Patients requiring re-irradiation for recurrent glioblastoma multiforme (GBM) may benefit from individualized therapy. This study aimed to identify predictors of survival and contribute to treatment ...personalization.
In 28 patients with recurrent GBM, nine factors were analyzed for associations with survival: Main location and type of recurrence, Karnofsky performance score (KPS), age, gender, interval between primary radiotherapy and recurrence, gross total resection (GTR), equivalent dose in 2-Gy fractions (EQD2) of re-irradiation and cumulative EQD2 of primary and re-irradiation.
On univariate analyses, GTR (p=0.047), EQD2 ≥30 Gy (p=0.029) and cumulative EQD2 ≥90 Gy (p=0.023) were significantly associated with better survival; frontal location (p=0.119) and KPS 80-100% (p=0.067) showed trends. In multivariate analyses, frontal location (p=0.032) and cumulative EQD2 ≥90 Gy (p=0.038) were significant; KPS 80-100% (p=0.110) and EQD2 ≥30 Gy (p=0.083) showed trends.
Predictors of survival after re-irradiation for recurrent GBM were identified that can help when designing personalized treatments. Use of irradiation with EQD2 ≥30 Gy appeared superior to lower doses.
Glioblastoma multiforme (GBM) and the GBM variant gliosarcoma (GS) are among the tumors with the highest morbidity and mortality, providing only palliation. Stem-like glioma cells (SLGCs) are ...involved in tumor initiation, progression, therapy resistance, and relapse. The identification of general features of SLGCs could contribute to the development of more efficient therapies. Commercially available protein arrays were used to determine the cell surface signature of eight SLGC lines from GBMs, one SLGC line obtained from a xenotransplanted GBM-derived SLGC line, and three SLGC lines from GSs. By means of non-negative matrix factorization expression metaprofiles were calculated. Using the cophenetic correlation coefficient (CCC) five metaprofiles (MPs) were identified, which are characterized by specific combinations of 7-12 factors. Furthermore, the expression of several factors, that are associated with GBM prognosis, GBM subtypes, SLGC differentiation stages, or neural identity was evaluated. The investigation encompassed 24 distinct SLGC lines, four of which were derived from xenotransplanted SLGCs, and included the SLGC lines characterized by the metaprofiles. It turned out that all SLGC lines expressed the epidermal growth factor EGFR and EGFR ligands, often in the presence of additional receptor tyrosine kinases. Moreover, all SLGC lines displayed a neural signature and the IDH1 wildtype, but differed in their p53 and PTEN status. Pearson Correlation analysis identified a positive association between the pluripotency factor Sox2 and the expression of FABP7, Musashi, CD133, GFAP, but not with MGMT or Hif1α. Spherical growth, however, was positively correlated with high levels of Hif1α, CDK4, PTEN, and PDGFRβ, whereas correlations with stemness factors or MGMT (MGMT expression and promoter methylation) were low or missing. Factors highly expressed by all SLGC lines, irrespective of their degree of stemness and growth behavior, are Cathepsin-D, CD99, EMMPRIN/CD147, Intβ1, the Galectins 3 and 3b, and N-Cadherin.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The Deans’ switch is an effluent switching device based on controlling flows of carrier gas instead of mechanical valves in the analytical flow path. This technique offers high inertness and a ...wear-free operation. Recently new monolithic microfluidic devices have become available. In these devices the whole flow system is integrated into a small metal device with low thermal mass and leak-tight connections. In contrast to a mechanical valve-based system, a flow-controlled system is more difficult to calculate. Usually the Deans’ switch is used to switch one inlet to one of two outlets, by means of two auxiliary flows. However, the Deans’ switch can also be used to deliver the GC effluent with a specific split ratio to both outlets. The calculation of the split ratio of the inlet flow to the two outlets is challenging because of the asymmetries of the flow resistances. This is especially the case, if one of the outlets is a vacuum device, such as a mass spectrometer, and the other an atmospheric detector, e.g. a flame ionization detector (FID) or an olfactory (sniffing) port. The capillary flows in gas chromatography are calculated with the Hagen–Poiseuille equation of the laminar, isothermal and compressible flow in circular tubes. The flow resistances in the new microfluidic devices have to be calculated with the corresponding equation for rectangular cross-section microchannels. The Hagen–Poiseuille equation underestimates the flow to a vacuum outlet. A corrected equation originating from the theory of rarefied flows is presented. The calculation of pressures and flows of a Deans’ switch based chromatographic system is done by the solution of mass balances. A specific challenge is the consideration of the antidiffusion resistor between the two auxiliary gas lines of the Deans’ switch. A full solution for the calculation of the Deans’ switch including this restrictor is presented. Results from validation measurements are in good accordance with the developed theories. A spreadsheet-based flow calculator is part of the Supporting Information.
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BackgroundFor endovascular rescue therapy (ERT) of cerebral vasospasm (CVS) due to spontaneous subarachnoid haemorrhage (sSAH), non-compliant (NCB) and compliant (CB) balloons are used with both ...balloon types bearing the risk of vessel injury due to specific mechanical properties. Although severe delayed arterial narrowing after transluminal balloon angioplasty (TBA) for CVS has sporadically been described, valid data concerning incidence and relevance are missing. Our aim was to analyse the radiological follow-up (RFU) of differently TBA-treated arteries (CB or NCB).MethodsTwelve patients with utilisation of either NCB or CB for CVS were retrospectively analysed for clinical characteristics, ERT, functional outcome after 3 months and RFU. Compared with the initial angiogram, we classified delayed arterial narrowing as mild, moderate and severe (<30%, 30%–60%, respectively >60% calibre reduction).ResultsTwenty-three arteries were treated with CB, seven with NCB. The median first RFU was 11 months after TBA with CB and 10 after NCB. RFU was performed with catheter angiography in 18 arteries (78%) treated with CB and in five (71%) after NCB; magnetic resonance angiography was acquired in five vessels (22%) treated with CB and in two (29%) after NCB. Mild arterial narrowing was detected in three arteries (13%) after CB and in one (14%) after NCB. Moderate or severe findings were neither detected after use of CB nor NCB.ConclusionWe found no relevant delayed arterial narrowing after TBA for CVS after sSAH. Despite previous assumptions that CB provides for more dilatation in segments adjacent to CVS, we observed no disadvantages concerning long-term adverse effects. Our data support TBA as a low-risk treatment option.
Negative temperature gradients along the gas chromatographic separation column can maximize the separation capabilities for gas chromatography by peak focusing and also lead to lower elution ...temperatures. Unfortunately, so far a smooth thermal gradient over a several meters long separation column could only be realized by costly and complicated manual setups. Here we describe a simple, yet flexible method for the generation of negative thermal gradients using standard and easily exchangeable separation columns. The measurements made with a first prototype reveal promising new properties of the optimized separation process. The negative thermal gradient and the superposition of temperature programming result in a quasi-parallel separation of components each moving simultaneously near their lowered specific equilibrium temperatures through the column. Therefore, this gradient separation process is better suited for thermally labile molecules such as explosives and natural or aroma components. High-temperature GC methods also benefit from reduced elution temperatures. Even for short columns very high peak capacities can be obtained. In addition, the gradient separation is particularly beneficial for very fast separations below 1 min overall retention time. Very fast measurements of explosives prove the benefits of using negative thermal gradients. The new concept can greatly reduce the cycle time of high-resolution gas chromatography and can be integrated into hyphenated or comprehensive gas chromatography setups.
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IJS, KILJ, NUK, PNG, UL, UM
Abstract
Background
Recently, antibodies against the alpha isoform of the glial-fibrillary-acidic-protein (GFAPα) were identified in a small series of patients with encephalomyelitis. Coexisting ...autoantibodies (NMDA receptor, GAD65 antibodies) have been described in a few of these patients. We describe a patient with rapidly progressive encephalomyeloradiculitis and a combination of anti-ITPR1, anti-GFAP and anti-MOG antibodies.
Case presentation and literature review
A 44-year old caucasian woman with a flu-like prodrome presented with meningism, progressive cerebellar signs and autonomic symptoms, areflexia, quadriplegia and respiratory insufficiency. MRI showed diffuse bilateral T2w-hyperintense brain lesions in the cortex, white matter, the corpus callosum as well as a longitudinal lesion of the medulla oblongata and the entire spinal cord. Anti-ITPR1, anti-GFAP and anti-MOG antibodies were detected in cerebrospinal fluid along with lymphocytic pleocytosis. Borderline tumor of the ovary was diagnosed. Thus, the disease of the patient was deemed to be paraneoplastic. The patient was treated by surgical removal of tumor, steroids, immunoglobulins, plasma exchange and rituximab. Four months after presentation, the patient was still tetraplegic, reacted with mimic expressions to pain or touch and could phonate solitary vowels. An extensive literature research was performed.
Conclusion
Our case and the literature review illustrate that multiple glial and neuronal autoantibodies can co-occur, that points to a paraneoplastic etiology, above all ovarian teratoma or thymoma. Clinical manifestation can be a mixture of typically associated syndromes, e.g. ataxia associated with anti-ITPR1 antibodies, encephalomyelitis with anti-GFAPα antibodies and longitudinal extensive myelitis with anti-MOG antibodies.
•Estimation of retention parameters by temperature programmed measurements.•Multivariate relationship of characteristic temperature and elution temperature.•Investigation of the stationary phase ...using a simulation of gas chromatography.•Investigation of the influence of the phase ratio using simulation and measurements.•Expansion of the prediction range compared to earlier approaches.
The method development process in gas chromatography can be accelerated by suitable computer simulation tools using knowledge about the solute-column interactions described by thermodynamic retention parameters. Since retention parameters usually are determined under isothermal conditions, the presented work offers a step to estimate one of the most important retention parameters, the characteristic temperature Tchar by less laborious temperature programmed measurements.
In the first part an empirical multivariate model was introduced describing the correlation between the elution temperature Telu of a solute and its characteristic temperature Tchar. Now in the second part a simulation model of GC and available retention data from a retention database was used to investigate the correlation between Telu and Tchar for an expanded range of heating rates and initial temperatures. In addition to part I, the simulation is used to investigate the influences of different properties of the separation column such as different phase ratios and column geometries like length and diameter or various stationary phases including SLB-5 ms, SPB-50, Stabilwax, Rtx-Dioxin2, Rxi-17Sil MS, Rxi-5Sil MS, ZB-PAH-CT, DB-5 ms, Rxi-5 ms, Rtx5 and FS5ms. The fit model is valid for all investigated stationary phases. The influence of the phase ratio to the correlation could be determined. Therefore, the model was expanded to this parameter.
The expanded range of heating rates and the normalization for the system independent dimensionless heating rate required a further modification of the previously presented correlation model. The model now fits also under isothermal conditions. The results were used for estimation of the Tchar of an analyte from the elution temperature in the temperature program. The prediction performance was investigated and evaluated for 20 different temperature program conditions and at two phase ratios (β=125 and β=250). Under best conditions the estimated and the measured Tchar values show relative differences <0.5 %. With this novel model estimations for Tchar are possible at 20 °C above the initial temperature, which expands the prediction range even for low and medium retained analytes compared to earlier approaches.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
•Rapid estimation of K-centric retention parameters calculated by LSER data.•Simulations of GC separations based on K-centric parameters with 95–99 % agreement.•Simulations of GC separation based on ...LSER data with 90–95 % agreement.•Temperature model for LSER system constants in a range between 40 °C to 200 °C.•Interpretation of the LSER system constants as enthalpy and entropy.
For method development in gas chromatography, suitable computer simulations can be very helpful during the optimization process. For such computer simulations retention parameters are needed, that describe the interaction of the analytes with the stationary phase during the separation process. There are different approaches to describe such an interaction, e.g. thermodynamic models like Blumberg's distribution-centric 3-parameter model (K-centric model) or models using chemical properties like the Linear Solvation Energy Relationships (LSER).
In this work LSER models for a Rxi-17Sil MS and a Rxi-5Sil MS GC column are developed for different temperatures. The influences of the temperature to the LSER system coefficients are shown in a range between 40 and 200 °C and can be described with Clark and Glew's ABC model as fit function. A thermodynamic interpretation of the system constants is given and its contribution to enthalpy and entropy is calculated. An estimation method for the retention parameters of the K-centric model via LSER models were presented. The predicted retention parameters for a selection of 172 various compounds, such as FAMEs, PCBs and PAHs are compared to isothermal determined values. 40 measurements of temperature programmed GC separations are compared to computer simulations using the differently determined or estimated K-centric retention parameters. The mean difference (RSME) between the measured and predicted retention time is less than 8 s for both stationary phases using the isothermal retention parameters. With the LSER predicted parameters the difference is 20 s for the Rxi-5Sil MS and 38 s for the Rxi-17Sil MS. Therefore, the presented estimation method can be recommended for first method development in gas chromatography.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
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