Retrospektive cytogenetische und molekularcytogenetische Abklärungvon ätiologisch ungeklärten Aborten mit morphologisch auffälligen Feten

Der hohe Anteil chromosomaler Imbalancen in der Frühschwangerschaft impliziert die Notwendigkeit einer intensiven cytogenetischen Untersuchung sowohl der Aborte als auch der Paare mit Aborten. Chromosomenanalysen aus Abortgewebe sind jedoch häufig durch die geringe mitotische Aktivität der Zellen und die geringe Bandenqualität der Chromosomen limitiert. Die Comparative Genomhybridisierung (CGH) ist eine molekularcytogenetische Methode, welche chromosomale Imbalancen durch reverse Fluoreszenz- in situ-Hybridisierung zuverlässig aufdecken kann. Um das diagnostische Potential der CGH zu evaluieren, wurden in der vorliegenden Studie 51 Aborte retrospektiv untersucht. Insbesondere sollte die Sensitivität der CGH anhand von 29 cytogenetisch bereits vordiagnostizierten Fällen ermittelt werden. In insgesamt 12 Fällen wurden neben der CGH noch weitere Techniken wie die chromosomale Mikrodissektion, Fluoreszenz- in situ-Hybridisierung (FISH) und die Mikrosatellitenanalyse zur präzisen Abklärung der genomischen Imbalancen angewandt. Mittels dieser Techniken konnte der Ursprung eines Markerchromosoms sowie einer neu entstandenen unbalancierten Translokation identifiziert werden. Die Mikrosatellitenanalyse ermöglichte die Bestimmung der parentalen Herkunft und Entstehungszeitpunkt von Trisomien sowie den Ausschluss einer uniparentalen Disomie in insgesamt 10 Fällen. Grundvoraussetzung für eine CGH-Analyse ist die Gewinnung einer möglichst hochmolekularen DNA. Dazu wurde DNA aus nativem und Formalin fixierten und paraffinierten Geweben in insgesamt 42 Abortfällen gewonnen. Anhand der Ergebnisse der CGH-Analysen wurden folgende Parameter beurteilt: Alter der Gewebeblöckchen, Dauer der Formalinfixierung und Mazeration/Autolyse des Ausgangsgewebes. Das Alter der asservierten Gewebeblöckchen reichte von wenigen Wochen bis zu 18 Jahre. Anhand der Untersuchungsergebnisse konnte festgestellt werden, dass die Lagerungsdauer in Paraffin keinen oder einen nur geringen Einfluss auf die Qualität der DNA hatte. Je kürzer jedoch die Fixationsdauer des Gewebes in Formalin war, umso eher ließ sich eine qualitativ und quantitativ hochwertige DNA gewinnen. Keine direkte Korrelation konnte dagegen zwischen DNA-Qualität und dem Mazerationsgrad/Autolysegrad des eingebetteten Gewebes festgestellt werden. Anhand der Ergebnisse der CGH-Analyse wurde die DNA in 3 Kategorien unterteilt: 1. DNA-Fragmente mit einer Länge von 200-1500bp und mehr (optimale Fragmentlänge) ermöglichten ein CGH-Ergebnis in 100% der Fälle. 2. Leicht degradierte DNA (Fragmentlänge 200-700bp) führte zu einem CGH-Ergebnis in 67% der Fälle. 3. Stark degradierte DNA mit Fragmentlängen <500bp eignete sich nicht für eine CGH-Analyse. In der vorliegenden Studie wurde die Comparative Genomhybridisierung zur retrospektiven Analyse von 51 Aborten angewandt. In 42/51 Fällen (82,4%) konnte mittels CGH in Verbindung mit Mikrosatellitentypisierung und Fluoreszenz- in situ-Hybridisierung ein Ergebnis erzielt werden. In 22/42 Fällen (52,4%) lag ein unauffälliges Ergebnis vor. In 5 Fällen konnte ein normaler Chromosomensatz mittels CGH bestätigt werden. In 2 Fällen wurde über eine anschließende Mikrosatellitenanalyse eine Triploidie gesichert. In 9/22 Fällen lag ein cytogenetischer Vorbefund mit einer Strukturaberration vor. Hierbei handelte es sich um Markerchromosomen (3 Fälle), Ringchromosomen (3 Fälle) und unbalancierte Translokationen (3 Fälle). Bezogen auf strukturelle Veränderungen war die Rate der falsch negativen Ergebnisse nach CGH in 9/14 Fällen mit 64,3% hoch. Hierfür ursächlich war neben degradierter DNA das limitierte Auflösungsvermögen der CGH. In 20 Fällen (47,6%) wurden sowohl numerische als auch strukturelle Aberrationen nachgewiesen. Darüber hinaus gab in einem Fall die CGH-Analyse neben dem Nachweis der chromosomalen Aberration auch Hinweis auf den Entstehungsmechanismus der Chromosomenaberration. Trotz der Einschränkung beim Nachweis struktureller Veränderungen, die jedoch im Abortgeschehen eher eine untergeordnete Rolle spielen, belegen die erhobenen Daten, dass die retrospektive CGH-Analyse an archiviertem Abortmaterial, eine potente Methode zur Aufdeckung genetischer Imbalancen bei Aborten ist. Zusammenfassend lässt sich sagen, dass die CGH in der Fetalpathologie sowohl zur Aufdeckung von de novo-Aberrationen in Nachkommen von genetisch unauffälligen Eltern, als auch zur Bestätigung von unbalancierten Situationen in Nachkommen von einem Elternteil mit reziproker Chromosomenaberration sinnvoll angewendet werden kann. Erst die Aufdeckung und Abklärung chromosomaler Aberrationen als Ursache für Aborte und fetale Fehlbildungen ermöglicht eine detaillierte Phänotyp-Genotyp-Korrelation, eine präzise Abschätzung des Wiederholungsrisikos für die Eltern im Rahmen einer genetischen der Beratungssituation

Ergebnisse der Einführung eines Tiergesundheitsplanes auf ökologisch wirtschaftenden Ferkelerzeugerbetrieben in Deutschland

The aim of this study was to evaluate the effectiveness of measures as part of an animal health plan on 17 organic sow farms in Germany. A weak-point analysis was performed using a modified critical control point concept for on-farm assessment and detailed status quo analysis. Optimisation strategies were set up in form of farmcustomized health plans based on the status quo assessment. Farms were attended continuously to ensure guidance along the animal health plan implementation. The results of the status quo analysis confirmed the deficits in animal health management from previous studies. Results showed that only 10 farms met the demands of the EC-Regulation with respect to housing conditions. Only 12 farms performed a comprehensive livestock data acquisition. Quality and intervals of cleaning and disinfection measures varied considerably between farms. After one year, half of the participating farms implemented about half of the short term measures recommended as part of their health plans. Animal health plans have proven to support identifying problem areas, to set up improvement strategies and to enforce the cooperation between the involved actors. However, many farms have not been able to meet the basic requirements necessary for improving animal health status

Social Mpower: An Educational Game for Energy Efficiency

A number of serious games have been developed for energy systems that act as an educational tool and help energy consumers to better understand concepts such as resource allocation, electricity prices and grid sustainability. In such gamified environments, players use technology to solve environmental problems including greener environment, optimised energy and water infrastructure, sustainable resources and reduced energy use. Social Mpower game is a representation of an autonomous energy community for local power generation and distribution in which the participants have to avoid a collective blackout by individually reducing their energy consumption by synchronising and coordinating their actions. Our experimental hypothesis is that collective awareness can be enhanced by appropriate features of the game interface, and therefore to increase the opportunities and prospects for successful collective action (e.g to avoid a blackout)

Measuring the effectiveness of in-hospital and on-base Prevent Alcohol and Risk-related Trauma in Youth (P.A.R.T.Y.) programs on reducing alcohol related harms in naval trainees: P.A.R.T.Y. Defence study protocol

Abstract Background Reducing alcohol related harms in Australian Defence Force (ADF) trainees has been identified as a priority, but there are few evidence-based prevention programs available for the military setting. The study aims to test whether the P.A.R.T.Y. program delivered in-hospital or on-base, can reduce harmful alcohol consumption among ADF trainees. Methods/design The study is a 3-arm randomized controlled trial, involving 953 Royal Australian Navy trainees from a single base. Trainees, aged 18 to 30 years, will be randomly assigned to the study arms: i. in-hospital P.A.R.T.Y.; ii. On-base P.A.R.T.Y.; and iii. Control group. All groups will receive the routine ADF annual alcohol awareness training. The primary outcome is the proportion of participants reporting an Alcohol Use Disorders Identification Test (AUDIT) score of 8 or above at 12 months’ post-intervention. The secondary outcome is the number of alcohol related incidents reported to the Royal Australian Navy (RAN) in the 12 months’ post-intervention. Discussion This is the first trial of the use of the P.A.R.T.Y. program in the military. If the proposed intervention proves efficacious, it may be a useful program in the early education of RAN trainees. Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12614001332617 , date of registration: 18/12/2014 ‘retrospectively registered’

Income inequality and alcohol attributable harm in Australia

<p>Abstract</p> <p>Background</p> <p>There is little research on the relationship between key socioeconomic variables and alcohol related harms in Australia. The aim of this research was to examine the relationship between income inequality and the rates of alcohol-attributable hospitalisation and death at a local-area level in Australia.</p> <p>Method</p> <p>We conducted a cross sectional ecological analysis at a Local Government Area (LGA) level of associations between data on alcohol caused harms and income inequality data after adjusting for socioeconomic disadvantage and remoteness of LGAs.</p> <p>The main outcome measures used were matched rate ratios for four measures of alcohol caused harm; acute (primarily related to the short term consequences of drinking) and chronic (primarily related to the long term consequences of drinking) alcohol-attributable hospitalisation and acute and chronic alcohol-attributable death. Matching was undertaken using control conditions (non-alcohol-attributable) at an LGA level.</p> <p>Results</p> <p>A total of 885 alcohol-attributable deaths and 19467 alcohol-attributable hospitalisations across all LGAs were available for analysis. After weighting by the total number of cases in each LGA, the matched rate ratios of acute and chronic alcohol-attributable hospitalisation and chronic alcohol-attributable death were associated with the squared centred Gini coefficients of LGAs. This relationship was evident after adjusting for socioeconomic disadvantage and remoteness of LGAs. For both measures of hospitalisation the relationship was curvilinear; increases in income inequality were initially associated with declining rates of hospitalisation followed by large increases as the Gini coefficient increased beyond 0.15. The pattern for chronic alcohol-attributable death was similar, but without the initial decrease. There was no association between income inequality and acute alcohol-attributable death, probably due to the relatively small number of these types of death.</p> <p>Conclusion</p> <p>We found a curvilinear relationship between income inequality and the rates of some types of alcohol-attributable hospitalisation and death at a local area level in Australia. While alcohol-attributable harms generally increased with increasing income inequality, alcohol-attributable hospitalisations actually showed the reverse relationship at low levels of income inequality. The curvilinear patterns we observed are inconsistent with monotonic trends found in previous research making our findings incompatible with previous explanations of the relationship between income inequality and health related harms.</p

Variability of wavefront aberration measurements in small pupil sizes using a clinical Shack-Hartmann aberrometer

BACKGROUND: Recently, instruments for the measurement of wavefront aberration in the living human eye have been widely available for clinical applications. Despite the extensive background experience on wavefront sensing for research purposes, the information derived from such instrumentation in a clinical setting should not be considered a priori precise. We report on the variability of such an instrument at two different pupil sizes. METHODS: A clinical aberrometer (COAS Wavefront Scienses, Ltd) based on the Shack-Hartmann principle was employed in this study. Fifty consecutive measurements were perfomed on each right eye of four subjects. We compared the variance of individual Zernike expansion coefficients as determined by the aberrometer with the variance of coefficients calculated using a mathematical method for scaling the expansion coefficients to reconstruct wavefront aberration for a reduced-size pupil. RESULTS: Wavefront aberration exhibits a marked variance of the order of 0.45 microns near the edge of the pupil whereas the central part appears to be measured more consistently. Dispersion of Zernike expansion coefficients was lower when calculated by the scaling method for a pupil diameter of 3 mm as compared to the one introduced when only the central 3 mm of the Shack – Hartmann image was evaluated. Signal-to-noise ratio was lower for higher order aberrations than for low order coefficients corresponding to the sphero-cylindrical error. For each subject a number of Zernike expansion coefficients was below noise level and should not be considered trustworthy. CONCLUSION: Wavefront aberration data used in clinical care should not be extracted from a single measurement, which represents only a static snapshot of a dynamically changing aberration pattern. This observation must be taken into account in order to prevent ambiguous conclusions in clinical practice and especially in refractive surgery

Immature and Maturation-Resistant Human Dendritic Cells Generated from Bone Marrow Require Two Stimulations to Induce T Cell Anergy In Vitro

Immature dendritic cells (DC) represent potential clinical tools for tolerogenic cellular immunotherapy in both transplantation and autoimmunity. A major drawback in vivo is their potential to mature during infections or inflammation, which would convert their tolerogenicity into immunogenicity. The generation of immature DC from human bone marrow (BM) by low doses of GM-CSF (lowGM) in the absence of IL-4 under GMP conditions create DC resistant to maturation, detected by surface marker expression and primary stimulation by allogeneic T cells. This resistence could not be observed for BM-derived DC generated with high doses of GM-CSF plus IL-4 (highGM/4), although both DC types induced primary allogeneic T cell anergy in vitro. The estabishment of the anergic state requires two subsequent stimulations by immature DC. Anergy induction was more profound with lowGM-DC due to their maturation resistance. Together, we show the generation of immature, maturation-resistant lowGM-DC for potential clinical use in transplant rejection and propose a two-step-model of T cell anergy induction by immature DC

Priorities for synthesis research in ecology and environmental science

Synthesis research in ecology and environmental science improves understanding, advances theory, identifies research priorities, and supports management strategies by linking data, ideas, and tools. Accelerating environmental challenges increases the need to focus synthesis science on the most pressing questions. To leverage input from the broader research community, we convened a virtual workshop with participants from many countries and disciplines to examine how and where synthesis can address key questions and themes in ecology and environmental science in the coming decade. Seven priority research topics emerged: (1) diversity, equity, inclusion, and justice (DEIJ), (2) human and natural systems, (3) actionable and use-inspired science, (4) scale, (5) generality, (6) complexity and resilience, and (7) predictability. Additionally, two issues regarding the general practice of synthesis emerged: the need for increased participant diversity and inclusive research practices; and increased and improved data flow, access, and skill-building. These topics and practices provide a strategic vision for future synthesis in ecology and environmental science

Was, wenn Bartleby eine Frau wäre?

Roth J. Was, wenn Bartleby eine Frau wäre? In: Dietze G, ed. Gender kontrovers. Genealogien und Grenzen einer Kategorie. Sulzbach/Taunus: Ulrike Helmer Verlag; 2006: 254-260