Determination of the molecular subtypes of diffuse large B-cell lymphomas using immunohistochemistry: a case series from the Inselspital, Bern, and a critical appraisal of this determination in Switzerland

The two major subtypes of diffuse large B-cell lymphoma (DLBCL) (germinal centre B-cell - like (GCB-DLBCL) and activated B-cell - like (ABC-DLBCL)) are defined by means of gene expression profiling (GEP). Patients with GCB-DLBCL survive longer with the current standard regimen R-CHOP than patients with ABC-DLBCL. As GEP is not part of the current routine diagnostic work-up, efforts have been made to find a substitute than involves immunohistochemistry (IHC). Various algorithms achieved this with 80-90% accuracy. However, conflicting results on the appropriateness of IHC have been reported. Because it is likely that the molecular subtypes will play a role in future clinical practice, we assessed the determination of the molecular DLBCL subtypes by means of IHC at our University Hospital, and some aspects of this determination elsewhere in Switzerland. The most frequently used Hans algorithm includes three antibodies (against CD10, bcl-6 and MUM1). From records of the routine diagnostic work-up, we identified 51 of 172 (29.7%) newly diagnosed and treated DLBCL cases from 2005 until 2010 with an assigned DLBCL subtype. DLBCL subtype information was expanded by means of tissue microarray analysis. The outcome for patients with the GCB subtype was significantly better compared with those with the non-GC subtype, independent of the age-adjusted International Prognostic Index. We found a lack of standardisation in the subtype determination by means of IHC in Switzerland and significant problems of reproducibility. We conclude that the Hans algorithm performs well in our hands and that awareness of this important matter is increasing. However, outside clinical trials, vigorous efforts to standardise IHC determination are needed as DLBCL subtype-specific therapies emerge.

The COLOSS BEEBOOK Volume II: Standard methods for Apis mellifera pest and pathogen research

n recent years, declines of honey bee populations have received massive media attention worldwide, yet attempts to understand the causes have been hampered by a lack of standardisation of laboratory techniques. Published as a response to this, the COLOSS BEEBOOK is a unique collaborative venture involving 234 bee scientists from 34 countries, who have produced the definitive guide to how to carry out research on honey bees. It is hoped that these volumes will become the standards to be adopted by bee scientists worldwide. Volume II includes approximately 600 separate protocols dealing with the study of the pests and diseases of the honey bee, Apis mellifera. These cover epidemiology and surveying techniques, virus diseases, bacterial diseases such as European and American foulbrood, fungal and microsporidian diseases such as Nosema, mites such as Acarapis, Varroa and Tropilaelaps, and other pests such as the small hive beetle.

The COLOSS BEEBOOK Volume I: Standard Methods for Apis mellifera Research

In recent years, declines of honey bee populations have received massive media attention worldwide, yet attempts to understand the causes have been hampered by a lack of standardisation of laboratory techniques. Published as a response to this, the COLOSS BEEBOOK is a unique collaborative venture involving 234 bee scientists from 34 countries, who have produced the definitive guide to how to carry out research on honey bees. It is hoped that these volumes will become the standards to be adopted by bee scientists worldwide. Volume I includes approximately 1,100 separate protocols dealing with the study of the honey bee, Apis mellifera. These cover anatomy, behavioural studies, chemical ecology, breeding, genetics, instrumental insemination and queen rearing, pollination, molecular studies, statistics, toxicology and numerous other techniques

Cell therapy for intervertebral disc repair: advancing cell therapy from bench to clinics

Intervertebral disc (IVD) degeneration is a major cause of pain and disability; yet therapeutic options are limited and treatment often remains unsatisfactory. In recent years, research activities have intensified in tissue engineering and regenerative medicine, and pre-clinical studies have demonstrated encouraging results. Nonetheless, the translation of new biological therapies into clinical practice faces substantial barriers. During the symposium "Where Science meets Clinics", sponsored by the AO Foundation and held in Davos, Switzerland, from September 5-7, 2013, hurdles for translation were outlined, and ways to overcome them were discussed. With respect to cell therapy for IVD repair, it is obvious that regenerative treatment is indicated at early stages of disc degeneration, before structural changes have occurred. It is envisaged that in the near future, screening techniques and non-invasive imaging methods will be available to detect early degenerative changes. The promises of cell therapy include a sustained effect on matrix synthesis, inflammation control, and prevention of angio- and neuro-genesis. Discogenic pain, originating from "black discs" or annular injury, prevention of adjacent segment disease, and prevention of post-discectomy syndrome were identified as prospective indications for cell therapy. Before such therapy can safely and effectively be introduced into clinics, the identification of the patient population and proper standardisation of diagnostic parameters and outcome measurements are indispensable. Furthermore, open questions regarding the optimal cell type and delivery method need to be resolved in order to overcome the safety concerns implied with certain procedures. Finally, appropriate large animal models and well-designed clinical studies will be required, particularly addressing safety aspects.

Eine tragfähige Datenbrücke – Phänologische Beobachtungen im Amtsblatt des Kantons Schaffhausen 1876–1950

The international standardisation of national meteorological networks in the late nineteenth century excluded biotic and abiotic observations from the objects to be henceforth published in the yearbooks. Skilled amateurs being in charge of three meteorological stations in Canton Schaffhausen (Switzerland) and their successors managed to continuously publish phenological observations gathered in the station environment alongside with meteorological data in the official gazette of this Canton from 1876 to 1950, i.e. up to the onset of phenological network observations in Switzerland. At least ten observations are available for 51 plant and animal phenological phases. Long series were assembled (N → = 30) for 14 plant phenological observations, among them for the first flowering of snowdrop (Galanthus nivalis), of hazel (Corylus avellana), of horse chestnut (Aesculus hippocastanum), of winter rye (Secale cereale) and of grape vine (Vitis vinifera) as well as the beginning of hay, winter rye and grape harvesting. Only the bare data were published without any metadata. The quality of 10 long series (N →=60) was checked by investigating the biographical and biological background of key observers and submitting their evidence to graphical (meteorological plausibility check of outliers) and statistical verification. The long term observers, mostly schoolteachers and high school professors, had a good knowledge of botany and the quality of their observations – disregarding obvious printing errors – is surprisingly good. A number of long series (seven) was completed with applicable data from the Swiss Phenological Network up to 2011. Besides anthropogenic shifts (beginning of hay and grape harvest) there is a contrast between a global warming-related earlier flowering of snowdrop and hazel and a later occurrence of grape vine flowering.

Building up and sharing knowledge for better decision making on soil and water conservation in a changing mountain environment - the WOCAT experience

For successful implementation of any soil and water conservation (SWC) or sustainable land management practice, it is essential to have a proper understanding of the natural and human environment in which these practices are applied. This understanding should be based on comprehensive information concerning the application of the technologies and not solely on the technological details. The World Overview of Conservation Approaches and Technologies (WOCAT) is documenting and evaluating SWC practices worldwide, following a standardised methodology that facilitates exchange and comparison of experiences. Notwithstanding this standardisation, WOCAT allows flexible use of its outputs, adapted to different users and different environments. WOCAT offers a valuable tool for evaluating the strengths and weaknesses of SWC practices and their potential for application in other areas. Besides collecting a wealth of information, gaps in available information are also exposed, showing the need for more research in those fields. Several key issues for development- oriented research have been identified and are being addressed in collaboration with a research programme for mitigating syndromes of global change.

The new final Clinical Skills examination in human medicine in Switzerland: Essential steps of exam development, implementation and evaluation, and central insights from the perspective of the national Working Group

Objective: Since 2011, the new national final examination in human medicine has been implemented in Switzerland, with a structured clinical-practical part in the OSCE format. From the perspective of the national Working Group, the current article describes the essential steps in the development, implementation and evaluation of the Federal Licensing Examination Clinical Skills (FLE CS) as well as the applied quality assurance measures. Finally, central insights gained from the last years are presented. Methods: Based on the principles of action research, the FLE CS is in a constant state of further development. On the foundation of systematically documented experiences from previous years, in the Working Group, unresolved questions are discussed and resulting solution approaches are substantiated (planning), implemented in the examination (implementation) and subsequently evaluated (reflection). The presented results are the product of this iterative procedure. Results: The FLE CS is created by experts from all faculties and subject areas in a multistage process. The examination is administered in German and French on a decentralised basis and consists of twelve interdisciplinary stations per candidate. As important quality assurance measures, the national Review Board (content validation) and the meetings of the standardised patient trainers (standardisation) have proven worthwhile. The statistical analyses show good measurement reliability and support the construct validity of the examination. Among the central insights of the past years, it has been established that the consistent implementation of the principles of action research contributes to the successful further development of the examination. Conclusion: The centrally coordinated, collaborative-iterative process, incorporating experts from all faculties, makes a fundamental contribution to the quality of the FLE CS. The processes and insights presented here can be useful for others planning a similar undertaking. Keywords: national final examination, licensing examination, summative assessment, OSCE, action research

Accuracy of diagnostic testing in primary ciliary dyskinesia.

Diagnosis of primary ciliary dyskinesia (PCD) lacks a "gold standard" test and is therefore based on combinations of tests including nasal nitric oxide (nNO), high-speed video microscopy analysis (HSVMA), genotyping and transmission electron microscopy (TEM). There are few published data on the accuracy of this approach.Using prospectively collected data from 654 consecutive patients referred for PCD diagnostics we calculated sensitivity and specificity for individual and combination testing strategies. Not all patients underwent all tests.HSVMA had excellent sensitivity and specificity (100% and 93%, respectively). TEM was 100% specific, but 21% of PCD patients had normal ultrastructure. nNO (30 nL·min(-1) cut-off) had good sensitivity and specificity (91% and 96%, respectively). Simultaneous testing using HSVMA and TEM was 100% sensitive and 92% specific.In conclusion, combination testing was found to be a highly accurate approach for diagnosing PCD. HSVMA alone has excellent accuracy, but requires significant expertise, and repeated sampling or cell culture is often needed. TEM alone is specific but misses 21% of cases. nNO (≤30 nL·min(-1)) contributes well to the diagnostic process. In isolation nNO screening at this cut-off would miss ∼10% of cases, but in combination with HSVMA could reduce unnecessary further testing. Standardisation of testing between centres is a future priority.

El modelo conyugal en la ciudad de Buenos Aires de la segunda posguerra : El compañerismo de complementariedad y el impulso familiarista

El período de la posguerra se ha caracterizado por el vigor del impulso familiarista. En la Argentina éste ha sido estudiado a partir de los discursos, las políticas y las regulaciones, en función de entender las políticas públicas y las especificidades del peronismo. Pero la comprensión de esta dimensión política e institucional del impulso familiarista requiere contar con un conocimiento detallado de los patrones de comportamiento que demarcaban la normatividad social en la vida cotidiana. Justamente, este artículo describe el modelo conyugal a mediados del siglo XX con intenciones de conocer las convenciones sociales, entendidas como las pautas de conducta y los sistemas de significados, que constituían el marco de la experiencia individual. Esta descripción está organizada a partir de tres aspectos concretos del modelo conyugal: la elección matrimonial, la importancia del estado conyugal para la identidad adulta y las expectativas depositadas en el matrimonio. Para este análisis se utilizan expresiones culturales de los medios de comunicación, como las revistas y la radio, fuentes que han sido aún poco explotadas pero que resultan de especial riqueza para aproximarse al universo cultural y las convenciones con las que interpela al público masivo. Estas fuentes se articulan con otras más transitadas como estadísticas, discursos, códigos de comportamientos, memorias, etc.

Escala de inteligencia para adultos de Wechsler. Wais - III. Indice de comprensión verbal : Normas para los subtests : Vocabulario, analogías e información, para la Ciudad de La Plata edades : 16 a 24 años

En este trabajo se presentan los resultados de la investigación destinada a la estandarización de los subtests que conforman el Indice de Comprensión Verbal de la Escala Wechsler para la medida de la inteligencia del adulto, Wais-III, población general de 16 a 24 años, en la ciudad de La Plata. Este Indice, constituye un valioso instrumento de evaluación de la Comprensión Verbal, se refiere a la conceptualización, conocimientos y expresión verbal. El sujeto debe contestar a preguntas que miden conocimientos prácticos, significados de palabras, razonamiento y habilidad para expresar ideas con palabras. Está constituido por los subtests de Vocabulario, Analogías e Información. En esta oportunidad se analiza el desempeño en dichos subtests de 887 estudiantes de ambos sexos, que cursan estudios secundarios y terciarios universitarios y no universitarios. Se utilizó una modalidad colectiva de administración. A partir de las respuestas obtenidas, los análisis realizados nos permiten efectuar algunas observaciones: a) no se observan para las distintas edades, diferencias significativas por género; b) a medida que aumenta la edad se incrementan los valores promedio obtenidos en los subtests de Vocabulario y Analogías situación que no se observa en el subtest de Información

El modelo conyugal en la ciudad de Buenos Aires de la segunda posguerra : El compañerismo de complementariedad y el impulso familiarista

El período de la posguerra se ha caracterizado por el vigor del impulso familiarista. En la Argentina éste ha sido estudiado a partir de los discursos, las políticas y las regulaciones, en función de entender las políticas públicas y las especificidades del peronismo. Pero la comprensión de esta dimensión política e institucional del impulso familiarista requiere contar con un conocimiento detallado de los patrones de comportamiento que demarcaban la normatividad social en la vida cotidiana. Justamente, este artículo describe el modelo conyugal a mediados del siglo XX con intenciones de conocer las convenciones sociales, entendidas como las pautas de conducta y los sistemas de significados, que constituían el marco de la experiencia individual. Esta descripción está organizada a partir de tres aspectos concretos del modelo conyugal: la elección matrimonial, la importancia del estado conyugal para la identidad adulta y las expectativas depositadas en el matrimonio. Para este análisis se utilizan expresiones culturales de los medios de comunicación, como las revistas y la radio, fuentes que han sido aún poco explotadas pero que resultan de especial riqueza para aproximarse al universo cultural y las convenciones con las que interpela al público masivo. Estas fuentes se articulan con otras más transitadas como estadísticas, discursos, códigos de comportamientos, memorias, etc.

Escala de inteligencia para adultos de Wechsler. Wais - III. Indice de comprensión verbal : Normas para los subtests : Vocabulario, analogías e información, para la Ciudad de La Plata edades : 16 a 24 años

En este trabajo se presentan los resultados de la investigación destinada a la estandarización de los subtests que conforman el Indice de Comprensión Verbal de la Escala Wechsler para la medida de la inteligencia del adulto, Wais-III, población general de 16 a 24 años, en la ciudad de La Plata. Este Indice, constituye un valioso instrumento de evaluación de la Comprensión Verbal, se refiere a la conceptualización, conocimientos y expresión verbal. El sujeto debe contestar a preguntas que miden conocimientos prácticos, significados de palabras, razonamiento y habilidad para expresar ideas con palabras. Está constituido por los subtests de Vocabulario, Analogías e Información. En esta oportunidad se analiza el desempeño en dichos subtests de 887 estudiantes de ambos sexos, que cursan estudios secundarios y terciarios universitarios y no universitarios. Se utilizó una modalidad colectiva de administración. A partir de las respuestas obtenidas, los análisis realizados nos permiten efectuar algunas observaciones: a) no se observan para las distintas edades, diferencias significativas por género; b) a medida que aumenta la edad se incrementan los valores promedio obtenidos en los subtests de Vocabulario y Analogías situación que no se observa en el subtest de Información

Escala de inteligencia para adultos de Wechsler. Wais - III. Indice de comprensión verbal : Normas para los subtests : Vocabulario, analogías e información, para la Ciudad de La Plata edades : 16 a 24 años

En este trabajo se presentan los resultados de la investigación destinada a la estandarización de los subtests que conforman el Indice de Comprensión Verbal de la Escala Wechsler para la medida de la inteligencia del adulto, Wais-III, población general de 16 a 24 años, en la ciudad de La Plata. Este Indice, constituye un valioso instrumento de evaluación de la Comprensión Verbal, se refiere a la conceptualización, conocimientos y expresión verbal. El sujeto debe contestar a preguntas que miden conocimientos prácticos, significados de palabras, razonamiento y habilidad para expresar ideas con palabras. Está constituido por los subtests de Vocabulario, Analogías e Información. En esta oportunidad se analiza el desempeño en dichos subtests de 887 estudiantes de ambos sexos, que cursan estudios secundarios y terciarios universitarios y no universitarios. Se utilizó una modalidad colectiva de administración. A partir de las respuestas obtenidas, los análisis realizados nos permiten efectuar algunas observaciones: a) no se observan para las distintas edades, diferencias significativas por género; b) a medida que aumenta la edad se incrementan los valores promedio obtenidos en los subtests de Vocabulario y Analogías situación que no se observa en el subtest de Información

El modelo conyugal en la ciudad de Buenos Aires de la segunda posguerra : El compañerismo de complementariedad y el impulso familiarista

El período de la posguerra se ha caracterizado por el vigor del impulso familiarista. En la Argentina éste ha sido estudiado a partir de los discursos, las políticas y las regulaciones, en función de entender las políticas públicas y las especificidades del peronismo. Pero la comprensión de esta dimensión política e institucional del impulso familiarista requiere contar con un conocimiento detallado de los patrones de comportamiento que demarcaban la normatividad social en la vida cotidiana. Justamente, este artículo describe el modelo conyugal a mediados del siglo XX con intenciones de conocer las convenciones sociales, entendidas como las pautas de conducta y los sistemas de significados, que constituían el marco de la experiencia individual. Esta descripción está organizada a partir de tres aspectos concretos del modelo conyugal: la elección matrimonial, la importancia del estado conyugal para la identidad adulta y las expectativas depositadas en el matrimonio. Para este análisis se utilizan expresiones culturales de los medios de comunicación, como las revistas y la radio, fuentes que han sido aún poco explotadas pero que resultan de especial riqueza para aproximarse al universo cultural y las convenciones con las que interpela al público masivo. Estas fuentes se articulan con otras más transitadas como estadísticas, discursos, códigos de comportamientos, memorias, etc.

Reconstruction of sea-surface conditions at middle to high latitudes of the Northern Hemisphere

A new calibration database of census counts of organic-walled dinoflagellate cyst (dinocyst) assemblages has been developed from the analyses of surface sediment samples collected at middle to high latitudes of the Northern Hemisphere after standardisation of taxonomy and laboratory procedures. The database comprises 940 reference data points from the North Atlantic, Arctic and North Pacific oceans and their adjacent seas, including the Mediterranean Sea, as well as epicontinental environments such as the Estuary and Gulf of St. Lawrence, the Bering Sea and the Hudson Bay. The relative abundance of taxa was analysed to describe the distribution of assemblages. The best analogue technique was used for the reconstruction of Last Glacial Maximum (LGM) sea-surface temperature and salinity during summer and winter, in addition to sea-ice cover extent, at sites from the North Atlantic (n=63), Mediterranean Sea (n=1) and eastern North Pacific (n=1). Three of the North Atlantic cores, from the continental margin of eastern Canada, revealed a barren LGM interval, probably because of quasi-permanent sea ice. Six other cores from the Greenland and Norwegian seas were excluded from the compilation because of too sparse assemblages and poor analogue situation. At the remaining sites (n= 54), relatively close modern analogues were found for most LGM samples, which allowed reconstructions. The new LGM results are consistent with previous reconstructions based on dinocyst data, which show much cooler conditions than at present along the continental margins of Canada and Europe, but sharp gradients of increasing temperature offshore. The results also suggest low salinity and larger than present contrasts in seasonal temperatures with colder winters and more extensive sea-ice cover, whereas relatively warm conditions may have prevailed offshore in summer. From these data, we hypothesise low thermal inertia in a shallow and low-density surface water layer.