Preliminary description and slope stability analyses of the 2008 Little Salmon lake and 2007 Mt. Steele landslides, Yukon

In August 2008, reactivation of the Little Salmon Lake landslide occurred. During this event, hundreds of conical mounds of variable size and composition formed in the deposition zone. The characteristics of these landforms are described and a potential mechanism for their formation is proposed. A preliminary slope stability analysis of the 2007 Mount Steele rock and ice avalanche was also undertaken. The orientation of very high persistence (>20 m long) structural planes (e.g., faults, joints and bedding) within bedrock in the source zone was obtained using an airborne-LiDAR digital elevation model and the software COLTOP-3D. Using these discontinuity orientation measurements, kinematic, surface wedge and simple three-dimensional distinct element slope stability analyses were performed.

Maternal age-specific risk of non-chromosomal anomalies.

OBJECTIVES: To determine the excess risk of non-chromosomal congenital anomaly (NCA) among teenage mothers and older mothers. DESIGN AND SETTING: Population-based prevalence study using data from EUROCAT congenital anomaly registers in 23 regions of Europe in 15 countries, covering a total of 1.75 million births from 2000 to 2004. PARTICIPANTS: A total of 38,958 cases of NCA that were live births, fetal deaths with gestational age > or = 20 weeks or terminations of pregnancy following prenatal diagnosis of a congenital anomaly. MAIN OUTCOME MEASURES: Prevalence of NCA according to maternal age, and relative risk (RR) of NCA and 84 standard NCA subgroups compared with mothers aged 25-29. RESULTS: The crude prevalence of all NCA was 26.5 per 1000 births in teenage mothers (<20 years), 23.8 for mothers 20-24 years, 22.5 for mothers 25-29 years, 21.5 for mothers 30-34 years, 21.4 for mothers 35-39 years and 22.6 for mothers 40-44 years. The RR adjusted for country for teenage mothers was 1.11 (95% CI 1.06-1.17); 0.99 (95% CI 0.96-1.02) for mothers 35-39; and 1.01 (95% CI 0.95-1.07) for mothers 40-44. The pattern of maternal age-related risk varied significantly between countries: France, Ireland and Portugal had higher RR for teenage mothers, Germany and Poland had higher RR for older mothers. The maternal age-specific RR varied for different NCAs. Teenage mothers were at a significantly greater risk (P < 0.01) of gastroschisis, maternal infection syndromes, tricuspid atresia, anencephalus, nervous system and digestive system anomalies while older mothers were at a significantly greater risk (P < 0.01) of fetal alcohol syndrome, encephalocele, oesophageal atresia and thanatophoric dwarfism. CONCLUSIONS: Clinical and public health interventions are needed to reduce environmental risk factors for NCA, giving special attention to young mothers among whom some risk factors are more prevalent. Reassurance can be given to older mothers that their age in itself does not confer extra risk for NCA.

Nasal immunization of mice with virus-like particles protects offspring against rotavirus diarrhea.

Rotavirus is the major cause of diarrhea among young infants in both humans and animals. Immune protection of newborns by vaccination is difficult to achieve since there is not enough time to mount an immune response before exposure to the virus. We have designed a vaccination strategy mediating transfer of neutralizing antibodies from the mother to the offspring during pregnancy and/or lactation. Adult female mice were nasally immunized with virus-like particles (VLPs) made of viral proteins VP2 and 6 (VLP2/6) or VP 2, 6, and 7 (VLP2/6/7) derived from the RF rotavirus strain in the presence or absence of cholera toxin. Both vaccines elicited serum and milk antibodies against the respective VPs. Four days after parturition, suckling pups were challenged orally with RF rotavirus. Pups from mothers immunized with VLP2/6/7 but not VLP2/6 were protected against rotavirus diarrhea, indicating that VP7 plays a key role in protection. Protection was mediated by milk rather than serum antibodies, and mucosal adjuvants were not required. In conclusion, VLPs containing VP7 administered nasally to mothers represent a promising vaccine candidate for the protection of suckling newborns against rotavirus-induced diarrhea, even in the absence of a mucosal adjuvant.

Visualizing olfactory receptor expression and localization in Drosophila.

Odor detection and discrimination by olfactory systems in vertebrates and invertebrates depend both on the selective expression of individual olfactory receptor genes in subpopulations of olfactory sensory neurons, and on the targeting of the encoded proteins to the exposed, ciliated endings of sensory dendrites. Techniques to visualize the expression and localization of olfactory receptor gene products in vivo have been essential to reveal the molecular logic of peripheral odor coding and to permit investigation of the developmental and cellular neurobiology of this sensory system. Here, we describe methods for detection of olfactory receptor transcripts and proteins in the antennal olfactory organ of the fruit fly, Drosophila melanogaster, an important genetic model organism. We include protocols both for antennal cryosections and whole-mount antennae. These methods can be adapted for detection of receptor expression in other olfactory and gustatory tissues in Drosophila, as well as in the chemosensory systems of other insects.

European cancer mortality predictions for the year 2012.

BACKGROUND: Estimating current cancer mortality figures is important for defining priorities for prevention and treatment.Materials and methods:Using logarithmic Poisson count data joinpoint models on mortality and population data from the World Health Organization database, we estimated numbers of deaths and age-standardized rates in 2012 from all cancers and selected cancer sites for the whole European Union (EU) and its six more populated countries. RESULTS: Cancer deaths in the EU in 2012 are estimated to be 1 283 101 (717 398 men and 565 703 women) corresponding to standardized overall cancer death rates of 139/100 000 men and 85/100 000 women. The fall from 2007 was 10% in men and 7% in women. In men, declines are predicted for stomach (-20%), leukemias (-11%), lung and prostate (-10%) and colorectal (-7%) cancers, and for stomach (-23%), leukemias (-12%), uterus and colorectum (-11%) and breast (-9%) in women. Almost stable rates are expected for pancreatic cancer (+2-3%) and increases for female lung cancer (+7%). Younger women show the greatest falls in breast cancer mortality rates in the EU (-17%), and declines are expected in all individual countries, except Poland. CONCLUSION: Apart for lung cancer in women and pancreatic cancer, continuing falls are expected in mortality from major cancers in the EU.

Intravitreous injection of PLGA microspheres encapsulating GDNF promotes the survival of photoreceptors in the rd1/rd1 mouse.

PURPOSE: To evaluate the potential delay of the retinal degeneration in rd1/rd1 mice using recombinant human glial cell line-derived neurotrophic factor (rhGDNF) encapsulated in poly(D,L-lactide-co-glycolide) (PLGA) microspheres. METHODS: rhGDNF-loaded PLGA microspheres were prepared using a water in oil in water (w/o/w) emulsion solvent extraction-evaporation process. In vitro, the rhGDNF release profile was assessed using radiolabeled factor. In vivo, rhGDNF microspheres, blank microspheres, or microspheres loaded with inactivated rhGDNF were injected into the vitreous of rd1/rd1 mice at postnatal day 11 (PN11). The extent of retinal degeneration was examined at PN28 using rhodopsin immunohistochemistry on whole flat-mount retinas, outer nuclear layer (ONL) cell counting on histology sections, and electroretinogram tracings. Immunohistochemical reactions for glial fibrillary acidic protein (GFAP), F4/80, and rhodopsin were performed on cryosections. RESULTS: Significant delay of rod photoreceptors degeneration was observed in mice receiving the rhGDNF-loaded microspheres compared to either untreated mice or to mice receiving blank or inactivated rhGDNF microspheres. The degeneration delay in the eyes receiving the rhGDNF microspheres was illustrated by the increased rhodopsin positive signals, the preservation of significantly higher number of cell nuclei within the ONL, and significant b-wave increase. A reduction of the subretinal glial proliferation was also observed in these treated eyes. No significant intraocular inflammatory reaction was observed after the intravitreous injection of the various microspheres. CONCLUSIONS: A single intravitreous injection of rhGDNF-loaded microspheres slows the retinal degeneration processes in rd1/rd1 mice. The use of injectable, biodegradable polymeric systems in the vitreous enables the efficient delivery of therapeutic proteins for the treatment of retinal diseases.

The early IL-4 response to Leishmania major responsible for progressive disease in BALB/c mice is subject to the control of autocrine IL-2 production and regulatory CD4+C25+ T cells

Résumé : La majorité des souches de souris de laboratoire sont résistantes à l'infection par le parasite Leishmania major (L. major). A l'opposé, les souris de la souche BALB développent une maladie évolutive. La résistance et la sensibilité sont corrélées avec l'apparition de lymphocytes T CD4+ spécifiques du parasite, Th1 (de l'anglais T helper) ou Th2 respectivement. La réponse aberrante Th2 chez les souris de la souche BALB/c dépend, au moins en partie, de façon critique de la production rapide d'IL-4 suite à l'infection. Ce pic précoce d'IL-4 est produit par une population de lymphocytes T CD4+ restreinte aux molécules du MHC de classe II, exprimant les chaînes du récepteur des cellules T Vß4-Va8. Ces lymphocytes sont spécifiques d'un épitope de l'homologue Leishmania de la molécule RACK1 des mammifères, appelée LACK. Il a été clairement démontré que l'IL-4 rapidement produite par ces cellules T CD4+ Vß4-Va8 induit la maturation Th2 responsable de la sensibilité vis-à-vis de L. major. Des expériences ont été entreprises pour étudier la régulation de cette réponse précoce d'IL-4. Dans ce travail, nous avons documenté, dans les cellules provenant des ganglions de souris sensibles infectées par L. major, une augmentation de la transcription de l'ARNm de l'IL-2 qui précède la réponse précoce d'IL-4. La neutralisation de l'IL-2 durant les premiers jours d'infection induit la maturation des cellules Thl et la résistance vis-à-vis de L. major. Ces effets de l'anticorps anti-IL-2 neutralisant sont liés à sa capacité d'interférer avec la transcription rapide d'IL-4 des cellules CD4+ réactives à l'antigène LACK. Une augmentation similaire d'IL-2 survient chez les souris résistantes C57BL/6 qui sont incapables de générer la réponse précoce d'IL-4. Cependant, la protéiné LACK induit une transcription précoce d'IL-2 uniquement chez les souris sensibles. Des expériences de reconstitution utilisant des souris C.B.-17 SCID et des cellules T CD4+ réactives à LACK provenant de souris BALB/c IL-2-~démontrent un mode d'action autocrine de l'IL-2 sur la régulation de la réponse précoce d'IL4. Par conséquent, chez les souris C57BL/6, l'absence du pic précoce d'ARNm de l'IL-4 important pour la progression de la maladie paraît liée à l'incapacité des cellules T CD4+ réactives à LACK de produire de l'IL-2. Un rôle dans le contrôle de la production précoce d'IL-4 par les cellules T régulatrices CD4+CD25+ a été investigué en déplétant in vivo cette population de cellules. La déplétion induit une élévation du pic précoce de l'ARNm de l'IL-4 dans les ganglions drainant de souris BALB/c, ainsi qu'une exacerbation du cours de la maladie avec des taux augmentés d'IL-4 dans les ganglions. La réponse rapide d'IL-2 vis-à-vis de L. major est aussi significativement augmentée chez les souris BALB/c déplétées en cellules CD4+CD25+. De plus, nous avons démontré que le transfert de 10puissance(7) cellules provenant de la rate de souris BALB/c déplétées en cellules T régulatrices CD4+CD25+ rend les souris SCID sensibles à l'infection et permet la différentiation Th2. Au contraire, les souris SCID reconstituées avec 10' cellules de la rate de souris BALB/c contrôle sont résistantes à infection par L. major et développent une réponse Thl. Chez les souris SCID reconstituées avec des cellules de rate déplétées en cellules exprimant le marqueur CD25, le traitement avec un anticorps neutralisant l'IL-4 au moment de l'infection par L. major prévient le développement de la réponse Th2 et rend ces souris résistantes à l'infection. Ces résultats démontrent que les cellules T régulatrices CD4+CD25+ jouent un rôle dans la régulation du pic précoce d'IL-4 responsable du développement cellulaire Th2 dans ce modèle d'infection. Summary Mice from most strains are resistant to infection with Leishmania major (L. major). In contrast, BALB mice develop progressive disease. Resistance and susceptibility result from parasite-specific CD4+ Thl or Th2 cells, respectively. The aberrant Th2 response in BALB/c mice depends, at least in part, upon the production of IL-4 early after infection. The CD4+ T cells responsible for this early IL-4 response to L. major express a restricted TCR repertoire (Vß4-Va8) and respond to an I-Ad-restricted epitope of the Leishmania homologue of mammalian RACK1, designated LACK. The role of these cells and the IL-4 they produce for subsequent Th2 cell development and disease progression in BALB/c mice was demonstrated. Experiments have been undertaken to study the regulation of the rapid IL-4 production to L. major. In this report, we document an IL-2 mRNA burst, preceding the reported early IL-4 response, in draining lymph nodes of susceptible mice infected with L. major. Neutralization of IL-2 during the first days of infection redirected Thl cell maturation and resistance to L. major, through interference with the rapid IL-4 transcription in LACKreactive CD4+ cells. A burst of IL-2 transcripts also occurred in infected C57BL/6 mice that do not mount an early IL-4 response. However, although the LACK protein induced IL-2 transcripts in susceptible mice, it failed to trigger this response in resistant C57BL/6 mice. Reconstitution experiments using C.B.-17 SCID mice and LACK-reactive CD4+ T cells from IL-2-/- BALB/c mice showed that triggering of the early IL-4 response required autocrine IL2. Thus, in C57BL/6 mice, the inability of LACK-reactive CD4+ T cells to express early IL-4 mRNA transcription, important for disease progression, appears due to an incapacity of these cells to produce IL-2. A role for CD4+CD25+ regulatory T cells in the control of this early IL-4 production was investigated by depleting in vivo this regulatory T cell population. Depletion induced an increase in the early burst of IL-4 mRNA in the draining lymph nodes of BALB/c mice, and exacerbated the course of disease with higher levels of IL-4 mRNA and protein in their lymph nodes. The rapid IL-2 response to L. major is also significantly enhanced in BALB/c mice depleted of CD4+CD25+ cells. We further showed that transfer of 10~ BALB/c spleen cells that were depleted of CD4+CD25+ regulatory T cells rendered SCID mice susceptible to infection and allowed Th2 differentiation while SCID mice reconstituted with 10 control BALB/c spleen cells were resistant to infection with L. major and developed a Thl response. Treatment with a mAb against IL-4 upon infection with L. major in SCID mice reconstituted with CD25-depleted spleen cells prevented the development of Th2 polarization and rendered them resistant to infection. These results demonstrate that CD4+CD25+ regulatory T cells play a role in regulating the early IL-4 mRNA and the subsequent development of a Th2 response in this model of infection.

Minerais, métaux, isotopes : recherches archéométriques sur les mines de plomb et d'argent en Valais, Suisse

RESUME Les nombreuses mines de plomb et d'argent du Valais témoignent d'une activité minière importante par le passé, sans toutefois dévoiler ni l'importance des minéralisations, ni l'ancienneté de l'exploitation. La présente recherche a pour but de comprendre pourquoi les grandes mines sont concentrées dans une région, et de déterminer la chronologie de leur exploitation. L'originalité de ce travail réside dans son interdisciplinarité, plus précisément dans l'application des méthodes minéralogiques pour résoudre une problématique historique. Afin d'évaluer les ressources minières en plomb et en argent du Valais, 57 mines et indices ont été repérés et échantillonnés. Les signatures isotopiques du Pb (74 analyses) et les compositions chimiques élémentaires (45 analyses) ont été déterminées. Les plus grandes exploitations se situent dans la nappe de Siviez-Mischabel, au Sud d'une ligne Vallée du Rhône / Val de Bagnes ainsi que dans le Lötschental. Elles sont liées, d'après leur signature isotopique de plomb, à des minéralisations d'âge calédonien (408 à 387 Ma) ou tardi-hercynien (333 à 286 Ma). À ces périodes, l'ancien continent est très lourd et subit une subsidence thermique. Des premières fractures d'extrême importance se forment. Comme il s'agit d'accidents tectoniques majeurs, des gisements de grande extension peuvent se former dans ce contexte. D'autres minéralisations se situent dans les domaines helvétiques (Massif des Aiguilles Rouges, Massif du Mont Blanc et couverture sédimentaire), couvrant une région au Nord de la Vallée du Rhône et du Val d'Entremont. D'âge post-hercynien à tardi-alpin (notons qu'il n'y a pas de minéralisations d'âge tertiaire), elles sont pour la plupart liées à des intrusions granitiques, sources de plomb juvénile. Les mines situées dans ces unités tectoniques sont nettement moins étendues que celles de la nappe de Siviez-Mischabel, ce qui permet de penser que les minéralisations correspondantes le sont également. Les périodes d'exploitation des mines peuvent être déterminées par quatre approches différentes l'archéologie minière, la lecture des textes historiques, l'étude des déchets métallurgiques et la comparaison de la signature isotopique du plomb, que l'on mesure dans un objet archéologique bien daté (monnaie, bijoux etc.), avec celles des minerais. Cette dernière méthode a été appliquée et développée dans le cadre de la présente recherche. Pour ce faire, 221 échantillons d'objet en plomb ou en argent datés entre l'Âge du Fer et le Moyen Age ont été analysés par la méthode des isotopes de plomb et comparés à environ 1800 signatures isotopiques de minerais des gisements les plus importants en Suisse et en Europe. Avant l'époque romaine et jusqu'au 1 er siècle de cette époque, le plomb provient principalement des mines de la péninsule ibérique alors en pleine activité. Un apport des mines d'Europe tempérée, notamment des Vosges, reste à confirmer. A partir du 1" siècle de notre ère, le plomb a principalement été importé en Suisse occidentale de grands centres de productions situées en Allemagne du Nord (région d'Eifel). Les mines de plomb valaisannes, notamment celles de Siviez, débutent leur exploitation en même temps, principalement pour couvrir les besoins locaux, mais également pour l'exportation jusque dans l'arc lémanique et, dans une moindre importance, au-delà. À partir du 4ème siècle, le besoin en plomb a été couvert par un apport des mines locales et par la refonte d'objets anciens. Ce changement d'approvisionnement est probablement lié aux tensions créées par les invasions germaniques durant la seconde moitié du 3' siècle ; le marché suisse n'est dès lors plus approvisionné par le nord, c'est-à-dire par la vallée du Rhin. Quant à l'argent, l'exploitation de ce métal est attestée à partir de la fin du La Tène, peu après l'apparition de ce métal dans la région valaisanne. L'échantillonnage ne couvrant pas l'époque romaine, rien n'est connu pour cette période. A partir du 5" siècle, une exploitation d'argent est de nouveau attestée. Cependant, l'exploitation d'argent des mines locales ne gagne en importance qu'à partir du Moyen Âge avec les frappes monétaires, notamment les frappes carolingiennes et épiscopales valaisannes. Les sources d'argent sont différentes selon leur utilisation : à part quelques exceptions notamment vers la fin du La Tène et au tardo-antique, les bijoux et objets de cultes ont été souvent créés à partir d'argent refondu, contrairement aux monnaies pour lesquelles l'argent provient des mines locales. On note un approvisionnement différent de ce métal pour les objets, notamment les monnaies, selon leur lieu de fabrication : on peut clairement distinguer les objets valaisans de ceux du Plateau Suisse. SUMMARY The many lead and silver mines of the Valais testify of an important mining activity in the past, without however revealing neither the importance of the mineralizations, nor the era of the exploitation. The purpose of this research is to understand why the large mines are concentrated in one region, and to determine the history of their exploitation. The uniqueness of this work lies in its interdisciplinarity, more precisely in the application of mineralogical methods to solve historical problems. In order to evaluate the lead and silver mining resources of the Valais region, 57 mines and ore deposits were located and sampled. The isotope signatures of Pb (74 analyses) and the compositions of the chemical elements (45 analyses) were determined. The largest activities are in the Siviez-Mischabel area, located in the South of the boundary formed by the Rhone, Bagnes and Lotschental valleys. According to their lead isotope signatures, they are linked to mineralizations of the Caledonian (408 to 387 my) or tardi-Hercynian (333 to 286 my) orogenies. In those times, the old continent was very heavy and underwent a thermal subsidence. First fractures of great significance were formed. Through these major tectonic events, large extended ore deposits can be formed. Other mineralizations are found in the helvetic regions situated north of the Rhone and the Entremont valley (the Aiguilles Rouges basement, Mount Blanc basement and the covering sediment). Because they are from post-hercynien to tardi-alpine age (there are no mineralizations of tertiary age), they are mainly linked to granite intrusions, the sources of juvenile lead. The mines found in these tectonic units are significantly less extensive than those of the Siviez-Mischabel area, leading to the assumption that the respective mineralizations extend accordingly. The history of exploitation of the mines can be determined by four different sources: mining archaeology, historical texts, metallurgical waste, and the comparison of the isotope signature of the lead from accurately dated archaeological objects (currency, jewels etc), with those of the ores. This last approach was applied and developed within the framework of this research. The lead isotope signatures of 221 lead or silver objects from the Iron Age to the Middle Age were compared with approximately 1800 samples of ore of the most important ore deposits in Switzerland and Europe. Before the Roman time up to the 1st century, lead comes mainly from the mines of the Iberian Peninsula then in full activity. A contribution of the mines of Central Europe, in particular of the Vosges, remains to be confirmed. From the 1st century on, lead was mainly imported into Western Switzerland from Northern Germany (Eiffel region). The lead mines in the Valais region, in particular those of Siviez, begin their exploitation at the same time, mainly to meet the local needs, but also for export to the lemanic basin and of lesser importance, beyond. As from the 4th century, the need of lead was met by the production from local mines and the recycling of old objects. This change of supply is probably related to the tensions created by the Germanic invasions during second half of the 3rd century; as a consequence, the Swiss market is not supplied any more by the north, i.e. the Rhine valley. Silver production is confirmed starting from the end of La Tene, shortly after the appearance of this metal in the Valais region. Since no objects of Roman origin were analyzed, nothing is known for this period. From the 5th century on, silver production is again confirmed. However, significant silver production from local mines starts only in the Middle Age with the coinage, in particular Carolingian and Episcopal minting from the Valais region. The sources of silver differ according to their use: besides some exceptions in particular towards the end of La Tene and the tardi-Roman, the jewels and objects of worships were often created from recycled silver, contrary to the coins the silver for which comes from the local mines. A different source of silver is observed according to the location of coin manufacture: Objects originating from the Valais region are clearly distinguished from those from the Plateau Suisse. ZUSAMMENFASSUNG Die grosse Zahl von Blei- und Silberminen im Wallis ist Zeugnis einer bedeutenden Bergbautätigkeit, es fehlen aber Hinweise über ihren Umfang und den Zeitraum ihrer Ausbeutung. Die vorliegende Arbeit sucht zu ergründen, warum grosse Minen sich in einer eng begrenzten Region häufen und in welchem Zeitraum sie genutzt wurden. Die Besonderheit der Studie liegt in ihrer Interdisziplinarität, genauer in der Anwendung von mineralogischen Methoden zur Beantwortung historischer Fragestellungen. Zur Beurteilung der Lagerstätten wurden von 57 Minen und Aufschlüssen Proben entnommen oder Nachweise erbracht und mittels 74 Isotopen-Analysen von Blei und 45 chemischen Gesamtanalysen ausgewertet. Die wichtigsten Vorkommen liegen in der Siviez- Mischabel- Decke südlich der Linie Rhonetal- Val de Bagnes, sowie im Lötschental. Die Bleiisotopen- Alter weisen ihre Entstehung der kaledonischen (408 - 387 Mio. J.) oder der spät- herzynischen (333 - 286 Mio. J.) Gebirgsbildungsphase zu. In dieser Periode ist die kompakte Landmasse sehr schwer und erfairt eine thermische Absenkung. Es bilden sich tektonische Brüche von kontinentaler Ausdehnung. Die grossen tektonischen Bewegungen ermöglichen die Bildung von ausgedehnten Lagerstätten. Andere Vorkommen finden sich im Bereich der Helvetischen Alpen (Aiguilles Rouges Massiv, Mont-Blanc-Massiv und Sediment-Decken) im Gebiet nördlich des Rhonetales bis zum Val d'Entremont. Altersmässig sind sie der nach-hercynischen bis zur spät-alpidischen Orogenese zuzuweisen (auffällig ist das Fehlen von Vorkommen im Tertiär) und haben sich meist in der Folge von Granit- Intrusion, dem Ursprung von primärem Blei ausgebildet. Die Bergwerke in diesem Bereich sind deutlich weniger ausgedehnt als jene in der Siviez-Mischabel-Decke und entsprechen wahrscheinlich dem geringen Umfang der zugehörigen Vorkommen. Die Nutzungsperioden der Minen können mit vier verschiedenen Methoden bestimmt werden: Minenarchäologie, Historische Quellen, Auswertung von metallischen Abfällen (Schlacken) und Vergleich der Bleiisotopen-Zusammensetzung von Erzen mit jener von zeitlich gut datierbaren archäologischen Gegenständen (Münzen, Schmuckstücke). Die letztere Methode wurde im Rahmen der vorliegenden Forschungsarbeit entwickelt und angewendet. Zu diesem Zweck wurden an 221 Proben von Blei- oder Silberobjekten, die in die Periode zwischen Eisenzeit und Mittelalter eingestuft werden können, Bleiisotopen- Analysen durchgeführt und mit ca. 1800 Proben aus den wichtigsten Lagerstätten der Schweiz und Europas verglichen. Vor der Römerzeit und bis ins 1. Jahrh. stammt das Blei vornehmlich aus den in jener Zeit in voller Ausbeutung begriffenen Minen der Iberischen Halbinsel. Der Beitrag von Mitteleuropa, besonders der Vogesen, muss noch bestätigt werden. Ab dem 1. Jahrh. nach Chr. wurde die Westschweiz hauptschlich mit Blei aus den grossen Produktionszentren Norddeutschlands, vorwiegend der Eifel, versorgt. In dieser Periode setzt die Ausbeutung der Bleiminen des Wallis, besonders von Siviez, ein. Sie dienen der Deckung des örtlichen Bedarfs aber auch der Ausfuhr in das Gebiet des Genfersees und in einem bescheidenen Rahmen sogar darüber hinaus. Ab dem 4. Jahrhundert wurden vermehrt alte Objekte eingeschmolzen. Dieser Wechsel der Versorgungsquellen war vermutlich eine Folge der Wölkerwanderung in der zweiten Hälfte des 3. Jahrhunderts. Ab diesem Zeitpunkt war Helvetien der Zugang zu den Versorgungsquellen des Nordens, besonders des Rheinlandes, verwehrt. Der Abbau von Silber ist ab dem Ende des La Tène nachgewiesen, nur wenig nach dem Auftreten dieses Metalls im Wallis. Über die Römerzeit können wegen dem Fehlen entsprechender Proben keine Aussagen gemacht werden. Eine erneute Abbauperiode ist ab dem 5. Jahrhundert nachgewiesen. Die Produktion der örtlichen Minen erreicht aber erst im Mittelalter eine gewisse Bedeutung mit der Prägung von Mnzen durch die Karolinger und die Walliser Bischöfe. Die Herkunft des Silbers ist abhängig von dessen Verwendung. Mit wenigen Ausnahmen in der Zeit des La Tène und der späteren Römerzeit wurde für Kunst- und Kult- Gegenstände rezykliertes Silber verwendet, für Münzprägungen neues Silber aus den örtlichen Minen. Von Einfluss auf die Herkunft war auch der Produktionsstandort: Die Objekte aus dem Wallis unterscheiden sich deutlich von jenen des Mittellandes.

Dental service utilization by Europeans aged 50 plus.

OBJECTIVES: To describe variations in the utilization of dental services by persons aged 50+ from 14 European countries and to identify the extent to which such variations are attributable to differences in oral health need and in accessibility of dental care. METHODS: We use data from the Survey of Health, Ageing, and Retirement in Europe (SHARE Waves 2 and 3) and estimate a series of multivariate logistic regression models to analyze variations in dental service utilization (overall dental attendance, preventive treatment and/or operative treatment, dental attendance in early life years) RESULTS: Overall dental attendance and incidence of solely preventive treatment are comparatively high in the Netherlands, Sweden, Denmark, Germany, and Switzerland. In contrast, overall dental attendance is relatively low in Spain, Italy, France, Greece, Poland, and Ireland. Moreover, a high incidence of solely operative treatment is observed in Austria, Italy, and France, whereas in the Netherlands, Sweden, Denmark, Switzerland, and Ireland, the incidence of solely operative treatment is comparably low. By and large, these variations persist even when controlling for cross-country differences in oral health need and in accessibility of dental care. CONCLUSIONS: In comparison with other European regions, there is a tendency toward more frequent and preventive dental treatment of the elderly populations residing in Scandinavia and Western Europe. Such utilization patterns appear only partially attributable to differences in need for and accessibility of dental care.

Trends in motor vehicle crash mortality in Europe, 1980-2007.

Recent trends (1980-2007) in mortality from road traffic crashes in European countries, and, for comparative purposes, in the USA and Japan were reviewed. Data came from the World Health Organisation database. Age-standardised rates, at all ages and at 15-24, 25-64, >=65 years, were computed. Joinpoint regression analyses to evaluate significant changes in trends were performed. In the European Union as a whole rates declined from 20.2 in 1987 to 13.5/100,000 in 2007 in men, and from 6.3 to 3.7/100,000 in women; European Union rates remained lower than USA, but higher than Japanese ones. In 2007, the highest male rates were in Lithuania (36.7/100,000), the Russian Federation (35.2), Ukraine (29.8), and Latvia (28.5), and the lowest ones in the Netherlands (6.2) and Sweden (6.9); the highest female rates were in the Russian Federation (11.3), Lithuania (9.7), Belarus, Latvia, and Ukraine (around 8), and the lowest ones in Switzerland (1.7), the UK, and Nordic countries (around 2). Mortality from motor vehicle crashes declined in northern and western European countries and - though to a lesser extent - in southern European countries, too. Mortality trends were also favourable in the Czech Republic and Poland since the mid 1990's, whereas they were still upwards in Romania and the Russian Federation. No trend was observed in Hungary and Ukraine. Trends were consistent in various age groups considered. Thus, additional urgent and integrated intervention is required to prevent avoidable deaths from motor vehicle crashes, particularly in selected central and eastern European countries.

JC virus-specific immune responses in human immunodeficiency virus type 1 patients with progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) is a frequently fatal disease caused by uncontrolled polyomavirus JC (JCV) in severely immunodeficient patients. We investigated the JCV-specific cellular and humoral immunity in the Swiss HIV Cohort Study. We identified PML cases (n = 29), as well as three matched controls per case (n = 87), with prospectively cryopreserved peripheral blood mononuclear cells and plasma at diagnosis. Nested controls were matched according to age, gender, CD4(+) T-cell count, and decline. Survivors (n = 18) were defined as being alive for >1 year after diagnosis. Using gamma interferon enzyme-linked immunospot assays, we found that JCV-specific T-cell responses were lower in nonsurvivors than in their matched controls (P = 0.08), which was highly significant for laboratory- and histologically confirmed PML cases (P = 0.004). No difference was found between PML survivors and controls or for cytomegalovirus-specific T-cell responses. PML survivors showed significant increases in JCV-specific T cells (P = 0.04) and immunoglobulin G (IgG) responses (P = 0.005). IgG responses in survivors were positively correlated with CD4(+) T-cell counts (P = 0.049) and negatively with human immunodeficiency virus RNA loads (P = 0.03). We conclude that PML nonsurvivors had selectively impaired JCV-specific T-cell responses compared to CD4(+) T-cell-matched controls and failed to mount JCV-specific antibody responses. JCV-specific T-cell and IgG responses may serve as prognostic markers for patients at risk.

Antigenicity and immunogenicity of Melan-A/MART-1 derived peptides as targets for tumor reactive CTL in human melanoma.

Some cancer patients mount spontaneous T- and B-cell responses against their tumor cells. Autologous tumor reactive CD8 cytolytic T lymphocyte (CTL) and CD4 T-cell clones as well as antibodies from these patients have been used for the identification of genes encoding the target antigens. This knowledge opened the way for new approaches to the immunotherapy of cancer. In this review, we describe the characterization of the structure-function properties of the melanocyte/melanoma tumor antigen Melan-A/MART-1, the assessment of the T-cell repertoire available against this antigen in healthy individuals, and the analysis of naturally acquired and/or vaccine-induced CTL responses to this antigen in patients with metastatic melanoma.

Synergistic and antagonistic interaction between different branches of the immune system is related to melanin-based coloration in nestling tawny owls.

When exposed to parasites, hosts often mount energetically expensive immune responses, and this may alter resource allocation between competing life history traits including other components of the immune system. Here, we investigated whether a humoral immune challenge towards a vaccine reduces or enhances the cutaneous immune responses towards an injection of lipopolysaccharid (LPS, innate immunity) and phytohaemagglutinin (PHA, T-cell immunity) in nestling tawny owls in interaction with the degree of plumage melanin-based coloration. The humoral immune challenge enhanced the response to LPS similarly in differently coloured nestlings. In contrast, the same humoral immune challenge enhanced immune response to PHA in dark reddish melanic nestlings while reducing it in pale reddish melanic nestlings. Our results highlight that both antagonistic and synergistic interactions can take place among branches of immune system, and that the sign and magnitude of these interactions can vary with immune responses involved and the degree of melanin-based coloration.

Regulation of innate immunity by signaling pathways emerging from the endoplasmic reticulum.

The innate immune system has evolved the capacity to detect specific pathogens and to interrogate cell and tissue integrity in order to mount an appropriate immune response. Loss of homeostasis in the endoplasmic reticulum (ER) triggers the ER-stress response, a hallmark of many inflammatory and infectious diseases. The IRE1/XBP1 branch of the ER-stress signaling pathway has been recently shown to regulate and be regulated by innate immune signaling pathways in both the presence and absence of ER-stress. By contrast, innate immune pathways negatively affect the activation of two other branches of the ER-stress response as evidenced by reduced expression of the pro-apoptotic transcription factor CHOP. Here we will discuss how innate immune pathways and ER-signaling intersect to regulate the intensity and duration of innate immune responses.

Religion in Times of Crisis

Religion is alive and well all over the world, especially in times of personal, political, and social crisis. Even in Europe, long regarded the most "secular" continent, religion has taken centre stage in how people respond to the crises associated with modernity, or how they interact with the nation-state. In this book, scholars working in and on Europe offer fresh perspectives on how religion provides answers to existential crisis, how crisis increases the salience of religious identities and cultural polarization, and how religion is contributing to changes in the modern world in Europe and beyond. Cases from Poland to Pakistan and from Ireland to Zimbabwe, among others, demonstrate the complexity and ambivalence of religion's role in the contemporary world.