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Introduction: Hip fracture surgery is associated with high in-hospital and 30-day mortality rates and serious adverse patient outcomes. Evidence from randomised controlled trials regarding effectiveness of spinal versus general anaesthesia on patient-centred outcomes after hip fracture surgery is sparse.
Methods and analysis: The iHOPE study is a pragmatic national, multicentre, randomised controlled, open-label clinical trial with a two-arm parallel group design. In total, 1032 patients with hip fracture (>65 years) will be randomised in an intended 1:1 allocation ratio to receive spinal anaesthesia (n=516) or general anaesthesia (n=516). Outcome assessment will occur in a blinded manner after hospital discharge and inhospital. The primary endpoint will be assessed by telephone interview and comprises the time to the first occurring event of the binary composite outcome of all-cause mortality or new-onset serious cardiac and pulmonary complications within 30 postoperative days. In-hospital secondary endpoints, assessed via in-person interviews and medical record review, include mortality, perioperative adverse events, delirium, satisfaction, walking independently, length of hospital stay and discharge destination. Telephone interviews will be performed for long-term endpoints (all-cause mortality, independence in walking, chronic pain, ability to return home cognitive function and overall health and disability) at postoperative day 30±3, 180±45 and 365±60.
Ethics and dissemination: iHOPE has been approved by the leading Ethics Committee of the Medical Faculty of the RWTH Aachen University on 14 March 2018 (EK 022/18). Approval from all other involved local Ethical Committees was subsequently requested and obtained. Study started in April 2018 with a total recruitment period of 24 months. iHOPE will be disseminated via presentations at national and international scientific meetings or conferences and publication in peer-reviewed international scientific journals.
Trial registration number: DRKS00013644; Pre-results
Isolated complex I deficiency is a common biochemical phenotype observed in pediatric mitochondrial disease and often arises as a consequence of pathogenic variants affecting one of the ∼65 genes encoding the complex I structural subunits or assembly factors. Such genetic heterogeneity means that application of next-generation sequencing technologies to undiagnosed cohorts has been a catalyst for genetic diagnosis and gene-disease associations. We describe the clinical and molecular genetic investigations of four unrelated children who presented with neuroradiological findings and/or elevated lactate levels, highly suggestive of an underlying mitochondrial diagnosis. Next-generation sequencing identified bi-allelic variants in NDUFA6, encoding a 15 kDa LYR-motif-containing complex I subunit that forms part of the Q-module. Functional investigations using subjects’ fibroblast cell lines demonstrated complex I assembly defects, which were characterized in detail by mass-spectrometry-based complexome profiling. This confirmed a marked reduction in incorporated NDUFA6 and a concomitant reduction in other Q-module subunits, including NDUFAB1, NDUFA7, and NDUFA12. Lentiviral transduction of subjects’ fibroblasts showed normalization of complex I. These data also support supercomplex formation, whereby the ∼830 kDa complex I intermediate (consisting of the P- and Q-modules) is in complex with assembled complex III and IV holoenzymes despite lacking the N-module. Interestingly, RNA-sequencing data provided evidence that the consensus RefSeq accession number does not correspond to the predominant transcript in clinically relevant tissues, prompting revision of the NDUFA6 RefSeq transcript and highlighting not only the importance of thorough variant interpretation but also the assessment of appropriate transcripts for analysis.
Aims: The ILUVIEN Registry Safety Study is an ongoing, multicentre, open-label, observational study collecting real-world data on the safety and effectiveness of the 0.2 µg/day fluocinolone acetonide (FAc) implant in patients treated according to the European label requirements.
Methods: Patients included in this analysis were treated for the licensed indication of chronic diabetic macular oedema (cDMO; that is, DMO that persists or recurs despite treatment). Data presented in the current analysis were collected from patient records up to 6 March 2017. Visual acuity (VA) data, including mean change in VA over time and at last observation, intraocular pressure (IOP) over the course of the study, IOP events, use of IOP-lowering therapy and cup:disc ratio were analysed. Information on additional DMO treatments post-FAc implant was also captured.
Results: Five hundred and sixty-three patients (593 eyes) were enrolled on the study. Mean IOP for the overall population remained within the normal range throughout follow-up and 76.7% of patients did not require IOP-lowering therapy following treatment with the FAc implant. Sixty-nine per cent of eyes did not require additional DMO treatments. Mean VA in the overall population increased from 51.9 letters at baseline to 55.6 letters at month 12, with a significant increase of 2.9 letters at last observation. Patients with short-term cDMO experienced greater VA gains than those with long-term cDMO.
Conclusions: The results of this analysis are comparable with those of other studies, including the Fluocinolone Acetate for Macular Edema study. The study reinforces the good safety and effectiveness profile of FAc, and demonstrates the benefit of early FAc treatment.
To crack the neural code and read out the information neural spikes convey, it is essential to understand how the information is coded and how much of it is available for decoding. To this end, it is indispensable to derive from first principles a minimal set of spike features containing the complete information content of a neuron. Here we present such a complete set of coding features. We show that temporal pairwise spike correlations fully determine the information conveyed by a single spiking neuron with finite temporal memory and stationary spike statistics. We reveal that interspike interval temporal correlations, which are often neglected, can significantly change the total information. Our findings provide a conceptual link between numerous disparate observations and recommend shifting the focus of future studies from addressing firing rates to addressing pairwise spike correlation functions as the primary determinants of neural information.
Autophagy acts through TRAF3 and RELB to regulate gene expression via antagonism of SMAD proteins
(2017)
Macroautophagy can regulate cell signalling and tumorigenesis via elusive molecular mechanisms. We establish a RAS mutant cancer cell model where the autophagy gene ATG5 is dispensable in A549 cells in vitro, yet promotes tumorigenesis in mice. ATG5 represses transcriptional activation by the TGFβ-SMAD gene regulatory pathway. However, autophagy does not terminate cytosolic signal transduction by TGFβ. Instead, we use proteomics to identify selective degradation of the signalling scaffold TRAF3. TRAF3 autophagy is driven by RAS and results in activation of the NF-κB family member RELB. We show that RELB represses TGFβ target promoters independently of DNA binding at NF-κB recognition sequences, instead binding with SMAD family member(s) at SMAD-response elements. Thus, autophagy antagonises TGFβ gene expression. Finally, autophagy-deficient A549 cells regain tumorigenicity upon SMAD4 knockdown. Thus, at least in this setting, a physiologic function for autophagic regulation of gene expression is tumour growth.
Peter Weiss'ın Direnmenin Estetiği romanı tematik kurgusu içinde geçmişteki direnişleri belgeleyen sanat ve edebiyat eserlerini yeniden yorumlayan bir çizgi izlemektedir. Sosyalizmin pratiklerini içeriden eleştiren bu roman sosyalist gerçekçiliği de konu etmektedir. Bu kapsamda işçi perspektifinden yazılmış bir roman olan Klaus Neukrantz'ın Wedding Barikatları ile - sosyalist gerçekçilik çizgisinin dekadan (yozlaşmış) yazar kabul ettiği - Franz Kafka'nın Şato romanı arasında bir yakınlık ilişkisi kurmakta, Şato için 'işçi sınıfının romanı' ifadesini kullanmaktadır. Bu bağlamda Peter Weiss'ın sosyalist gerçekçiliği nasıl yorumladığı, sosyalist iktidarların sanat ve edebiyat üzerindeki denetimlerine itiraz etmesine rağmen sosyalist gerçekçilikte hangi değeri gördüğü ve Kafka’nın Şato romanına 'işçi sınıfının romanı' derken nasıl bir bağlantı kurduğu çarpıcı bir soru haline gelmektedir.
Bu makale, adı geçen iki eserin özelliklerini ve düzen karşısındaki konumlanmalarını karşılaştırmalı olarak incelemektedir; Direnmenin Estetiği'nde bu iki romanla ilgili bölümlerde, romanın genel kurgusu ve yaklaşımı dikkate alınarak değerlendirilmektedir. Bu incelemeyle, Peter Weiss'ın sosyalist gerçekçiliğe bakışındaki özgünlüğü ve bu bağlamda nasıl bir Kafka yorumu yaptığını göstermek amaçlanıyor. İncelemenin vardığı sonuç: Peter Weiss; Kafka'nın, mücadelenin hedefini gösteren sosyalist gerçekçiliğin eksik bıraktığı şeyi yaptığını, yani ezilenlerin kendi içsel yaşantılarını bulmalarını sağladığını düşünmektedir. Yine Direnmenin Estetiği'nde izlerine rastlandığı gibi, Peter Weiss hayatının önemli bir bölümünde kendini Kafka’nın dünyasında hissetmiştir. Bu da Kafka'yı Peter Weiss için önemli kılan bir başka unsurdur. Bu anlamda Direnmenin Estetiği romanı Franz Kafka, Klaus Neukrantz ve Peter Weiss'ın ortak noktalarının izini süren, üç kurgusal metnin iç içe geçtiği bir üst metin olarak görülebilir.
Die aktuellen Ereignisse in Europa und die Migrationskrise bewegen die ganze Welt. Mit diesem Thema beschäftigte sich die internationale Konferenz, die im Rahmen des europäischen Projekts "My!Europe" der Sonnenberg-Kreis der Tschechischen Republik in Zusammenarbeit mit dem Lehrstuhl für Fremdsprachen der Philosophischen Fakultät der Universität Pardubice von 7.- 8. April 2016 veranstaltete. Am akademischen Boden der ostböhmischen Universität trafen sich 130 Fachleute, Interessenten, Studenten und Schüler.
Das wissenschaftliche Interesse auf dem Feld der Germanistik ist in den letzten Jahren in Rumänien, besonders nach der blutigen und gewaltsamen Wende, stark gestiegen. Die Germanistikabteilung der Philologischen Fakultät in Kronstadt/Braşov veranstaltete in Zusammenarbeit mit der Gesellschaft der Germanisten Rumäniens [GGR] (Zweigstelle Kronstadt) zwischen dem 07. - 09. April 2016 ihre XIX. Internationale Tagung zum Thema Konstruktionen von Männlichkeit und Weiblichkeit in der deutschen Kultur, Literatur und Sprache.
Erfahrungen mit Wikipedia.de
(2016)
Ausgehend von der unsystematischen Mitarbeit einerseits, der laufenden Beobachtung einiger mit dieser Absicht geschriebenen Artikel (zur Volksliedforschung) andererseits sollen weitgehend allgemein gültige Beobachtungen und Erfahrungen mit der deutschen Wikipedia skizziert werden. Damit soll diese für türkische Studierende äußerst wichtige Informationsquelle transparenter gemacht werden, und damit soll zu einer kreativ-kritischen Verwendung von Wikipedia angeregt werden.
Wikipedia kann im Unterricht verwendet werden, ja den richtigen Gebrauch von Wikipedia zu lernen, sollte wichtiges Unterrichtsthema sein. Wikipedia regt zur Mitarbeit an; man sollte allerdings wissen, worauf man sich einlässt.
İkinci dil öğrenme yaşına ilişkin tartışmalar sürerken, birçok gelişmiş ülkede olduğu gibi ülkemizde de anaokulundan itibaren yabancı dil öğretimi gerçekleştirilmektedir. Yabancı dil öğreniminde, görsel-işitsel araç kullanarak dile ait konuşma seslerinin ve sözcüklerin doğru telaffuzunu duymak, doğru telaffuz edebilmek ve dilin ait olduğu kültürü tanımak çok önemlidir. Erken yaşta yabancı dil öğrenimine bu açıdan yaklaşıldığında dil öğreniminde yabancı bir dile ve kültüre ait çizgi filmlerin yeri, üzerinde durulması gereken bir konu olarak karşımıza çıkmaktadır. Bu çalışmada, okul öncesi dönem çocuklarının yabancı dil öğreniminde çizgi filmlerin yeri incelenmiştir. Bu kapsamda, yabancı dil öğrenme yaşı, yabancı dil öğretim yöntemleri kuramsal açıdan ele alınmış; çizgi filmlerin yabancı dil öğrenimindeki yeri üzerinde durularak, ne tür çizgi filmlerin erken yaşta yabancı dil öğreniminde daha etkin ve yararlı olduğu ortaya konulmaya çalışılmıştır.