A new method to facilitate valid and consistent grading cardiac events in childhood cancer survivors using medical records

BACKGROUND Cardiac events (CEs) are among the most serious late effects following childhood cancer treatment. To establish accurate risk estimates for the occurrence of CEs it is essential that they are graded in a valid and consistent manner, especially for international studies. We therefore developed a data-extraction form and a set of flowcharts to grade CEs and tested the validity and consistency of this approach in a series of patients. METHODS The Common Terminology Criteria for Adverse Events version 3.0 and 4.0 were used to define the CEs. Forty patients were randomly selected from a cohort of 72 subjects with known CEs that had been graded by a physician for an earlier study. To establish whether the new method was valid for appropriate grading, a non-physician graded the CEs by using the new method. To evaluate consistency of the grading, the same charts were graded again by two other non-physicians, one with receiving brief introduction and one with receiving extensive training on the new method. We calculated weighted Kappa statistics to quantify inter-observer agreement. RESULTS The inter-observer agreement was 0.92 (95% CI 0.80-1.00) for validity, and 0.88 (0.79-0.98) and 0.99 (0.96-1.00) for consistency with the outcome assessors who had the brief introduction and the extensive training, respectively. CONCLUSIONS The newly developed standardized method to grade CEs using data from medical records has shown excellent validity and consistency. The study showed that the method can be correctly applied by researchers without a medical background, provided that they receive adequate training.

Combining Bottom-up and Top-down Generation of Interactive Knowledge Maps for Enterprise Search

Our research project develops an intranet search engine with concept- browsing functionality, where the user is able to navigate the conceptual level in an interactive, automatically generated knowledge map. This knowledge map visualizes tacit, implicit knowledge, extracted from the intranet, as a network of semantic concepts. Inductive and deductive methods are combined; a text ana- lytics engine extracts knowledge structures from data inductively, and the en- terprise ontology provides a backbone structure to the process deductively. In addition to performing conventional keyword search, the user can browse the semantic network of concepts and associations to find documents and data rec- ords. Also, the user can expand and edit the knowledge network directly. As a vision, we propose a knowledge-management system that provides concept- browsing, based on a knowledge warehouse layer on top of a heterogeneous knowledge base with various systems interfaces. Such a concept browser will empower knowledge workers to interact with knowledge structures.

The views of European clinicians on guidelines for long-term follow-up of childhood cancer survivors.

BACKGROUND Evidence-based guidelines are needed to guide effective long-term follow-up (LTFU) of childhood cancer survivors (CCS) at risk of late adverse effects (LAEs). We aimed to ascertain the use of LTFU guidelines throughout Europe, and seek views on the need for pan-European LTFU guidelines. PROCEDURES One expert clinician from each of 44 European countries was invited to participate in an online survey. Information was sought regarding the use and content of LTFU guidelines in the respondent's centre and country, and their views about developing pan-European LTFU guidelines. RESULTS Thirty-one countries (70%) responded, including 24 of 26 full EU countries (92%). LTFU guidelines were implemented nationally in 17 countries (55%). All guidelines included recommendations about physical LAEs, specific risk groups and frequency of surveillance, and the majority about psychosocial LAEs (70%), and healthy lifestyle promotion (65%). A minority of guidelines described recommendations about transition to age-appropriate LTFU services (22%), where LTFU should be performed (22%) and by whom (30%). Most respondents (94%) agreed on the need for pan-European LTFU guidelines, specifically including recommendations about surveillance for specific physical LAEs (97%), action to be taken if a specific LAE is detected (90%), minimum requirements for LTFU (93%), transition and health promotion (both 87%). CONCLUSIONS Guidelines are not universally used throughout Europe. However, there is strong support for developing pan-European LTFU guidelines for CCS. PanCareSurFup (www.pancare.eu) will collaborate with partners to develop such guidelines, including recommendations for hitherto relatively neglected topics, such as minimum LTFU requirements, transition and health promotion.

Genetic Engineering of Induced Pluripotent Stem Cells and Reprogramming to Motor Neurons to Elucidate Selective Motor Neuron Death in Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease, fatal within 1 to 5 years after onset of symptoms. About 3 out of 100’000 persons are diagnosed with ALS and there is still no cure available [1, 2]. 95% of all cases occur sporadically and the aetiology remains largely unknown [XXXX]. However, up to now 16 genes were identified to play a role in the development of familial ALS. One of these genes is FUS that encodes for the protein fused in sarcoma/translocated in liposarcoma (FUS/TLS). Mutations in this gene are responsible for some cases of sporadic as well as of inherited ALS [3]. FUS belongs to the family of heterogeneous nuclear ribonucleoproteins and is predicted to be involved in several cellular functions like transcription regulation [4], RNA splicing [5, 6], mRNA transport in neurons [7] and microRNA processing [8]. Aberrant accumulation of mutated FUS has been found in the cytoplasm of motor neurons from ALS patients [9]. The mislocalization of FUS is based on a mutation in the nuclear localization signal of FUS [10]. However, it is still unclear if the cytoplasmic localization of FUS leads to a toxic gain of cytoplasmic function and/or a loss of nuclear function that might be crucial in the course of ALS. The goal of this project is to characterize the impact of ALS-associated FUS mutations on in vitro differentiated motor neurons. To this end, we edit the genome of induced pluripotent stem cells (iPSC) using transcription activator-like effector nucleases (TALENs) [11,12] to create three isogenic cell lines, each carrying an ALS-associated FUS mutation (G156E, R244C and P525L). These iPSC’s will then be differentiated to motor neurons according to a recently establishe protocol (Ref Wichterle) and serve to study alterations in the transcriptome, proteome and metabolome upon the expression of ALS-associated FUS. With this approach, we hope to unravel the molecular mechanism leading to FUS-associated ALS and to provide new insight into the emerging connection between misregulation of RNA metabolism and neurodegeneration, a connection that is currently implied in a variety of additional neurological diseases, including spinocerebellar ataxia 2 (SCA-2), spinal muscular atrophy (SMA), fragile X syndrome, and myotonic dystrophy.

Genetic Engineering of Induced Pluripotent Stem Cells and Reprogramming to Motor Neurons to Elucidate Selective Motor Neuron Death in Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease, fatal within 1 to 5 years after onset of symptoms. About 3 out of 100’000 persons are diagnosed with ALS and there is still no cure available [1, 2]. 95% of all cases occur sporadically and the aetiology remains largely unknown [3]. However, up to now 16 genes were identified to play a role in the development of familial ALS. One of these genes is FUS that encodes for the protein fused in sarcoma (FUS). Mutations in this gene are responsible for some cases of sporadic as well as of inherited ALS [4]. FUS belongs to the family of heterogeneous nuclear ribonucleoproteins and is predicted to be involved in several cellular functions like transcription regulation, RNA splicing, mRNA transport in neurons and microRNA processing [5] Aberrant accumulation of mutated FUS has been found in the cytoplasm of motor neurons from ALS patients [6]. The mislocalization of FUS is based on a mutation in the nuclear localization signal of FUS [7]. However, it is still unclear if the cytoplasmic localization of FUS leads to a toxic gain of cytoplasmic function and/or a loss of nuclear function that might be crucial in the course of ALS. The goal of this project is to characterize the impact of ALS-associated FUS mutations on in vitro differentiated motor neurons. To this end, we edit the genome of induced pluripotent stem cells (iPSC) using transcription activator-like effector nucleases (TALENs) [8,9] to create three isogenic cell lines, each carrying an ALS-associated FUS mutation (G156E, R244C and P525L). These iPSC’s will then be differentiated to motor neurons according to a recently established protocol [10] and serve to study alterations in the transcriptome, proteome and metabolome upon the expression of ALS-associated FUS. With this approach, we hope to unravel the molecular mechanism leading to FUS-associated ALS and to provide new insight into the emerging connection between misregulation of RNA metabolism and neurodegeneration, a connection that is currently implied in a variety of additional neurological diseases, including spinocerebellar ataxia 2 (SCA-2), spinal muscular atrophy (SMA), fragile X syndrome, and myotonic dystrophy. [1] Cleveland, D.W. et al. (2001) Nat Rev Neurosci 2(11): 806-819 [2] Sathasivam, S. (2010) Singapore Med J 51(5): 367-372 [3] Schymick, J.C. et al. (2007) Hum Mol Genet Vol 16: 233-242 [4] Pratt, A.J. et al. (2012). Degener Neurol Neuromuscul Dis 2012(2): 1-14 [5] Lagier-Tourenne, C. Hum Mol Genet, 2010. 19(R1): p. R46-64 [6] Mochizuki, Y. et al. (2012) J Neurol Sci 323(1-2): 85-92 [7] Dormann, D. et al. (2010) EMBO J 29(16): 2841-2857 [8] Hockemeyer, D. et al. (2011) Nat Biotech 29(8): 731-734 [9] Joung, J.K. and J.D. Sander (2013) Nat Rev Mol Cell Biol 14(1): 49-55 [10]Amoroso, M.W. et al. (2013) J Neurosci 33(2): 574-586.

Accuracy of computed tomography angiography in the detection of pulmonary embolism in patients with high body weight

BACKGROUND The accuracy of CT pulmonary angiography (CTPA) in detecting or excluding pulmonary embolism has not yet been assessed in patients with high body weight (BW). METHODS This retrospective study involved CTPAs of 114 patients weighing 75-99 kg and those of 123 consecutive patients weighing 100-150 kg. Three independent blinded radiologists analyzed all examinations in randomized order. Readers' data on pulmonary emboli were compared with a composite reference standard, comprising clinical probability, reference CTPA result, additional imaging when performed and 90-day follow-up. Results in both BW groups and in two body mass index (BMI) groups (BMI <30 kg/m(2) and BMI ≥ 30 kg/m(2), i.e., non-obese and obese patients) were compared. RESULTS The prevalence of pulmonary embolism was not significantly different in the BW groups (P=1.0). The reference CTPA result was positive in 23 of 114 patients in the 75-99 kg group and in 25 of 123 patients in the ≥ 100 kg group, respectively (odds ratio, 0.991; 95% confidence interval, 0.501 to 1.957; P=1.0). No pulmonary embolism-related death or venous thromboembolism occurred during follow-up. The mean accuracy of three readers was 91.5% in the 75-99 kg group and 89.9% in the ≥ 100 kg group (odds ratio, 1.207; 95% confidence interval, 0.451 to 3.255; P=0.495), and 89.9% in non-obese patients and 91.2% in obese patients (odds ratio, 0.853; 95% confidence interval, 0.317 to 2.319; P=0.816). CONCLUSION The diagnostic accuracy of CTPA in patients weighing 75-99 kg or 100-150 kg proved not to be significantly different.

Bevezetés a színháztudományba

A 21. század eleji színházértelmezésben bizonyos súlypont-áthelyezôdéseket vehetünk észre, amelyek szerint színház jobbára ott jön létre, ahol az ember és a tárgy nem helyettesíthetô. A legtöbb nézô számára a színház nem idegen sem az igazságtól, sem a valóságtól, hanem testileg intenzív és valóságos. Amíg az új audiovizuális médiumok új virtuális realitásokat hoznak létre, addig a színházban a test és a tárgyak létének egyszerisége, jelenléte és multifunkcionalitása kelt érdeklôdést.

Phenotype and genotype in 103 patients with tricho-rhino-phalangeal syndrome.

Tricho-rhino-phalangeal syndrome (TRPS) is characterized by craniofacial and skeletal abnormalities, and subdivided in TRPS I, caused by mutations in TRPS1, and TRPS II, caused by a contiguous gene deletion affecting (amongst others) TRPS1 and EXT1. We performed a collaborative international study to delineate phenotype, natural history, variability, and genotype-phenotype correlations in more detail. We gathered information on 103 cytogenetically or molecularly confirmed affected individuals. TRPS I was present in 85 individuals (22 missense mutations, 62 other mutations), TRPS II in 14, and in 5 it remained uncertain whether TRPS1 was partially or completely deleted. Main features defining the facial phenotype include fine and sparse hair, thick and broad eyebrows, especially the medial portion, a broad nasal ridge and tip, underdeveloped nasal alae, and a broad columella. The facial manifestations in patients with TRPS I and TRPS II do not show a significant difference. In the limbs the main findings are short hands and feet, hypermobility, and a tendency for isolated metacarpals and metatarsals to be shortened. Nails of fingers and toes are typically thin and dystrophic. The radiological hallmark are the cone-shaped epiphyses and in TRPS II multiple exostoses. Osteopenia is common in both, as is reduced linear growth, both prenatally and postnatally. Variability for all findings, also within a single family, can be marked. Morbidity mostly concerns joint problems, manifesting in increased or decreased mobility, pain and in a minority an increased fracture rate. The hips can be markedly affected at a (very) young age. Intellectual disability is uncommon in TRPS I and, if present, usually mild. In TRPS II intellectual disability is present in most but not all, and again typically mild to moderate in severity. Missense mutations are located exclusively in exon 6 and 7 of TRPS1. Other mutations are located anywhere in exons 4-7. Whole gene deletions are common but have variable breakpoints. Most of the phenotype in patients with TRPS II is explained by the deletion of TRPS1 and EXT1, but haploinsufficiency of RAD21 is also likely to contribute. Genotype-phenotype studies showed that mutations located in exon 6 may have somewhat more pronounced facial characteristics and more marked shortening of hands and feet compared to mutations located elsewhere in TRPS1, but numbers are too small to allow firm conclusions.

Na 1 Nachlass Max Horkheimer, 13 - Korrespondenzen u.a. mit Familie Eder (p. I 7, 1-223)

7 Briefe zwischen Edward Mead Earle, American Committee for International Studies, Princeton N. J. und Max Horkheimer, 1940-1941; 3 Briefe zwischen Margaret Ebert und Margot von Mendelssohn, 1941, 28.08.1941; 6 Briefe zwischen C. C. Eckhardt und Max Horkheimer, 1940; 5 Briefe zwischen Kay Eckstein und Max Horkheimer, 1940; 2 Briefe zwischen George Eckstein und Max Horkheimer, 16.05.1939, 35.05.1939; 1 Brief von F. K. Eden an Max Horkheimer, 02.04.1944; 33 Briefe zwischen Leopold Eder, Frieda Eder, Ruth Eder und Max Horkheimer, 1937-1940; 2 Briefe zwischen Dale Edwards und Max Horkheimer, 16.07.1940; 1 Brief von Hedwig Ehrlich an Max Horkheimer; 1 Brief von Max Horkheimer an Albert Einstein, 20.02.1935; 1 Brief von Max Horkheimer an W. Eisemann, 02.11.1939; 1 Brief von Else Eisner an Max Horkheimer, 09.12.1935; 2 Briefe zwischen Edit Elbogen und Max Horkheimer, 24.03.1942, 26.03.1942; 1 Brief von Käte von Hirsch an Max Horkheimer, 03.08.1941; 2 Briefe von Emmy Elbogen an Margot von Mendelssohn, 1945; 2 Briefe zwischen Paul Elbogen und Max Horkheimer, 02.06.1944, 09.06.1944; 4 Briefe zwischen Norbert Elias und Max Horkheimer, 1934-1935; 1 Brief von Werner B. Ellinger an Max Horkheimer, 16.12.1937; 19 Briefe zwischen dem Emergency Committee in Aid of Displaced Foreign Scholars New York und Max Horkheimer, 1938-1944; 2 Briefe zwischen dem Emergency Rescue Committee New York und Max Horkheimer, 12.06.1941, 14.06.1941; 1 Brief von F.L. Neumann an Emhardt, 13.02.1939; 23 Briefe zwischen Alice Engel und Max Horkheimer, 1937-1941; 9 briefe zwischen Paul Doernberg, Sofie Doernberg und Max Horkheimer, 1940-1942; 3 Briefe zwischen der Hebrew Sheltering and Immigrant Aid Society New York und Max Horkheimer, 05.01.1942, 1942; 1 Brief von der Selfhelp of Emigres from Central Europe, New York an Max Horkheimer, 18.08.1941; 2 Briefe zwischen R. Weissmann und Max Horkheimer, 09.01.1941, 03.02.1941; 5 Briefe zwischen Ernst Engelberg und Max Horkheimer, 1939-1940, 07.06.1939; 1 Brief von Fritz Epstein an Max Horkheimer, 10.04.1937; 1 Brief von Erika Ermel an Max Horkheimer, 15.09.1948; 2 Briefe zwischen Max Ernst und Max Horkheimer, 23.01.1936; 4 Briefe zwischen Margot Esser und Max Horkheimer, 1935-1936; 16 Briefe zwischen Rene Etiemble und Max Horkheimer, 1936-1938; 4 Briefe zwischen L.M. Ettlinger und Max Horkheimer, 1937; 8 Briefe zwischen Walter Fabien und Max Horkheimer, 1937-1941; 1 Brief von Max Horkheimer an Henry Pratt Fairchild, 25.03.1941; 2 Briefe zwischen Marvin Farber und Max Horkheimer, 14.03.1940, 17.05.1940; 4 Briefe zwischen Walter Farley udn Max Horkheimer, 1935, 01.10.1935; 8 Briefe zwischen Alexander Farquharson und Max Horkheimer, 1935-1939;

Bibliothecae Ebraicae Graecae Florentinae sive bibliothecae Mediceo-Laurentianae catalogus : duobus tomis in unum compactus

ab Antonio Maria Biscionio digestus atque edit. ... [ [Publ. Andreas Petrus Iulianellius]]

Questiones: de paruulis Iudeorum Baptisandis: a co[m]mumi doctorum assertione dissidentes : In quibus pr[a]eter stili nitorem: rara: iucunda & grata inuenias

ab excellentiss. viro Vdalrico Zasio ... edit[a]e

Millcayac. Anuario de Ciencias Políticas y Sociales

Millcayac, Anuario de Ciencias Políticas y Sociales renueva una tradición de publicaciones anuales destinada a difundir conocimientos y resultados de investigaciones correspondientes a los diversos ámbitos del saber que se cultivan en la Facultad de Ciencias Políticas y Sociales de la Universidad Nacional de Cuyo, a través de las carreras de Ciencia Política y Administración Pública, Sociología, Comunicación Social y Trabajo Social. Es continuación del "Boletín de la Facultad de Ciencias Políticas y Sociales" (publicación periódica que apareció desde 1971 hasta 1985) y luego cambió su nombre por "Anales de la Facultad de Ciencias Políticas y Sociales" (desde 1987 hasta 1995). Entre 1995 y el año 2002 se produjo una interrupción de la publicación y reapareció esta revista se editó por primera vez en 2003 y no volvió a aparecer hasta 2009, momento en que recuperó la periodicidad anual que mantiene desde entonces.