Assistierter Suizid : welche Rolle spielt die zunehmende Akzeptanz breiter Kreise?

Während sich die Rate der nicht assistierten Suizide deutlich nach unten bewegt, steigt die Zahl der assistierten Suizide steil an. Fördert die verbreitete positive Einstellung zu Letzteren die Suizidwünsche bei Kranken

Testable likelihoods for beyond-the-standard model fits

Studying potential BSM effects at the precision frontier requires accurate transfer of information from low-energy measurements to high-energy BSM models. We propose to use normalising flows to construct likelihood functions that achieve this transfer. Likelihood functions constructed in this way provide the means to generate additional samples and admit a “trivial” goodness-of-fit test in form of a χ2 test statistic. Here, we study a particular form of normalising flow, apply it to a multi-modal and non-Gaussian example, and quantify the accuracy of the likelihood function and its test statistic

Sclerotherapy and prolotherapy for chronic patellar tendinopathies - a promising therapy with limited available evidence, a systematic review

Chronic Patellar tendinopathy (CPT) is a frequent overuse disorder in athletes and active people. Sclerotherapy (ST) and prolotherapy (PT) are, among a wide range of conservative treatment options, two promising therapies and have shown positive results in other tendinopathies. Since the treatments' efficacy and safety are still not defined, this review sought to answer questions on recommendations for use in clinical utility, safety, and how to perform the injection in the most effective way. An electronic database search was conducted following the PRISMA guidelines. Inclusion criteria were set up according to the PICOS-scheme. Included were athletes and non-athletes of all ages with diagnosed painful CPT. Studies including patients suffering from patellar tendinopathy which can be originated to any systemic condition affecting the musculoskeletal system (e.g. disorders associated with rheumatism) and animal studies were excluded. Methodological quality (modified Coleman Methodology Score) and risk of bias (Cochrane Risk of Bias Assessment Tool 2.0) were assessed by two independent reviewers, with disagreements resolved with a third reviewer. The search yielded a total of 416 entries. After screening titles, abstracts, and full texts, ten articles were found for qualitative analysis. The mean Coleman Score was 64.57. Three randomized-controlled trials showed positive results with an increase in VISA-P score or a decrease in VAS or NPPS, respectively. The non-randomized studies confirmed the positive results as well. Among all ten studies no serious adverse events were reported. Based on this limited set of studies, there seems to be some evidence that ST and PT may be effective treatment options to treat pain and to improve function in patients with CPT. To strengthen this recommendation, more research is needed with larger volume studies and randomized controlled studies with long term follow up. LEVEL OF EVIDENCE: IV

Kunsten å ikke miste kunnskap - hvordan redusere uønsket turnover

Master i bedriftsledelse (MBA) - 201

"Freundschaft" bei Huftieren? - Soziopositive Beziehungen zwischen nicht-verwandten artgleichen Herdenmitgliedern

Die Ziele der Arbeit lagen im Nachweis und in der Quantifizierung von Freundschaften bei Pferden, Eseln, Schafen und Rindern. Weiterführende Analysen erfolgten bzgl. Situationsspezifität, Dynamik und Dauer der Bindungen, Asymmetrie innerhalb der Beziehungen, begünstigender Faktoren und Funktionen. Zehn Nutztierherden (2-3 je Art) mit 11-60 Mitgliedern (insges. 234 Tiere) wurden zwei Jahre im Freiland (SO-England) untersucht (ca. 1500h). Die Rinder waren weiblich, die Schafe männlich, die Equiden lebten in gemischtgeschlechtlichen Herden (männl. Tiere kastriert). Außer den Rindern (subadult) waren die Tiere erwachsen. Gewählt wurde ein vergleichender, quantitativer, objektiver, systematischer und individuenbasierter Untersuchungsansatz mit Langzeitcharakter. Die Rahmenbedingungen schlossen Verwandtschaft und sexuelle Motivation als alternative Basis soziopositiver Bindungen aus. Die Erfassung des spontanen Verhaltens wurde um experimentelle Ansätze erweitert; verschiedene Sampling- und Recording-Methoden kamen zum Einsatz. Indikatoren für interindividuelle Präferenzen waren Nachbarschafts- (zwei nächste Nachbarn) und Partnerwahl-Häufigkeiten bei soziopositiven Interaktionen (soziale Fellpflege, Körperkontakte beim Ruhen, Futterteilen, Dokumentieren s.l.). Zur differenzierten Auswertung der Nachbarschaftsdaten wurde das Computerprogramm NENESYS entwickelt. Die abschließende statistische Bearbeitung erfolgte v.a. durch multivariate Verfahren (z.B. MDS, Clusteranalyse, Mantel-Test). Obwohl der Gesichtspunkt 'Freundschaft' der Humanpsychologie entliehen ist, bietet diese keine einheitliche Definition und Terminologie. Daher wurde eine eigene Definition anhand struktureller und inhaltlicher (nicht funktionaler) Kriterien erarbeitet. Der Nachweis von Freundschaften war bei allen vier Tierarten erfolgreich und erfordert eine Ausweitung des Freundschaftskonzepts über die Ordnung der Primaten hinaus. Bei allen Arten außer den Rindern konnte der Nachweis doppelt (beständige Nachbarschafts- und Interaktionspartnerpräferenzen) abgesichert werden. Die Quantifizierung der Bindungen ergab zwischen- und innerartliche Unterschiede. Ausmaß und Stärke der Nachbarschaftspräferenzen waren bei den Pferden am größten, den Schafen intermediär, den Rindern am geringsten. Bei den Eseln war das Ausmaß der Freundschaften am geringsten, die Stärke hingegen entsprach ca. der der Pferde. Der Vergleich der interindividuellen Präferenzen in bis zu vier verschiedenen Situationen (Nachbarschaft beim Grasen bzw. Ruhen, soz. Fellpflege, Futterteilen) ergab deutliche interspezifische Unterschiede. Die Pferde zeigten das geringste Ausmaß an Situationsspezifität (weitgehend dieselben Partner in allen Situationen), die Esel und Rinder das höchste, die Schafe ein intermediäres. Entgegen der bisherigen Ansicht, Schafe betrieben keine soziale Fellpflege, wurden zwei Verhaltensweisen identifiziert, die zumindest die psychosozialen Funktionen sozialer Fellpflege besitzen: Horn- bzw. Kopfreiben und Verweilen im Wangenkontakt. Während ersteres in der Literatur gelegentlich erwähnt und kontrovers interpretiert wird (agonistisch vs. respektanzeigend), wurde Verweilen im Wangenkontakt erstmals dokumentiert. Für beide wird eine Einordnung in den soziopositiven Verhaltenskontext vorgeschlagen. Die Untersuchungsspanne erlaubte, Freundschaften max. 18 Monate zu verfolgen. Die Dauer der Bindungen der Pferde und Schafe entsprach den Literaturangaben für Herden mit einem Sozialgefüge aus Freundschafts- und Verwandtschaftsanteilen, die der Rinder war kürzer, die der Esel zweimal so lang wie bisher bekannt. Präferenzen in verschiedenen Situationen scheinen in unterschiedlichen Phasen der Freundschaftsentwicklung verschieden häufig aufzutreten. Der Aspekt der Asymmetrie wird besonders bei der unilateralen sozialen Fellpflege der Boviden deutlich. Ähnlichkeit bzgl. des Alters (Rinder) und des Besitzes von Hörnern (Schafe) begünstigte Freundschaften signifikant. Die gängige Ansicht, Pferde ähnlicher Farbe bevorzugten einander, bestätigte sich nicht. Die Funktionen von Huftierfreundschaften äußern sich weniger in einem direkten, praktischen Nutzen, sondern treten als psychologischer Nutzen in Form von sozialer, emotionaler Unterstützung in Erscheinung. Emotionale Unterstützung und soziale Fellpflege reduzieren psychologische und physiologische Streßsymptome. Über diese gesundheitsfördernde Wirkung besitzen Tierfreundschaften einen indirekten praktischen Nutzen. Davon profitieren sowohl Tiere als auch Tierhalter (ethischer und anthropozentrischer Tierschutz). Voraussetzung für gesunde, effiziente Tiere sind Haltungsbedingungen, die ihren physischen und psychosozialen Bedürfnissen entsprechen. Für die Umsetzung der Ergebnisse in der Tierhaltungspraxis wurden Anwendungsempfehlungen erstellt. Ein Regelkreismodell integriert die verschiedenen Aspekte der Arbeit, visualisiert ihre Wechselbeziehungen und erleichtert das Formulieren präziser Hypothesen für zukünftige Forschung

Biochemical, clinical and genetic characteristics in adults with persistent hypophosphatasaemia; Data from an endocrinological outpatient clinic in Denmark

BACKGROUND: Hypophosphatasia (HPP) is an inborn disease caused by pathogenic variants in ALPL. Low levels of alkaline phosphatase (ALP) are a biochemical hallmark of the disease. Scarce knowledge about the prevalence of HPP in Scandinavia exists, and the variable clinical presentations make diagnostics challenging. The aim of this study was to investigate the prevalence of ALPL variants as well as the clinical and biochemical features among adults with endocrinological diagnoses and persistent hypophosphatasaemia. METHODS: A biochemical database containing ALP measurements of 26,121 individuals was reviewed to identify adults above 18 years of age with persistently low levels of ALP beneath range (≤ 35 ± 2.7 U/L). ALPL genetic testing, biochemical evaluations and assessment of clinical features by a systematic questionnaire among included patients, were performed. RESULTS: Among 24 participants, thirteen subjects (54.2%) revealed a disease-causing variant in ALPL and reported mild clinical features of HPP, of which musculoskeletal pain was the most frequently reported (n = 9). The variant c. 571G > A; p.(Glu191Lys) was identified in six subjects, and an unreported missense variant (c.1019A > C; p.(His340Pro)) as well as a deletion of exon 2 were detected by genetic screening. Biochemical analyses showed no significant differences in ALP (p = 0.059), the bone specific alkaline phosphatase (BALP) (p = 0.056) and pyridoxal-5′-phosphate (PLP) (p = 0.085) between patients with an ALPL variant and negative genetic screening. Patients with a variant in ALPL had significantly higher PLP levels than healthy controls (p = 0.002). We observed normal ALP activity in some patients classified as mild HPP, and slightly increased levels of PLP in two subjects with normal genetic screening and four healthy controls. Among 51 patients with persistent hypophosphatasaemia, fifteen subjects (29.4%) received antiresorptive treatment. Two patients with unrecognized HPP were treated with bisphosphonates and did not show complications due to the treatment. CONCLUSIONS: Pathogenic variants in ALPL are common among patients with endocrinological diagnoses and low ALP. Regarding diagnostics, genetic testing is necessary to identify mild HPP due to fluctuating biochemical findings. Antiresorptive treatment is a frequent reason for hypophosphatasaemia and effects of these agents in adults with a variant in ALPL and osteoporosis remain unclear and require further studies

Protease-Triggered Release of Stabilized CXCL12 from Coated Scaffolds in an Ex Vivo Wound Model

Biomaterials are designed to improve impaired healing of injured tissue. To accomplish better cell integration, we suggest to coat biomaterial surfaces with bio-functional proteins. Here, a mussel-derived surface-binding peptide is used and coupled to CXCL12 (stromal cell-derived factor 1α), a chemokine that activates CXCR4 and consequently recruits tissue-specific stem and progenitor cells. CXCL12 variants with either non-releasable or protease-mediated-release properties were designed and compared. Whereas CXCL12 was stabilized at the N-terminus for protease resistance, a C-terminal linker was designed that allowed for specific cleavage-mediated release by matrix metalloproteinase 9 and 2, since both enzymes are frequently found in wound fluid. These surface adhesive CXCL12 derivatives were produced by expressed protein ligation. Functionality of the modified chemokines was assessed by inositol phosphate accumulation and cell migration assays. Increased migration of keratinocytes and primary mesenchymal stem cells was demonstrated. Immobilization and release were studied for bioresorbable PCL-co-LC scaffolds, and accelerated wound closure was demonstrated in an ex vivo wound healing assay on porcine skin grafts. After 24 h, a significantly improved CXCL12-specific growth stimulation of the epithelial tips was already observed. The presented data display a successful application of protein-coated biomaterials for skin regeneration

Microstructural Analysis of Human White Matter Architecture Using Polarized Light Imaging: Views from Neuroanatomy

To date, there are several methods for mapping connectivity, ranging from the macroscopic to molecular scales. However, it is difficult to integrate this multiply-scaled data into one concept. Polarized light imaging (PLI) is a method to quantify fiber orientation in gross histological brain sections based on the birefringent properties of the myelin sheaths. The method is capable of imaging fiber orientation of larger-scale architectural patterns with higher detail than diffusion MRI of the human brain. PLI analyses light transmission through a gross histological section of a human brain under rotation of a polarization filter combination. Estimates of the angle of fiber direction and the angle of fiber inclination are automatically calculated at every point of the imaged section. Multiple sections can be assembled into a 3D volume. We describe the principles of PLI and present several studies of fiber anatomy as a synopsis of PLI: six brainstems were serially sectioned, imaged with PLI, and 3D reconstructed. Pyramidal tract and lemniscus medialis were segmented in the PLI datasets. PLI data from the internal capsule was related to results from confocal laser scanning microscopy, which is a method of smaller scale fiber anatomy. PLI fiber architecture of the extreme capsule was compared to macroscopical dissection, which represents a method of larger-scale anatomy. The microstructure of the anterior human cingulum bundle was analyzed in serial sections of six human brains. PLI can generate highly resolved 3D datasets of fiber orientation of the human brain and has high comparability to diffusion MR. To get additional information regarding axon structure and density, PLI can also be combined with classical histological stains. It brings the directional aspects of diffusion MRI into the range of histology and may represent a promising tool to close the gap between larger-scale diffusion orientation and microstructural histological analysis of connectivity

In situ measurements of explosive compound dissolution fluxes from exposed munition material in the Baltic Sea

Underwater munitions containing millions of tons of toxic explosives are present worldwide in coastal marine waters as a result of unexploded ordnance and intentional dumping. Dissolution flux of solid explosives following corrosion of metal munition housings controls exposure of biological receptors to toxic munition compounds (MC; including TNT: 2,4,6-Trinitrotoluene, RDX: 1,3,5-Trinitro-1,3,5-triazinane, and DNB: 1,3-Dinitrobenzene). Very little is known about the dissolution behavior of MC in the marine environment. In this work, we exploit a unique marine study site in the Baltic Sea with exposed solid explosives to quantify in situ MC dissolution fluxes using dissolved MC gradients near the exposed explosive surface, as well as benthic chamber incubations. The gradient method gave dissolution fluxes that ranged between 0.001 and 3.2, 0.0001 and 0.04, and 0.003 and 1.7 mg cm-2 d-1 for TNT, RDX, and DNB, respectively. Benthic chamber incubations indicated dissolution fluxes of 0.0047-0.277, 0-0.11, and 0.00047-1.45 mg cm-2 d-1 for TNT, RDX, and DNB, respectively. In situ dissolution fluxes estimated in the current study were lower than most dissolution rates reported for laboratory experiments, but clearly demonstrated that MC are released from underwater munitions to the water column in the Baltic Sea