Berwald spacetimes and very special relativity

In this work we study Berwald spacetimes and their vacuum dynamics, where the latter are based on a Finsler generalization of the Einstein's equations derived from an action on the unit tangent bundle. In particular, we consider a specific class of spacetimes which are non-flat generalizations of the very special relativity (VSR) line element, to which we refer as very general relativity (VGR). We derive necessary and sufficient conditions for the VGR line element to be of Berwald type. We present two novel examples with the corresponding vacuum field equations: a Finslerian generalization of vanishing scalar invariant (VSI) spacetimes in Einstein's gravity as well as the most general homogeneous and isotropic VGR spacetime.Comment: 17 pages, example section updated, journal references adde

Successful long-term outcome after renal transplantation in a patient with atypical haemolytic uremic syndrome with combined membrane cofactor protein CD46 and complement factor I mutations

Background: Atypical haemolytic uremic syndrome (aHUS) is often associated with a high risk of disease recurrence and subsequent graft loss after isolated renal transplantation. Evidence-based recommendations for a mutation-based management after renal transplantation in aHUS caused by a combined mutation with complement factor I (CFI) and membrane cofactor protein CD46 (MCP) are limited. Case-diagnosis/Treatment: We describe a 9-year-old boy with a first manifestation of aHUS at the age of 9months carrying combined heterozygous mutations in the CFI and MCP genes. At the age of 5years, he underwent isolated cadaveric renal transplantation. Fresh frozen plasma was administered during and after transplantation, tapered and finally stopped after 3years. Conclusions: During the 5-year follow-up after transplantation there have been no signs of aHUS recurrence and graft function has remained good. The combination of heterozygous MCP and CFI mutations with aHUS might have a positive impact on the post-transplant course, possibly predicting a lower risk of aHUS recurrence after an isolated cadaveric renal transplantatio

Evaluationsbericht ARIADNEmed: Ergebnisse zur Pilotphase des Mentoring-Programms für Nachwuchswissenschaftlerinnen an der Medizinischen Fakultät der Friedrich-Alexander-Universität Erlangen-Nürnberg

"Der vorliegende Bericht stellt die Ergebnisse der Evaluation der Pilotphase des ARIADNEmed-Mentoring-Programms der Medizinischen Fakultät der Friedrich-Alexander-Universität Erlangen-Nürnberg vor. Dieses erste Mentoring-Programm für promovierte Wissenschaftlerinnen an der Medizinischen Fakultät begann am 24. Juni 2008 mit einer Einführungsveranstaltung. Seitdem begleiteten 47 habilitierte WissenschaftlerInnen und ProfessorInnen insgesamt 48 Nachwuchswissenschaftlerinnen aus verschiedenen Bereichen der Medizinischen Fakultät auf deren Weg in Richtung Habilitation, unterstützt von einem Rahmenprogramm, das die Mentoringpartnerbeziehungen begleitete und sie optimieren sollte. Die Abschlussveranstaltung der Pilotphase fand am 30. November 2009 statt. Die nachfolgenden Ausführungen geben einen Einblick in das Programm und seine Ausgestaltung. Im Mittelpunkt steht allerdings die Darstellung der Ergebnisse dreier Befragungen aller 95 Beteiligten zum Rahmenprogramm und zur eingegangenen Mentoringbeziehung sowie zu ihren Erwartungen an das Programm und zu ihrer Bewertung der Realisierung des Programms." (Textauszug

Sequential anti-cytomegalovirus response monitoring may allow prediction of cytomegalovirus reactivation after allogeneic stem cell transplantation

Background: Reconstitution of cytomegalovirus-specific CD3+CD8+ T cells (CMV-CTLs) after allogeneic hematopoietic stem cell transplantation (HSCT) is necessary to bring cytomegalovirus (CMV) reactivation under control. However, the parameters determining protective CMV-CTL reconstitution remain unclear to date. Design and Methods: In a prospective tri-center study, CMV-CTL reconstitution was analyzed in the peripheral blood from 278 patients during the year following HSCT using 7 commercially available tetrameric HLA-CMV epitope complexes. All patients included could be monitored with at least CMV-specific tetramer. Results: CMV-CTL reconstitution was detected in 198 patients (71%) after allogeneic HSCT. Most importantly, reconstitution with 1 CMV-CTL per µl blood between day +50 and day +75 post-HSCT discriminated between patients with and without CMV reactivation in the R+/D+ patient group, independent of the CMV-epitope recognized. In addition, CMV-CTLs expanded more daramtaically in patients experiencing only one CMV-reactivation than those without or those with multiple CMV reactivations. Monitoring using at least 2 tetramers was possible in 63% (n = 176) of the patients. The combinations of particular HLA molecules influenced the numbers of CMV-CTLs detected. The highest CMV-CTL count obtained for an individual tetramer also changed over time in 11% of these patients (n = 19) resulting in higher levels of HLA-B*0801 (IE-1) recognizing CMV-CTLs in 14 patients. Conclusions: Our results indicate that 1 CMV-CTL per µl blood between day +50 to +75 marks the beginning of an immune response against CMV in the R+/D+ group. Detection of CMV-CTL expansion thereafter indicates successful resolution of the CMV reactivation. Thus, sequential monitoring of CMV-CTL reconstitution can be used to predict patients at risk for recurrent CMV reactivation

THOC5, a member of the mRNA export complex, contributes to processing of a subset of wingless/integrated (Wnt) target mRNAs and integrity of the gut epithelial barrier

THO (Suppressors of the transcriptional defects of hpr1 delta by overexpression) complex 5 (THOC5), an mRNA export protein, is involved in the expression of only 1% of all genes. Using an interferon inducible knockout mouse system, we have previously shown that THOC5 is an essential element in the maintenance of hematopoietic stem cells and cytokine-mediated hematopoiesis in adult mice. Here we interrogate THOC5 function in cell differentiation beyond the hematopoietic system and study pathological changes caused by THOC5 deficiency. To examine whether THOC5 plays a role in general differentiation processes, we generated tamoxifen inducible THOC5 knockout mice. We show here that the depletion of THOC5 impaired not only hematopoietic differentiation, but also differentiation and self renewal of the gut epithelium. Depletion of the THOC5 gene did not cause pathological alterations in liver or kidney.We further show that THOC5 is indispensable for processing of mRNAs induced by Wnt (wingless/integrated) signaling which play key roles in epithelial cell differentiation/proliferation. A subset of Wnt target mRNAs, SRY-box containing gene 9 (Sox9), and achaete-scute complex homolog 2 (Ascl2), but not Fibronectin 1 (Fn1), were down-regulated in THOC5 knockout intestinal cells. The down-regulated Wnt target mRNAs were able to bind to THOC5. Furthermore, pathological alterations in the gastrointestinal tract induced translocation of intestinal bacteria and caused sepsis in mice. The bacteria translocation may cause Toll-like receptor activation. We identified one of the Toll-like receptor inducible genes, prostaglandin-endoperoxidase synthase 2 (Ptgs2 or COX2) transcript as THOC5 target mRNA. THOC5 is indispensable for processing of only a subset of mRNAs, but plays a key role in processing of mRNAs inducible by Wnt signals. Furthermore, THOC5 is dispensable for general mRNA export in terminally differentiated organs, indicating that multiple mRNA export pathways exist. These data imply that THOC5 may be a useful tool for studying intestinal stem cells, for modifying the differentiation processes and for cancer therapy

Aplicación de protocolo de entrenamiento en pacientes con enfermedad pulmonar obstructiva crónica en atención primaria y cómo influye en la tolerancia al ejercicio, disnea, Vef1 y calidad de vida relacionada con la salud.

Tesis (Kinesiólogo)El objetivo de este estudio ha sido elaborar un protocolo de RR de fácil implementación, para pacientes con diagnostico médico de EPOC y evidenciar si genera cambios significativos posterior a el entrenamiento, en la CVRS, VEF1, Disnea y tolerancia al ejercicio. Permitiendo su reproductibilidad en los demás centros de atención primaria. Pacientes y método: Se realizó un estudio aplicado a 14 pacientes, 7 hombres (edad media 74, 14 ± 7,22 años) y 7 mujeres (edad media 67,71 ± 10,67 años) pertenecientes al CESFAM Baron. Previo al entrenamiento se educó a los pacientes mediante una charla, además se efectuó una medición de la tolerancia al ejercicio mediante la PM6M, CVRS por medio del CRQ y VEF1 a través de la espirometría. Resultados: La intervención sobre estos pacientes modificó significativamente la PM6M (p < 0,05), la disnea (p< 0,05) y la CVRS excepto en su variable de control de la enfermedad, al igual que en el VEF1 donde no se obtuvieron diferencias significativas. Conclusiones: Los resultados de este trabajo indican que la intervención sobre los pacientes con diagnostico médico de EPOC, por medio de un entrenamiento físico, provoca cambios significativos en la mayoría de las variables realizadas y demuestra que el entrenamiento físico es beneficioso para la salud de los pacientes con EPOC.The aim of this study was to develop a protocol of RR for easy implementation to patients with medical diagnosis of COPO and make us clear if the patient creates significant changes after training in HRQL, FEV1 dyspnea and exercise tolerance. Allowing their reproducibility in other primary care centers. Patients and methods: A study applied to 14 patients, 7 men (mean age 74, 14 ± 7,22 years) and 7 women (mean age 67,71 ± 10,67 years) witch belong s to CESFAM Baron, prior to training patients were educated by a talk and almost taking place a measure of tolerance to exercise by the 6MWT, HRQL using the CRQ and FEV1 by spirometry. Results: The intervention in these patients change significantly the 6MWT (p <O.OS), dyspnea (p <O.OS) and HRQL except in its variable disease control, as in FEV1 where were not found significant differences. Conclusions: The results of this study indicate that the intervention on patients with medical diagnosis of COPO, passing through physical training, causes significant changes in most of the variables made and it shows that exercise training is beneficia! for health patients with COPO

BendaEAM versus BEAM as conditioning regimen for ASCT in patients with relapsed lymphoma (BEB): a multicentre, randomised, phase 2 trial.

BACKGROUND Replacement of carmustine (BCNU) in the BEAM regimen (BCNU, etoposide, cytarabine, melphalan) with bendamustine (BendaEAM) before autologous stem cell transplantation (ASCT) is feasible in lymphoma. However, randomised trials are lacking. Here, we present the first trial addressing this topic. METHODS This multicentre, randomised, phase 2 study (BEB-trial) conducted at four haematological centres in Austria and Switzerland compares BEAM with BendaEAM in patients with relapsed lymphoma. Both regimens were administered intravenously before ASCT, in BEAM according to the standard protocol (300 mg/m2 BCNU on day -6), in BendaEAM, BCNU was replaced by 200 mg/m2 bendamustine given on days -7 and -6. Eligible patients were aged 18-75 years and had mantle cell lymphoma, diffuse large B-cell lymphoma, or follicular lymphoma in first or second remission or chemosensitive relapse. The primary endpoint of the study was to evaluate whether replacement of BCNU by bendamustine reduces lung toxicity, defined as a decrease of the diffusion capacity of the lung for carbon monoxide by at least 20% at three months after ASCT. Data analyses were performed on an intention-to-treat basis. This study is registered with ClinicalTrials.gov, number NCT02278796, and is complete. FINDINGS Between April 20, 2015, and November 28, 2018, 108 patients were enrolled; of whom 53 were randomly assigned to receive BendaEAM (36 male, 17 female) and 55 to receive BEAM (39 male, 16 female). All patients engrafted rapidly. Lung toxicity did not differ between groups (BendaEAM: n = 8, 19.5%; BEAM: n = 11, 25.6%; risk difference = -6.1%: 95% confidence interval: -23.9% to 11.7%). Acute toxicities of at least grade 3 were comparable in both groups (BendaEAM: 35.8%, BEAM: 30.9%). Overall survival (BendaEAM: 92.5%, BEAM: 89.1%) and complete remission (BendaEAM: 76.7%, BEAM: 74.3%) after 1 year (median follow-up: 369 days) were similar. No difference in quality of life was observed. INTERPRETATION Results were similar for both regimens in terms of survival and response rates. A phase 3 non-inferiority study is required to investigate whether BendaEAM can be considered as an alternative to BEAM. FUNDING Mundipharma

Caracterizacion de cuerpos en verde precursores de materiales porosos de cordierita conformados por consolidacion termica de almidones nativos

En este trabajo se presenta una parte de los resultados obtenidos en el marco de un proyecto de cooperación internacional en el que se estudian materiales porosos a base de cordierita obtenidos por consoli-dación térmica de suspensiones cerámicas con diferentes almidones nativos, en particular, aquéllos relacionados a la caracterización de los compactos en verde. Para la obtención del material de cordierita se partió de una mezcla precursora de caolín, talco y alúmina, y como agente consolidante/ligante y formador de poros a alta temperatura se emplean: almidones nativos de papa, maíz o tapioca. La caracteriza-ción de los materiales en verde se llevó a cabo por medidas de densi-dad y porosidad, análisis microestructural y evaluación del comporta-miento mecánico. En base a la información obtenida, se concluyó que el almidón con mejor comportamiento global es el de papa.Fil: Lambertini, A.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mar del Plata. Instituto de Investigación En Ciencia y Tecnología de Materiales (i); Argentina. Universidad Nacional de Mar del Plata. Facultad de Ingeniería; ArgentinaFil: Sandoval, María Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mar del Plata. Instituto de Investigación En Ciencia y Tecnología de Materiales (i); Argentina. Universidad Nacional de Mar del Plata. Facultad de Ingeniería; ArgentinaFil: Talou, Mariano Hernán. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mar del Plata. Instituto de Investigación En Ciencia y Tecnología de Materiales (i); Argentina. Universidad Nacional de Mar del Plata. Facultad de Ingeniería; ArgentinaFil: Tomba Martinez, Analia Gladys. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mar del Plata. Instituto de Investigación En Ciencia y Tecnología de Materiales (i); Argentina. Universidad Nacional de Mar del Plata. Facultad de Ingeniería; ArgentinaFil: Camerucci, Maria Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mar del Plata. Instituto de Investigación En Ciencia y Tecnología de Materiales (i); Argentina. Universidad Nacional de Mar del Plata. Facultad de Ingeniería; ArgentinaFil: Gregorová, E.. Institute of Chemical Technology; República ChecaFil: Pabst, W.. Institute of Chemical Technology; República Chec

AgeWell.de – study protocol of a pragmatic multi-center cluster-randomized controlled prevention trial against cognitive decline in older primary care patients

Background: In the absence of treatment options, the WHO emphasizes the identification of effective prevention strategies as a key element to counteract the dementia epidemic. Regarding the complex nature of dementia, trials simultaneously targeting multiple risk factors should be particularly effective for prevention. So far, however, only few such multi-component trials have been launched, but yielding promising results. In Germany, comparable initiatives are lacking, and translation of these complex interventions into routine care was not yet done. Therefore, AgeWell.de will be conducted as the first multi-component prevention trial in Germany which is closely linked to the primary care setting. Methods: AgeWell.de will be designed as a multi-centric, cluster-randomized controlled multi-component prevention trial. Participants will be older community-dwelling general practitioner (GP) patients (60–77 years; n = 1,152) with increased dementia risk according to CAIDE (Cardiovascular Risk Factors, Aging, and Incidence of Dementia) Dementia Risk Score. Recruitment will take place at 5 study sites across Germany. GP practices will be randomized to either intervention A (advanced) or B (basic). GPs will be blinded to their respective group assignment, as will be the statistician conducting the randomization. The multi-component intervention (A) includes nutritional counseling, physical activity, cognitive training, optimization of medication, management of vascular risk factors, social activity, and, if necessary, further specific interventions targeting grief and depression. Intervention B includes general health advice on the intervention components and GP treatment as usual. We hypothesize that over the 2-year follow-up period the intervention group A will benefit significantly from the intervention program in terms of preserved cognitive function/delayed cognitive decline (primary outcome), and other relevant (secondary) outcomes (e.g. quality of life, social activities, depressive symptomatology, cost-effectiveness). Discussion: AgeWell.de will be the first multi-component trial targeting risk of cognitive decline in older adults in Germany. Compared to previous trials, AgeWell.de covers an even broader set of interventions suggested to be beneficial for the intended outcomes. The findings will add substantial knowledge on modifiable lifestyle factors to prevent or delay cognitive decline. Trial registration: German Clinical Trials Register (reference number: DRKS00013555)