency toward the IPS and IPSE interventions being dominant, that is, cheaper with greater effect in health-related quality of life and hours in employment or education compared to usual care.
Conclusion
Individual placement support with and without a supplement of cognitive remediation tends to be cost saving and more effective compared to SAU.
This study compared live instructor-led training with video-based instruction in personal protective equipment (PPE) donning and doffing. It assessed the difference in performance between (1) attending 1 instructor-led training session in donning and doffing PPE at 1 month prior to assessment, and (2) watching training videos for 1 month.
Methods:
This randomized controlled trial pilot study divided 21 medical students and junior doctors into 2 groups. Control group participants attended 1 instructor-led training session. Video group participants watched training videos demonstrating the same procedures, which they could freely watch again at home. After 1 month, a doctor performed a blind evaluation of performance using checklists.
Results:
Nineteen participants were assessed after 1 month. The mean donning score was 84.8/100 for the instructor-led group and 88/100 for the video group; mean effect size was 3.2 (95% CI: -7.5 to 9.5). The mean doffing score was 79.1/100 for the instructor-led group and 73.9/100 for the video group; mean effect size was 5.2 (95% CI: -7.6 to 18).
Conclusion:
Our study found no significant difference in donning and doffing scores between instructor-led and video lessons. Video training could be a fast and resource-efficient method of training in PPE donning and doffing in responding to the COVID-19 pandemic.
Objectives: To investigate a possible confabulation resilience of the developing brain. Methods: We performed a literature search on confabulation in PubMed and identified all empirical studies of children and adolescents under the age of 18. Results: The analysis identified only three case studies of confabulation in children under the age of 18 of 286 empirical studies of confabulation. This reveals a striking discrepancy in the number of reported cases caused by brain injury between children and adults. We hypothesize that there may be a resilience toward confabulation in the developing brain and present three tentative explanations regarding the possible underlying mechanisms. Conclusions: Additional awareness on the scarcity of reported cases of confabulation in children could lead to important insights on the nature of confabulation and greater understanding of the resilience and plasticity of the developing brain. (JINS, 2019, 25, 426–431)
The Nordic countries have comprehensive, population-based health and medical registries linkable on individually unique personal identity codes, enabling complete long-term follow-up. The aims of this study were to describe the NorTwinCan cohort established in 2010 and assess whether the cancer mortality and incidence rates among Nordic twins are similar to those in the general population. We analyzed approximately 260,000 same-sexed twins in the nationwide twin registers in Denmark, Finland, Norway and Sweden. Cancer incidence was determined using follow-up through the national cancer registries. We estimated standardized incidence (SIR) and mortality (SMR) ratios with 95% confidence intervals (CI) across country, age, period, follow-up time, sex and zygosity. More than 30,000 malignant neoplasms have occurred among the twins through 2010. Mortality rates among twins were slightly lower than in the general population (SMR 0.96; CI 95% [0.95, 0.97]), but this depends on information about zygosity. Twins have slightly lower cancer incidence rates than the general population, with SIRs of 0.97 (95% CI [0.96, 0.99]) in men and 0.96 (95% CI [0.94, 0.97]) in women. Testicular cancer occurs more often among male twins than singletons (SIR 1.15; 95% CI [1.02, 1.30]), while cancers of the kidney (SIR 0.82; 95% CI [0.76, 0.89]), lung (SIR 0.89; 95% CI [0.85, 0.92]) and colon (SIR 0.90; 95% CI [0.87, 0.94]) occur less often in twins than in the background population. Our findings indicate that the risk of cancer among twins is so similar to the general population that cancer risk factors and estimates of heritability derived from the Nordic twin registers are generalizable to the background populations.
Let 𝔭 be a prime ideal in a commutative noetherian ring R. It is proved that if an R-module M satisfies ${\rm Tor}_n^R $(k (𝔭), M) = 0 for some n ⩾ R𝔭, where k(𝔭) is the residue field at 𝔭, then ${\rm Tor}_i^R $(k (𝔭), M) = 0 holds for all i ⩾ n. Similar rigidity results concerning ${\rm Tor}_R^{\ast} $(k (𝔭), M) are proved, and applications to the theory of homological dimensions are explored.
Little is known about potential harmful effects as a consequence of self-guided internet-based cognitive behaviour therapy (iCBT), such as symptom deterioration rates. Thus, safety concerns remain and hamper the implementation of self-guided iCBT into clinical practice. We aimed to conduct an individual participant data (IPD) meta-analysis to determine the prevalence of clinically significant deterioration (symptom worsening) in adults with depressive symptoms who received self-guided iCBT compared with control conditions. Several socio-demographic, clinical and study-level variables were tested as potential moderators of deterioration.
Methods
Randomised controlled trials that reported results of self-guided iCBT compared with control conditions in adults with symptoms of depression were selected. Mixed effects models with participants nested within studies were used to examine possible clinically significant deterioration rates.
Results
Thirteen out of 16 eligible trials were included in the present IPD meta-analysis. Of the 3805 participants analysed, 7.2% showed clinically significant deterioration (5.8% and 9.1% of participants in the intervention and control groups, respectively). Participants in self-guided iCBT were less likely to deteriorate (OR 0.62, p < 0.001) compared with control conditions. None of the examined participant- and study-level moderators were significantly associated with deterioration rates.
Conclusions
Self-guided iCBT has a lower rate of negative outcomes on symptoms than control conditions and could be a first step treatment approach for adult depression as well as an alternative to watchful waiting in general practice.
Antipsychotics are associated with a polymorphic ventricular tachycardia, torsades de pointes, which, in the worst case, can lead to sudden cardiac death. The QT interval corrected for heart rate (QTc) is used as a clinical proxy for torsades de pointes. The QTc interval can be prolonged by antipsychotic monotherapy, but it is unknown if the QTc interval is prolonged further with antipsychotic polypharmaceutical treatment. Therefore, this study investigated the associations between QTc interval and antipsychotic monotherapy and antipsychotic polypharmaceutical treatment in schizophrenia, and measured the frequency of QTc prolongation among patients.
Methods
We carried out an observational cohort study of unselected patients with schizophrenia visiting outpatient facilities in the region of Central Jutland, Denmark. Patients were enrolled from January of 2013 to June of 2015, with follow-up until June of 2015. Data were collected from clinical interviews and clinical case records.
Results
Electrocardiograms were available for 65 patients, and 6% had QTc prolongation. We observed no difference in average QTc interval for the whole sample of patients receiving no antipsychotics, antipsychotic monotherapy, or antipsychotic polypharmaceutical treatment (p=0.29). However, women presented with a longer QTc interval when receiving polypharmacy than when receiving monotherapy (p=0.01). A limitation of this study was its small sample size.
Conclusions
We recommend an increased focus on monitoring the QTc interval in women with schizophrenia receiving antipsychotics as polypharmacy.
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.
For over 100 years, the genetics of human anthropometric traits has attracted scientific interest. In particular, height and body mass index (BMI, calculated as kg/m2) have been under intensive genetic research. However, it is still largely unknown whether and how heritability estimates vary between human populations. Opportunities to address this question have increased recently because of the establishment of many new twin cohorts and the increasing accumulation of data in established twin cohorts. We started a new research project to analyze systematically (1) the variation of heritability estimates of height, BMI and their trajectories over the life course between birth cohorts, ethnicities and countries, and (2) to study the effects of birth-related factors, education and smoking on these anthropometric traits and whether these effects vary between twin cohorts. We identified 67 twin projects, including both monozygotic (MZ) and dizygotic (DZ) twins, using various sources. We asked for individual level data on height and weight including repeated measurements, birth related traits, background variables, education and smoking. By the end of 2014, 48 projects participated. Together, we have 893,458 height and weight measures (52% females) from 434,723 twin individuals, including 201,192 complete twin pairs (40% monozygotic, 40% same-sex dizygotic and 20% opposite-sex dizygotic) representing 22 countries. This project demonstrates that large-scale international twin studies are feasible and can promote the use of existing data for novel research purposes.
Physical inactivity and low birth weight (LBW) may lead to an increased risk for developing type 2 diabetes. The extent to which LBW individuals may benefit from physical exercise training when compared with those with normal birth weight (NBW) controls is uncertain. We assessed the impact of an outdoor exercise intervention on body composition, insulin secretion and action in young men born with LBW and NBW in rural India. A total of 61 LBW and 56 NBW healthy young men were recruited into the study. The individuals were instructed to perform outdoor bicycle exercise training for 45 min every day. Fasting blood samples, intravenous glucose tolerance tests and bioimpedance body composition assessment were carried out. Physical activity was measured using combined accelerometry and heart rate monitoring during the first and the last week of the intervention. Following the exercise intervention, the LBW group displayed an increase in physical fitness [55.0 ml (O2)/kg min (52.0−58.0)−57.5 ml (O2)/kg min (54.4−60.5)] level and total fat-free mass [10.9% (8.0−13.4)−11.4% (8.0−14.6)], as well as a corresponding decline in the ratio of total fat mass/fat-free mass. In contrast, an increase in total fat percentage as well as total fat mass was observed in the NBW group. After intervention, fasting plasma insulin levels, homoeostasis model assessments (HOMA) of insulin resistance (HOMA-IR) and insulin secretion (HOMA-IS), improved to the same extent in both the groups. In summary, young men born with LBW in rural India benefit metabolically from exercise training to an extent comparable with NBW controls.
In situ small-angle x-ray scattering (SAXS) is used to investigate the electrochemical durability of Pt-Metal (Pt-M) catalysts sputtered onto nitrogen-modified high surface area carbon powder. The results demonstrate that nitrogen modification promotes catalyst durability through reduction of nanoparticle dissolution and coarsening. Although particle sizes of Pt-M on high surface area carbon supports can be difficult to determine with transmission electron microscopy (TEM), a novel SAXS method has been employed to calculate particle size. SAXS analysis shows that the Pt-M nanoparticle size distribution remained stable for 3000 electrochemical cycles after nitrogen modification, whereas the unmodified support material leads to Pt-M nanoparticle instabilities. These results for industrial-relevant catalyst/support architectures underscore the potential of nitrogen-modified carbon support structures for enhanced Pt-M catalyst durability.
Congenital heart defect patients may experience neurodevelopmental impairment. We investigated their educational attainments from basic schooling to higher education.
Patients and methods
Using administrative databases, we identified all Danish patients with a cardiac defect diagnosis born from 1 January, 1977 to 1 January, 1991 and alive at age 13 years. As a comparison cohort, we randomly sampled 10 persons per patient. We obtained information on educational attainment from Denmark's Database for Labour Market Research. The study population was followed until achievement of educational levels, death, emigration, or 1 January, 2006. We estimated the hazard ratio of attaining given educational levels, conditional on completing preceding levels, using discrete-time Cox regression and adjusting for socio-economic factors. Analyses were repeated for a sub-cohort of patients and controls born at term and without extracardiac defects or chromosomal anomalies.
Results
We identified 2986 patients. Their probability of completing compulsory basic schooling was approximately 10% lower than that of control individuals (adjusted hazard ratio = 0.79, ranged from 0.75 to 0.82 0.79; 95% confidence interval: 0.75–0.82). Their subsequent probability of completing secondary school was lower than that of the controls, both for all patients (adjusted hazard ratio = 0.74; 95% confidence interval: 0.69–0.80) and for the sub-cohort (adjusted hazard ratio = 0.80; 95% confidence interval: 0.73–0.86). The probability of attaining a higher degree, conditional on completion of youth education, was affected both for all patients (adjusted hazard ratio = 0.88; 95% confidence interval: 0.76–1.01) and for the sub-cohort (adjusted hazard ratio = 0.92; 95% confidence interval: 0.79–1.07).
Conclusion
The probability of educational attainment was reduced among long-term congenital heart defect survivors.