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Rauchen ist wegen der hohen Prävalenz gerade bei psychiatrisch Erkrankten von besonderer Bedeutung. Die Entwicklung einer körperlichen und psychischen Abhängigkeit macht es oft schwierig, den Konsum zu beenden. Die aktuelle S3-Leitlinie liefert evidenzbasierte Strategien zur Behandlung dieser Suchterkrankung und zum erfolgreichen Rauchstopp und gibt Empfehlungen für die Besonderheiten psychiatrischer Patienten und deren Medikation.

Mastocytosis is a heterogeneous disease characterized by an abnormal accumulation of mast cells (MCs) in 1 or several organs. Although a somatic KIT D816V mutation is detected in ∼85% of patients, attempts to demonstrate its oncogenic effect alone have repeatedly failed, suggesting that additional pathways are involved in MC transformation. From 3 children presenting with both Greig cephalopolysyndactyly syndrome (GCPS, Mendelian Inheritance in Man [175700]) and congenital mastocytosis, we demonstrated the involvement of the hedgehog (Hh) pathway in mastocytosis. GCPS is an extremely rare syndrome resulting from haploinsufficiency of GLI3, the major repressor of Hh family members. From these familial cases of mastocytosis, we demonstrate that the Hh pathway is barely active in normal primary MCs and is overactive in neoplastic MCs. GLI3 and KIT mutations had a synergistic, tumorigenic effect on the onset of mastocytosis in a GCPS mouse model. Finally, Hh inhibitors suppressed neoplastic MC proliferation in vitro and extend the survival time of mice with aggressive systemic mastocytosis (ASM). This work revealed, for the first time, the involvement of Hh signaling in the pathophysiology of mastocytosis and demonstrated the cooperative effects of the KIT and Hh oncogenic pathways in mice with ASM, leading to the identification of new promising therapeutic targets.

BACKGROUND: Implant specific complications and outcome for the use of proximal humeral nails in different fracture types are not well described. OBJECTIVE: Evaluation of adverse effects and outcome of patients treated with the new Targon PH+ implant for proximal humeral fractures in a geriatric population. METHODS: A consecutive series of patients from a single institution was retrospectively evaluated. Adverse events (AE) were assessed from patients’ files and during follow-up examination. Current pain level was evaluated using the Visual Analogue Scale (VAS). The disability score of arm, shoulder and hand (DASH) as well as the Constant-Murley score were assessed. Patient satisfaction was evaluated by questionnaire. RESULTS: Forty-nine patients with a mean age of 72.0 ± 10.0 years were included with a follow-up of 2.2 years. Five patients showed twopart fractures (10%), 24 threepart fractures (50%) and 20 fourpart fractures (40%). Additional shaft fracture occurred in twelve cases (24%). Implant-related AE were recorded in six cases (12%). Pain under strain was moderate with a mean of 27.6 ± 27.1 mm. DASH score showed a mean of 25.9 ± 24.9. Constant score of the affected shoulder was 57 ± 23.8 with a mean difference of 16 points compared to reference shoulder. No significant differences in AE, VAS, DASH or Constant score could be found according to fracture groups. Most patients were satisfied with the surgical outcome (84%). CONCLUSIONS: The Targon PH+ nail demonstrated good functional results and low adverse events in geriatric patients. Additional studies including less experienced centres are required to further evaluate the possible benefits of this implant.

The aim of this study was to describe atypical dyskinesias (AtypDs) occurring during treatment with antipsychotic drugs (APDs). AtypDs are dyskinesias showing either an unusual temporal relationship between onset of treatment and start of the adverse drug reaction (ADR) or an unusual presentation of clinical symptoms.Data on the utilisation of APDs and reports of severe APD-induced AtypDs were collected using data from the observational pharmacovigilance programme - 'Arzneimittelsicherheit in der Psychiatrie (English: drug safety in psychiatry)' (AMSP) - from 1993 to 2016.A total of 495,615 patients were monitored, of which 333,175 were treated with APDs. Sixty-seven cases (0.020%) of severe AtypDs under treatment with APDs were registered. The diagnoses of schizophrenic disorders as well as organic mental disorders were related to significantly higher rates of AtypDs. Second-generation antipsychotic drugs (SGAs) showed slightly higher rates of AtypDs (0.024%) than high-potency (0.011%) or low-potency first-generation antipsychotic drugs (FGAs; 0.006%). In 41 cases (61.2%), two or more drugs were found to cause AtypDs.Our study indicates that AtypDs are rare ADRs. SGAs may have a higher risk for the occurrence of AtypDs than FGAs. Clinicians should be aware of this ADR and patients should be monitored and examined carefully.

Zusammenfassung Hintergrund Die Behandlung der Femurschaftfrakturen bei Kindern war in den letzten Jahren einem zunehmenden Wandel unterzogen. Die früher dominierenden Therapieverfahren wurden durch minimal-invasive Techniken (z. B. elastisch stabile intramedulläre Nagelung [ESIN]) weitgehend abgelöst. Ziel der vorliegenden Studie war der Vergleich der Komplikationsraten in Abhängigkeit sowohl von Patientenfaktoren als auch von verschiedenen Behandlungsverfahren. Material und Methoden Bei der vorliegenden Arbeit handelt es sich um eine retrospektive röntgenmorphometrische Datenauswertung. Es wurden die Patientenakten und Röntgenbilder von 101 Kindern, die an zwei Level-I-Traumazentren behandelt wurden, ausgewertet. Ergebnisse In 19 % der Fälle wurde eine konservative Therapie durchgeführt. Bei den operativen Verfahren dominierte die ESIN-Technik (n = 60). Revisionspflichtige Komplikationen fanden sich nach konservativer Therapie bei ca. 10 % der Kinder. Bei den operativ behandelten Kindern musste in über 6 % der Fälle eine Revisionsoperation durchgeführt werden. Die ESIN-Stabilisierung zeigte bei den operativen Verfahren mit ca. 3 % die niedrigste Revisionsrate. Wurden im Verhältnis zum Markraumdurchmesser zu dünne ESIN-Drähte verwendet, so zeigte sich eine um 30 % höhere Komplikationswahrscheinlichkeit. Bei Kindern unter 3 Jahren und Adoleszenten war die Komplikationswahrscheinlichkeit erhöht. Diskussion In der durchgeführten Studie zeigt sich ein moderates Komplikationsrisiko bei der Behandlung von Femurschaftfrakturen bei Kindern. Das Komplikationsrisiko nach Fixateur-externe-Anlage und konservativer Behandlung war in dieser Studie am höchsten. Die ESIN-Technik zeigt insgesamt das geringste Komplikationsrisiko. Die vorliegende Arbeit konnte die bekannten Limitationen der ESIN-Technik in Abhängigkeit von Alter und Gewicht bestätigen.

Zusammenfassung. Einleitung: Neben der Prävention des Tabakkonsums bleibt die Herstellung und Sicherung eines hohen Niveaus der Behandlungsqualität bei schädlichem Gebrauch und Abhängigkeit von Tabakprodukten eine wichtige gesundheitsbezogene Aufgabe in Deutschland. Eine regelmäßige Aktualisierung der AWMF-S3-Leitlinie „Rauchen und Tabakabhängigkeit: Screening, Diagnostik und Behandlung“ schafft eine nachhaltige und seriöse Quelle für den Wissensstand zur Tabakentwöhnung. Methoden: Unter Federführung der Deutschen Gesellschaft für Psychiatrie, Psychotherapie, Psychosomatik und Nervenheilkunde (DGPPN) und der Deutschen Gesellschaft für Suchtforschung und Suchttherapie e. V. (DG-Sucht) wurde die Tabakleitlinie 2019–2020 von insgesamt 63 am Entstehungsprozess des Textes beteiligten Personen in 11 Arbeitsgruppen überarbeitet. Der Einfluss von Interessenkonflikten (COI) konnte durch ein sorgfältiges COI-Management minimiert werden. Über die 80 Leitlinienempfehlungen diskutierten Delegierte aus 50 Fachgesellschaften und stimmten in einem moderierten Konsensprozess online ab. Ergebnisse: Neben Empfehlungen zum Screening und zur Diagnostik nimmt die Leitlinie positiv Stellung zur Nutzung niederschwelliger Beratungs- und Unterstützungsangebote. Falls aufgrund des Schweregrads der tabakbezogenen Störung Kurzberatung, Telefonberatung oder Internet- bzw. Smartphone-gestützte Verfahren nicht hinreichend wirksam sind, ist eine verhaltenstherapeutisch basierte Einzel- oder Gruppenbehandlung, ggf. in Verbindung mit Medikamenten, indiziert. Wenn eine Nikotinersatztherapie nicht wirksam sein sollte, soll Vareniclin oder Bupropion angeboten werden. Alternative Strategien mit niedrigerem Empfehlungsgrad sind Hypnotherapie, achtsamkeitsbasierte Verfahren, oder auch Cytisin. Bei Jugendlichen und Schwangeren ist das Angebot von Medikamenten auf genau spezifizierte Ausnahmen und Nikotinersatz zu beschränken. Die mittlere Zustimmung für die Empfehlungen der Leitlinie erreichte 98 %. Eine Gesamtübersicht über die Behandlungsempfehlungen der Tabakleitlinie geben drei klinische Algorithmen.

The energy balance and performance of all Photovoltaic (PV) systems installed at Fotovoltaica/UFSC solar energy laboratory ( www.fotovoltaica.ufsc.br ) in Florianopolis, Brazil (27° S; 48° W) were demonstrated over time, from Aug/2017 to Feb/2020. The laboratory was designed as a zero-energy building (ZEB) with PV systems installed on rooftops and facades, not maximising annual generation, but to achieve a compromise between aesthetic appeal and the energy output. Further PV systems were installed on the same site in the shapes of a carport, an electric bus (eBus) shelter and charging station, and different ground-mounted PV systems fixed at latitude tilt and single-axis tracking. Monthly analyses were carried out during the period, such as the solar irradiation availability on site, changes in the number of building occupants, the increase of installed capacity of PV systems, and energy generation and consumption. With 111 kWp, the total PV generation in the period could supply 148% of building energy needs and 97% of the Fotovoltaica/UFSC Laboratory (building plus eBus). However, there were some downtime events in certain PV systems due to RD they demonstrate the potential of BIPV in enabling energy positive buildings.

ZusammenfassungFemurschaftfrakturen sind komplikationsträchtige Verletzungen. Die exakte Reposition der Fragmente, weichteilschonendes Operieren und stabile Osteosyntheseverfahren stellen hohe Anforderungen dar. Kommt es zur Pseudarthrosenbildung, ist in jedem Fall ein individueller Behandlungsplan zu erstellen. Frakturen mit erhaltender Biologie und geringem Knochenverlust lassen sich durch vergleichsweise einfache Techniken zur Durchbauung bringen. Die infizierte Defektpseudarthrose stellt die aufwendigste Komplikation dar. Hierbei muss einerseits die Osteitis saniert werden, andererseits müssen Knochen und Weichteile rekonstruiert werden. Vielfach ist hier ein interdisziplinäres Vorgehen zwischen Unfallchirurg, Gefäßchirurg und plastischem Chirurgen erforderlich. Besonderes Augenmerk muss auf die Führung des Patienten gelegt werden. Behandlungsverläufe von vielen Monaten sind keine Seltenheit. Durch eine korrekte Erstbehandlung lassen sich viele Komplikationen vermeiden, daher sind an die erste Operation genauso hohe Anforderungen zu stellen wie an die weitere Behandlung der Pseudarthrose. Die postoperative Torsionsfehlstellung nach antegrader Marknagelosteosynthese ist eine häufig unterschätze Komplikation mit erheblichen Folgen. Eine intra- und postoperative Kontrolle der Torsion sollte obligat durchgeführt und dokumentiert werden.

In a positive-energy building (PEB), the energy generation is higher than the required for the building’s operation, including charging electric vehicles. That is the case of the Fotovoltaica-UFSC Laboratory, a solar energy research building, located in Florianopolis – Brazil (27°S; 48°W), and its electric bus (eBus), supplied by on-site building-integrated (BIPV) and ground-mounted (GM) photovoltaic (PV) systems. In order to assess the performance of BIPV systems from architectural perspectives, three not ideally positioned BIPV systems that use different technologies (c-Si, CdTe and CIGS), tilt angles, and azimuthal deviations were compared with two ideally oriented and tilted GM systems (CdTe), operating at the same warm and sunny site with simultaneous irradiance and energy data collected at high time resolution. All PV systems are installed in an urban environment, with complex aspects of architectural integration, orientation, partial shadings and performance. These aspects were analyzed in detail in this study. In addition, comparisons between real data measurements of all PV systems and PVSyst® software simulations were carried out. Results have shown that BIPV systems presented, in average, higher yields and performance ratios (PRs) than GM systems, and the real measurements validated the expected energy, even for PV systems with complex environment and tilt angle variations connected to the same inverter. In conclusion, PV modules can be more freely used as building skin and/or materials in architectural integration, as BIPV systems can perform well even when not ideally positioned and partially shaded, since the electrical system design supports architectural decisions.

Objectives Drug-induced liver injury (DILI) has been associated with various antipsychotic drugs (APDs). Comparative studies between individual APDs are largely not available. Methods Antipsychotic drug utilisation data and reports of severe antipsychotic DILI were assessed by using data from an observational pharmacovigilance programme-Arzneimittelsicherheit in der Psychiatrie (AMSP)-during the period 1993-2016. Results Of the 333,175 patients treated with APDs, a total of 246 (0.07%) events of severe DILI were identified. Phenothiazines were associated with significantly higher rates of severe DILI (0.03%, 95% CI = 0.02-0.04) than thioxanthenes (0.01%, 95% CI = 0.00-0.02) or butyrophenones (0.01%, 95% CI = 0.00-0.01). Among individual drugs, olanzapine (0.12%, 95% CI = 0.10-0.16), perazine (0.09%, 95% CI = 0.05-0.15) and clozapine (0.09%, 95% CI = 0.10-0.12 ranked highest. In 78 cases (31.7%), combination therapies with antipsychotic and antidepressant drugs or with two or more APDs were considered responsible. Male sex and a diagnosis of mania were associated with significantly higher rates of severe DILI while older patients (≥65 years old) were significantly less often affected. Conclusions In the present analysis of a representative psychiatric inpatient cohort, olanzapine, perazine, and clozapine were the most common individual APDs associated with severe DILI.

Irritant contact dermatitis is a wide spread occupational skin condition. In addition to generalized protection and teaching schemes, a knowledge about individual risk might add to an improved awareness for hazards. Here, we report on a novel candidate biomarker, which might stage individual susceptibility to irritant skin damage. Subclinical sensitivity was proven in recent studies. As a nano-anatomical measure, it works non-invasively on corneocytes from tape strips. Here, we report on a 7-day course after exposure to sodium lauryl sulphate and compare the novel cell texture index with the classical markers water loss (transepidermal water loss) and natural moisturizing factor. All parameters show a high degree of correlation.

Background This study addresses the question of whether psychosocial functioning measured by the Personal and Social Performance (PSP) Scale is related to various psychopathological measures in a cohort of patients with schizophrenia. Methods The ‘Neuroleptic Strategy Study’ (NeSSy) performed at 14 German hospitals between 2010 and 2013 compared two treatment strategies instead of individual drugs. Secondary end-points were the two PSP scales as well as measures of quality of life (SF-36) and the Positive and Negative Syndrome Scale (PANSS). Results 149 patients were randomised. There was no difference between the two treatment strategies (first-generation versus second-generation antipsychotics) with regard to the PSP. There were differences in doctors’ assessments regarding psychosocial functioning compared with patients’ own assessments. Furthermore, there were relationships between the PSP and quality of life, level of skills (ICF), and severity of disease (PANSS), level of sexual activities and poor well-being under antipsychotic medication but not with cognitive changes. Conclusions The findings on psychosocial functioning of patients with schizophrenia related to severity and skill level could be confirmed. Further findings were the correlation between psychosocial functioning and quality of life, well-being under treatment, and sexuality what emphasizes the substantial importance of a reduced psychosocial functioning.

ZusammenfassungHintergrundBei Patienten, die im Rahmen eines Traumas an Knie- und Sprunggelenk eine Verletzung mit Abscheren eines osteochondralen „flake“ erleiden, ist heute die Refixation mittels resorbierbarer Implantate eine häufig verwendete Therapieoption. Hierzu gibt es bisher wenige Studien mit klinischen Langzeitergebnissen. Ziel dieser Studie war die Erfassung der klinischen und MR-morphologischen Langzeitergebnisse nach Refixation mittels resorbierbarer PLLA-Implantate.Material und MethodenIn dieser retrospektiven Studie wurden 12 Patienten mit 13 Läsionen erfasst, die im Schnitt 13,9 (±1,2) Jahre zuvor eine Refixation eines durchschnittlich 3,33 cm2(±2,33) großen osteochondralen Flake an Knie- (10 Patienten) und oberem Sprunggelenk (2 Patienten) mit resorbierbaren Implantaten (Nägel, Stifte, Schrauben) aus Polylactid (PLLA) (Fa. Bionx, Tampere, Finnland) erhalten hatten. Zur Objektivierung des klinischen Ergebnisses wurden 8 etablierte Scores (VASS, Tegner, Lysholm, McDermott, KSS, WOMAC, AOFAS, FADI+Sports) verwendet. Des Weiteren wurden die knöcherne Integration und Knorpelmorphologie mittels protonengewichteter und knorpelsensitiver „3D-double-echo-steady-state“(DESS)-Sequenzen im MRT (3 T) erfasst. Zur Objektivierung der Ergebnisse diente ein modifizierter MRT-Score nach Henderson et al.ErgebnisseNach 13,9 (±1,2) Jahren zeigten sich sowohl für die Knie- als auch die Sprunggelenkpatienten sehr gute Ergebnisse (Knie: VASS: 1,2 (±1,7); Tegner 4,4 (±1,3); Lysholm 85,7 (±12,2); McDermott 90,7 (±8,6); KSS 189 (±14,2); WOMAC (6,16 % (±8,45))), (OSG: VASS: 2,5 (±2,5); Tegner 5,5 (±1,5); Lysholm 87 (±13), McDermott 88 (±12); WOMAC (8,54 % (±8,54); AOFAS 75,5 (±24,5); FADI+Sports 118 (±18))). In der MRT zeigte sich in allen 12 Fällen eine gute Integration des refixierten Flake. In 5 Fällen kam es zu einer moderaten subchondralen Zystenbildung (∅ ≤1 mm). Allerdings zeigten alle Patienten milde Veränderungen der Knorpelkontur. Hieraus ergab sich ein durchschnittlicher modifizierter Henderson-Score-Wert von 14,4 (±2,0) (Bestwert: 8, schlechtester Wert: 32), was einem guten MR-morphologischen Ergebnis entspricht.SchlussfolgerungAufgrund der klinischen und auch MR-morphologischen Langzeitergebnisse ist die Refixation von osteochondralen Flakes mittels resorbierbarer Implantate (PLLA) als empfehlenswertes Verfahren zu werten.

Generell stellen Wirbelsaulenverletzungen bei Kindern im Alter unter 16 Jahren eine seltene Verletzungsentitat dar. Fur Deutschland liegen keine belastbaren Daten bezuglich der Epidemiologie von Verletzungen der Wirbelsaule im Kindesalter vor. Gerade bei padiatrischen Patienten, bei denen sowohl die Anamnese, die klinische Untersuchung, aber auch die Durchfuhrung der bildgebenden Diagnostik haufig erschwert sind, mussen samtliche Hinweise auf eine Verletzung der Wirbelsaule mitberucksichtigt werden. Das Ziel der vorliegenden Studie war die Bereitstellung epidemiologischer Daten von padiatrischen Patienten mit Wirbelsaulenverletzungen in Deutschland, um diese zukunftig in die Entscheidungsfindung bei der Diagnostik und Therapie dieser Patienten einfliesen lassen zu konnen. Im Rahmen einer nationalen Multizenterstudie wurden retrospektiv Patientendaten innerhalb eines Zeitraums von 7 Jahren aus 6 Wirbelsaulenzentren erhoben. Neben den demografischen Daten wurden der Unfallmechanismus, die betroffene Wirbelsaulenregion und auch die Begleitverletzungen erhoben. Zudem erfolgte die Erfassung der bildgebenden Diagnostik sowie der jeweiligen Therapie. Es konnten 367 Kinder (weiblich: mannlich = 1:1,2) mit insgesamt 610 Verletzungen an der Wirbelsaule in die Studie eingeschlossen werden. Das mittlere Alter betrug 12 (±3,5) Jahre. Die haufigsten Unfallmechanismen in allen Altersgruppen waren ein Sturz aus unter 3 m Hohe sowie Verkehrsunfalle. Die bildgebende Diagnostik musste nur in Ausnahmefallen in Narkose durchgefuhrt werden. Wahrend jungere Kinder (0 bis 9 Jahre) eher Verletzungen im Bereich der Halswirbelsaule erlitten, zeigten sich Verletzungen der thorakolumbalen Wirbelsaule eher bei Kindern >10 Jahren. Die Kinder wiesen haufige Begleitverletzungen an Kopf und Extremitaten auf. Im Bereich der Wirbelsaule befanden sich weitere Verletzungen meist benachbart und nur selten in anderen Regionen. Rund 75 % der Kinder wurden konservativ behandelt. Die Ergebnisse unterscheiden sich von den Erkenntnissen aus der Erwachsenenmedizin und beschreiben spezielle Gegebenheiten fur padiatrische Patienten mit Wirbelsaulenverletzungen. Trotz gewisser Limitationen konnen sie so bei der Entscheidungsfindung uber die durchzufuhrende Diagnostik und Therapie dieser Patienten helfen.

Wirbelsaulenverletzungen im Kindesalter sind insgesamt sehr selten. Aktuelle einschlagige Studien mit grosen Fallzahlen, aus welchen sich evidenzbasierte Empfehlungen zu Diagnostik und Therapie von Wirbelsaulenverletzungen bei padiatrischen Patienten ableiten lassen, existieren nicht. Formulierung von Empfehlungen zu Diagnostik und Therapie von Verletzungen der Brust- und Lendenwirbelsaule im Kindesalter. Zunachst erfolgte eine Recherche von Primar-, aber auch Sekundarliteratur zum Themenkomplex Diagnostik und Therapie von Verletzungen der Wirbelsaule bei Kindern. Eine entsprechende interne Literaturdatenbank wurde angelegt und gepflegt. Im Zeitraum von April 2017 bis Dezember 2019 fanden sich die Mitglieder der Arbeitsgemeinschaft Wirbelsaulentrauma im Kindesalter der Sektion Wirbelsaule der Deutschen Gesellschaft fur Orthopadie und Unfallchirurgie zu einem Konsensusprozess zusammen. In 9 Arbeitstreffen wurden systematisch Empfehlungen zu Diagnostik und Therapie von Verletzungen der Wirbelsaule bei Kindern formuliert. Es konnten Empfehlungen zu Diagnostik und Therapie von Verletzungen der Brust- und Lendenwirbelsaule fur 3 Altersstufen (Altersstufe I: 0 bis 6 Jahre; Altersstufe II: 7 bis 9 Jahre; Altersstufe III: 10 bi s16 Jahre) formuliert werden. Die Prinzipien der Diagnostik und Therapie aus der Erwachsenenmedizin konnen nicht problemlos ubertragen werden. Wirbelsaulenverletzungen im Kindesalter sind selten und sollten der Behandlung in geeigneten Zentren zugefuhrt werden. Die MRT-Diagnostik sollte beim kardiopulmonal stabilen Kind mit Verdacht auf ein Monotrauma der Wirbelsaule als initiale Bildgebung indiziert werden. Die grundlegenden Therapieziele bei Verletzungen der Brust- und Lendenwirbelsaule im Kindesalter sind die Wiederherstellung der Stabilitat, der Schutz der neurogenen Strukturen und das Wiederherstellen der anatomisch korrekten Verhaltnisse. Bei der Indikationsstellung zur konservativen vs. operativen Therapie mussen das Korrektur- und Regenerationspotenzial der einzelnen Wirbelsaulenabschnitte in Abhangigkeit vom Patientenalter berucksichtigt werden. Die operative Stabilisierung soll v. a. uber minimalinvasive Techniken, im Sinne einer Instrumentierung ohne Spondylodese und fruhzeitiger Metallentfernung, erfolgen.

ZusammenfassungDie Opioidsubstitution ist mittlerweile eine etablierte medizinische Maßnahme zur Behandlung opiatabhängiger Menschen. Fast 80 000 Menschen in Deutschland erhalten damit bessere medizinische und psychosoziale Lebensbedingungen.Ungeachtet dessen ist eine Opioidabstinenz das erklärte langfristige Ziel der Behandlung, was allerdings für viele Betroffene nicht herstellbar ist. Unter Substitution ist allerdings der Zugang zu rehabilitativen Leistungen unseres medizinischen Systems erschwert. Um auch diesen Personen eine Chancengleichheit zu ermöglichen, hat der Dachverband der Suchtfachgesellschaft (DSG) ein Positionspapier erarbeitet.Im Konsens der beteiligten Fachgesellschaften wird gefordert, Zugangsschwellen für abstinenzorientierte Angebote im ambulanten, teilstationären und stationären Setting zu senken, reguläre Behandlungsangebote unter durchgehender Substitution ohne eingangs formuliertes Abstinenzziel und Zugangsmöglichkeiten für eine allgemeinmedizinische Rehabilitation auch für Patienten in Substitutionsbehandlungen zu schaffen und stabil substituierten Menschen mit zusätzlichen psychischen Beeinträchtigungen einen leichteren Zugang zu ambulanten, teilstationären und stationären psychotherapeutischen Behandlung zu ermöglichen.

Utility-scale photovoltaic (PV) generation is being ramped-up in Brazil in recent years, as a result of intense price reductions. Extreme operating temperatures, high humidity levels, and a blue-biased distribution of irradiance in comparison with the standard ASTM G-173 spectrum, lead to contrasting operational outputs of the various commercially-available PV technologies. The performance assessment of six different PV technologies installed at eight different climatic regions in Brazil is presented. This R&D project evaluates eight identical, 54 kWp Evaluation Sites (ESs), all with the following PV technologies: amorphous-silicon (a-Si), microcrystalline-silicon (μc-Si), cadmium-telluride (CdTe), copper-indium-gallium-diselenide (CIGS), mono- and multi-crystalline silicon (c-Si and m-Si). All installations operate at a fixed-tilt equal to the corresponding local latitude. Electrical and environmental parameters at all sites are measured continuously at 1-s intervals. Results show a detailed energy loss analysis for all technologies. Thin-film PV modules with a low temperature-coefficient of power presented superior performance. Crystalline silicon modules revealed intense degradation in areas with high relative humidity and temperature. Cloud-edge and cloud-enhancement effects of solar irradiance resulted in irradiance peaks of 1823 W/m2, with long overirradiance events which lasted many minutes over 1600 W/m2, resulting in frequent blowing of string fuses when manufacturers maximum fuse ratings were observed.

A rare coding variant (rs72824905, p.P522R) conferring protection against Alzheimer’s disease (AD) was identified in the gene encoding the enzyme phospholipase-C-γ2 (PLCG2) that is highly expressed in microglia. To explore the protective nature of this variant, we employed latent process linear mixed models to examine the association of p.P522R with longitudinal cognitive decline in 3595 MCI patients, and in 10,097 individuals from population-based studies. Furthermore, association with CSF levels of pTau181, total tau, and Aβ1-42 was assessed in 1261 MCI patients. We found that MCI patients who carried the p.P522R variant showed a slower rate of cognitive decline compared to non-carriers and that this effect was mediated by lower pTau181 levels in CSF. The effect size of the association of p.P522R with the cognitive decline and pTau181 was similar to that of APOE-ε4, the strongest genetic risk factor for AD. Interestingly, the protective effect of p.P522R was more pronounced in MCI patients with low Aβ1-42 levels suggesting a role of PLCG2 in the response to amyloid pathology. In line with this hypothesis, we observed no protective effect of the PLCG2 variant on the cognitive decline in population-based studies probably due to the lower prevalence of amyloid positivity in these samples compared to MCI patients. Concerning the potential biological underpinnings, we identified a network of co-expressed proteins connecting PLCG2 to APOE and TREM2 using unsupervised co-regulatory network analysis. The network was highly enriched for the complement cascade and genes differentially expressed in disease-associated microglia. Our data show that p.P522R in PLCG2 reduces AD disease progression by mitigating tau pathology in the presence of amyloid pathology and, as a consequence, maintains cognitive function. Targeting the enzyme PLCG2 might provide a new therapeutic approach for treating AD.

BackgroundDiagnostic assessment of ASD requires substantial clinical experience and is particular difficult in the context of other disorders with behavioral symptoms in the domain of social interaction and communication. Observation measures such as the Autism Diagnostic Observation Schedule (ADOS) do not take into account such comorbid and differential disorders.MethodWe used a well-characterized clinical sample of individuals (n=1262) that had received detailed outpatient evaluation for the presence of an ASD diagnosis (n=481) and covered a range of additional differential or overlapping diagnoses, including anxiety related disorders (ANX, n=100), ADHD (n=440), and conduct disorder (CD, n=192). We focused on ADOS module 3, covering the age range with particular high prevalence of such differential diagnoses. We used machine learning (ML) and trained random forest models on ADOS single item scores to predict a clinical best estimate diagnosis of ASD in the context of these differential diagnoses (ASD vs. ANX, ASD vs. ADHD, ASD vs. CD) and an unspecific model using all available data. We employed nested cross-validation for an unbiased estimate of classification performance (ASD vs. non-ASD).ResultsWe obtained very good overall sensitivity (0.89-0.94) and specificity (0.87-0.89) for the classification of ASD vs. non-ASD. In particular for individuals with less severe symptoms (around the ADOS cut-off) our models showed increases of up to 20% in sensitivity or specificity. Furthermore, we analyzed item importance profiles of the ANX-, ADHD- and CD-models in comparison to the unspecific model. These analyses revealed distinct patterns of importance for specific ADOS-items with respect to differential diagnoses.ConclusionUsing ML-based diagnostic classification may improve clinical decisions by utilizing the full range of information from comprehensive and detailed diagnostic observation such as the ADOS. Importantly, this strategy might be of particular relevance for individuals with less severe symptoms that typically present a very difficult decision for the clinician.

This study aimed to investigate exposure adjusted injury incidence rates and profiles associated with training and competition in an elite taekwondo athlete population. 82 athletes were investigated for injuries over a period of 5 years. Individual fight time exposure for training and competition was recorded. The type and location of the injuries were classified and exposure-adjusted injury incidence rates (IIR) were calculated per 1000 h for training and competition. 66 athletes with a mean age of 19.3±4.2 years and 172 injuries were included in the final data assessment. The exposure adjusted IIR was significantly higher during competition (p

Background Impaired subjective well-being in schizophrenia patients treated with antipsychotics has often been linked inter alia to the antidopaminergic effects of medication. Thus, it is important to capture the association between striatal dopamine D2 receptor occupancy (D2-RO) and global subjective well-being. We examined this association using data from our multicenter, randomized, double-blind Neuroleptic Strategy Study (NeSSy). Methods An innovative double randomization process was used for allocation of patients to the specific treatment groups. Plasma drug concentrations were measured after 6 and 24 weeks of treatment to obtain the estimated D2-RO (eD2-RO) relative to literature values. We made an exploratory analysis of associations between eD2-RO and subjective well-being scores. One hundred two blood samples from 69 patients were available for the analysis. Because of the lack of a satisfactory occupancy model for quetiapine, only haloperidol, flupentixol, and olanzapine treatment groups were pooled, whereas aripiprazole data were analyzed separately, because of its partial agonistic properties. Results In the pooled antagonist group, eD2-RO correlated negatively with the summarized well-being score. In a more detailed analysis, this association could be confirmed for all first-generation antipsychotic-treated patients, but not for the separate second-generation antipsychotic groups. In the aripiprazole group, higher eD2-RO was associated with impaired physical well-being, but had no association with mental well-being. Conclusions Our results suggest that high plasma levels and consequently high occupancy at D2 receptors are disadvantageous for subjective well-being, as distinct from the objective extrapyramidal side effects. To minimize patients' malaise, which disfavors adherence, implementation of therapeutic drug monitoring in the clinical routine may be useful.

A 63-year-old female patient with total hip arthroplasty (THA) presented at our clinic with a massive swelling of the right hip joint. 13 years ago, cementless THA with an alumina ceramic-on-cerami...

This work assesses the electricity consumption profile of domestic solar hot water systems (DSHWS) and analyses, at high measurement-time resolutions for the first time, their economic viability in popular housing projects in Brazil. It analyses the impacts of the active power demand measurement-time resolution on the financial attractiveness of DSHWS. The predominance of a late-evening profile of electricity consumption for showering, coinciding with distribution utilities’ peak demand hours, leads to over 40% avoided active power during peak hours per consumer unit when adopting DSHWS. There is potential to finance DSHWS in popular housing with very favourable conditions for the distribution utility. For discount rates ranging from 0 to 9.5%, payback times ranged between less than four and five years, NPV between $ 2,191 and $ 782, and IRR between 25% and 14%. The measurement of power demand at 15-min intervals, widely adopted by distribution utilities, is not adequate to properly evaluate the financial attractiveness of DSHWS, resulting in pessimistic financial analyses of the return on investment. The low load-factor of electric showerheads used in >90% of Brazilian households, leads to the accounting of only 37% of the real avoided cost of adopting DSHWS when measuring power demand in 15-min intervals.

This paper presents an analysis of spectral impacts on mc-Si and new generation CdTe in two distinct regions of Brazil: Florianopolis-SC (27°S, 48°W) in the South, and Assu-RN (5°S, 37°W) in the Northeast. As utility-scale PV power plants are progressively being deployed in the Brazilian Northeast, the need for evaluation of the spectral effects of local blue-biased spectra on the energy yield of different PV technologies arises, as well as the need for spectral correction of field peak-power measurements done during commissioning and system performance tests. Considering the high cost of adequate spectral measurement equipment, this paper proposes a new approach for the estimation of spectral impacts without the need for in loco measurements. The proposed methodology consists of the use of satellite data acquired from NASA's Giovanni platform as inputs for the SMARTS 2.9.5 spectra model. Results for measured spectra showed that, for both locations, new generation CdTe (i.e. First Solar Series 4 and 6) has significant spectral gains: up to 10% for Assu-RN (Northeastern Brazil) and 2% for Florianopolis-SC (Southern Brazil). A seasonal variation could also be detected for the Florianopolis site, with lower spectral gains for CdTe - and higher for mc-Si - close to the Southern Hemisphere’s winter solstice, due to higher air mass values and lower precipitable water content of the atmosphere. The proposed method using Giovanni data and SMARTS spectra modeling produced very similar spectra to those measured for clear days in the field at both sites, yielding good results for the calculation of spectral factors for both mc-Si and CdTe. For days with a higher diffuse fraction the results were not as satisfactory, as expected. The proposed method was also applied to instantaneous measurements for three different times (and AM values) of the day for Florianopolis: 9:00, 12:00 and 15:00, yielding satisfactory results for IV curve spectral correction.

Aims The aim of this study was to evaluate the diagnostic accuracy of the synovial alpha-defensin enzyme-linked immunosorbent assay (ELISA) for the diagnosis of prosthetic joint infection (PJI) in the work-up prior to revision of total hip (THA) and knee arthroplasty (TKA). Patients and Methods Inclusion criteria for this prospective cohort study were acute or chronic symptoms of the index joint without specific exclusion criteria. Synovial fluid aspirates of 202 patients were analyzed and semiquantitative laboratory alpha-defensin ELISA was performed. Final diagnosis of PJI was established by examination of samples obtained during revision surgery. Results Sensitivity and specificity of the alpha-defensin ELISA for PJI were 78.2% (95% confidence interval (CI) 66.7 to 88.5) and 96.6% (95% CI 93.0 to 99.3). Positive and negative predictive values were 89.6% (95% CI 80.6 to 97.8) and 92.2% (95% CI 87.5 to 96.1). The test remained false-negative in 22% of septic revisions, most of which were due to coagulase-negative staphylococci all occurring in either late-chronic or early-postoperative PJI. Conclusion The routine use of synovial fluid alpha-defensin laboratory ELISA in the preoperative evaluation of symptomatic THAs and TKAs is insufficient to accurately diagnose PJI. Particularly in cases involving low-virulence organisms, such as coagulase-negative staphylococci, there remains a need for tests with a higher sensitivity. Cite this article: Bone Joint J 2019;101-B:970–977.

Ocriplasmin (Jetrea®) ist eine therapeutische Option fur Patienten mit fokaler vitreomakularer Traktion (VMT) mit oder ohne kleine durchgreifende Makulaforamen (FTMH)

The purpose of this study was to investigate the relationship between clinical disease activity in patients with advanced stage rheumatoid arthritis (RA) on treatment with Disease Modifying Antirheumatic Drugs (DMARDs) and histopathological scores of synovial inflammation. To this end, synovial biopsies of 62 RA patients who underwent surgery for either synovectomy or total joint arthroplasty were assessed by a general synovitis score (GSS) and an immunologic synovitis score (IMSYC). The clinical disease activity index (CDAI) was significantly correlated with both the GSS and the IMSYC (r = 0.65, p =

Background & Aims Osteoporotic fractures are a major cause of morbidity and reduced quality of life in patients with primary sclerosing cholangitis (PSC), a progressive bile duct disease of unknown origin. Although it is generally assumed that this pathology is a consequence of impaired calcium homeostasis and malabsorption, the cellular and molecular causes of PSC-associated osteoporosis are unknown. Methods We determined bone mineral density by dual-X-ray absorptiometry and assessed bone microstructure by high-resolution peripheral quantitative computed tomography in patients with PSC. Laboratory markers of liver and bone metabolism were measured, and liver stiffness was assessed by FibroScan. We determined the frequency of Th17 cells by the ex vivo stimulation of peripheral blood mononuclear cells in a subgroup of 40 patients with PSC. To investigate the potential involvement of IL-17 in PSC-associated bone loss, we analyzed the skeletal phenotype of mice lacking Abcb4 and/or Il-17. Results Unlike in patients with primary biliary cholangitis, bone loss in patients with PSC was not associated with disease duration or liver fibrosis. However, we observed a significant negative correlation between the bone resorption biomarker deoxypyridinoline and bone mineral density in the PSC cohort, indicating increased bone resorption. Importantly, the frequency of Th17 cells in peripheral blood was positively correlated with the urinary deoxypyridinoline level and negatively correlated with bone mass. We observed that Abcb4-deficient mice displayed a low-bone-mass phenotype, which was corrected by an additional Il-17 deficiency or anti-IL-17 treatment, whereas the liver pathology was unaffected. Conclusions Our findings demonstrate that an increased frequency of Th17 cells is associated with bone resorption in PSC. Whether antibody-based IL-17 blockade is beneficial against bone loss in patients with PSC should be addressed in future studies. Lay summary Primary sclerosing cholangitis (PSC) is a cholestatic liver disease characterized by progressive bile duct destruction. One serious complication of PSC is reduced bone mass resulting in increased fracture risk. Herein, we demonstrate that Th17 cells mediate bone loss in PSC by inducing bone resorption, which suggests that antibody-based IL-17 blockade might be beneficial for the treatment of bone loss in affected patients.

This review aims to determine the specific effects of PA on systemic levels of interleukins and inflammatory markers. A systematic literature search was conducted in three computerized bibliographic databases (Medline, Embase, CENTRAL) to identify randomized controlled trials and matched case studies. Applied key words were: RA and PA including the terms exercise, exercise therapy, gymnastics and exercise movement techniques. Inclusion criteria were data on all types of proinflammatory interleukins (IL), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). For data synthesis, the populations, interventions and outcomes were described according to the PRISMA statement. A total of 1289 publications were found. Fifteen papers, related to 14 different study populations, met the inclusion criteria. No study revealed a significant change regarding IL or CRP levels in response to the intervention (PA). In three study populations, a significant reduction of the ESR was identified, but the effect from PA was not discernible from effects of changes of the anti-rheumatic medication in these studies. The strong variability in study designs, cohort size and types of physical training programs remains an obstacle in the assessment of the measurable effects of PA on inflammatory markers in patients with RA. At present, there is no sufficient evidence to conclude that PA has a significant impact on systemic levels of inflammatory markers in RA.

Coronary calcification (CAC) is an established marker for coronary atherosclerosis and has a highly specific predictive value for cardiovascular events. This study aimed to determine the predictive value in the specific group of asymptomatic smokers in comparison to non-smokers. We included 1432 asymptomatic individuals (575 women, 857 men, age 59.2 ± 7.7 years.) in this study. Coronary calcification was calculated by multi-slice computed tomography following a standardized protocol including calcium score (CS). Coronary risk factors were determined at inclusion. After mean observation time of 76.3 ± 8.5 months the patients were contacted and evaluated for cardiovascular events (myocardial infarction, cardiac death and revascularisation). Mean CS was 231 ± 175 in smokers and 239 ± 188 in non-smokers. Cardiovascular events were found in 14.9% of our patients and there were significantly more events in smokers (119 events, 8.3%) than in non-smokers (94 events, 6.6%, p = 0.001). CS > 400 showed a hazard ratio for future cardiac events of 5.1 (95% CI 4.3–7.6) in smokers and 4.4 (95% CI 3.4–6.2) in non-smokers, p = 0.01. Also in smokers determination of CAC is a valuable predictor of future cardiovascular events. In our study smokers showed throughout all score groups a significantly higher risk compared to non-smokers with equal CS. Therefore, CS may underestimate the risk for future cardiac events in smokers compared to non-smokers.

This study is aimed at performing and analyzing the inverter sizing optimization process for large-scale grid-connected solar photovoltaics (PV). The local solar resource was evaluated and compared to the available satellite data. Analyses of the solar irradiance distribution and its potential effects on inverter sizing were performed. The performance of five different, commercially-available PV module technologies was also evaluated by means of remote data analysis of irradiation and temperature, as well as electrical parameters. This was performed using the metrics of energy yield and performance ratio (PR) for PV systems. A methodology was developed for estimating the optimal inverter sizing in the region considering overload losses and economic aspects, aiming at the optimization and cost reduction of PV-generated electricity. Considering the five technologies, the mean yield was 150 kWh/kWp on a monthly basis. The annual PR ranged from 77% to 85% depending on technology. The local solar resource, measured during three years, was compared to five distinct satellite-derived solar databases. Cloud enhancement and cloud edge effects were observed through the monthly solar irradiation distribution over the three years of measurements. Around 28% of the incident annual irradiation was at irradiance levels at or above 1000 W/m2. The methodology developed for the optimal inverter loading ratio (ILR) was applied over one full year of solar generation data for the five technologies. It was observed that for inverter loading ratios commonly used on utility-scale PV power plants (around 120%), the overload losses varied from 0.3% to 2.4%, depending on technology. The optimal ILR for the more traditional crystalline Si PV technology was estimated to be 126%.

This paper aims to analyze different methods and software for the orthomosaic reconstruction of aerial infrared thermography (aIRT) images of a 3 MW PV plant in Brazil. Results showed that the method could improve the process of inspections of PV plants through aerial imagery, facilitating the localization of faults. Some challenges observed include the long duration of the flights caused by the high overlapping of images required, and the distortions presented in the resulting orthomosaics. The combination of the method with artificial intelligence algorithms that detect faults in aIRT images is a fast and effective tool to inspect PV power plants.

Reporting of new or unexpected adverse drug reactions of medicines that are subject to additional monitoring (“black triangle” label), such as the antipsychotic drug cariprazine, is of paramount importance to improve pharmacotherapy safety.

Data on drug prescription for outpatients with major depressive disorder (MDD) suggest women are more likely to be treated with psychotropic drugs, while data on sex differences regarding pharmacological treatment of psychiatric inpatients are currently not available. Drug utilization data from the program “Drug Safety in Psychiatry” (German: Arzneimittelsicherheit in der Psychiatrie, AMSP) of 44,418 psychiatric inpatients with MDD were analyzed for sex differences between 2001 and 2017. Sex differences were analyzed using relative risks (RR) and 95% confidence intervals (95% CI). Time trends were analyzed by comparing the first (2001–2003) with the last time period (2015–2017). In general, men and women were equally likely to use psychotropic drugs. Monotherapy was more common in men. Women were more likely to utilize ≥ 4 psychotropic drugs. Antidepressant drugs (ADDs) were the most prescribed drug class. Men had a higher utilization of noradrenergic and specific serotonergic antidepressants (RR 1.15; 95% CI 1.12–1.19), especially mirtazapine (RR 1.16; 95% CI 1.12–1.19), but also of other ADDs such as bupropion (RR 1.50; 95% CI 1.35–1.68). Males had a slightly higher utilization of second-generation antipsychotic drugs (RR 1.06; 95% CI 1.03–1.09) and were less often treated with low-potency first-generation antipsychotic drugs (RR 0.86; 95% CI 0.83–0.90). Tranquilizing (e.g., benzodiazepines; RR 0.89; 95% CI 0.86–0.92) and hypnotic drugs (e.g., Z-drugs; RR 0.85; 95% CI 0.81–0.89) were less utilized in the treatment of male patients. Not all sex differences were stable over time. More sex differences were detectable in 2015–2017 than in 2001–2003. Findings suggest that certain psychotropic drugs are preferred in the treatment of men vs. women, however, sex differences found in this study are not as large as in ambulatory settings. To make evidence-based sex-specific recommendations in the treatment of MDD, differences in drug response and tolerability need to be further researched.

The EC HYPOS (HYdro-POwer-Suite) project (https://hypos-project.eu/) has the main goal of assessing the environmental impact of existing and future hydropower systems. The project will provide a suite of data analysis applications which integrates Earth Observation (EO) technologies and hydrological modelling. These include an online Decision Support Tool (DST) for investment planning and monitoring, as well as a subscription portal combining satellite data over time, current measurements and detailed estimates for present and near future assessments. A dedicated analysis on the “blue footprint” (i.e. the amount of water used to produce a service) of reservoirs is included for addressing sustainable monitoring solutions. Such analysis comprises the evaluation of the climate change effects on reservoirs management and hydropower production. For instance, extreme weather events like short-term heavy precipitations are connected with flooding and transport of large amounts of sediments in dammed reservoirs, with critical consequences for their management. Similarly, global warming can heat the surface of water bodies and induce higher evaporation rates, thus decreasing the amount of water available for energy production. In this study we present the first products from HYPOS project. These products are representative of what can be generated within the DST using elaboration techniques of EO data. Gridded products of water quality parameters (e.g. water turbidity, Chlorophyll-a concentration, suspended sediments concentration) are generated for the test sites of the project, which are small dammed reservoirs located in Switzerland, France, Albania and Georgia. These products are obtained using the Modular Inversion and Processing System (MIP), a sensor independent image processing chain based on radiative transfer models, which works in a multi-layer system, solving the light transfer in the atmosphere, at the water surface and inside the waterbody.For the assessment of the “blue footprint” of a reservoir, the water loss due to evaporation is computed by applying a consolidated mass transfer evaporation method to EO data. The resulting evaporation rates are first compared with the outputs of semi-automatic evapotranspiration EO-based models (e.g. SEBAL), and then with the estimates ​​obtained from two different numerical models: a hydrological model (E-Hype) and a 3D hydrodynamic model (Delft3D). The key parameters influencing water evaporation rates, their behavior and the issues related to each approach are analyzed. The first comparison results are made for lake Garda, where a complete set of data is available for the production of evaporation maps.

Zusammenfassung Hintergrund Muskelverletzungen finden sich häufig in Sprint- und Kontaktsportarten mit explosiven Bewegungsmustern. Bisher liegen keine detaillierten Daten zu Muskelverletzungen im olympischen Taekwondo vor, obwohl in dieser Sportart die Muskulatur der unteren Extremitäten physiologisch extrem stark beansprucht wird. Methoden Alle im Training und Wettkampf erlittenen Verletzungen von 76 Athleten eines nationalen olympischen Trainingszentrums wurden über einen Zeitraum von 5 Jahren prospektiv erfasst. Die Daten zur Lokalisation der Muskelverletzungen und dem Zeitraum bis zum „Return-to-Training“ wurden retrospektiv ausgewertet. Die Klassifikation der Verletzungen erfolgte mittels British Athletes Muscle Injury Classification System im MRT. Der Zusammenhang zwischen den Untergruppen der MRT-Klassifikation und dem Zeitraum bis zum „Return-to-Training“ wurde untersucht. Ergebnisse Das Durchschnittsalter der Athleten betrug 22,5 ± 3,2 (16–27) Jahre mit einer mittleren Taekwondo-Praxis von 12,1 ± 4,0 (7–20) Jahren. Am häufigsten betroffen war die ischiocrurale Muskelgruppe (48,4 %), gefolgt vom M. quadriceps femoris (32,3 %) und der Wadenmuskulatur (9,6 %). Die Auswertung der MRT-Klassifikation ergab am häufigsten leichtgrade Muskelverletzungen Grad 1 (3,3 %) und 2 (41,9 %). Es zeigte sich eine positive Korrelation (r = 0,56) zwischen den Subgruppen der MRT-Klassifikation und den Ausfallzeiten der Athleten. Der Vergleich der Ausfallzeiten zwischen den Subgruppen war ebenfalls signifikant unterschiedlich (p Zusammenfassung Die ischiocrurale Muskelgruppe ist neben dem M. quadriceps im Taekwondo am häufigsten von Muskelverletzungen betroffen. Am häufigsten wurden indirekte, leichtgradige Muskelverletzungen gefunden (Grad 1–2). Die Ausfallzeit nimmt mit zunehmendem Schweregrad der Verletzung im MRT signifikant zu.

Wood-based thermal insulation materials have interesting hygroscopic characteristics because of their high moisture capacity. The present paper investigates the moisture conditions in wood-frame walls with wood fibre thermal insulation. The effect of forced convection of moist air into the construction is studied in particular. Laboratory measurements were carried out on a full-scale wall model divided in five sections with various configurations. The wall sections had different combinations of exterior air barrier, thermal insulation and interior vapour retarder. Each section was prepared with an air leakage to simulate supply of moist air to the wall construction through forced convection. The measurement results provided insight in the moisture conditions in the wall and internal distribution of moisture in the wall sections. The results show that walls with wood fibre insulation may have the same risk of high moisture levels as walls with mineral wool insulation. However, the results indicate that wood fibre insulation absorbs condensation and melting water, while the mineral wool does not. Hence, the results imply that the wood fibre insulation has the benefit of distributing the moisture over a larger volume than the mineral wool insulation. Furthermore, the investigations indicate that using an exterior air barrier with high thermal resistance results in a generally lower moisture level in the wall construction, which can be considered favourable regarding risk of mould growth. This is an open access article distributed under the terms of the Creative Commons CC-BY license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

The emergence of e-cigarettes on the consumer market led to a tremendous rise in e-cigarette consumption among adolescents in the United States. The success of JUUL and other pod systems was linked to its high nicotine delivery capacity. In compliance with the European Tobacco Product directive, liquid nicotine contents in the European JUUL variants are limited to 20 mg/mL or below. A short time after launching the initial version in Europe, JUUL pods have been modified in terms of the wick material used. This modification has been demonstrated previously to lead to an elevated aerosol generation, consequently, to a larger amount of nicotine per puff generated. The present study was designed to assess whether the mentioned differences between the “initial” and “modified” JUUL versions may cause a significant difference during consumption, and how nicotine delivery compares with tobacco cigarettes. In this single-center three-arm study, nicotine pharmacokinetics and influence on urge to smoke/vape were compared for tobacco cigarettes, the “initial” version of the European JUUL, and the “modified” version of the European JUUL. Participants, 15 active smokers and 17 active e-cigarette users, were instructed to consume their study product according to a pre-directed puffing protocol. Venous blood was sampled for nicotine analysis to cover the acute phase and the first 30 min after starting. Nicotine delivery and the reduction of urge to smoke/vape upon usage of both European JUUL variants were lower in comparison to tobacco cigarettes. This suggests a lower addictive potential. Modification of the pod design did not result in significant differences at the first ten puffs, as confirmed by a vaping machine experiment. Apparently, the limitations by the initially used wick material only come into effect after longer usage time.

IntroductionMajor depression (MD) often has its onset during adolescence and is associated with significant morbidity and mortality. One important factor for the development and maintenance of adolescent MD are disturbances in emotion regulation and the underlying neural processes. Cognitive reappraisal (CR) is a particular adaptive emotion regulation strategy. Previously, it has been shown in healthy adults that a task-based training in CR is efficient to reduce negative affect, and that these effects translate into everyday life.This randomised controlled trial examines for the first time whether a task-based training in CR proves effective in MD adolescents. Specifically, we will investigate whether the CR training improves the ability to downregulate negative affect in MD individuals as assessed by behavioural and neurobiological indices, and whether training effects generalise outside the laboratory.Methods and analysisAdolescents with MD will be randomly allocated to a group that either receives a task-based training in CR or a control training. Both involve four training sessions over a time period of 2 weeks. In the CR training, participants will be instructed to downregulate negative affective responses to negative pictures via CR, while the control training involves picture viewing. During the training sessions, the Late Positive Potential, gaze fixations on negative picture aspects and affective responses to pictures will be collected. Before and after the training programmes, and at a 2-week follow-up, overall negative and positive affect, rumination and perceived stress will be assessed as primary outcomes. Analyses of variance will be conducted to test the effectiveness of the CR training with regard to both primary outcomes and task-based behavioural and neurobiological parameters.Ethics and disseminationThe study was approved by the Ethics Committee of the Medical Faculty of the LMU Munich, Germany. The results will be published in peer-reviewed journals and disseminated through conferences, social media and public events.Trial registration detailsClinicalTrials.gov NCT03957850, registered 21st May 2019; URL: https://clinicaltrials.gov/ct2/show/NCT03957850.

Introduction Osteoarthritis (OA) and rheumatoid arthritis (RA) represent the most common forms of arthritis, which are mainly caused by mechanical and inflammatory components, respectively. Determination of synovial inflammation in synovial biopsies via the histopathological Krenn score may be crucial for correct diagnosis and treatment. Specifically, it remains unclear whether synovitis scores differ among multiple biopsy locations within a single joint. Materials and methods Eighty synovial samples were taken from four standardized regions of the knee in 20 patients (ten primary OA, ten secondary OA) undergoing total knee arthroplasty (TKA) or total synovectomy. The Krenn synovitis score (grade 0–9) was determined in a blinded manner by two expert pathologists in all biopsies. Next to the inter-rater reliability, we evaluated the agreement of the determined scores among the four biopsy locations within each knee. Results The inter-rater reliability between the two pathologists was very high (Cohen’s kappa = 0.712; r = 0.946; ICC = 0.972). The mean synovitis score was significantly higher in knees with secondary than in primary OA (p = 0.026). Importantly, we found clear differences between the scores of the four different biopsy locations within the individual knee joints, with an average deviation of 10.6%. These deviations were comparable in knees with primary and secondary OA (p = 0.64). Conclusions While we confirmed the synovitis score as a reliable and reproducible parameter to assess the histopathological synovitis grade in the knee, the considerable variability within the joint indicates that multiple synovial biopsies from different regions should be obtained to enable reliable results of the synovitis score.

The systematic use of evidence to inform healthcare decisions, particularly health technology assessment (HTA), has gained increased recognition. HTA has become a standard policy tool for informing decision makers who must manage the entry and use of pharmaceuticals, medical devices, and other technologies (including complex interventions) within health systems, for example, through reimbursement and pricing. Despite increasing attention to HTA activities, there has been no attempt to comprehensively synthesize good practices or emerging good practices to support population-based decision-making in recent years. After the identification of some good practices through the release of the ISPOR Guidelines Index in 2013, the ISPOR HTA Council identified a need to more thoroughly review existing guidance. The purpose of this effort was to create a basis for capacity building, education, and improved consistency in approaches to HTA-informed decision-making. Our findings suggest that although many good practices have been developed in areas of assessment and some other key aspects of defining HTA processes, there are also many areas where good practices are lacking. This includes good practices in defining the organizational aspects of HTA, the use of deliberative processes, and measuring the impact of HTA. The extent to which these good practices are used and applied by HTA bodies is beyond the scope of this report, but may be of interest to future researchers.

In several human biomonitoring surveys, changes in the usage patterns of phthalates have come to light, but their influence on the risks associated with combined exposures is insufficiently understood. Based on the largest study to date, the 27-year survey of urinary phthalate metabolite levels in 24-hour urine samples from the German Environmental Specimen Bank, we present a deep analysis of changing phthalate exposures on mixture risks. This analysis adopts the Hazard Index (HI) approach based on the five phthalates DBP, DIBP, BBP, DEHP and DINP. Calculations of the hazard index for each study participant included updated phthalate reference doses for anti-androgenicity (RfDAAs) that take account of new evidence of phthalates’ developmental toxicity. The Maximum Cumulative Ratio (MCR) approach was used to establish whether a subject’s combined exposure was dominated by one phthalate or was influenced by several phthalates simultaneously. Generally, over the years there was a shift towards lower HIs and higher MCRs, reflecting an increased complexity of the combined exposures. The decade from 1988 to about 1999 was characterised by rather high HIs of between 3 and 7 (95th percentile) which were driven by exposure to DBP and DEHP, often exceeding their single acceptable exposures. Traditional single phthalate risk assessments would have underestimated these risks by up to 50%. From 2006 onwards, no study participant experienced exposures above acceptable levels for a single phthalate, but combined exposures were still in excess of HI = 1. From 2011 onwards most individuals stayed below HI = 1. In interpreting these results, we caution against the use of HI = 1 as an acceptable limit and develop proposals for improved and more realistic mixture risk assessments that take account of co-exposures to other anti-androgenic substances also capable of disrupting the male reproductive system. From this perspective, we regard HIs between 0.1 and 0.2 as more appropriate for evaluating combined phthalate exposures. Assessed against lowered HIs of 0.1 – 0.2, the combined phthalate exposures of most study participants exceeded acceptable levels in all study years, including 2015. Continued monitoring efforts for phthalate combinations are required to provide the basis for appropriate risk management measures. Federal Ministry for the Environment, Nature Conservation, and Nuclear Safety (BMU), Germany; Horizon 2020 research and innovation programme