Turnover and accumulation of genetic diversity across large time-scale cycles of isolation and connection of populations.

Major climatic and geological events but also population history (secondary contacts) have generated cycles of population isolation and connection of long and short periods. Recent empirical and theoretical studies suggest that fast evolutionary processes might be triggered by such events, as commonly illustrated in ecology by the adaptive radiation of cichlid fishes (isolation and reconnection of lakes and watersheds) and in epidemiology by the fast adaptation of the influenza virus (isolation and reconnection in hosts). We test whether cyclic population isolation and connection provide the raw material (standing genetic variation) for species evolution and diversification. Our analytical results demonstrate that population isolation and connection can provide, to populations, a high excess of genetic diversity compared with what is expected at equilibrium. This excess is either cyclic (high allele turnover) or cumulates with time depending on the duration of the isolation and the connection periods and the mutation rate. We show that diversification rates of animal clades are associated with specific periods of climatic cycles in the Quaternary. We finally discuss the importance of our results for macroevolutionary patterns and for the inference of population history from genomic data.

Interactions between feather-degrading bacteria and an avian host : zebra finches (Taeniopygia guttata)

Abstract: Birds harbor a variety of bacteria on their plumage, some of which can degrade feathers in vitro. Whether these keratinolytic bacteria are active on live birds and can effect feather degradation on birds is debatable. The effect of such bacteria on the body condition and behavior of birds, is unknown. Using a community of feather-degrading bacteria (EB), we investigate the interaction between the activity and load of such bacteria, on the morphology, body condition, and behavior of zebra finches (Taeniopygia guttata). In Chapter 2, we find that the elevated loads of such microbes lead to a reduction in the expression of morphological traits, such as male bill color (a sexually selected trait) and uropygial gland volume, without reducing body mass, or evoking a cellular immune response. We also suggest the presence of a carotenoid based defense response in hosts, to such elevated loads of microbes and document a sex-based difference in the source of carotenoids used for such a response. In Chapter 3, we investigated the effect of EB loads on male mate choice of zebra finches, wherein male choice of females with elevated and un-altered bacterial loads, varied with male size. We found that larger males preferred females with higher bacterial load and smaller males preferred females with lower bacterial load. Chapter 4 demonstrates that the presence of melanin in feathers reduces the growth and activity of the community of feather-degrading bacteria (EB) and that the EB community can effect feather degradation in humid conditions, without broth. Additional results also demonstrate that the EB community consists of bacteria that can attach themselves to feathers on live birds and those that can live freely on avian plumage. Finally, chapter 5 demonstrates that the self-maintenance, social and sexual behaviors of birds are implicated in the infection and horizontal transmission of bacteria. It also suggests a linked oral - faecal - genital mode of transmission of pathogens in birds. These results demonstrate that differential loads of normal flora of vertebrate hosts can effect changes in their morphology and behavior. They also shed light on the role of feather-degrading bacteria in the evolution of melanin polymorphism in birds and suggest that bacteria can be active on live birds. This thesis also highlights the importance of social and, sexual behaviors of birds, in epidemiology. Résumé: Les Oiseaux ont dans leur plumage diverses bactéries dont certaines dégradent les plumes in vitro, néanmoins. Il n'est pas clair, au vu de précédentes études, si ces bactéries kératinolytiques sont actives sur des oiseaux vivants, et si celles-ci dégradent effectivement le plumage de leur hôte, L'effet de ces bactéries sur la condition corporelle ainsi que le comportement des oiseaux n'est pas connu. A l'aide d'une communauté de bactéries dégradant les plumes (EB), non pathogènes, nous examinons les interactions entre l'activité et la charge bactérienne sur la morphologie, la condition corporelle et le comportement du diamant mandarins (Taeniopygia guttata). Dans le chapitre 2, nous montrons qu'une charge élevée de ces microbes mène à une réduction de l'expression de certains traits morphologiques, tels que la couleur du bec chez le mâle (un trait soumis à sélection sexuelle), ainsi que le volume de la glande uropygienne, sans qu'il y ait une réduction de la masse corporelle, ni déclenchement d'une réponse immune cellulaire. Nos données suggèrent la présence d'une défense chez l'hôte à des charges élevées de bactéries basée sur la présence de caroténoïdes. Nous montrons, de plus une différence liée au sexe dans la source des caroténoïdes utilisé pour cette réponse. Dans le chapitre 3 nous examinons l'influence de la charge bactérienne EB sur le choix des mâles chez le diamant mandarins. Des femelles avec une charge bactérienne normale et augmentée sont choisies par les mâles et ce choix varie avec la taille des mâles. Nous avons mis en évidence que les grands mâles préfèrent les femelles avec une charge bactérienne plus élevée. Les petits mâles préfèrent les femelles avec une charge bactérienne réduite. Le chapitre 4 démontre que la présence de mélanine dans les plumes réduit la croissance et l'activité de la communauté de bactéries dégradant le plumage (EB), et que cette communauté EB peut dégrader les plumes dans des conditions humides, sans milieu de culture liquide. De plus nous montrons que cette communauté consiste en des bactéries qui peuvent s'attacher sur les plumes d'oiseaux vivants ainsi que des bactéries libres. Pour finir nous montrons dans le chapitre 5 que la maintenance corporelle, l'interaction sociale et le comportement sexuel de ces oiseaux sont impliqués dans l'infection et la transmission horizontale de ces bactéries. Nos données suggèrent une transmission orale-fécale-génitale des pathogènes chez les oiseaux. Ces résultats montrent que des charges différentes de la flore bactérienne habituelle et non pathogène de vertébrés peuvent affecter leur morphologie et leur comportement. Ils éclaircissent également le rôle des bactéries dégradant les plumes dans l'évolution du polymorphisme mélanique chez les oiseaux et suggèrent que ces bactéries peuvent être actives sur des oiseaux vivants. Cette thèse souligne également l'importance du comportement social et sexuel des oiseaux dans l'épidémiologie.

ESCMID* guideline for the diagnosis and management of Candida diseases 2012: adults with haematological malignancies and after haematopoietic stem cell transplantation (HCT).

Fungal diseases still play a major role in morbidity and mortality in patients with haematological malignancies, including those undergoing haematopoietic stem cell transplantation. Although Aspergillus and other filamentous fungal diseases remain a major concern, Candida infections are still a major cause of mortality. This part of the ESCMID guidelines focuses on this patient population and reviews pertaining to prophylaxis, empirical/pre-emptive and targeted therapy of Candida diseases. Anti-Candida prophylaxis is only recommended for patients receiving allogeneic stem cell transplantation. The authors recognize that the recommendations would have most likely been different if the purpose would have been prevention of all fungal infections (e.g. aspergillosis). In targeted treatment of candidaemia, recommendations for treatment are available for all echinocandins, that is anidulafungin (AI), caspofungin (AI) and micafungin (AI), although a warning for resistance is expressed. Liposomal amphotericin B received a BI recommendation due to higher number of reported adverse events in the trials. Amphotericin B deoxycholate should not be used (DII); and fluconazole was rated CI because of a change in epidemiology in some areas in Europe. Removal of central venous catheters is recommended during candidaemia but if catheter retention is a clinical necessity, treatment with an echinocandin is an option (CII(t) ). In chronic disseminated candidiasis therapy, recommendations are liposomal amphotericin B for 8 weeks (AIII), fluconazole for >3 months or other azoles (BIII). Granulocyte transfusions are only an option in desperate cases of patients with Candida disease and neutropenia (CIII).

Train-the-trainer: E-learning zur Förderung einer praxisorientiertem Vermittlung von evidenzbasierter Medizin

Hintergrund: Trotz ihrer Etablierung als essentieller Bestandteil der medizinischen Weiter-/Fortbildung werden europa- wie schweizweit kaum Kurse in evidenzbasierter Medizin (ebm) angeboten, die - integriert im klinischen Alltag - gezielt Fertigkeiten in ebm vermitteln. Noch grössere Defizite finden sich bei ebm- Weiterbildungsmöglichkeiten für klinische Ausbilder (z.B. Oberärzte). Als Weiterführung eines EU-finanzierten, klinisch integrierten E-learning- Programms für Weiterbildungsassistenten (www.ebm-unity.org) entwickelte eine europäische Gruppe von medical educators gezielt für Ausbilder ein e-learning-Curriculum zur Vermittlung von ebm im Rahmen der klinischen Weiterbildung. Methode: Die Entwicklung des Curriculums umfasst folgende Schritte: Beschreibung von Lernzielen, Identifikation von klinisch relevanten Lernumgebungen, Entwicklung von Lerninhalten und exemplarischen didaktischen Strategien, zugeschnitten auf die jeweilige Lernumgebungen, Design von web-basierten Selbst-Lernsequenzen mit Möglichkeiten zur Selbstevaluation, Erstellung eines Handbuchs. Ergebnisse: Lernziele des Tutoren-Lehrgangs sind der Erwerb von Fertigkeiten zur Vermittlung der 5 klassischen ebm-Schritte: PICO- (Patient-Intervention-Comparison-Outcome)-Fragen, Literatursuche, kritische Literaturbewertung, Übertragung der Ergebnisse im eigenen Setting und Implementierung). Die Lehrbeispiele zeigen angehenden ebm-Tutoren, wie sich typische klinische Situationen wie z.B. Stationsvisite, Ambulanzsprechstunde, Journalclub, offizielle Konferenzen, Audit oder das klinische Assessment von Weiterbildungsassistenten gezielt für die Vermittlung von ebm nutzen lassen. Kurze E-Learning-Module mit exemplarischen «real-life»-Video-Clips erlauben flexibles Lernen zugeschnitten auf das knappe Zeitkontingent von Ärzten. Eine Selbst-Evaluation ermöglicht die Überprüfung der gelernten Inhalte. Die Pilotierung des Tutoren-Lehrgangs mit klinisch tätigen Tutoren sowie die Übersetzung des Moduls in weitere Sprachen sind derzeit in Vorbereitung. chlussfolgerung: Der modulare Train-the-Trainer-Kurs zur Vermittlung von ebm im klinischen Alltag schliesst eine wichtige Lücke in der Dissemination von klinischer ebm. Webbasierte Beispiele mit kurzen Sequenzen demonstrieren typische Situationen zur Vermittlung der ebm-Kernfertigkeiten und bieten medical educators wie Oberärzten einen niedrigschwelligen Einstieg in «ebm» am Krankenbett. Langfristiges Ziel ist eine europäische Qualifikation für ebm- Learning und -Teaching in der Fort- und Weiterbildung. Nach Abschluss der Evaluation steht das Curriculum interessierten Personen und Gruppen unter «not-for-profit»-Bedingungen zur Verfügung. Auskünfte erhältlich von rkunz@uhbs.ch. Finanziert durch die Europäische Kommission - Leonardo da Vinci Programme - Transfer of Innovation - Pilot Project for Lifelong Learn- ing 2007 und das Schweizerische Staatssekretariat für Bildung und Forschung.

Inferring epidemic contact structure from phylogenetic trees.

Contact structure is believed to have a large impact on epidemic spreading and consequently using networks to model such contact structure continues to gain interest in epidemiology. However, detailed knowledge of the exact contact structure underlying real epidemics is limited. Here we address the question whether the structure of the contact network leaves a detectable genetic fingerprint in the pathogen population. To this end we compare phylogenies generated by disease outbreaks in simulated populations with different types of contact networks. We find that the shape of these phylogenies strongly depends on contact structure. In particular, measures of tree imbalance allow us to quantify to what extent the contact structure underlying an epidemic deviates from a null model contact network and illustrate this in the case of random mixing. Using a phylogeny from the Swiss HIV epidemic, we show that this epidemic has a significantly more unbalanced tree than would be expected from random mixing.

The REporting of studies Conducted using Observational Routinely-collected health Data (RECORD) statement.

Routinely collected health data, obtained for administrative and clinical purposes without specific a priori research goals, are increasingly used for research. The rapid evolution and availability of these data have revealed issues not addressed by existing reporting guidelines, such as Strengthening the Reporting of Observational Studies in Epidemiology (STROBE). The REporting of studies Conducted using Observational Routinely collected health Data (RECORD) statement was created to fill these gaps. RECORD was created as an extension to the STROBE statement to address reporting items specific to observational studies using routinely collected health data. RECORD consists of a checklist of 13 items related to the title, abstract, introduction, methods, results, and discussion section of articles, and other information required for inclusion in such research reports. This document contains the checklist and explanatory and elaboration information to enhance the use of the checklist. Examples of good reporting for each RECORD checklist item are also included herein. This document, as well as the accompanying website and message board (http://www.record-statement.org), will enhance the implementation and understanding of RECORD. Through implementation of RECORD, authors, journals editors, and peer reviewers can encourage transparency of research reporting.