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The project OPTIMAP is at the current stage a joint initiative of BGIC, GSSAC and DGFI-TUM. The development of an operational tool for ionospheric mapping and prediction is the main goal of the project.The ionosphere is a dispersive medium. Therefore, GNSS signals are refracted while they pass through the ionosphere. The magnitude of the refraction rate depends on the frequencies of the transmitted GNSS signals. The ionospheric disturbance on the GNSS signals paves the way of extracting Vertical Total Electron Content (VTEC) information of the ionosphere.In OPTIMAP, the representation of the global and regional VTEC signal is based on localizing B-spline basis functions. For global VTEC modeling, polynomial B-splines are employed to represent the latitudinal variations, whereas trigonometric B-splines are used for the longitudinal variations. The regional modeling in OPTIMAP relies on a polynomial B-spline representation for both latitude and longitude.The VTEC modeling in this study relies on both a global and a regional sequential estimator (Kalman filter) running in a parallel mode. The global VTEC estimator produces VTEC maps based on data from GNSS receiver stations which are mainly part of the global real-time IGS network. The global estimator relies on additional VTEC information obtained from a forecast procedure using ultra-rapid VTEC products. The regional estimator makes use of the VTEC product of the real-time global estimator as background information and generates high-resolution VTEC maps using real-time data from the EUREF Permanent GNSS Network. EUREF provides a network of very dense GNSS receivers distributed alongside Europe.Carrier phase observations acquired from GPS and GLONASS, which are transmitted in accordance with RTCM standard, are used for real-time regional VTEC modeling. After the acquisition of GNSS data, cycle slips for each satellite-receiver pair are detected, and ionosphere observations are constructed via the linear combination of carrier-phase observations in the data pre-processing step. The unknown B-spline coefficients, as well as the biases for each phase-continuous arc belonging to each receiver-satellite pair, are simultaneously estimated in the Kalman filter.Within this study, we compare the performance of regional and global VTEC products generated in real-time using the well-known dSTEC analysis.

The project OPTIMAP is at the current stage a joint initiative of BGIC, GSSAC and DGFI-TUM. The development of an operational tool for ionospheric mapping and prediction is the main goal of the project.The ionosphere is a dispersive medium. Therefore, GNSS signals are refracted while they pass through the ionosphere. The magnitude of the refraction rate depends on the frequencies of the transmitted GNSS signals. The ionospheric disturbance on the GNSS signals paves the way of extracting Vertical Total Electron Content (VTEC) information of the ionosphere.In OPTIMAP, the representation of the global and regional VTEC signal is based on localizing B-spline basis functions. For global VTEC modeling, polynomial B-splines are employed to represent the latitudinal variations, whereas trigonometric B-splines are used for the longitudinal variations. The regional modeling in OPTIMAP relies on a polynomial B-spline representation for both latitude and longitude.The VTEC modeling in this study relies on both a global and a regional sequential estimator (Kalman filter) running in a parallel mode. The global VTEC estimator produces VTEC maps based on data from GNSS receiver stations which are mainly part of the global real-time IGS network. The global estimator relies on additional VTEC information obtained from a forecast procedure using ultra-rapid VTEC products. The regional estimator makes use of the VTEC product of the real-time global estimator as background information and generates high-resolution VTEC maps using real-time data from the EUREF Permanent GNSS Network. EUREF provides a network of very dense GNSS receivers distributed alongside Europe.Carrier phase observations acquired from GPS, GLONASS and GALILEO constellations, which are transmitted in accordance with RTCM standard, are used for real-time regional VTEC modeling. After the acquisition of GNSS data, cycle slips for each satellite-receiver pair are detected, and ionosphere observations are constructed via the linear combination of carrier-phase observations in the data pre-processing step. The unknown B-spline coefficients, as well as the biases for each phase-continuous arc belonging to each receiver-satellite pair, are simultaneously estimated in the Kalman filter.Within this study, we compare the performance of regional and global VTEC products generated in real-time using the well-known dSTEC analysis.

Background: Chemoimmunotherapy is typically the standard of care for patients with Waldenström macroglobulinemia; however, infectious and hematologic toxic effects are problematic. Acalabrutinib is a selective, potent Bruton tyrosine-kinase inhibitor. The aim of this trial was to evaluate the activity and safety of acalabrutinib in patients with Waldenström macroglobulinemia. Methods: This single-arm, multicentre, phase 2 trial was done in 19 European academic centres in France, Italy, Greece, the Netherlands, and the UK, and eight academic centres in the USA. Eligible patients were 18 years or older and had treatment naive (declined or not eligible for chemoimmunotherapy) or relapsed or refractory (at least one previous therapy) Waldenström macroglobulinemia that required treatment, an Eastern Cooperative Oncology Group performance status of 2 or less, and received no previous Bruton tyrosine-kinase inhibitor therapy. Patients received 100 mg oral acalabrutinib twice per day in 28-day cycles until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed overall response (at least a minor response) according to the 6th International Workshop for Waldenström Macroglobulinemia (IWWM) and the modified 3rd IWWM workshop criteria. The primary outcome and safety were assessed in all patients who received at least one dose of treatment. This study is registered with ClinicalTrials.gov, number NCT02180724, and is ongoing, but no longer enrolling. Findings: Between Sept 8, 2014, and Dec 24, 2015, 122 patients were assessed for eligibility, of which 106 (87%) patients were given acalabrutinib (14 were treatment naive and 92 had relapsed or refractory disease). With a median follow-up of 27·4 months (IQR 26·0–29·7), 13 (93% [95% CI 66–100]) of 14 treatment naive patients achieved an overall response and 86 (93% [86–98]) of 92 relapsed or refractory patients per both the modified 3rd and 6th IWWM criteria. Seven (50%) of 14 treatment naive patients and 23 (25%) of 92 relapsed or refractory patients discontinued treatment on study. Grade 3–4 adverse events occurring in more than 5% of patients were neutropenia (17 [16%] of 106 patients) and pneumonia (7 [7%]). Grade 3–4 atrial fibrillation occurred in one (1%) patient and grade 3–4 bleeding occurred in three (3%) patients. The most common serious adverse events were lower respiratory tract infection (n=7 [7%]), pneumonia (n=7 [7%]), pyrexia (n=4 [4%]), cellulitis (n=3 [3%]), fall (n=3 [3%]), and sepsis (n=3 [3%]). Pneumonia (n=5 [5%]) and lower respiratory tract infection (n=4 [4%]) were considered treatment related. One treatment-related death was reported (intracranial hematoma). Interpretation: This study provides evidence that acalabrutinib is active as single-agent therapy with a manageable safety profile in patients with treatment-naive, or relapse or refractory Waldenström macroglobulinemia. Further studies are needed to establish its efficacy against current standard treatments and to investigate whether outcomes can be improved with combination therapies. Funding: Acerta Pharma. © 2020 Elsevier Ltd

Einleitung: In der Literatur findet man zunehmend Berichte uber die Unvollstandigkeit der arztlichen Aufklarungen durch „Residents“. Diese fuhlen sich wiederum unsicher und nicht adaquat auf diese Aufgabe vorbereitet. Ziel dieses Projekts war es, die Aufklarung von Patienten in die studentische Ausbildung unter kontrollierten Bedingungen zu integrieren, anstatt dies nur im Rollenspiel mit Kommilitonen oder Schauspielpatienten zu uben. Methoden: An der Universitat Magdeburg wurde vor Kurzem die neue Unterrichtseinheit „STeP“ („Students Teaching Patients“) fur Medizinstudierende eingefuhrt. Die Medizinstudierenden werden zunachst von einem approbierten Arzt auf die arztliche Aufklarung vorbereitet. Sie fuhren nach adaquater Einfuhrung beim bereits arztlich aufgeklarten Patienten eine strukturierte Abfrage der Aufklarungsinhalte durch. Im Rahmen der Nachbereitung berichten sie dem Arzt uber das stattgefundene Gesprach. Schlieslich vergewissert sich der Arzt im 4-Augen-Gesprach mit dem Patienten daruber, dass keine Unsicherheiten entstanden sind. In Erweiterung zum ursprunglichen Ablauf wurde im vorliegenden Teilprojekt die studentische Abfrage 2-mal am gleichen Patienten durchgefuhrt, um die Wissenszunahme der Patienten durch das studentische Gesprach zu untersuchen. Ergebnisse: Trotz absolviertem Chirurgiekurs ist es den Medizinstudierenden nicht hinreichend klar, welche Komplikationen im Rahmen der laparoskopischen Cholezystektomie eine hohe Relevanz aufweisen. Ahnlich schwierig war es auch fur Patienten, die bereits arztlich aufgeklart worden waren, wiederzugeben, welche Folgen und Komplikationen aus diesem Eingriff entstehen konnen. So konnte eine Stichprobe von Patienten bspw. nach erfolgter arztlicher Aufklarung durchschnittlich nur eine einzige Komplikation in der STeP-Abfrage wiedergeben, und nur ein kleiner Anteil konnte sich unter der „Verletzung des Ductus hepatocholedochus“ etwas vorstellen. Die Anzahl an Komplikationen, die von den 10 Patienten in der 2. STeP-Abfrage benannt werden konnte, stieg. Die generelle Bereitschaft der Patienten, das Gesprach 2-mal durchzufuhren, sank allerdings und fuhrte in der Folge zum Abbruch dieses Teilprojekts. Schlussfolgerung: Die Analyse der Limitationen der hier beschriebenen methodischen Veranderung (Zweitbefragung) resultiert in einer Weiterentwicklung der Methodik von STeP: Das studentische Gesprach soll nun vor der arztlichen Aufklarung im Sinne eines „Beratungsgesprachs“ stattfinden und vom Studierenden in Form einer Selbstreflexion evaluiert werden. Die Auswertung von Wissenszuwachs und Zufriedenheit der Patienten erfolgt dann durch die Studierenden – allerdings erst postoperativ. Die Ergebnisse dieser veranderten Masnahme stehen zurzeit noch aus.

The source of continental rift-related basalts and their relation to rifting processes is a continuous matter of debate. We present major and trace element and Sr, Nd, Hf and Pb isotope data for axial rift basalts from eight volcanic centres (Ayelu, Hertali, Dofan, Fantale, Kone, Bosetti and Gedemsa, from NE to SW) in Afar and Main Ethiopian Rift (MER) to assess their source regions and their genetic relationships. These lavas have geochemical characteristics, i.e., a peak at Ba, Nb and troughs at K and Rb in primitive mantle-normalised multielement diagrams, which are consistent with predominant melting of an amphibole-bearing lithospheric mantle. However, the isotopic compositions for these lavas are heterogeneous (Sr-87/Sr-86 = 0.70354-0.70431, Nd-143/Nd-144 = 0.51280-0.51294,(176)Hr/Hf-177 = 0.28301-0.28315, Pb-206/Pb-204 = 18.48-19.31, Pb-207/Pb-204 = 15.53-15.62, Pb-208/Pb-204 = 38.61-39.06) and require various mantle reservoirs with distinctive isotopic signatures. The range of isotopic compositions requires the involvement of three distinct source components from the asthenospheric and veined lithospheric mantle. Progressive rifting leads to lithosperic thinning and upwelling of hot asthenospheric mantle, which induces melting of the veined lithospheric mantle. The trace element characteristics of the lavas are dominated by the vein material, which has a higher trace element content than the surrounding mantle. The isotopic composition of the vein material, however, is not very different from the ambient mantle, giving rise of apparent uncoupling of trace element and isotope constraints for the melt source. The uprising basaltic liquids in part inherit a lithospheric trace element signature, while their isotopic compositions are mostly unaffected due to short residence times within the lithosphere in context with progressive rifting and lithospheric thinning. Thus, the geochemical and isotope data are consistent with a multi-component source prevailing beneath the Afar and MER areas in which the basalts are generated during progressive rifting and, thus, passive upwelling of a mantle source. (C) 2016 The Authors. Published by Elsevier B.V.

Several prognostic indices (PI) have been developed to stratify patients with brain metastases in groups with good or bad prognosis. The aim of our study was to compare nine prognostic scores for patients with brain metastases (BM) of breast cancer receiving radiotherapy. The clinical data of 139 breast cancer patients with BM were collected retrospectively. All patients were treated with cerebral radiotherapy or surgery followed by radiotherapy between January 2007 and December 2012. The prognostic value and accuracy of recursive partitioning analysis (RPA), RPA II, graded prognostic assessment (GPA), basic score for BM, Breast-RPA, Breast-GPA, Rades Score 2011, Germany Score and Breast Rades Score were assessed. The median survival after BM diagnosis in our cohort was 14 months. The overall 6-month, 1-, 2- and 3-year survival rates were 49.6, 37.4, 20.9 and 13.7 %, respectively. Most of the PI were associated with OS, but univariate analysis favored GPA regarding OS. GPA was the most accurate score to identify patients with long (longer than 12 months) and Breast-GPA patients with short (

The HAWAI registry evaluated the role of heart rate variability in predicting the occurrence of ventricular tachycardia and fibrillation (VT/VF) and sinus tachycardia in patients with an implantable cardioverter-defibrillator (45 patients with 155 RR recordings). A significant decrease of the mean value of all RR intervals (MeanNN) was observed in the period starting 20 and 40 min prior to VT/VF and sinus tachycardia, respectively. The standard deviation of RR intervals (SDNN) and the power at low frequency (LF) were the only parameters with significant changes prior to VT/VF. For sinus tachycardia, the root mean square of successive differences of all successive RR intervals (r-MSSD) and the power at low and high frequency (HF) decreased, whereas SDNN and the power at very low frequency increased. Comparison of RR recordings preceding VT/VF and sinus tachycardia revealed significant differences of the MeanNN, SDNN, r-MSSD, LF and HF. Based on a classification and regression tree analysis, MeanNN, SDNN and r-MSSD showed a sensitivity of 94.4% and a specificity of 50.6% as predictors of VT/VF. Our results suggest that the temporal changes in heart rate before an arrhythmic event can be used to predict the occurrence of VT/VF. These parameters may be used to optimize pacing therapies designed to prevent VT/VF recurrences as well as for improving device-based discriminators for VT/VF and sinus tachycardia.

In patients with malignant middle cerebral artery infarction (MMI) decompressive surgery within 48 h improves functional outcome. In this respect, early identification of patients at risk of developing MMI is crucial. While the acute diffusion weighted imaging (DWI) lesion volume was found to predict MMI with high predictive values, the potential impact of preexisting brain atrophy on the course of space-occupying middle cerebral artery (MCA) infarction and the development of MMI remains unclear. We tested the hypothesis that the combination of the acute DWI lesion volume with simple measures of brain atrophy improves the early prediction of MMI. Data from a prospective, multicenter, observational study, which included patients with acute middle cerebral artery main stem occlusion studied by MRI within 6 h of symptom onset, was analyzed retrospectively. The development of MMI was defined according to the European randomized controlled trials of decompressive surgery. Acute DWI lesion volume, as well as brain and cerebrospinal fluid volume (CSF) were delineated. The intercaudate distance (ICD) was assessed as a linear brain atrophy marker by measuring the hemi-ICD of the intact hemisphere to account for local brain swelling. Binary logistic regression analysis was used to identify significant predictors of MMI. Cut-off values were determined by Classification and Regression Trees analysis. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the resulting models were calculated. Twenty-one (18 %) of 116 patients developed a MMI. Malignant middle cerebral artery infarctions patients had higher National Institutes of Health Stroke Scale scores on admission and presented more often with combined occlusion of the internal carotid artery and MCA. There were no differences in brain and CSF volume between the two groups. Diffusion weighted imaging lesion volume was larger (p0.001), while hemi-ICD was smaller (p = 0.029) in MMI patients. Inclusion of hemi-ICD improved the prediction of MMI. Best cut-off values to predict the development of MMI were DWI lesion volume87 ml and hemi-ICD ≤ 9.4 mm. The addition of hemi-ICD to the decision tree strongly increased PPV (0.93 vs. 0.70) resulting in a reduction of false positive findings from 7/23 (30 %) to 1/15 (7 %), while there were only slight changes in specificity, sensitivity and NPV. The absolute number of correct classifications increased by 4 (3.4 %). The integration of hemi-ICD as a linear marker of brain atrophy, that can easily be assessed in an emergency setting, may improve the prediction of MMI by lesion volume based predictive models.

Item does not contain fulltext The murine-derived MC3T3-E1 cell line provided by the American Type Culture Collection (ATCC) is a well-known osteogenic cell culture model system to test materials in vitro. However, the effect of passaging on its mineralization capacity has never been described and their culture supplements can be further optimized. Therefore, we evaluated the influence of the passage number and different osteogenic culture supplements, including ascorbic acid (AsAP) and dexamethasone (Dex) on the osteogenic capacity of MC3T3-E1 cells. This capacity was measured by the deposited calcium, the alkaline phosphatase activity, and the expression of osteogenic-related genes, including bone sialoprotein (BSP), osteocalcin (OC), and osteopontin (OPN). The results indicated that the mineralization capacity of MC3T3-E1 cells significantly decreased during passaging and got exhausted at passage 34, as assessed by measuring calcium deposition after 28 days of osteogenic induction. Moreover, the combination of AsAP and Dex triggered significantly more mineralization in MC3T3-E1 cells than the ATCC recommended addition of AsAP alone, as indicated by increased calcium deposition and higher expression of BSP and OPN. However, Dex alone could not trigger this effect, but only in combination with the AsAP, which indicates that Dex has no direct effect on mineralization. In conclusion, the passage number of MC3T3-E1 cells is of great importance and the use of cells above 30 passages should be avoided. In addition, the favored osteogenic supplements providing an improved osteogenic differentiation of MC3T3-E1 cells are the combination of AsAP and Dex.

Bone regenerative medicine, based on the combined use of cells and scaffolds, represents a promising strategy in bone regeneration. Hydrogels have attracted huge interests for application as a scaffold for minimally invasive surgery. Collagen and oligo(poly(ethylene glycol)fumarate) (OPF) hydrogels are the representatives of two main categories of hydrogels, that is, natural- and synthetic-based hydrogels. With these the optimal cell-loading (i.e., cell distribution inside the hydrogels) method was assessed. The cell behavior of both bone marrow- and adipose tissue-derived mesenchymal stem cells (BM- and AT-MSCs) in three loading methods, which are dispersed (i.e., homogeneous cell encapsulation, D), sandwich (i.e., cells located in between two hydrogel layers, S), and spheroid (i.e., cell pellets encapsulation, Sp) loading in two hydrogel systems (i.e., collagen and OPF), was compared. The results suggested that the cell behavior was influenced by the hydrogel type, meaning cells cultured in collagen hydrogels had higher proliferation and osteogenic differentiation capacity than in OPF hydrogels. In addition, AT-MSCs exhibited higher proliferation and osteogenic properties compared to BM-MSCs. However, no difference was observed for mineralization among the three loading methods, which did not approve the hypothesis that S and Sp loading would increase osteogenic capacity compared to D loading. In conclusion, D and Sp loading represents two promising cell loading methods for injectable bone substitute materials that allow application of minimally invasive surgery for cell-based regenerative treatment. (c) 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 935-946, 2014.

Background: The anti-cardiolipin and β2-glycoprotein I antibodies represent the important diagnostic parameters in routine autoimmune screening and represent the important diagnostic criteria for systemic lupus erythematosus (SLE). In this study, five different automated, semiautomated, and manual immunoassays detecting IgG/IgM anti-cardiolipin and anti-β2-glycoprotein I antibodies were tested. Methods: A total of 43 samples from the patients with SLE diagnosed in the rheumatology outpatient centers in Germany were included in this study. Results: For anticardiolipin and anti-β2-glycoprotein I, considerable differences in the percentage of the positive results were found between all the five methods, and the itemization of all the positive test results reached only a poor accordance. These findings were confirmed by Cohen’s κ coefficients. Conclusions: We found a moderate to poor accordance between the five different modern test systems for anticardiolipin and anti-β2-glycoprotein I antibodies. Such discrepancies can result in the clinical misinterpretation of data and may lead to wrong diagnoses. Therefore, further standardization of the tests for the antiphospholipid antibodies (APAs) is required.

We expand upon the recent semi-stochastic adaptation to full configuration interaction quantum Monte Carlo (FCIQMC). We present an alternate method for generating the deterministic space without a priori knowledge of the wave function and present stochastic efficiencies for a variety of both molecular and lattice systems. The algorithmic details of an efficient semi-stochastic implementation are presented, with particular consideration given to the effect that the adaptation has on parallel performance in FCIQMC. We further demonstrate the benefit for calculation of reduced density matrices in FCIQMC through replica sampling, where the semi-stochastic adaptation seems to have even larger efficiency gains. We then combine these ideas to produce explicitly correlated corrected FCIQMC energies for the Beryllium dimer, for which stochastic errors on the order of wavenumber accuracy are achievable., 10 pages, 7 figures

Contains fulltext : 59181.pdf (Publisher’s version ) (Closed access) Progression of human cutaneous primary melanoma is, among others, accompanied by de novo expression of activated leukocyte cell adhesion molecule (ALCAM/CD166) and enhanced activity of proteolytic cascades in the invasive, vertical growth phase (VGP) of lesions. The homophilic cell adhesion function of wild-type ALCAM mediates homotypic clustering of melanoma cells and would, thus, antagonize cell release from the primary tumor, an early prerequisite for metastasis. Stable transfection of a transmembrane, amino-terminally truncated ALCAM (DeltaN-ALCAM) into metastatic cells diminished cell clustering mediated by wild-type ALCAM. We have addressed the biological effects of DeltaN-ALCAM on tumorigenicity and found that the relief of cell clustering constraints promoted motility in vitro and the transition from expansive tumor growth to tissue invasion in reconstructed skin in culture. In a transplant tumor model, the changes were reflected in reduced subcutaneous tumor growth and in accelerated, spontaneous lung metastasis. These data indicate that the intact cell adhesion function of ALCAM may both favor primary tumor growth and represent a rate-limiting step for tissue invasion from VGP melanoma. ALCAM induction could, thus, provide an attractive target for proteolysis as a part of a more complex cellular program that couples growth and migration and facilitates dissemination.

A detailed morphological and functional description of equine endometrial involution is necessary for the understanding of alterations leading to a reduced fertility rate following peripartal disturbances. A complete involution of the microcaruncles, glands and stroma by the 9th day post parturition and the return to cyclical activity is essential for an early post partal pregnancy. After normal parturition, a loss of the glandular cytokeratin-expression, the absence of laminin in the glandular basal lamina and an intraepithelial expression of vimentin occurs especially on the 3rd and 6th day post partum (p.p.). The expression of estrogen receptors and progesterone receptors of intact glandular epithelial cells decreases from the 3rd to the 6th day p.p. and increases from the 6th to 9th day p.p.. Decreased fertility rate in the first post-partum heats in mares with dystocia or retained placental delivery may be due to a higher incidence of periglandular fibrosis and a disturbed glandular redifferentiation, which is characterized by a delayed inset of epithelial cytokeratin-expression and an unphysiological expression of the hormone receptors. Moreover, in mares with dystocia a disturbed microcaruncular involution may contribute to the decreased conception rate.

B/Ca ratios in Cibicides mundulus and Cibicides wuellerstorfi have been shown to correlate with the degree of calcite saturation in seawater (Δ[CO32−]). In the South Pacific, a region of high importance in the global carbon cycle, these species are not continuously present in down-core records. Small numbers of epibenthic foraminifera in samples present an additional challenge, which can be overcome by using laser ablation-inductively coupled-mass spectrometry (LA-ICP-MS). We present a laser ablation based core-top calibration for Cibicides cf. wuellerstorfi, a C. wuellerstorfi morphotype that is abundant in the South Pacific and extend the existing global core top calibration for C. mundulus and C. wuellerstorfi to this region. B/Ca in C. cf. wuellerstorfi are linearly correlated with Δ[CO32−] and possibly display a higher sensitivity to calcite saturation changes than C. wuellerstorfi. Trace element profiles through C. wuellerstorfi and C. mundulus reveal an intra-shell B/Ca variation of ±36% around the mean shell value. Mg/Ca and B/Ca display opposite trends along the shell. Both phenomena likely result from ontogenetic effects. Intra-shell variability equals intra-sample variability, mean sample B/Ca values can thus be reliably calculated from averaged spot results of single specimen. In the global B/Ca–Δ[CO32−] range, we observe an inverse relationship between water mass age and Δ[CO32−].

Background A large diffusion-weighted imaging lesion ⩽six-hours of symptom onset was found to predict the development of ‘malignant’ middle cerebral artery infarction with high specificity, positive predictive value, and negative predictive value, but sensitivity was low. Hypothesis We tested the hypothesis that sensitivity can be improved by adding information from clinical follow-up examination after 24 h. Methods We analyzed data from a prospective, multicenter, observational cohort study of patients with acute ischemic stroke and middle cerebral artery occlusion studied by stroke magnetic resonance imaging ⩽six-hours of symptom onset. We used the National Institutes of Health Stroke Scale to assess severity of symptoms after 24 h. We used the Classification and Regression Trees analysis to define the optimal thresholds of diffusion-weighted imaging lesion volume and the National Institutes of Health Stroke Scale after 24 h in patients developing ‘malignant’ middle cerebral artery infarction. We calculated sensitivity, specificity, positive predictive value, and negative predictive value for two simple predictive models based on acute diffusion-weighted imaging lesion volume alone and acute diffusion-weighted imaging lesion volume together with the National Institutes of Health Stroke Scale after 24 h. Results Of 135 patients, 27 (20%) developed a ‘malignant’ middle cerebral artery infarction. The Classification and Regression Trees analysis identified acute diffusion-weighted imaging lesion ⩾78 ml and the National Institutes of Health Stroke Scale score after 24 h ⩾22 as optimal cut-offs. Inclusion of the National Institutes of Health Stroke Scale score after 24 h in a simple two-step decision tree increased sensitivity from 0·59 to 0·79, while specificity, positive predictive value, and negative predictive value remained largely unchanged. Conclusion Clinical follow-up examination after 24 h helps identify patients at risk of ‘malignant’ middle cerebral artery infarction that are missed by predictive algorithms based on early diffusion-weighted imaging lesion volume alone.

Item does not contain fulltext Ideally, bone substitute materials would undergo cell-mediated degradation during the remodeling process of the host bone tissue while being replaced by newly formed bone. In an attempt to exploit the capacity of Receptor Activator of Nuclear factor Kappa-B Ligand (RANKL) to stimulate osteoclast-like cells formation, this study explored different loading methods for RANKL in injectable calcium phosphate cement (CPC) and the effect on release and biological activity. RANKL was loaded via the liquid phase of CPC by adsorption onto or incorporation into poly(lactic-co-glycolic acid) (PLGA) microspheres with two different morphologies (i.e., hollow and dense), which were subsequently embedded in CPC. As controls nonembedded PLGA-microspheres were used as well as plain CPC scaffolds with RANKL adsorbed onto the surface. RANKL release and activity were evaluated by Reverse Phase High-Performance Liquid Chromatography (RP-HPLC) and osteoclast-like cells formation in cell culture experiments. Results indicated that sustained release of active RANKL can be achieved upon RANKL adsorption to PLGA microspheres, whereas inactive RANKL was released from CPC-PLGA formulations with RANKL incorporated within the microspheres or within the liquid phase of the CPC. These results demonstrate that effective loading of RANKL in injectable CPC is only possible via adsorption to PLGA microspheres, which are subsequently embedded within the CPC-matrix. (c) 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 101A: 3123-3130, 2013.

We report the results of a large single-center study evaluating predictors and outcomes after transcatheter aortic valve implantation (TAVI) with different devices and access routes according to the Valve Academic Research Consortium (VARC).The widespread adoption of TAVI warrants a systematic analysis of outcomes. Only few comprehensive data exist comparing different approaches as selected by a heart team.TAVI was performed in 326 consecutive patients (mean age 80.6 ± 7.1 years, 55.5% female) at high risk for surgery with balloon-expandable and self-expanding devices through transfemoral or transapical access. Data were analyzed according to VARC endpoints; predictors of mortality were identified.All-cause mortality was 10.1% (30 days) and 29.9% (1 year) overall and comparable with regard to valve or access choice (P = 0.295) despite different risk profiles at baseline. Device success and 30-day safety endpoints were achieved in 87.1 and 21.2%. Myocardial infarction [hazard ratio (HR) 6.52], stage-2 and -3 acute kidney injury (HR 2.52 and 6.80) and major access site complications (HR 1.96) were independent predictors of 1-year all-cause mortality. Device success had a protective effect (HR 0.58). Baseline predictors included body mass index20 kg/m(2) (HR 3.20), NYHA class IV (HR 1.87), left ventricular ejection-fraction30% (HR 2.30), higher STS-PROM scores (HR 1.05 per percent), and age (group 75-85 years, HR 0.47).Comparable results were achieved with different devices and access routes in a heart team approach. Baseline and perioperative predictors of all-cause mortality were identified, contributing to the refinement of patient and device selection criteria for TAVI.

SummaryIntroduction Anti-cardiolipin and β2-glycoprotein I antibodies represent important diagnostic parameters in routine hematology. In this study, five different automated, semi-automated, and manual immunoassays detecting IgG/IgM anti-cardiolipin and anti-β2-glycoprotein I antibodies were tested. Methods A total of 162 samples from women with a history of miscarriage were recruited from 110 different G&O outpatient centers in Germany. Results For both anti-cardiolipin and anti-β2-glycoprotein I antibodies, considerable differences in the percentage of positive results were seen between all five methods, and itemization of all positive test results revealed a poor accordance. These findings were confirmed by Cohen's kappa coefficients. Conclusion Our study revealed a moderate to poor accordance between five different test systems for anti-cardiolipin and anti-β2-glycoprotein I antibodies. Such deviations may result in clinical misinterpretation of data and may lead to wrong therapeutic consequences. Therefore, further standardization of all tests for anti-phospholipid antibodies should be achieved.

SUMMARY Objectives In this study, we studied whether the contents of the two compartments of automatically processed cord blood (CB) units are comparable with respect to cell counts and viability and therefore suitable for clinical therapy. Background CB-derived stem cells are increasingly used for allogeneic transplantation. Many centres prepare the transplants by automated methods allowing to split the product into two portions. Methods CB was collected at different sites in Germany and transported to a single centre for processing. Before and after cryopreservation laboratory analyses were performed to compare the quality of the two CB segments. Results In total, 33 products were processed [mean collection volume: 18·6 ± 1·2 mL (range 15·2–20·2 mL) segment A; mean: 4·7 ± 0·3 mL (range 4·2–5·2 mL) segment B]. CD34+ cell counts, viability of CD34+ cells and many other haematological parameters showed a good comparibility between the two segments. However, lymphocyte counts and results of clonogenic assays were significantly different between the two segments of the split product. Conclusion We conclude that the preparation of the cord blood unit by the automated process results in a homogenous distribution of stem and progenitor cells. However, our findings show that the clonogenic capacity differs between the two segments.

The major outer membrane proteins (OMPs) from Neisseria meningitidis, which are expressed at high levels, are subdivided in five classes based on molecular weight (1,2) (see Table 1). Table 1 Major Meningococcal Outer-Membrane Proteins Outer-membrane proteins Name Molecular maass Function/characteristics Class 1 PorA 44-47 kDa Porin Class 2/3 PorB 37-42 kDa Porin Class 4 Rmp Reductionmodifiableprotein, unknown Class 5 Opa 26-30 kDa Adhesion,opacity protein Opc 25 kDa Invasion, opacity protein Iron-regulated proteins Mirp 37 kDa Iron acquisition (?);majoriron-regulatedprotein FrpB 70 kDa Ferric enterobactin receptor (also FetA) Adapted from ref. (1).

Introduction: Activated Leukocyte Cell Adhesion Molecule (ALCAM/CD166) gained increasing attention regarding tumorprogression and metastatic spread in breast cancer. The aim of this study was to examine ALCAM expression levels in primary breast cancer and distant metastases of the same patient within 29 autopsy cases to better understand the underlying mechanisms of metastases and the role of adhesion molecules in this process. Material and Methods: Paraffin-embedded tissue of the primary and distant metastases (N = 84) were collected and ALCAM immunohistochemistry was performed. Results: The primary tumor and all metastases showed a statistically normally distributed ALCAM expression. ALCAM expression level average differs between immunoreactive score (IRS) (mean) 4.16 (lung)-5.00 (adrenal gland). Of the metastatic ALCAM expression levels we obtained an intra-class correlation (ICC) of 80.9%, indicating a strong cluster effect of measurements in the same patient. ALCAM expression scores in metastatic sites and in the primary analyzed by hierarchical regression analysis showed that ALCAM expression in the primary is prognostic for ALCAM expression in all different sites of metastases (slope = 0.773, p < 0.001, r2 = 0.504). Conclusion: ALCAM expression in the primary is positively correlated to ALCAM expression in metastases within one single patient. This could show a tumorbiological context of ALCAM for the development of metastases in breast cancer.

Early identification of patients at risk of space-occupying "malignant" middle cerebral artery (MCA) infarction (MMI) is needed to enable timely decision for potentially life-saving treatment such as decompressive hemicraniectomy. We tested the hypothesis that acute stroke magnetic resonance imaging (MRI) predicts MMI within 6 hours of stroke onset.In a prospective, multicenter, observational cohort study patients with acute ischemic stroke and MCA main stem occlusion were studied by MRI including diffusion-weighted imaging (DWI), perfusion imaging (PI), and MR-angiography within 6 hours of symptom onset. Multivariate regression analysis was used to identify clinical and imaging predictors of MMI.Of 140 patients included, 27 (19.3%) developed MMI. The following parameters were identified as independent predictors of MMI: larger acute DWI lesion volume (per 1 ml odds ratio [OR] 1.04, 95% confidence interval [CI] 1.02-1.06; p0.001), combined MCA + internal carotid artery occlusion (5.38, 1.55-18.68; p = 0.008), and severity of neurological deficit on admission assessed by the National Institutes of Health Stroke Scale score (per 1 point 1.16, 1.00-1.35; p = 0.053). The prespecified threshold of a DWI lesion volume82 ml predicted MMI with high specificity (0.98, 95% CI 0.94-1.00), negative predictive value (0.90, 0.83-0.94), and positive predictive value (0.88, 0.62-0.98), but sensitivity was low (0.52, 0.32-0.71).Stroke MRI on admission predicts malignant course in severe MCA stroke with high positive and negative predictive value and may help in guiding treatment decisions, such as decompressive surgery. In a subset of patients with small initial DWI lesion volumes, repeated diagnostic tests are required.

We are probing the potential of two techniques to monitor the quality of antigens in vitro. Structural and conformational differences between diphtheria toxin and toxoid are detected via biosensor analysis (BIA-core) and fluorescence spectrometry. With BIA-core the interaction kinetics between toxin and toxoid and a monoclonal antibody were established. The fluorescence properties of both antigens were determined with respect to fluorescence intensity and emission maximum as a function of guanidinium hydrochloride concentration. In all cases clear differences were found between toxin and toxoid. Antibody affinity of the toxoid was lower compared with toxin, caused by lower binding and higher release rates. Fluorescence intensity of toxoid was reduced by about 50%. Toxoid was less sensitive to guanidinium hydrochloride-induced denaturation, reflected in a diminished shift of the emission maximum.

Mit der Methode der PBC-Vektoren von HARTMAN und PERDOK wird die Gleichgewichtsform von β-Kupferphthalocyanin-Einkristallen bestimmt und mit der experimentell ermittelten Wachstumsform aus der Gasphase gezuchteter Kristalle verglichen. Es zeigt sich prinzipielle Ubereinstimmung. Die Kristalle sind von nadelformigem Habitus, die Tracht wird durch die Formen {001}, {201}, {100}, {101} und {110} gebildet. Das Langen–Breiten-Verhaltnis der Kristalle last sich durch die Variierung des Inertgasdruckes beeinflussen. Diese Abhangigkeit wird auf die Diffusion des Nahrstoffdampfes zuruckgefuhrt.

Charakteristika des Wachstums bei der Kristallzuchtung durch Sublimation/Desublimation im Inertgas haben ihre Ursache in der Diffusion des Nahrstoffes zur Wachstumsfront, Fur zwei idealisierte Grenzfalle werden die Diffusionsfelder berechnet und fur die bei praktischen Zuchtungen vorliegenden Bedingungen diskutiert. The crystal growth in the vapour phase is governed by the diffusion of the nutrient to the surface of the growing crystal. The diffusion fields are calculated for two idealized limiting cases. The conditions of the real growth process are discussed.

Bei der Zuchtung von Kupferphthalocyanin-Einkristallen aus der Gasphase bilden sich haufig Hohlformen. Diese Erscheinung erschwert bzw. verhindert vorgesehene experimentelle Studien. Untersuchungen zur Uberwindung dieser Schwierigkeiten werden beschrieben. Ursachen des Hohlwachstums sind, wie aus den Beobachtungen von Oberflachenstorungen und aus zielgerichteten Zuchtungsexperimenten hervorgeht, Wachstumsinstabilitaten, hervorgerufen durch diffusionsbedingte Inhomogenitat der Uberschreitung uber der Wachstumsfront. Durch die Einfuhrung besonderer Verfahrensweisen der Zuchtung und Wahl bestimmter Parameter gelang es, volle Kristalle groserer Abmessungen, bis zu einem Millimeter in Querrichtung, zu erhalten. Veroffentlichungen zum Hohlwachstum anderer Substanzen aus der Gasphase werden referiert. Hollow crystals are obtained frequently during the growth of copper phthalocyanine single crystals from the vapour phase. This appearance makes some physical investigations impossible. To overcome these difficulties some ways are discussed. The reasons for hollow growth are instabilities in the growth caused by diffusion controlled inhomogeneities in supersaturation on the growth front. This was found by observations of surface defects and by defined growth experiments. By introduction of special methods of growth and use of defined parameters one obtains bulk crystals of larger extent up to 1 mm in cross direction. References are given in the field of hollow crystal growth in the vapour phase of other substances.

Fur den Nachweis von Versetzungen in β-Kupferphthalocyanin-Einkristallen wurde eine Atztechnik entwickelt und angewandt. Unter Berucksichtigung des zu erwartenden Versetzungsgehaltes und der Symmetrie der Gruben werden praktisch symmetrische Gruben auf den {201}- und {001}-Flachen auf [010]-Stufenversetzungen mit (001)- bzw. (201)-Gleitebenen und unsymmetrische Gruben sowohl auf {001} als auch auf {201} auf [010]-Stufenversetzungen mit (100)- und (101)-Gleitebenen zuruckgefuhrt. Die Versetzungsdichte auf Wachstums- und Spaltflachen liegt in der Regel unter 100 cm−2. Das Auftreten von [010]-Schraubenversetzungen wurde nicht nachgewiesen, kann jedoch nicht ausgeschlossen werden. An etching technique was developed to investigate dislocations in β-copper phthalocyanine single crystals. Considering the expected content of dislocations and the etch pit symmetry the symmetric etch pits are correlated to [010]-edge dislocations on {201}- and {001}-lattice planes with (001)- and (201)-slip planes. Asymmetric etch pits on {001}- and {201}-planes are connected with [010]-edge dislocations related to (100)- and (101)-slip planes. The dislocation density on growth planes and cleavage planes is commonly lower than 100 cm−2. [010]-screw dislocations are not observed, but their existence could not be excluded.

In einer universell einsetzbaren Zuchtungsapparatur wurden die Ursachen fur die schlechte Reproduzierbarkeit und Konstanz der Wachstumsbedingungen bei einem seit 1936 bekannten Zuchtungsverfahren sowie storendes Hohlwachstum untersucht. Die Charakteristika des Wachstums in Abhangigkeit von verschiedenen Zuchtungsmethoden und Verfahrensweisen fur Keimbildung und Wachstum werden beschrieben. Die Einfuhrung neuer Zuchtmethoden ermoglicht die Herstellung groserer Kristalle. Das Wachstum der nadelformigen Kristalle ist diffusionskontrolliert, die Wachstumsform weicht qualitativ nicht von der Gleichgewichtsform ab. Die Kristalle sind von mikroskopisch glatten Flachen begrenzt, nur auf den Stirnflachen treten oberhalb bestimmter kritischer Abmessungen morphologische Storungen auf. An apparatus useful for many kinds of vapour phase growth used in order to clarify reasons for bad reproducibility and constancy of growth conditions by an growing method known since 1936 and reasons for cavity growth. The characteristics of growth are described dependent on different growing methods and on various kinds of nucleation and crystal growth. The introduction of new growing methods allows the production of larger crystals. The growth of the needle-like crystals is governed by diffusion. The shape of the crystals does not differ qualitatively from their equilibrium shape. The crystals grow with smooth surfaces. Only the front surfaces show morphological imperfections, if the crystals exceed a critical size.

A 57-year-old woman had metastatic liposarcoma of the left orbit that underwent transformation. The primary focus in the abdomen, resected in 1975, was a well-differentiated liposarcoma. Later metastases to the neck and orbit were poorly differentiated, pleomorphic, and highly anaplastic liposarcomas. The ultrasonographic and histopathologic correlations of the different stages of the tumor during the disease process were analyzed and compared. This patient's disease had echopathologic similarities to other orbital sarcomas and adult cavernous hemangiomas.

The number of cases of meningococcal disease increased in The Netherlands during the period 1982–1986. In 1986 we estimated the attack rate to be over 3/100,000 pop./year, which is still below the epidemic levels reached in 1946–1947 and in 1966. The serogroup B increased from 98 strains in 1982 to 275 strains in 1986 (an increase of 281%) and its fraction among the isolated strains rose from 47 to 77%. The B: 15:p1.16 complex was not the driving force: its share of the group B strains never exceeded 20%. Many epidemiological and clinical aspects of disease due to B: 15:p1. 16 strains were similar to those described in other countries.