The effect of longitudinal sleep monitoring on clinician agreement in obstructive sleep apnea diagnosis: The ELSA study

There is strong evidence for clinically relevant night‐to‐night variability of respiratory events in patients with suspected obstructive sleep apnea. Sleep experts retrospectively evaluated diagnostic data in 56 patients with suspected obstructive sleep apnea. Experts were blinded to the fact that they were diagnosing the same case twice, once based on a short report of a single in‐laboratory respiratory polygraphy and once with the additional information of 14 nights of pulse oximetry at home. All experts (n = 22) were highly qualified, 13 experts (59.1%) treated > 100 patients with suspected obstructive sleep apnea per year. In 12 patients, the apnea–hypopnea index in the respiratory polygraphy was  100 per year compared with 0–29 patients per year (Coef. [95% confidence interval] −0.63 [−1.22/−0.04] and −0.61 [−1.07/−0.15], respectively). Experts found already a high level of consensus regarding obstructive sleep apnea diagnosis, severity and continuous positive airway pressure recommendation after a single respiratory polygraphy. However, longitudinal sleep monitoring could help increase consensus in selected patients with diagnostic uncertainty

Ancient DNA from European Early Neolithic Farmers Reveals Their Near Eastern Affinities

The first farmers from Central Europe reveal a genetic affinity to modern-day populations from the Near East and Anatolia, which suggests a significant demographic input from this area during the early Neolithic

Erneuerbare Energien in der Raumplanung. Ein Hindernislauf mit Tücken.

Die Energiewende stellt die Raumplanung vor große Herausforderungen. Insbesondere die Plannung und der Bau von Anlagen zur Gewinnung erneuerbarer Energien sind immer wieder hoch umstritten und selten einfach umzusetzen. Der Sammenband präsentiert mehrere Seminararbeiten, die unterschiedliche Aspekte zum Thema erörtern und viele Beispiele aus der Praxis darstellen

Association of Group A Streptococcus Exposure and Exacerbations of Chronic Tic Disorders

Objective: To examine prospectively the association between group A Streptococcus (GAS) pharyngeal exposures and exacerbations of tics in a large multicenter population of youth with chronic tic disorders (CTD) across Europe. Methods: We followed up 715 children with CTD (age 10.7 ± 2.8 years, 76.8% boys), recruited by 16 specialist clinics from 9 countries, and followed up for 16 months on average. Tic, obsessive-compulsive symptom (OCS), and attention-deficit/hyperactivity disorder (ADHD) severity was assessed during 4-monthly study visits and telephone interviews. GAS exposures were analyzed using 4 possible combinations of measures based on pharyngeal swab and serologic testing. The associations between GAS exposures and tic exacerbations or changes of tic, OC, and ADHD symptom severity were measured, respectively, using multivariate logistic regression plus multiple failure time analyses and mixed effects linear regression. Results: A total of 405 exacerbations occurred in 308 of 715 (43%) participants. The proportion of exacerbations temporally associated with GAS exposure ranged from 5.5% to 12.9%, depending on GAS exposure definition. We did not detect any significant association of any of the 4 GAS exposure definitions with tic exacerbations (odds ratios ranging between 1.006 and 1.235, all p values >0.3). GAS exposures were associated with longitudinal changes of hyperactivity-impulsivity symptom severity ranging from 17% to 21%, depending on GAS exposure definition. Conclusions: This study does not support GAS exposures as contributing factors for tic exacerbations in children with CTD. Specific workup or active management of GAS infections is unlikely to help modify the course of tics in CTD and is therefore not recommended

Mutations in sphingosine-1-phosphate lyase cause nephrosis with ichthyosis and adrenal insufficiency

Steroid-resistant nephrotic syndrome (SRNS) causes 15% of chronic kidney disease cases. A mutation in 1 of over 40 monogenic genes can be detected in approximately 30% of individuals with SRNS whose symptoms manifest before 25 years of age. However, in many patients, the genetic etiology remains unknown. Here, we have performed whole exome sequencing to identify recessive causes of SRNS. In 7 families with SRNS and facultative ichthyosis, adrenal insufficiency, immunodeficiency, and neurological defects, we identified 9 different recessive mutations in SGPL1, which encodes sphingosine-1-phosphate (S1P) lyase. All mutations resulted in reduced or absent SGPL1 protein and/or enzyme activity. Overexpression of cDNA representing SGPL1 mutations resulted in subcellular mislocalization of SGPL1. Furthermore, expression of WT human SGPL1 rescued growth of SGPL1-deficient dpl1. yeast strains, whereas expression of disease-associated variants did not. Immunofluorescence revealed SGPL1 expression in mouse podocytes and mesangial cells. Knockdown of Sgpl1 in rat mesangial cells inhibited cell migration, which was partially rescued by VPC23109, an S1P receptor antagonist. In Drosophila, Sply mutants, which lack SGPL1, displayed a phenotype reminiscent of nephrotic syndrome in nephrocytes. WT Sply, but not the disease-associated variants, rescued this phenotype. Together, these results indicate that SGPL1 mutations cause a syndromic form of SRNS

Vitamin D levels in children and adolescents with chronic tic disorders: a multicentre study

This study investigated whether vitamin D is associated with the presence or severity of chronic tic disorders and their psychiatric comorbidities. This cross-sectional study compared serum 25-hydroxyvitamin D [25(OH)D] (ng/ml) levels among three groups: children and adolescents (3-16 years) with CTD (n = 327); first-degree relatives (3-10 years) of individuals with CTD who were assessed for a period of up to 7 years for possible onset of tics and developed tics within this period (n = 31); and first-degree relatives who did not develop tics and were ≥ 10 years old at their last assessment (n = 93). The relationship between 25(OH)D and the presence and severity of tics, as well as comorbid obsessive-compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD), were analysed controlling for age, sex, season, centre, latitude, family relatedness, and comorbidities. When comparing the CTD cohort to the unaffected cohort, the observed result was contrary to the one expected: a 10 ng/ml increase in 25(OH)D was associated with higher odds of having CTD (OR 2.08, 95% CI 1.27-3.42, p < 0.01). There was no association between 25(OH)D and tic severity. However, a 10 ng/ml increase in 25(OH)D was associated with lower odds of having comorbid ADHD within the CTD cohort (OR 0.55, 95% CI 0.36-0.84, p = 0.01) and was inversely associated with ADHD symptom severity (β = - 2.52, 95% CI - 4.16-0.88, p < 0.01). In conclusion, lower vitamin D levels were not associated with a higher presence or severity of tics but were associated with the presence and severity of comorbid ADHD in children and adolescents with CTD

European Multicentre Tics in Children Studies (EMTICS): protocol for two cohort studies to assess risk factors for tic onset and exacerbation in children and adolescents

Genetic predisposition, autoimmunity and environmental factors [e.g. pre- and perinatal difficulties, Group A Streptococcal (GAS) and other infections, stress-inducing events] might interact to create a neurobiological vulnerability to the development of tics and associated behaviours. However, the existing evidence for this relies primarily on small prospective or larger retrospective population-based studies, and is therefore still inconclusive. This article describes the design and methodology of the EMTICS study, a longitudinal observational European multicentre study involving 16 clinical centres, with the following objectives: (1) to investigate the association of environmental factors (GAS exposure and psychosocial stress, primarily) with the onset and course of tics and/or obsessive-compulsive symptoms through the prospective observation of at-risk individuals (ONSET cohort: 260 children aged 3-10 years who are tic-free at study entry and have a first-degree relative with a chronic tic disorder) and affected individuals (COURSE cohort: 715 youth aged 3-16 years with a tic disorder); (2) to characterise the immune response to microbial antigens and the host's immune response regulation in association with onset and exacerbations of tics; (3) to increase knowledge of the human gene pathways influencing the pathogenesis of tic disorders; and (4) to develop prediction models for the risk of onset and exacerbations of tic disorders. The EMTICS study is, to our knowledge, the largest prospective cohort assessment of the contribution of different genetic and environmental factors to the risk of developing tics in putatively predisposed individuals and to the risk of exacerbating tics in young individuals with chronic tic disorders

Lack of Association of Group A Streptococcal Infections and Onset of Tics: European Multicenter Tics in Children Study

Background and objectives: The goal of this work was to investigate the association between group A streptococcal (GAS) infections and tic incidence among unaffected children with a family history of chronic tic disorders (CTDs). Methods: In a prospective cohort study, children with no history for tics who were 3 to 10 years of age with a first-degree relative with a CTD were recruited from the European Multicentre Tics in Children Study (EMTICS) across 16 European centers. Presence of GAS infection was assessed with throat swabs, serum anti-streptolysin O titers, and anti-DNAse titers blinded to clinical status. GAS exposure was defined with 4 different definitions based on these parameters. Cox regression analyses with time-varying GAS exposure were conducted to examine the association of onset of tics and GAS exposure during follow-up. Sensitivity analyses were conducted with Cox regression and logistic regression analyses. Results: A total of 259 children were recruited; 1 child was found to have tic onset before study entry and therefore was excluded. Sixty-one children (23.6%) developed tics over an average follow-up period of 1 (SD 0.7) year. There was a strong association of sex and onset of tics, with girls having an ≈60% lower risk of developing tics compared to boys (hazard ratio [HR] 0.4, 95% confidence interval [CI] 0.2-0.7). However, there was no statistical evidence to suggest an association of any of the 4 GAS exposure definitions with tic onset (GAS exposure definition 1: HR 0.310, 95% CI 0.037-2.590; definition 2: HR 0.561, 95% CI 0.219-1.436; definition 3: HR 0.853, 95% CI 0.466-1.561; definition 4: HR 0.725, 95% CI 0.384-1.370). Discussion: These results do not suggest an association between GAS exposure and development of tics. Classification of evidence: This study provides Class I evidence that group A streptococcal exposure does not associate with the development of tics in children with first-degree relatives with chronic tic disorder

Abundance and scarcity: classical theories of money, bank balance sheets and business models, and the British restriction of 1797‐1818.

The thesis looks through the lens of bank balance sheet accounting to investigate the structural change in the British banking system between 1780 and 1832, and how classical quantity theorists of money attempted to respond to the ensuing financialisation of the wartime economy with its growing reliance on credit funded with paper-based instruments (the ‘Vansittart system’ of war finance). The thesis combines contributions to three separate fields to construct a holistic historical example of the challenges faced by monetary economists when ‘modelling’ financial innovation, credit growth, ‘fringe’ banking, and agent incentives – at a time of radical experimentation: the suspension of the 80-year-old gold standard (“the Restriction”). First, critical text analysis of the history of economics argues that the 1809-10 debate between Ricardo and Bosanquet at the peak of the credit boom, bifurcated classical theory into two timeless competing policy paradigms advocating the ‘Scarcity’ or ‘Abundance’ of money relative to exchange transactions. The competing hypotheses regarding the role of money and credit are identified and the rest of the thesis examines the archival evidence for each. Second, the core of the thesis contributes to the historical literature on banking in relation to money by reconstructing a taxonomy of bank business models, their relationships with the London inter-bank settlement system, and their responses to the Restriction - drawing on some 17,000 mostly new data points collected from the financial records of London and Country banks. The final section contributes to the economic history of money by constructing aggregated views of total bank liabilities from the firm-level data, scaled to recently available British GDP estimates. These are examined to establish (with hindsight) the relative merits and lacuna of the competing theoretical hypotheses postulated by political economists. It was the period of deleveraging after 1810 that revealed the lacuna of both paradigms

Multifaktorielle Echtzeitdiagnose des Nutzerzustands in adaptiver Mensch-Maschine-Interaktion

Konzepte adaptiver Systemgestaltung zielen darauf ab, den Operateur zustands- und situationsabhängig zu unterstützen, um Leistungsausfällen und -minderungen frühzeitig entgegenzuwirken und die Gesamtleistung des Mensch-Maschine-Systems zu optimieren. Gegenstand dieser Dissertation ist die Entwicklung einer Echtzeitdiagnose des Nutzerzustands, die Problemzustände und mögliche Ursachen während der Aufgabenbearbeitung erkennt und damit eine dynamische zustandsabhängige Auswahl und Anwendung von Adaptierungsstrategien ermöglicht. Auf Grundlage theoriebasierter und empirischer Erkenntnisse wurde mit RASMUS (Real-Time Assessment of Multidimensional User State) ein generisches Diagnosekonzept für eine ganzheitliche Erfassung und Bewertung des Nutzerzustands entwickelt. Im Unterschied zu anderen Forschungsarbeiten wird der Nutzerzustand hierbei multidimensional als Zusammenwirken von sechs mentalen Konstrukten definiert, die nachweislich die menschliche Leistungsfähigkeit beeinflussen können: Mentale Beanspruchung, Müdigkeit, Motivation, Aufmerksamkeit, Situationsbewusstsein sowie der emotionale Zustand. Die Erfassung dieser Zustände erfolgt multifaktoriell durch Kombination von physiologischen und verhaltensbasierten Maßen mit umwelt- und nutzerinternen Einflussfaktoren. Das Diagnosekonzept sieht vor, Adaptierungsbedarf auf Basis von Leistungsmaßen zu bestimmen. Auf diese Weise wird sichergestellt, dass die Adaptierung produktiven Selbstregulierungsstrategien des Nutzers nicht entgegenwirkt, die sich in Veränderungen des Nutzerzustands äußern können. Die multifaktorielle Bewertung des Nutzerzustands ermöglicht es im Weiteren, mögliche Ursachen für Leistungsverschlechterungen zu identifizieren, denen durch Auswahl und Anwendung geeigneter Adaptierungsstrategien entgegengewirkt werden kann. RASMUS wurde exemplarisch für den Anwendungsbereich der Luftraumüberwachung und drei ausgewählte Problemzustände (hohe Beanspruchung, passive aufgabenbezogene Müdigkeit sowie eine falsche Aufmerksamkeitsverteilung) umgesetzt und validiert. Die erfolgreiche Umsetzung des Diagnosekonzepts und die bestätigte Validität der Diagnoseergebnisse von RASMUS ermöglicht es, die Echtzeitdiagnose künftig als Grundlage für die dynamische Auswahl und Konfiguration von Unterstützungsstrategien in adaptiven Systemen heranzuziehen. Darüber hinaus sind auch Einsatzmöglichkeiten im Bereich der Usability-Bewertung sowie in Training und Ausbildung denkbar, z.B. um gewünschte Trainingszustände gezielt hervorzurufen oder den Trainingserfolg zu bewerten