Progressive multifocal leukoencephalopathy in common variable immunodeficiency: mitigated course under mirtazapine and mefloquine.

Demonstration of survival and outcome of progressive multifocal leukoencephalopathy (PML) in a 56-year-old patient with common variable immunodeficiency, consisting of severe hypogammaglobulinemia and CD4+ T lymphocytopenia, during continuous treatment with mirtazapine (30 mg/day) and mefloquine (250 mg/week) over 23 months. Regular clinical examinations including Rankin scale and Barthel index, nine-hole peg and box and block tests, Berg balance, 10-m walking tests, and Montreal Cognitive Assessment (MoCA) were done. Laboratory diagnostics included complete blood count and JC virus (JCV) concentration in cerebrospinal fluid (CSF). The noncoding control region (NCCR) of JCV, important for neurotropism and neurovirulence, was sequenced. Repetitive MRI investigated the course of brain lesions. JCV was detected in increasing concentrations (peak 2568 copies/ml CSF), and its NCCR was genetically rearranged. Under treatment, the rearrangement changed toward the archetype sequence, and later JCV DNA became undetectable. Total brain lesion volume decreased (8.54 to 3.97 cm(3)) and atrophy increased. Barthel (60 to 100 to 80 points) and Rankin (4 to 2 to 3) scores, gait stability, and box and block (7, 35, 25 pieces) and nine-hole peg (300, 50, 300 s) test performances first improved but subsequently worsened. Cognition and walking speed remained stable. Despite initial rapid deterioration, the patient survived under continuous treatment with mirtazapine and mefloquine even though he belongs to a PML subgroup that is usually fatal within a few months. This course was paralleled by JCV clones with presumably lower replication capability before JCV became undetectable. Neurological deficits were due to PML lesions and progressive brain atrophy.

Tseʾenah u-reʾenah : ʿal ḥamishah ḥumshe torah ...

fun Yitsḥaḳ mi-ḳ. ḳ. Yanoṿ. ʿIm Shelah ha-ḳadosh ṿe-ʿim Sefer ha-Yashar ṿe-Sefer Ohel Yaʿaḳov fun Yaʿaḳov mi-Dubno ...

Mobility and Bandwidth Prediction as a Service in Virtualized LTE Systems

Recently telecommunication industry benefits from infrastructure sharing, one of the most fundamental enablers of cloud computing, leading to emergence of the Mobile Virtual Network Operator (MVNO) concept. The most momentous intents by this approach are the support of on-demand provisioning and elasticity of virtualized mobile network components, based on data traffic load. To realize it, during operation and management procedures, the virtualized services need be triggered in order to scale-up/down or scale-out/in an instance. In this paper we propose an architecture called MOBaaS (Mobility and Bandwidth Availability Prediction as a Service), comprising two algorithms in order to predict user(s) mobility and network link bandwidth availability, that can be implemented in cloud based mobile network structure and can be used as a support service by any other virtualized mobile network services. MOBaaS can provide prediction information in order to generate required triggers for on-demand deploying, provisioning, disposing of virtualized network components. This information can be used for self-adaptation procedures and optimal network function configuration during run-time operation, as well. Through the preliminary experiments with the prototype implementation on the OpenStack platform, we evaluated and confirmed the feasibility and the effectiveness of the prediction algorithms and the proposed architecture.

Rückblicke auf die Preußische National-Versammlung von 1848 und ihre Koryphäen

Boberach: In "Konterfeis" werden vor den Kammerwahlen die Abgeordneten der Linken der Nationalversammlung Waldeck, Jacoby, Stein, D'Ester, Elsner, Nees v. Esenbeck, Temme, Berends, Jung, Graf Reichenbach, Schneider, Rodbertus, v. Berg, v. Kirchmann, v. Unruh, [und] Parrisius mit ihrer Taktik vorgestellt

Deutschland und die deutsche Nationalversammlung

Boberach: Seine Wähler in den Kreisen Düren und Jülich sollen erfahren, daß er die Politik Gagerns, der Preußen in seine Provinzen auflösen wolle, und der Erbkaiserpartei ablehnt und den Standpunkt des Pariser Hofes einnimmt. Ein Direktorium aus mehreren Fürsten soll an der Spitze Deutschlands stehen

Bivalirudin Versus Heparin Anticoagulation in Transcatheter Aortic Valve Replacement: The Randomized BRAVO-3 Trial.

BACKGROUND Anticoagulation is required during transcatheter aortic valve replacement (TAVR) procedures. Although an optimal regimen has not been determined, heparin is mainly used. Direct thrombin inhibition with bivalirudin may be an effective alternative to heparin as the procedural anticoagulant agent in this setting. OBJECTIVES The goal of this study was to determine whether bivalirudin offers an alternative to heparin as the procedural anticoagulant agent in patients undergoing TAVR. METHODS A total of 802 patients with aortic stenosis were randomized to undergo transfemoral TAVR with bivalirudin versus unfractionated heparin during the procedure. The 2 primary endpoints were major bleeding within 48 h or before hospital discharge (whichever occurred first) and 30-day net adverse clinical events, defined as the combination of major adverse cardiovascular events (all-cause mortality, myocardial infarction, or stroke) and major bleeding. RESULTS Anticoagulation with bivalirudin versus heparin did not meet superiority because it did not result in significantly lower rates of major bleeding at 48 h (6.9% vs. 9.0%; relative risk: 0.77; 95% confidence interval [CI]: 0.48 to 1.23; p = 0.27) or net adverse cardiovascular events at 30 days (14.4% vs. 16.1%; relative risk: 0.89; 95% CI: 0.64 to 1.24; risk difference: -1.72; 95% CI: -6.70 to 3.25; p = 0.50); regarding the latter, the prespecified noninferiority hypothesis was met (pnoninferiority < 0.01). Rates of major adverse cardiovascular events at 48 h were not significantly different (3.5% vs. 4.8%; relative risk: 0.73; 95% CI: 0.37 to 1.43; p = 0.35). At 48 h, the bivalirudin group had significantly fewer myocardial infarctions but more acute kidney injury events than the heparin group; at 30 days, these differences were no longer significant. CONCLUSIONS In this randomized trial of TAVR procedural pharmacotherapy, bivalirudin did not reduce rates of major bleeding at 48 h or net adverse cardiovascular events within 30 days compared with heparin. Although superiority was not shown, the noninferiority hypothesis was met with respect to the latter factor. Given the lower cost, heparin should remain the standard of care, and bivalirudin can be an alternative anticoagulant option in patients unable to receive heparin in TAVR. (International, Multi-center, Open-label, Randomized Controlled Trial in Patients Undergoing TAVR to Determine the Treatment Effect [Both Safety and Efficacy] of Using Bivalirudin Instead of UFH [BRAVO-2/3]; NCT01651780).

Ressourcenmanagement in historischer Perspektive

Der Begriff der Nachhaltigkeit taucht erstmals 1713 in der forstwirtschaftlichen Schrift „Sylvicultura oeconomica“ des sächsischen Kammer- und Bergrats Hans Carl von Carlowitz auf. Damit wird schon deutlich, dass sich Fragen eines nachhaltigen Umgangs mit Ressourcen im „Zeitalter des Holzes“ (Joachim Radkau) vornehmlich auf die Bewirtschaftung von Wäldern konzentrierten. Wälder boten einen der wichtigsten Baustoffe für Häuser, Mühlen und Brücken, Holz war lange Zeit der wichtigste Brennstoff. Schon für die Wälder im Besitz der mittelalterlichen Städte sind daher ausführliche Regelungen erhalten, die nachhaltiges Bewirtschaften erkennen lassen und zum Teil schwere Strafen gegen ein Zuwiderhandeln vorsehen. Das frühneuzeitliche Berg- und Hüttenwesen verbrauchte Unmengen an Holz für den Stollenbau und die Verhüttung, sodass Montanindustrie und Forstwirtschaft eigentlich gar nicht voneinander zu trennen sind. In der ersten Hälfte des 19. Jahrhunderts stand die nachhaltige Aufforstung von (Gebirgs-)Wäldern Pate bei der Einrichtung forstwirtschaftlich-akademischer Ausbildung, so auch in der Schweiz. Hauptziel der Aufforstung war jetzt der Schutz vor Überschwemmungen im Flachland, die man auf die zu umfangreiche, unkontrollierte Abholzung im Gebirge zurückführte. Bis ins 19. Jahrhundert konzentrierte sich daher der Nachhaltigkeitsdiskurs auf die Forstwirtschaft. Seitdem rücken auch der Abbau von Bodenschätzen, die Förderung fossiler Brennstoffe wie Erdöl und Erdgas sowie der nachhaltige Umgang mit Wasser in den Mittelpunkt. Aus Zeitgründen kann dabei aber nur mehr exemplarisch auf die Entstehung der Erdölindustrie seit dem Beginn des 20. Jahrhunderts eingegangen werden. Zusammenfassend kann somit festgestellt werden, dass ein nachhaltiges Bewirtschaften von Ressourcen, v.a. der Wälder, eine der wichtigsten Voraussetzungen für die Wirtschaft zwischen dem 14. und 19. Jahrhundert war, bzw. umgekehrt Bergbauregionen auch deswegen nicht mehr rentabel blieben, weil die Herbeischaffung von Holz über grosse Distanzen zu kostspielig wurde.

Regional facial asymmetries in unilateral orofacial clefts

OBJECTIVES Assess facial asymmetry in subjects with unilateral cleft lip (UCL), unilateral cleft lip and alveolus (UCLA), and unilateral cleft lip, alveolus, and palate (UCLP), and to evaluate which area of the face is most asymmetrical. METHODS Standardized three-dimensional facial images of 58 patients (9 UCL, 21 UCLA, and 28 UCLP; age range: 8.6-12.3 years) and 121 controls (age range 9-12 years) were mirrored and distance maps were created. Absolute mean asymmetry values were calculated for the whole face, cheek, nose, lips, and chin. One-way analysis of variance, Kruskal-Wallis, and t-test were used to assess the differences between clefts and controls for the whole face and separate areas. RESULTS Clefts and controls differ significantly for the whole face as well as in all areas. Asymmetry is distributed differently over the face for all groups. In UCLA, the nose was significantly more asymmetric compared with chin and cheek (P = 0.038 and 0.024, respectively). For UCL, significant differences in asymmetry between nose and chin and chin and cheek were present (P = 0.038 and 0.046, respectively). In the control group, the chin was the most asymmetric area compared to lip and nose (P = 0.002 and P = 0.001, respectively) followed by the nose (P = 0.004). In UCLP, the nose, followed by the lips, was the most asymmetric area compared to chin, cheek (P < 0.001 and P = 0.016, respectively). LIMITATIONS Despite division into regional areas, the method may still exclude or underrate smaller local areas in the face, which are better visualized in a facial colour coded distance map than quantified by distance numbers. The UCL subsample is small. CONCLUSION Each type of cleft has its own distinct asymmetry pattern. Children with unilateral clefts show more facial asymmetry than children without clefts.

A genome-wide association study confirms PNPLA3 and identifies TM6SF2 and MBOAT7 as risk loci for alcohol-related cirrhosis

Alcohol misuse is the leading cause of cirrhosis and the second most common indication for liver transplantation in the Western world. We performed a genome-wide association study for alcohol-related cirrhosis in individuals of European descent (712 cases and 1,426 controls) with subsequent validation in two independent European cohorts (1,148 cases and 922 controls). We identified variants in the MBOAT7 (P = 1.03 × 10(-9)) and TM6SF2 (P = 7.89 × 10(-10)) genes as new risk loci and confirmed rs738409 in PNPLA3 as an important risk locus for alcohol-related cirrhosis (P = 1.54 × 10(-48)) at a genome-wide level of significance. These three loci have a role in lipid processing, suggesting that lipid turnover is important in the pathogenesis of alcohol-related cirrhosis.

A frequent hypofunctional IRAK2 variant is associated with reduced spontaneous hepatitis C virus clearance.

UNLABELLED Patients carrying very rare loss-of-function mutations in interleukin-1 receptor-associated kinase 4 (IRAK4), a critical signaling mediator in Toll-like receptor signaling, are severely immunodeficient, highlighting the paramount role of IRAK kinases in innate immunity. We discovered a comparatively frequent coding variant of the enigmatic human IRAK2, L392V (rs3844283), which is found homozygously in ∼15% of Caucasians, to be associated with a reduced ability to induce interferon-alpha in primary human plasmacytoid dendritic cells in response to hepatitis C virus (HCV). Cytokine production in response to purified Toll-like receptor agonists was also impaired. Additionally, rs3844283 was epidemiologically associated with a chronic course of HCV infection in two independent HCV cohorts and emerged as an independent predictor of chronic HCV disease. Mechanistically, IRAK2 L392V showed intact binding to, but impaired ubiquitination of, tumor necrosis factor receptor-associated factor 6, a vital step in signal transduction. CONCLUSION Our study highlights IRAK2 and its genetic variants as critical factors and potentially novel biomarkers for human antiviral innate immunity.

This Was Not on the Syllabus!: An Examination of First-Year Urban Teachers' Self-Efficacy

Many first-year teachers find it difficult to reach the needs of all their students in part, because they feel their college coursework left them ill-prepared for the complexity they face in the classroom. This is particularly true among urban teachers who often face crowded classrooms of diverse students with a wide range of instructional needs. This study is a comparative case study of two University of Connecticut graduates during their first year teaching in urban schools. Using mixed-methods, the study draws on interviews, questionnaires, and videotape data shared as a part of a monthly teacher study group of similar graduates. I also draw on group conversations in which teachers discussed their ability to reach the needs of all of their students as this was related to their preservice coursework. My findings suggest that many first-year teachers feel university coursework failed to help them. One teacher felt it did not help her at all, while the other felt it helped her but she still could not meet all of her students' needs. Many first-year, urban teachers do not feel confident in the classroom as a result of their preparation from coursework. With this lack in confidence, the teachers may be more likely to leave their urban position, and this may contribute to the high turnover of teachers in urban placements.