Variation in Structure and Process of Care in Traumatic Brain Injury: Provider Profiles of European Neurotrauma Centers Participating in the CENTER-TBI Study.

INTRODUCTION: The strength of evidence underpinning care and treatment recommendations in traumatic brain injury (TBI) is low. Comparative effectiveness research (CER) has been proposed as a framework to provide evidence for optimal care for TBI patients. The first step in CER is to map the existing variation. The aim of current study is to quantify variation in general structural and process characteristics among centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. METHODS: We designed a set of 11 provider profiling questionnaires with 321 questions about various aspects of TBI care, chosen based on literature and expert opinion. After pilot testing, questionnaires were disseminated to 71 centers from 20 countries participating in the CENTER-TBI study. Reliability of questionnaires was estimated by calculating a concordance rate among 5% duplicate questions. RESULTS: All 71 centers completed the questionnaires. Median concordance rate among duplicate questions was 0.85. The majority of centers were academic hospitals (n = 65, 92%), designated as a level I trauma center (n = 48, 68%) and situated in an urban location (n = 70, 99%). The availability of facilities for neuro-trauma care varied across centers; e.g. 40 (57%) had a dedicated neuro-intensive care unit (ICU), 36 (51%) had an in-hospital rehabilitation unit and the organization of the ICU was closed in 64% (n = 45) of the centers. In addition, we found wide variation in processes of care, such as the ICU admission policy and intracranial pressure monitoring policy among centers. CONCLUSION: Even among high-volume, specialized neurotrauma centers there is substantial variation in structures and processes of TBI care. This variation provides an opportunity to study effectiveness of specific aspects of TBI care and to identify best practices with CER approaches

Variation in neurosurgical management of traumatic brain injury

Background: Neurosurgical management of traumatic brain injury (TBI) is challenging, with only low-quality evidence. We aimed to explore differences in neurosurgical strategies for TBI across Europe. Methods: A survey was sent to 68 centers participating in the Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. The questionnaire contained 21 questions, including the decision when to operate (or not) on traumatic acute subdural hematoma (ASDH) and intracerebral hematoma (ICH), and when to perform a decompressive craniectomy (DC) in raised intracranial pressure (ICP). Results: The survey was completed by 68 centers (100%). On average, 10 neurosurgeons work in each trauma center. In all centers, a neurosurgeon was available within 30 min. Forty percent of responders reported a thickness or volume threshold for evacuation of an ASDH. Most responders (78%) decide on a primary DC in evacuating an ASDH during the operation, when swelling is present. For ICH, 3% would perform an evacuation directly to prevent secondary deterioration and 66% only in case of clinical deterioration. Most respondents (91%) reported to consider a DC for refractory high ICP. The reported cut-off ICP for DC in refractory high ICP, however, differed: 60% uses 25 mmHg, 18% 30 mmHg, and 17% 20 mmHg. Treatment strategies varied substantially between regions, specifically for the threshold for ASDH surgery and DC for refractory raised ICP. Also within center variation was present: 31% reported variation within the hospital for inserting an ICP monitor and 43% for evacuating mass lesions. Conclusion: Despite a homogeneous organization, considerable practice variation exists of neurosurgical strategies for TBI in Europe. These results provide an incentive for comparative effectiveness research to determine elements of effective neurosurgical care

Resolution Analysis of Infrared Sensor Arrays

Iske B, Schlößer S, Rückert U. Resolution Analysis of Infrared Sensor Arrays. In: Proceedings of the 2nd International Conference on Autonomous Minirobots for Research and Edutainment (AMiRE). Brisbane, Australia; 2003: 153-162.This work deals with simple and low-cost IR-sensor systems for autonomous systems. Specifically, a circular array of IR-photodiodes is investigated in the context of object recognition, localisation and differentiation. Such sensors are usually only used for the detection of objects in the near field of the system in order to avoid obstacles. However, under certain conditions, the information provided by circular IR-sensor arrays can be used to determine the angle, distance and brightness of an object. Besides a theoretical analysis of the minimal requirements for determining the number of objects and their parameters, noisy sensor readings are investigated concerning maximum possible preciseness of the estimation of the object’s distance. Finally, an algorithm that allows the determination of the distance and angle of an object, independent of knowledge of its brightness, is presented

Die Fremdkörperingestion – eine seltene Ursache persistierender, unklarer abdomineller Schmerzen

Anamnese und klinischer befund: Ein 50-jähriger Patient stellt sich mit rechtsseitigen Unterbauchschmerzen in der Notaufnahme vor. Er gibt an, dass jene Beschwerden seit ca. 5 Monaten bestünden und bei der Miktion an Intensität zunähmen.Untersuchungen: Nach einer Vielzahl frustraner diagnostischer Maßnahmen (CT Abdomen, MR-Sellink, Ileokoloskopie) gelingt es letztlich mittels Darmsonografie, einen ingestierten Zahnstocher im terminalen Ileum als Ursache für die Beschwerden zu identifizieren. Jener perforiert die Darmwand lokal und affektiert die angrenzende Blasenwand bei jeder Erhöhung des intraabdominellen Druckes schmerzhaft.Therapie und verlauf: Explorative Laparotomie mit Nachweis eines entzündlichen Konglomerattumors mit ileosigmoidaler Fistel im rechten Unterbauch. Die Entzündungsreaktion wird durch einen das terminale Ileum zweifach perforierenden Zahnstocher verursacht. Die operative Versorgung erfolgt mittels Ileumsegmentresektion und Sigmaresektion mit End-zu-End-Anastomosierung. Im postoperativen Verlauf kommt es zu einer subkutanen Wundheilungsstörung, die mittels VAC-Therapie versorgt wird. Am 16. postoperativen Tag kann der Patient in einem guten Allgemeinzustand nach Hause entlassen werden.Folgerung: Eine Fremdkörperingestion stellt eine seltene, aber relevante Differenzialdiagnose unklarer abdomineller Schmerzen, insbesondere im Kindesalter, dar. Neben einer ausführlichen Anamnese sollte als primäre apparative Maßnahme stets zunächst eine qualifizierte und sorgfältig durchgeführte Abdomensonografie erfolgen, mithilfe derer auch strahlentransparente ingestierte Fremdkörper detektiert werden können.</p

Epidemiology and one-year follow-up of neonates with CDH-data from health insurance claims in Germany

Congenital diaphragmatic hernia (CDH) is a major congenital malformation with high mortality. Outcome data on larger unselected patient groups in Germany are unavailable as there is no registry for CDH. Therefore, routine data from the largest German health insurance fund were analyzed for the years 2009–2013. Main outcome measures were incidence, survival and length of hospital stay. Follow-up was 12 months. 285 patients were included. The incidence of CDH was 2.73 per 10,000 live births. Overall mortality was 30.2%. A total of 72.1% of the fatalities occurred before surgery. Highest mortality (64%) was noted in patients who were admitted to specialized care later as the first day of life. Patients receiving surgical repair had a better prognosis (mortality: 10.8%). A total of 67 patients (23.5%) were treated with ECMO with a mortality of 41.8%. The median cumulative hospital stay among one-year survivors was 40 days and differed between ECMO- and non-ECMO-treated patients (91 vs. 32.5 days, p < 0.001). This is the largest German cohort study of CDH patients with a one-year follow-up. The ECMO subgroup showed a higher mortality. Another important finding is that delayed treatment in specialized care increases mortality. Prospective clinical registries are needed to elucidate the treatment outcomes in detail

Proteolysis of mature HIV-1 p6 Gag protein by the insulin-degrading enzyme (IDE) regulates virus replication in an Env-dependent manner

<div><p>There is a significantly higher risk for type II diabetes in HIV-1 carriers, albeit the molecular mechanism for this HIV-related pathology remains enigmatic. The 52 amino acid HIV-1 p6 Gag protein is synthesized as the C-terminal part of the Gag polyprotein Pr55. In this context, p6 promotes virus release by its two late (L-) domains, and facilitates the incorporation of the viral accessory protein Vpr. However, the function of p6 in its mature form, after proteolytic release from Gag, has not been investigated yet. We found that the mature p6 represents the first known viral substrate of the ubiquitously expressed cytosolic metalloendopeptidase insulin-degrading enzyme (IDE). IDE is sufficient and required for degradation of p6, and p6 is approximately 100-fold more efficiently degraded by IDE than its eponymous substrate insulin. This observation appears to be specific for HIV-1, as p6 proteins from HIV-2 and simian immunodeficiency virus, as well as the 51 amino acid p9 from equine infectious anaemia virus were insensitive to IDE degradation. The amount of virus-associated p6, as well as the efficiency of release and maturation of progeny viruses does not depend on the presence of IDE in the host cells, as it was shown by CRISPR/Cas9 edited IDE KO cells. However, HIV-1 mutants harboring IDE-insensitive p6 variants exhibit reduced virus replication capacity, a phenomenon that seems to depend on the presence of an X4-tropic Env. Furthermore, competing for IDE by exogenous insulin or inhibiting IDE by the highly specific inhibitor 6bK, also reduced virus replication. This effect could be specifically attributed to IDE since replication of HIV-1 variants coding for an IDE-insensitive p6 were inert towards IDE-inhibition. Our cumulative data support a model in which removal of p6 during viral entry is important for virus replication, at least in the case of X4 tropic HIV-1.</p></div

Cytoplasmic S10 from HeLa cells contains an enzymatic activity that degrades <i>s</i>p6 and <i>v</i>p6.

<p><b>(A)</b> 100 ng <i>s</i>p6 were incubated with 5 μg S10 extract from HeLa cells for 30 min at 37°C. In one reaction, S10 extract was heat-inactivated (95°C, 5 min) prior to incubation (*). <b>(B)</b> 100 ng <i>s</i>p6 were incubated with 5 μg S10 extract for the times indicated at 37°C. <b>(C)</b> Amounts of p6 were quantified for four independently performed experiments. Values represent the arithmetic mean ± SD. <b>(D)</b> 10 ng <i>s</i>p6BY were incubated with 5 μg S10 extract for 30 min at 37°C. <i>s</i>p6BY was detected by measurement of fluorescence excitation. <b>(E)</b> 10 ng <i>s</i>p6BY were incubated with 5 μg S10 extract for the times indicated. Band intensities were quantified with AIDA for seven independently performed experiments. Values represent the arithmetic mean ± SD. <b>(F)</b> VLPs produced in HEK293T cells transfected with the subgenomic HIV-1 expression plasmid pΔR [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0174254#pone.0174254.ref011" target="_blank">11</a>] were isolated, lysed with 0.5% Triton X-100 and incubated with 5 μg S10 extract for 30 min at 37°C. (*) S10 extract, or VLP lysate, was heat-inactivated for 5 min at 95°C prior to incubation. Samples were analyzed by Western blotting. <b>(G)</b> VLPs were produced and treated as described in (F) and analyzed for Vpr content.</p

<i>s</i>p6 is an up to 100-fold better IDE-substrate than insulin.

<p><b>(A)</b> 10 ng of <i>s</i>p6BY or insulin-FITC were incubated with indicated amounts of rIDE for 30 min at 37°C. Remaining amounts of <i>s</i>p6BY and insulin-FITC were detected by measurement of fluorescence excitation. <b>(B)</b> Results of four independently performed experiments. Values represent the arithmetic mean ± SD. <b>(C)</b> Increasing concentrations of <i>s</i>p6BY were incubated with rIDE for 10 min at 37°C. The velocities were calculated from the degradation of <i>s</i>p6BY and normalized for the amount of rIDE. Data points represent values from three independent experiments in a double-reciprocal Lineweaver-Burk plot. The inset shows a magnification of the intersections of the regression lines with the axes. <b>(D)</b> Comparison of K_M and v_max values for <i>s</i>p6BY and IDE as determined in (C) to those of IDE and insulin or Aβ as reported [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0174254#pone.0174254.ref047" target="_blank">47</a>].</p

Multiplication of PTAPPA-motifs stabilizes p6.

<p>20 ng of <i>s</i>p6 or 30 ng of <i>v</i>p6 were incubated either with 5 μg S10 extract <b>(A/B/C)</b> or 2 ng of rIDE <b>(D)</b> for up to 60 min. Degradation efficiency was quantified <i>via</i> densitometric analyses of Western blots. Values represent the arithmetic mean ± SD of at least 3 independent experiments for each setting.</p