The AMC Linear Disability Score in patients with newly diagnosed Parkinson disease

Objective: The aim of this study was to examine the clinimetric properties of the AMC Linear Disability Score (ALDS), a new generic disability measure based on Item Response Theory, in patients with newly diagnosed Parkinson disease (PD).\ud \ud Methods: A sample of 132 patients with PD was evaluated using the Hoehn and Yahr (H&Y), the Unified PD Rating Scale motor examination, the Schwab and England scale (S&E), the Short Form–36, the PD Quality of Life Questionnaire, and the ALDS.\ud \ud Results: The internal consistency reliability of the ALDS was good ([alpha] = 0.95) with 55 items extending the sufficient item-total correlation criterion (r > 0.20). The ALDS was correlated with other disability measures (r = 0.50 to 0.63) and decreasingly associated with measures reflecting impairments (r = 0.36 to 0.37) and mental health (r = 0.23 to -0.01). With regard to know-group validity, the ALDS indicated that patients with more severe PD (H&Y stage 3) were more disabled than patients with mild (H&Y stage 1) or moderate PD (H&Y stage 2) (p < 0.0001). The ALDS discriminated between more or less severe extrapyramidal symptoms (p = 0.001) and patients with postural instability showed lower ALDS scores compared to patients without postural instability (p = < 0.0001). Compared to the S&E (score 100% = 19%), the ALDS showed less of a ceiling effect (5%).\ud \ud Conclusion: The AMC Linear Disability Score is a flexible, feasible, and clinimetrically promising instrument to assess the level of disability in patients with newly diagnosed Parkinson disease

Purinergic P2X7 receptors regulate secretion of interleukin-1 receptor antagonist and beta cell function and survival

In obesity, beta cells activate compensatory mechanisms to adapt to the higher insulin demand. Interleukin-1 receptor antagonist (IL-1Ra) prevents obesity-induced hyperglycaemia and is a potent target for the treatment of diabetes, but the mechanisms of its secretion and regulation in obesity are unknown. In the present study, we hypothesise the regulation of IL-1Ra secretion by purinergic P2X7 receptors in islets. Production and regulation of P2X7 were studied in pancreatic sections from lean and obese diabetic patients, non-diabetic controls and in isolated islets. IL-1Ra, IL-1β and insulin secretion, glucose tolerance and beta cell mass were studied in P2x7 (also known as P2Rx7)-knockout mice. P2X7 levels were elevated in beta cells of obese patients, but downregulated in patients with type 2 diabetes mellitus. Elevated glucose and non-esterified fatty acids rapidly activated P2X7 and IL-1Ra secretion in human islets, and this was inhibited by P2X7 blockade. In line with our results in vitro, P2x7-knockout mice had a lower capacity to secrete IL-1Ra. They exhibited severe and rapid hyperglycaemia, glucose intolerance and impaired beta cell function in response to a high-fat/high-sucrose diet, were unable to compensate by increasing their beta cell mass in response to the diet and showed increased beta cell apoptosis. Our study shows a tight correlation of P2X7 activation, IL-1Ra secretion and regulation of beta cell mass and function. The increase in P2X7 production is one mechanism that may explain how beta cells compensate by adapting to the higher insulin demand. Disturbances within that system may result in the progression of diabetes

Klimarisikomanagement (KRM) in Österreich: Bestandsaufnahme der Stakeholder-Landschaft und der Governance-Strukturen für die Klimarisiken Hochwasser & Trockenheit/Dürre. RESPECT Working Paper No.1

Klima- und wetterbedingte Schäden haben in den letzten Jahrzenten österreichweit zugenommen. Aufgrund des fortschreitenden Klimawandels und sozioökonomischer Entwicklungen ist mit einer weiteren Zunahme klimabezogener Risiken zu rechnen. Bereits heute wird im Naturgefahrenmanagement versucht, die durch die natürliche Klimavariabilität ausgelösten Ereignisse zu vermeiden, zu minimieren bzw. zu bewältigen. Die Klimawandelanpassungspraxis hingegen fokussiert darauf, die durch den voranschreitenden Klimawandel verstärkten Risiken zu managen. Um klimabezogenes Risikomanagement zukünftig effektiver zu gestalten erscheint es sinnvoll, die beiden derzeit eigenständigen Bereiche in einem gesamtheitlichen Ansatz – dem Klimarisikomanagement (KRM) – zu verknüpfen. Der vorliegende Bericht stellt eine erste Bestandsaufnahme der Stakeholder-Landschaft und der Governance-Strukturen im Bereich Klimarisikomanagement dar, mit den Schwerpunkten Hochwasser und Trockenheit/Dürre in Österreich. Mittels einer zweistufigen Stakeholder-Analyse, bestehend aus Stakeholder-Interviews und zwei anschließenden Stakeholder-Workshops, konnten die einzelnen Akteure und Institutionen dem, ebenfalls im Rahmen von RESPECT entwickelten, 4-Phasen KRM-Zyklus zugeordnet und Interaktionen zwischen den einzelnen Akteuren aufgezeigt werden. Aufgrund der Interviewergebnisse und der Stakeholder-Workshops wurde festgestellt, dass ein umfassendes proaktives KRM in der österreichischen Praxis noch kein relevantes Thema ist, obwohl bereits punktuell einzelne Maßnahmen gesetzt werden. Wir schlagen vor, durch die Gründung eines gesetzlich verankerten nationalen Klimarisikorats die noch fehlenden KRM-Entscheidungsstrukturen zu etablieren, bzw. eine Schnittstelle zur politischen Entscheidungsfindung herzustellen. Zur Identifikation von konkreten Rollen und Verantwortlichkeiten, welche derzeit unklar geregelt sind und somit zur KRM Umsetzungslücke beitragen, eignen sich partizipative Forschungsmethoden wie die RESPECT Rollenspiel Simulation Klimarisikomanagement. Weitere konkrete Vorschläge hin zu einer Operationalisierung eines umfassenden KRMs betreffen die Erweiterung des Katastrophenfondsgesetzes um eine vorbeugende Komponente im privaten Bereich, sowie die Kombination mit privaten Versicherungsmodellen. Da die Umsetzung einer klimarisikobewussten Politik auch von einer breiten gesellschaftlichen Unterstützung abhängt, sollte die Bevölkerung durch Informationskampagnen für Klimarisiken sensibilisiert werden

The status of climate risk management in Austria. Assessing the governance landscape and proposing ways forward for comprehensively managing flood and drought risk

Climate and weather-related damage have been increasing globally in recent decades. Due to climate change and socio-economic developments, a further increase in climate-related risks is expected. Numerous countries have a long and successful history in disaster risk management (DRM) to avoid, minimize and manage damage caused by extreme weather events. In addition, climate change adaptation (CCA) focuses on managing the risks resulting from climate change today and in the future. To improve the effectiveness and efficiency of managing climate-related risks, these two independent approaches need to be linked closer in a more holistic approach – a concept that has been termed climate risk management (CRM). In order to build stronger ties in practice, it is crucial to first understand current governance structures in specific countries or regions. This paper focuses on Austria, a country with experience in both DRM and CCA. In this paper, we present a comprehensive picture of the stakeholder landscape and governance structures in the context of managing climate-related risks. We focus on flooding and agricultural drought, two key risks in Austria. Building on a literature review and a two-stage stakeholder process, consisting of stakeholder interviews and stakeholder workshops, relevant institutions and actors were identified and assigned to a 4-phase CRM cycle. Moreover, specific activities of the identified actors and interactions between them were determined. Based on these insights, we conclude that a comprehensive CRM, which aligns DRM and CCA practice, does not yet exist in Austria. We propose to establish the missing CRM decision-making structures by e.g. instituting a legally-anchored national climate risk council, which can act as an interface between CRM practice and political decision-making

A gene expression profile for detection of sufficient tumour cells in breast tumour tissue: microarray diagnosis eligibility

<p>Abstract</p> <p>Background</p> <p>Microarray diagnostics of tumour samples is based on measurement of prognostic and/or predictive gene expression profiles. Typically, diagnostic profiles have been developed using bulk tumour samples with a sufficient amount of tumour cells (usually >50%). Consequentially, a diagnostic results depends on the minimal percentage of tumour cells within a sample. Currently, tumour cell percentage is assessed by conventional histopathological review. However, even for experienced pathologists, such scoring remains subjective and time consuming and can lead to ambiguous results.</p> <p>Methods</p> <p>In this study we investigated whether we could use transcriptional activity of a specific set of genes instead of histopathological review to identify samples with sufficient tumour cell content. Genome-wide gene expression measurements were used to develop a transcriptional gene profile that could accurately assess a sample's tumour cell percentage.</p> <p>Results</p> <p>Supervised analysis across 165 breast tumour samples resulted in the identification of a set of 13 genes which expression correlated with presence of tumour cells. The developed gene profile showed a high performance (AUC 0.92) for identification of samples that are suitable for microarray diagnostics. Validation on 238 additional breast tumour samples indicated a robust performance for correct classification with an overall accuracy of 91 percent and a kappa score of 0.63 (95%CI 0.47–0.73).</p> <p>Conclusion</p> <p>The developed 13-gene profile provides an objective tool for assessment whether a breast cancer sample contains sufficient tumour cells for microarray diagnostics. It will improve the efficiency and throughput for diagnostic gene expression profiling as it no longer requires histopathological analysis for initial tumour percentage scoring. Such profile will also be very use useful for assessment of tumour cell percentage in biopsies where conventional histopathology is difficult, such as fine needle aspirates.</p

Responsibility & Risk: Operationalizing comprehensive climate risk layering in Austria among multiple actors (RESPECT)

Damages caused by climate and weather extremes, such as floods and droughts, have increased over the last few decades and will likely broaden with the progression of climate change and socioeconomic development. Such climate-related risks are already being governed within the framework of natural disaster risk management, as well as climate change adaptation. However, to manage these climate risks more effectively it is necessary to link these two domains under the umbrella of Climate Risk Management (CRM)

The Role of Osteopontin (OPN/SPP1) Haplotypes in the Susceptibility to Crohn's Disease

Osteopontin represents a multifunctional molecule playing a pivotal role in chronic inflammatory and autoimmune diseases. Its expression is increased in inflammatory bowel disease (IBD). The aim of our study was to analyze the association of osteopontin (OPN/SPP1) gene variants in a large cohort of IBD patients. Genomic DNA from 2819 Caucasian individuals (n = 841 patients with Crohn's disease (CD), n = 473 patients with ulcerative colitis (UC), and n = 1505 healthy unrelated controls) was analyzed for nine OPN SNPs (rs2728127, rs2853744, rs11730582, rs11739060, rs28357094, rs4754 = p.Asp80Asp, rs1126616 = p.Ala236Ala, rs1126772 and rs9138). Considering the important role of osteopontin in Th17-mediated diseases, we performed analysis for epistasis with IBD-associated IL23R variants and analyzed serum levels of the Th17 cytokine IL-22. For four OPN SNPs (rs4754, rs1126616, rs1126772 and rs9138), we observed significantly different distributions between male and female CD patients. rs4754 was protective in male CD patients (p = 0.0004, OR = 0.69). None of the other investigated OPN SNPs was associated with CD or UC susceptibility. However, several OPN haplotypes showed significant associations with CD susceptibility. The strongest association was found for a haplotype consisting of the 8 OPN SNPs rs2728127-rs2853744-rs11730582-rs11439060-rs28357094-rs112661-rs1126772-rs9138 (omnibus p-value = 2.07×10⁻⁸). Overall, the mean IL-22 secretion in the combined group of OPN minor allele carriers with CD was significantly lower than that of CD patients with OPN wildtype alleles (p = 3.66×10⁻⁵). There was evidence for weak epistasis between the OPN SNP rs28357094 with the IL23R SNP rs10489629 (p = 4.18×10⁻²) and between OPN SNP rs1126616 and IL23R SNP rs2201841 (p = 4.18×10⁻²) but none of these associations remained significant after Bonferroni correction. Our study identified OPN haplotypes as modifiers of CD susceptibility, while the combined effects of certain OPN variants may modulate IL-22 secretion

Rollen und Verantwortlichkeiten im lokalen Klimarisikomanagement. Handbuch zum Rollenspiel-Workshop Klimarisikomanagement

Dieses Handbuch richtet sich an lokale Akteur*innen, die in ihrer Gemeinde oder Region die Entwicklung eines pro-aktiven Klimarisikomanagements an der Schnittstelle von Klimawandelanpassung und Naturgefahrenmanagement vorantreiben möchten. Durch einen gemeinsamen partizipativen Workshop von Vertreter*innen privater und öffentlicher Interessensgruppen unter Begleitung eines*r Expert*in werden Rollen und Verantwortlichkeiten erarbeitet, um vom Reden ins Handeln zu kommen

Immediate implant-retained prosthetic obturation after maxillectomy based on zygomatic implant placement by 3D-guided surgery:a cadaver study

Abstract Background The aim of this study was to introduce a complete 3D workflow for immediate implant retained prosthetic rehabilitation following maxillectomy in cancer surgery. The workflow consists of a 3D virtual surgical planning for tumor resection, zygomatic implant placement, and for an implant-retained prosthetic-obturator to fit the planned outcome situation for immediate loading. Materials and methods In this study, 3D virtual surgical planning and resection of the maxilla, followed by guided placement of 10 zygomatic implants, using custom cutting and drill/placement-guides, was performed on 5 fresh frozen human cadavers. A preoperatively digitally designed and printed obturator prosthesis was placed and connected to the zygomatic implants. The accuracy of the implant positioning was obtained using 3D deviation analysis by merging the pre- and post-operative CT scan datasets. Results The preoperatively designed and manufactured obturator prostheses matched accurately the per-operative implant positions. All five obturators could be placed and fixated for immediate loading. The mean prosthetic point deviation on the cadavers was 1.03 ± 0.85 mm; the mean entry point deviation was 1.20 ± 0.62 mm; and the 3D angle deviation was 2.97 ± 1.44°. Conclusions It is possible to 3D plan and accurately execute the ablative surgery, placement of zygomatic implants, and immediate placement of an implant-retained obturator prosthesis with 3D virtual surgical planning.The next step is to apply the workflow in the operating room in patients planned for maxillectomy