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In 2016 the Islamic State (IS) dramatically altered the centerpiece of its Western outreach, shuttering Dabiq magazine and replacing it with Rumiyah. While Dabiq was marked by twin appeals to theme...

In the past several decades, social scientists and theorists have steadily moved away from understandings of power emphasizing the role of the nation-state, instead favoring explanations centering ...

This project discusses the development and implementation of a three-credit graduate/undergraduate course, offered to police officers and incarcerated men, that would eventually become part of the city’s recruit training academy. The initial class consisted of six veteran officers and six men serving life sentences. The programme has the potential to integrate the fundamentals of restorative justice within the occupational culture of policing in order to produce direct benefits for public safety and may also be effective for building more authentic relationships between police and communities of colour. The article explains what went into creating this class, how it progressed and what resulted.

A central aspect of post-conflict policing literature holds that the new force must differentiate itself from its predecessor. In the efforts to democratize Iraqi police, trainers and recru...

This research situates Brothers and Keepers, the memoir of John Edgar Wideman (one of the greatest writers of the past hundred years), within the tradition of Black sociology, arguing that it politicizes the theories in Stigma, the foundational study by Erving Goffman (one of the greatest sociologists of the past hundred years), by grounding them in the lived experience of an African American man. In turn, Goffman’s writing facilitates a reading of Wideman’s work as an attempt to surrender the mask of the “exceptional” Black man among elite whites and reconcile his stellar accomplishments with his stigmatized beginnings as well as his brother’s incarceration. With this effort, Wideman begins to shift from tacit complicity with racial stigmatization to active resistance against it. Our goal in this project is to use Goffman’s concepts of “stigma” and “moral career” to explain Wideman’s growth, and in turn, add a degree of depth and breadth to Goffman’s notions of the “own” and the “wise” lacking in their original formulation.

Im Rahmen der Entscheidung uber die Wahl des Nierenersatzverfahrens ist eine umfassende Aufklarung des Patienten notwendig. Dies fuhrt zu sichereren Entscheidungen und senkt die Mortalitat. Eine besondere Herausforderung stellen Patienten dar, die ungeplant dialysepflichtig werden. Hier sind Konzepte zur Ad-hoc-Losung und zur weiteren Versorgung notwendig. Getunnelte zentralvenose Katheter als Dauerlosung sind fur einige wenige Patienten gut. Der Beginn der Dialysetherapie sollte bei klinischen Symptomen oder medikamentos nicht mehr beherrschbaren Problemen erfolgen. Ein fruhzeitiger Dialysebeginn ist weder bei mittelalten Erwachsenen noch bei geriatrischen Patienten von Vorteil. Die Sonographie hilft zur Beurteilung der Shuntreifung und im Rahmen der Erstpunktion. Geeignete Schulungskonzepte, auch fur das pflegerische Personal, sind zu entwickeln.

Spike Lee’s latest film, Chi-Raq, draws upon a portmanteau coined by local rappers to describe the violence and chaos of Chicago’s South Side, home of some of the most violent neighborhoods in America. City leaders condemned the title as inflammatory and hyperbolic, but this article argues the comparison is not as far afield as they suggest. Drawing from the literatures on state legitimacy, American gang formation, and the emerging scholarship surrounding the Islamic State, it is argued the two locations and their organized violent nonstate actors exhibit a host of important similarities. In both situations, the absence of services and protection delivered through the legitimate government has left a vacuum of both material goods and legitimacy, which fuels the genesis, growth, and stability of these extralegal organizations.

Existing scientific literature on post-conflict police reconstruction is largely divided between two camps. The first, and most widely employed in practice, can be termed a neo-liberal model, which argues progress comes through technological and organizational sophistication delivered by Western officials. This neo-liberal model has been the guiding principle of the reconstruction of the Iraqi state and police force. However, many scholars have argued this model is woefully inadequate for post-conflict reconstruction and have instead developed an alternative approach which can be termed a reflexive model. Similar to what is known as fourth generation peacebuilding in the International Relations literature, the reflexive model stresses building relationships with local stakeholders and relying on indigenous knowledge to guide post-conflict reconstruction. Drawing from 48 intensive interviews, 87 qualitative surveys, and six months of ethnographic examination of an Iraqi police training academy, this article argues that both the neo-liberal and reflexive models suffer from ignoring the material basis of reconstruction. This article employs the term ‘material’ in the theoretical sense; while police reconstruction programs spend significant effort on reshaping the ideologies of police, few address the real conditions police face, from the necessary levels of funding and equipment in their training centers, to basic concerns such as adequate pay to draw qualified applicants and prevent corruption. This study examines how economic inequality affects the ‘other side’ of conflicts, the security sector. The central finding is that the material deprivation experienced by Iraqi police has resulted in an underqualified force consisting of uninterested officers whose capacity and skill deficits have fed directly into the rise of powerful non-state organizations such as the Islamic State. This article explicates a central underlying cause of the problem with the reconstruction of the Iraqi police specifically and the larger case of neo-liberal post-conflict police reconstruction generally.

Among the ecological services provided by arbuscular mycorrhizal fungi (AMF), the process of soil aggregation is hypothesized to be partially mediated by glomalin, an alkaline-soluble glycoprotein released by AM fungi into soil during hyphal turnover and after the death of the fungus in the soil. The protein is characterized by abundant production and hydrophobic properties. Although glomalin has been identified in Rhizophagus irregularis DAOM 197198 as a putative homolog of heat shock protein 60, the use of expressed fungal genes encoding glomalin as a marker for functional AMF diversity was never exploited. The present work describes the first attempt to identify the glomalin gene in several AMF species, verify its reliability as gene marker for the identification and discrimination of AMF, and test the possibility to detect its expression in soil. We designed a specific PCR primers set able to amplify many known lineages of AMF glomalin gene. We demonstrated its applicability to create a new reference glomalin sequence dataset for comparative sequence analysis. The designed primer set was successfully used to amplify glomalin transcript from soil cDNA template.

Objective: To compare the efficacy and tolerance of 7-days-a-week accelerated postoperative radiotherapy (p-CAIR) vs postoperative radio-chemotherapy (p-RTCT) Methods: Between September 2007 and October 2013, 111 patients were enrolled and randomly assigned to receive 63 Gy in 1.8 Gy fractions 7-days-a-week (n = 57, p-CAIR) or 63 Gy in 1.8 Gy fractions 5-days-a-week with concurrent cisplatin 80–100 mg per square meter of body-surface area on days 1, 22 and 43 of the radiotherapy course (p-RTCT). It represents approximately 40% of the intended trial size, that was closed prematurely due to slowing accrual. Only high-risk patients with squamous cell cancer of the oropharynx/oral cavity, considered fit for concurrent treatment were enrolled. Results: The rate of locoregional control (LRC) did not differ significantly between treatment arms (p = 0.18, HR = 0.56), 5 year LRC tended, however, to favour p-RTCT (81%) vs p-CAIR (62%). There was no difference in overall survival between treatment arms (p = 0.90, HR = 1.03). The incidence and severity of acute mucosal reactions and late reactions did not differ significantly between treatment arms. Haematological toxicity of p-RTCT was, however, considerably increased compared to p-CAIR Conclusion: Concurrent postoperative RTCT tended to improve locoregional control rate as compared to p-CAIR. This, however, did not transferred into improved overall survival. Postoperative RTCT was associated with a substantial increase in haematological toxicity that negatively affected treatment compliance in this arm. Advances in knowledge: To our knowledge, this is the first trial that compares accelerated radiotherapy and radio-chemotherapy in postoperative treatment for oralcavity/oropharyngeal cancer

This article examines Excited Delirium, a controversial medical explanation offered as an explanation for a variety of in-custody deaths. It appears to fit all essential criteria to incite a moral panic, featuring a powerful moral entrepreneur playing off of well-established fears of drugs use and psychosis, with a classic folk devil in the form of young men of color. Yet Excited Delirium has failed to provoke a widespread response, raising the question of how a phenomenon that meets all the classic criteria can fail to incite a moral panic. I argue this stems from the entrepreneurs involved failing to present themselves as sufficiently moral, their campaign to medicalize the phenomenon meeting an unreceptive medical field, and their broad conception of Excited Delirium too easily facilitating strong counter-narratives. This study uses Excited Delirium as a negative case to demonstrate several important factors to consider in the development of moral panics.

Our purpose was to compare the acute toxicity of ultrahypofractionated CyberKnifeTM based stereotactic radiotherapy (SBRT Arm) and conventional radiotherapy (EBRT Arm) in prostate cancer patients. Two-hundred-sixteen men with prostate cancer were enrolled in our prospective studies. One-hundred and nine were irradiated using CyberKnife to total dose of 36,25 Gy in 5 fractions. One-hundred and seven were irradiated conventionally to total dose of 76 Gy in 38 fractions. Mean age of patients was 69. Acute genitourinary (GU) and gastrointestinal (GI) adverse-events were collected. The maximal acute toxicity EORTC/RTOG score was assumed. A total of 41%, 44%, 12% and 3% of patients presented grade 0, 1, 2 and 3 acute genitourinary toxicity in SBRT arm, respectively. A total of 21%, 33%, 43% and 3% of patients demonstrated acute grade 0, 1, 2 and 3 genitourinary toxicity in EBRT arm. A significant difference between number of patients with grade 2 GU toxicity was observed (p-0.000) and between patients without any toxicity (p-0.0017).A significant difference in frequency of acute GI toxicity between both groups was observed, too. 71% vs. 44% had no toxicity (p-0.0001), and 3% vs. 18% (p-0.0004) presented grade 2 GI toxicity in SBRT and EBRT arms respectively.The acute toxicity rates of fractionated stereotactic radiotherapy is lower compared to conventional irradiation.

This paper serves as a call to reinvigorate the practice of “gonzo sociology,” an immersive, reflexive methodology which eschews rigidity and formulaic design in favor of innovative and imaginative research on places and peoples ignored by the academy. Employing an autoethnographic account of the author’s experiences researching the reconstruction of the Iraqi police force, this paper serves as both an invitation and a rough how-to guide for gonzo research projects. While a variety of factors—ranging from funding sources to time constraints to anxiety to institutional review concerns—make this type of unorthodox research difficult, it is argued this is exactly what makes it both a necessary corrective to the staid formalism of the field as well as an avenue for incorporating the voices of those least represented in the academy.

Summary Proximity-dependent biotin labeling (BioID) may identify new targets for cancers driven by difficult-to-drug oncogenes such as Ras. Therefore, BioID was used with wild-type (WT) and oncogenic mutant (MT) H-, K-, and N-Ras, identifying known interactors, including Raf and PI3K, as well as a common set of 130 novel proteins proximal to all Ras isoforms. A CRISPR screen of these proteins for Ras dependence identified mTOR, which was also found proximal to MT Ras in human tumors. Oncogenic Ras directly bound two mTOR complex 2 (mTORC2) components, mTOR and MAPKAP1, to promote mTORC2 kinase activity at the plasma membrane. mTORC2 enabled the Ras pro-proliferative cell cycle transcriptional program, and perturbing the Ras-mTORC2 interaction impaired Ras-dependent neoplasia in vivo. Combining proximity-dependent proteomics with CRISPR screening identified a new set of functional Ras-associated proteins, defined mTORC2 as a new direct Ras effector, and offers a strategy for finding new proteins that cooperate with dominant oncogenes.

Die im Juni 2012 veroffentlichte Leitlinie zur Lokaltherapie chronischer Wunden mit den Risiken periphere arterielle Verschlusskrankheit (PAVK), Diabetes mellitus (DM) und chronisch venose Insuffizienz (CVI) hat mangels Verfugbarkeit methodisch guter Studien mit hochwertiger Evidenz viele Fragen in Hinblick auf die konkrete Anwendung der zur Verfugung stehenden Wundbehandlungsprodukte offen gelassen. Dennoch gibt es keinen Zweifel, dass die moderne hydroaktive Wundtherapie nicht nur aus medizinischen, sondern auch aus okonomischen Grunden den allgemein akzeptierten Standard in der Wundbehandlung darstellt. In der Praxis sollte sich die Auswahl der geeigneten Lokaltherapie im Rahmen einer phasenadaptierten Wundversorgung vornehmlich an der Exsudataufnahmekapazitat des Verbandes unter Berucksichtigung der Patientenpraferenzen orientieren. Im Rahmen dieser Publikation werden auf der Grundlage einer innerhalb der Wundkommission der DGG abgestimmten internen Expertenmeinung praxisorientierte Handlungsempfehlungen zu den Kapiteln Wundreinigung, Wundspulung, Debridement, periodische aktive und passive Wundreinigung, Dekontamination, Antiseptika und wirkstofffreie Wundauflagen der S3-Leitlinie dargestellt.

Central venous dialysis catheters are indispensible as a rapid large lumen access to the blood compartment. If such a central venous catheter is necessary for longer than 2-3 weeks it is better to implant a tunnelled cuffed catheter initially or to switch early from the non-tunnelled acute catheter to a tunnelled cuffed catheter. Tunnelled cuffed catheters can be used for many weeks or even years and the complication rate is less than that of non-tunnelled acute catheters. The proportion of dialysis patients with long-term dialysis using tunnelled cuffed catheters has increased rapidly in recent years and now stands at approximately 20 % in Germany. These catheters are, however, prone to more infectious complications and more thromboses than native arteriovenous fistulas or prosthetic shunts. The mortality of patients with long-term dialysis catheters is also higher than those with arteriovenous shunts. For these reasons central venous catheters will always be regarded as the third choice dialysis access when arteriovenous fistulas are not possible. Catheters are available in a wide variety of designs but the individual advantages are still unclear. In order to avoid short-term and long-term complications a variety of measures for implantation and use during dialysis treatment have been developed which make the use safer.

Vor der Anlage eines arteriovenosen (AV) Gefaszugangs zur Hamodialyse wird zusatzlich zur klinischen Untersuchung die Durchfuhrung bildgebender Verfahren empfohlen. Dieser Artikel diskutiert die relative Bedeutung der unterschiedlichen Methoden und legt hierbei seinen Schwerpunkt auf die Duplexsonographie, die als einzige Methode nichtinvasiv Arterien und Venen gemeinsam untersuchen kann. Die Wertigkeit verschiedener sonographischer Befunde fur die Planung der Shuntanlage wird aufgezeigt und Vorschlage fur eine rationelle Diagnostik werden unterbreitet.

Approximately one out of two patients do not take their medication three months after therapy starts, while in patients with mental disorders this number varies i.e. 35%-45% for bipolar disorder. The WHO published a guide for clinicians, advising them to develop strategies for improving medication adherence. Based on this need, the aim of our project is to develop and evaluate a smartphone application that will help patients adhere to their psychotropic medication and help clinicians to keep track of their patients’ adherence. This project incorporates 4 phases: a) investigating the application’s features, using patients and clinicians focus groups, b) building the application, c) investigating usability using the focus groups and d) evaluating and validating the application with a clustered randomized control trial. We are expecting that the application users will show higher levels of medication adherence, in comparison with patients receiving usual care. Project is in the early stages of development. Implementing such an app will lead to an effective and low cost method for improving psychotropic medication adherence with significant improvement for both patients and clinicians.

Seit 2005 sieht die Musterweiterbildungsordnung (WBO) einen eigenen Facharzt/Facharztin fur Gefaschirurgie mit einem 4-jahrigen Weiterbildungscurriculum nach erfolgter 2-jahriger Basisweiterbildung in der Chirurgie („common trunk“) vor. Eine strukturierte und allumfassende Weiterbildung zum Facharzt/-in fur Gefaschirurgie gliedert sich im Wesentlichen in 4 Saulen auf, in denen die erforderlichen gefasmedizinischen Kenntnisse, Erfahrungen und Fertigkeiten fur die offen operative Therapie, die endovaskulare Therapie, die Gefasdiagnostik und die konservative Therapie von Gefaserkrankungen aufgelistet sind (sog. 4-Saulen-Modell). Diese sollen den WB-Ermachtigten als Orientierungshilfe und den Auszubildenden als Einforderungskriterien fur eine strukturierte Weiterbildung dienen. Fur die fur den Facharzt erforderlichen endovaskularen Fertigkeiten werden Lerninhalte und Mindestmengen definiert und Voraussetzungen fur Zusatzqualifikationen (endovaskularer Chirurg/-in, bzw. endovaskularer Spezialist/-in) aufgelistet. Die Vereinbarung von Familie und Beruf im Rahmen der Weiterbildung ist der Deutschen Gesellschaft fur Gefaschirurgie und Gefasmedizin e.V. ein Anliegen. Deshalb tritt sie fur eine Realisierung von Arbeitsplatzbedingungen ein, die eine Vereinbarkeit ermoglichen.

The purpose of the study was to analyse the influence of HPV infection on the outcome of a randomized clinical trial of conventional (CF) versus 7-days-a-week postoperative radiotherapy (p-CAIR) for squamous cell cancer of the head and neck (SCCHN). Between 2001 and 2004, 279 patients with high-risk SCC of the larynx or cancer of the oral cavity/oropharynx were randomized to receive 63 Gy in fractions of 1.8 Gy given 5 days a week or 7 days a week (Radiother Oncol 87:155–163, 2008). The presence of HPV DNA in 131 archival paraffin blocks was assessed with multiplex quantitative real-time PCR using five consensus primers for the conservative L1 region and molecular beacon probes targeting 14 high-risk HPV subtypes. Following the RT-PCR procedure, we could determine the presence and type of HPV16, HPV18 and the other 12 less frequent oncogenic subtypes. Out of 131 samples, 9 were positive for HPV infection (6.9%), all of them with HPV16 subtype. None of the 65 laryngeal tumours was HPV positive. The 5-year LRC in HPV-positive patients was 100%, compared to 58% in the HPV-negative group (p = 0.02, log-rank test). Amongst 122 patients with HPV-negative tumours, 5-year LRC was 50.3% in p-CF versus 65.2 in p-CAIR (p = 0.37). HPV infection was associated with low expression of EGFR and cyclin D. This study demonstrates a favourable outcome for HPV-positive patients with SCCHN treated with postoperative radiotherapy. While considering the small number of HPV+ tumours, the data set can be considered as hypothesis generating only, the outcome raises new questions on the necessity of aggressive postoperative treatment in HPV+ patients.

Neben Trauma, Tumor und Infekt stellt die Durchblutungsstorung eine der Hauptursachen fur eine notwendig werdende Amputation dar. In besonderer Weise und mit zunehmender sozialmedizinischer Bedeutung muss der Diabetes mellitus mit seinen Komplikationen eingestuft werden. Hier sind es ganz besonders die Ulzerationen im Fusbereich, die mit bis zu 85% den grosten Anteil nichttraumatischer Amputationen ausmachen und sehr gefurchtet sind. Aufgrund der demographischen Entwicklung wird ein Anstieg an Menschen mit Diabetes mellitus auf ca. 10 Millionen fur das Jahr 2010 prognostiziert. Etwa 15% aller Diabetiker sollen im Verlauf ihrer Erkrankung ein Fusulkus entwickeln, wobei wiederum ca. 20% davon in eine Amputation munden. Atiologisch sind etwa 50% der Fusulzera auf eine periphere Neuropathie, 15% auf eine periphere Angiopathie und etwa 35% auf eine Mischform zuruckzufuhren. Nach Auswertung von AOK-Daten wurden 2001 in Deutschland etwa 26.000 Amputationen im Bereich der unteren Extremitat auf Diabetes mellitus als Risikofaktor zuruckgefuhrt. Etwa die Halfte davon sollen Majoramputationen gewesen sein.

Der elektive Beginn der Dialysetherapie uber einen gut geplanten gereiften Dialysezugang erfordert die fruhzeitige Vorstellung beim Nephrologen. Als Zugang sind native Fisteln mit ihren zahlreichen Modifikationen den Prothesenshunts deutlich uberlegen, sowohl hinsichtlich des Uberlebens der Patienten als auch hinsichtlich der Infektions- und Verschlussraten. Dialyseshunts sollten mindestens 3 Monate vor Dialysebeginn angelegt werden, Prothesenshunts 4 Wochen zuvor. Sollten AV-Fisteln oder Prothesenshunts nicht moglich sein oder sonstige Kontraindikationen wie z. B. eine schwere Herzinsuffizienz vorliegen, ware die Dialyse uber einen getunnelten Dialysekatheter zu beginnen. In Deutschland wird aktuell die Dialyse bei einer durchschnittlichen GFR von 7,8 ml/min begonnen. Ein Dialysebeginn bei einer GFR 15 ml/min.

Our purpose was to evaluate the toxicity of CyberKnifeTM based fractionated stereotactic radiotherapy (FSRT) in prostate cancer patients. One-hunred-thirty-two men with low (62) and intermediate (70) prostate cancer were enrolled in our prospective study. Mean age was 69. Total dose of 36,25 Gy in 5 fractions was prescribed. Image guided FSRT was performed on CyberKnife. Minimum follow-up ranged from 3 to 28 months. EORTC/RTOG scale was used to evaluate toxicity. A total of 47%, 10% and 2% of patients presented grade 1, 2 and 3 acute genitourinary toxicity, respectively. In 25% and 3% of patients, respectively, grade 1 and 2 acute gastrointestinal toxicity was observed. No significant association between acute grade ≥ 2 toxicity and clinical factors: age, androgen deprivation therapy or infections were found. Neither CTV nor PTV volumes had significant impact on acute grade ≥ 2 toxicity. Late toxicity was assessed in 104 patients. In 16% and 1% of patients late GU toxicity in grade 1 and 2, respectively, was presented. Late GI toxicity grade 1, 2 and 3 occurred in 8%, 3% and 1% of patients, respectively. The acute toxicity rates of fractionated stereotactic radiotherapy are low. Early data suggest also low late toxicity rates.

UNLABELLED Our purpose was to evaluate interfractional organ and patient movement during radiotherapy of prostate cancer and to calculate the necessary CTV to PTV margins. Fifty patients irradiated between 2009 and 2011were included into the prospective study. The 2D-2D KV system combined with the intraprostatic fiducial marker were used for daily position verification. Based on the 8629 measurements of isocentre displacement an interfractional motion of pelvis and prostate was evaluated. The CTV to PTV margins were calculated. Margins of 0.7 cm (AP), 1 cm (SI) and 0.35 cm (LR) are necessary when only bony based IGRT is performed. Margins of 1.0 cm, 1.8 cm and 0.5 cm in AP, SI and LR directions respectively are necessary in case of no IGRT.There was no clinically relevant changes in patient/target mobility throughout the whole treatment. The IGRT is essential for state of art radiotherapy of prostate cancer. Necessary CTV to PTV margins are much bigger in case of no IGRT performed. Changing of margins size throughout regular treatment is not necessary. KEYWORDS IGRT, prostate cancer, fiducial marker.

The YEATS domain, found in a number of chromatin-associated proteins, has recently been shown to have the capacity to bind histone lysine acetylation. Here, we show that the YEATS domain of Taf14, a member of key transcriptional and chromatin-modifying complexes in yeast, is a selective reader of histone H3 Lys9 acetylation (H3K9ac). Structural analysis reveals that acetylated Lys9 is sandwiched in an aromatic cage formed by F62 and W81. Disruption of this binding in cells impairs gene transcription and the DNA damage response. Our findings establish a highly conserved acetyllysine reader function for the YEATS domain protein family and highlight the significance of this interaction for Taf14.

AIM Recent knowledge about repair mechanisms in different types of tissue is the basic of actual therapeutic efforts. Center of several experimental and clinical approaches is the influencing of angiogenesis with an also distinct meaning concerning wound healing. Therefore, application of growth factors, gene transfer, and employment of genetically manipulated cells often aim at angiogenesis. Nevertheless, manipulation of angiogenesis also leads to secondary problems such as hyperpermeability followed by impairment of local wound milieu. Our study was done to identify mechanisms to protect from disturbances of endothelial barrier function. METHOD In a first experimental investigation on cultured endothelial cells, the influence of plasma-transglutaminase (Factor XIII) to endothelial barrier function was studied. In a second step, the influence of Factor XIII on wound healing properties was investigated in patients with a chronic venous ulceration. RESULTS Activated Factor XIII (FXIIIA*) led to a dose-dependent reduction of endothelial cell permeability of 30 % compared to control with a maximum effect using 1 to 5 U/mL. Clinical investigation revealed a nearly complete reduction of wound secretion. CONCLUSION Experimental studies revealed that activated Factor XIII stabilizes endothelial barrier under basic conditions as well as under conditions of induced hyperpermeability. Clinical study revealed that Factor XIII also distinctly reduces wound secretion. Therefore, plasma-transglutaminase may offer a new therapeutic option to treat the local or generalized leakage-syndrome.

Aim: Studies have shown lower infection rates of port systems compared to established, transcutaneous cuffed-tunneled dialysis catheters. This was shown in otherwise quite healthy patients starting hemodialysis treatment. It is unclear to what extent these results can be applied to countries such as Germany where, unlike the US, central venous access systems are used mainly for patients with a high comorbidity. We investigated complications in patients with exhausted access sites and a high comorbidity. Method: In a retrospective, representative multicenter study, 34 patients with a high rate of comorbidity were assessed. The age was 67.5 ± 12.5 years, the median number of failed AV fistulas or AV grafts was 4 (0 - 18). Results: The survival rate was 84.9%, 55.2% and 55.2% after 6, 12 and 24 months, respectively. The rate of local and systemic infections was 2.83 per 1,000 patient days. Thrombotic events occurred at a rate of 2.26 per 1,000 patient days. We did not see a statistically significant effect using 0.2% sodium oxychlorosene (n = 13) or 70% isopropyl alcohol solution (n = 21) as the antimicrobial solution used before opening the valve of the port with the dialysis needle. Conclusions: We showed that complications of hemodialysis treatment using LifeSite vascular access systems in patients with very high co-morbidity in Germany seem to occur less often than those reported for cuffed-tunneled catheters and were not more frequent than those reported for other patient groups using LifeSites in the US. Technical survival rates were encouraging for up to two years. LifeSite port systems might be a good or even better central venous access than cuffed-tunneled catheters for patients in which an AV fistula or -graft is not possible.

Eine evidenzbasierte Datenlage zur Behandlung chronischer Wunden ist im Vergleich zur Fulle an gelisteten Publikationen uber „wound healing“ (1990 bis heute: 48.247 Veroffentlichungen) nur in ausgesprochen geringem Umfang vorhanden und auch nur schwer zu finden. Zwar kann man in der Medline eine Anzahl von Treffern landen, doch muss dem Sucher bewusst sein, dass die Begrifflichkeit, nach der gesucht wird, in der Regel sehr willkurlich vom ursprunglichen Autor vergeben wurde. Schlieslich sollen insbesondere die Keywords den Sucher auf eine Arbeit aufmerksam machen, die in den allermeisten Fallen nur ganz am Rande relevante Informationen in Bezug auf die eigentliche Thematik enthalten. Ein interner Filter im Hinblick auf den Entstehungsmechanismus der publizierten Daten, der die Gewichtung der Arbeiten sicherlich erleichtern wurde, ist nicht vorhanden, sodass z. B. unter den Begriffen „evidence-based medicine and chronic wound“ eine Arbeit erscheint, die als Grundlage ihrer Bewertung uber die Anwendung von Honig bei chronischen Wunden Erwachsener „case studies and serial case studies“ angibt. So besteht neben dem Problem einer eher dunnen Datenlage zusatzlich die Schwierigkeit in einer angemessenen Zeit die tatsachlich relevanten Arbeiten aufzufinden, was in der Regel uberhaupt nur bei einer sehr eng begrenzten Suchspezifikation gelingt. Hier soll der Versuch gemacht werden, die unglaubliche Datenfulle im Hinblick auf die Behandlung chronischer Wunden in eine gewisse Systematik zu bringen und schlieslich in groben Schlaglichtern einzelne Schwerpunkte etwas zu erhellen.

Summary Somatic progenitors sustain tissue self-renewal while suppressing premature differentiation. Protein arginine methyltransferases (PRMTs) affect many processes; however, their role in progenitor function is incompletely understood. PRMT1 was found to be the most highly expressed PRMT in epidermal progenitors and the most downregulated PRMT during differentiation. In targeted mouse knockouts and in long-term regenerated human mosaic epidermis in vivo, epidermal PRMT1 loss abolished progenitor self-renewal and led to premature differentiation. Mass spectrometry of the PRMT1 protein interactome identified the CSNK1a1 kinase, which also proved essential for progenitor maintenance. CSNK1a1 directly bound and phosphorylated PRMT1 to control its genomic targeting to PRMT1-sustained proliferation genes as well as PRMT1-suppressed differentiation genes. Among the latter were GRHL3, whose derepression was required for the premature differentiation seen with PRMT1 and CSNK1a1 loss. Maintenance of the progenitors thus requires cooperation by PRMT1 and CSNK1a1 to sustain proliferation gene expression and suppress premature differentiation driven by GRHL3.

Monoubiquitylation of histone H2B on Lys123 (H2BK123ub1) plays a multifaceted role in diverse DNA-templated processes, yet the mechanistic details by which this modification is regulated are not fully elucidated. Here we show in yeast that H2BK123ub1 is regulated in part through the protein stability of the E3 ubiquitin ligase Bre1. We found that Bre1 stability is controlled by the Rtf1 subunit of the polymerase-associated factor (PAF) complex and through the ability of Bre1 to catalyze H2BK123ub1. Using a domain in Rtf1 that stabilizes Bre1, we show that inappropriate Bre1 levels lead to defects in gene regulation. Collectively, these data uncover a novel quality control mechanism used by the cell to maintain proper Bre1 and H2BK123ub1 levels, thereby ensuring proper control of gene expression.