Second non-breast primary cancer following adjuvant therapy for early breast cancer: a report from the International Breast Cancer Study Group.

The incidence of second non-breast primary cancer following adjuvant treatment was evaluated using data from patients enrolled from 1978 to 1999 in four International Breast Cancer Study Group (IBCSG) trials. The occurrence of these tumours as sites of the first failure was assessed separately for two treatment comparisons: toremifene versus tamoxifen for 5 years in 1035 patients in IBCSG Trials 12-93 and 14-93 with a median follow-up of 8 years and endocrine therapy (toremifene or tamoxifen) versus chemo-endocrine therapy (CMF or AC plus toremifene or tamoxifen) in 1731 patients from IBCSG Trials III, VII and 12-93, with a combined median follow-up of 14 years. No significant differences in second non-breast primary tumours were observed in either comparison. In particular, the incidences of second primary uterine tumours with toremifene and tamoxifen were similar and no significant increase of secondary leukaemias was observed with chemo-endocrine therapy compared with endocrine therapy.

Hyperhidrosis: a new and often early symptom in Fabry disease. International experience and data from the Fabry Outcome Survey.

Hypohidrosis is a classic feature of Fabry disease; in contrast, hyperhidrosis has only been rarely described. The aim of the study is to characterise the baseline descriptive data on hyperhidrosis (frequency, age at onset, sex ratio and outcome with and without enzyme replacement therapy) in hemizygous male and heterozygous female patients with Fabry disease. We describe case histories of five patients with Fabry disease and hyperhidrosis seen at three different centres. We have also analysed a cohort of 21 paediatric patients in the UK and a large European cohort of patients enrolled in the Fabry Outcome Survey (FOS). Five patients (three female, two male) with hyperhidrosis were originally identified, although each had additional symptoms related to Fabry disease. The age at onset of hyperhidrosis was less than 18 years in four cases. In the cohort of 21 paediatric patients (12 female, nine male), one female had hyperhidrosis; the age at onset of this symptom was 11 years. In the FOS cohort, 66 of 714 patients with Fabry disease had hyperhidrosis (44 of 369 females, 11.9%; 22 of 345 males, 6.4%). The female predominance was observed in seven of nine countries from which data were analysed. Hyperhidrosis is an increasingly recognised feature of the Fabry disease phenotype. It is more prevalent in females than in males and often appears in childhood or adolescence. The efficacy of enzyme replacement therapy on this recently recognised symptom should be assessed.

Cancer testis antigen expression in gastrointestinal stromal tumors: new markers for early recurrence.

Cancer testis antigens (CTAs) are expressed in a variety of malignant tumors but not in any normal adult tissues except germ cells and occasionally placenta. Because of this tumor-associated pattern of expression, CTAs are regarded as potential vaccine targets. The expression of CTAs in gastrointestinal stromal tumors (GIST) has not been analyzed systematically previously. The present study was performed to analyze the expression of CTA in GIST and to determine if CTA expression correlates with prognosis. Thirty-five GIST patients were retrospectively analyzed for their expression of CTAs by immunohistochemistry using the following monoclonal antibodies (mAb/antigen): MA454/MAGE-A1, M3H67/MAGE-A3, 57B/MAGE-A4, CT7-33/MAGE-C1 and E978/NY-ESO-1. Fourteen tumors (40%) expressed 1 or more of the 5 CTAs tested. Fourteen percent (n = 5/35) were positive for MAGE-A1, MAGE-A3 or MAGE-A4, respectively. Twenty-six percent (n = 9/35) stained positive for MAGE-C1 and 20% (n = 7/35) for NY-ESO-1. A highly significant correlation between CTA expression and tumor recurrence risk was observed (71% vs. 29%; p = 0.027). In our study population, the high-risk GIST expressed CTAs more frequently than low-risk GIST (p = 0.012). High-risk GISTs which stained positive for at least 1 CTA, recurred in 100% (n = 25) of the cases. This is the first study analyzing CTA expression in GIST and its prognostic value for recurrence. The CTA staining could add information to the individual patient prognosis and represent an interesting target for future treatment strategies.

Predictors of the risk of fibrosis at 10 years after breast conserving therapy for early breast cancer: a study based on the EORTC Trial 22881-10882 'boost versus no boost'.

The EORTC 22881-10882 trial in 5178 conservatively treated early breast cancer patients showed that a 16 Gy boost dose significantly improved local control, but increased the risk of breast fibrosis. To investigate predictors for the long-term risk of fibrosis, Cox regression models of the time to moderate or severe fibrosis were developed on a random set of 1797 patients with and 1827 patients without a boost, and validated in the remaining set. The median follow-up was 10.7 years. The risk of fibrosis significantly increased (P<0.01) with increasing maximum whole breast irradiation (WBI) dose and with concomitant chemotherapy, but was independent of age. In the boost arm, the risk further increased (P<0.01) if patients had post-operative breast oedema or haematoma, but it decreased (P<0.01) if WBI was given with >6 MV photons. The c-index was around 0.62. Nomograms with these factors are proposed to forecast the long-term risk of moderate or severe fibrosis.

Lung cancer mortality in European men: Trends and predictions.

Lung cancer mortality in men from the European Union (EU) peaked in the late 1980s at an age-standardised (world standard population) rate over 53/100,000 and declined subsequently to reach 44/100,000 in the early 2000s. To provide a comprehensive picture of recent trends in male lung cancer mortality in Europe, we analyzed available data from the World Health Organization up to 2009 and predicted future rates to 2015. Lung cancer mortality rates in EU men continued to fall over recent years, to reach a value of 41.1/100,000 in 2005-2009. The fall was similar at all-ages and in middle-aged men (less than 2% per year over most recent years), but was appreciably larger in young men (aged 20-44years, over 5% per year). A favourable trend is thus likely to be maintained in the foreseeable future, although the predicted overall EU rate in 2015 is still over 35/100,000, i.e., higher than the US rate in 2007 (33.7/100,000). Over most recent calendar years, overall male lung cancer rates were around 35-40/100,000 in western Europe, as compared to over 50/100,000 in central and eastern Europe. Within western Europe, lung cancer rates were lower in northern countries such as Sweden, but also Finland and the UK (below 30/100,000), where the tobacco-related epidemic started earlier and rates have long been declining, whereas mortality was high in Belgium (51.6), France (42.3), the Netherlands and Spain (around 43.0), where the epidemic started later but is persisting. Widespread measures for smoking control and cessation in middle-aged European men, i.e., in the generations where smoking prevalence used to be high, would lead to appreciable reductions in male lung cancer mortality in the near future. This is particularly urgent in central and eastern European countries.

U-Pb zircon dating in the middle Penninic basement of the Western Alps (Valais, Switzerland)

New ages (U-Pb isotopic data) on zircon and monazite in the pre-Alpine basement of the Penninic realm (Valais, Switzerland) are presented. They are related to a Variscan metamorphic high-grade event (ca. 330 Ma) and to post-Variscan magmatic activities (ca. 270 Ma).

Lung cancer mortality in European women: trends and predictions.

Female lung cancer mortality increased by 50% between the mid 1960s and the early 2000s in the European Union (EU). To monitor the current lung cancer epidemic in European women, we analyzed mortality trends in 33 European countries between 1970 and 2009 and estimated rates for the year 2015 using data from the World Health Organization. Female lung cancer mortality has been increasing up to recent calendar years in most European countries, with the exceptions of Belarus, Russia, and Ukraine, with relatively low rates, and the UK, Iceland and Ireland, where high rates were reached in mid/late 1990s to leveled off thereafter. In the EU, female lung cancer mortality rates rose over the last decade from 11.3 to 12.7/100,000 (+2.3% per year) at all ages and from 18.6 to 21.5/100,000 (+3.0% per year) in middle-age. A further increase is predicted, to reach 14/100,000 women in 2015. Lung cancer mortality trends have been more favorable over the last decade in young women (20-44 years), particularly in the UK and other former high-risk countries from northern and central/eastern Europe, but also in France, Italy, and Spain where mortality in young women has been increasing up to the early 2000s. In the EU as a whole, mortality at age 20-44 years decreased from 1.6 to 1.4/100,000 (-2.2% per year). Although the female lung cancer epidemic in Europe is still expanding, the epidemic may be controlled through the implementation of effective anti-tobacco measures, and it will probably never reach the top US rates.

The early Miocene rotation of the Corso-Sardinian block. New paleomagnetic constraints for the end of the motion

The paleomagnetic investigations carried out in the 70's on Oligo-Miocene volcanics of Sardinia have demonstrated that the island was turned by 35-30 degrees clockwise from 33 Ma up to 3-1-20.5 Ma and rotated counterclockwise in a few million years [De Jong et al., 1969, 1973; Bobier et Coulon, 1970; Coulon et al., 1974; Manzoni, 1974, 1975; Bellon rr nl.. 1977: Edel et Lortscher, 1977; Edel, 1979, 1980]. Since then, the end of the rotation fixed at 19 Ma by Montigny er al. [1981] was the subject of discussions and several studies associating paleomagnetism and radiometric dating were undertaken [Assorgia er al., 1994: Vigliotti et Langenheim, 1995: Deino et al., 1997; Gattacceca rt Deino, 1999]. This is a contribution to this debate that is hampered by thr important secular variation recorded in the volcanics. The only way to get our of this problem is to sample series of successive flows as completely as possible, and to reduce the effect of secular variation by the calculation of means. Sampling was performed north of Bonorva in 5 pyroclastic flows that belong to the upper ignimbritic series SI2 according to Coulon rr nl. [1974] or LBLS according to Assorgia et al. [1997] (fig. I). Ar-40/Ar-39 dating of biotites from the debris flow (MDF) has yielded an age or 18.35 +/- 0.03 Ma [Dubois, 2000]. Five of the investigated sites are located beneath the debris flow ITV, TVB, TVD, SPM85, SPM86), one site was cured in the matrix of the debris flow (MDF) and one in 4 metric blocks included in the flow (DFC). Another site was sampled in the upper ash flow (PDM) that marks the end of the pyroclastic activity, just before the marine transgression. According to micropaleontological and radiometric dating this transgression has occurred between 18.35 and 17.6 Ma [Dubois, 2000]. After removal of a soft viscous component, the thermal demagnetization generally shows a univectorial behaviour of the remanent magnetization (fig. 2a). The maximum unblocking temperatures of 580-620 degrees (tab. I) and a rapid saturation below 100 mT (fig. 3) indicate that the carrier of the characteristic magnetization is magnetite. The exception comes: from the upper site PDM in which were found two characteristic components, one with a normal polarity and low unblocking temperatures up to 350 degreesC and one with a reversed polarity and maximum unblocking temperatures at 580-600 degreesC of magnetite. After calculation of a mean direction for each flow, the mean << Al >> direction 4 degrees /57 degrees (alpha (95) = 13 degrees) computed with the mean directions for the 5 flows may be considered as weakly affected by secular variation. But the results require a more careful examination. The declinations are N to NNW beneath the debris flow. NNW in the debris flow. and NNE (or SSW) above the debris flow, The elongated distribution of the directions obtained at sites TVB and TVD. scattered from the mean direction of TV to the mean direction of MDF is interpreted as due to partial overprinting during the debris How volcanic episode, The low temperature component PDMa is likely related to the alteration seen on thin sections and is also viewed as an overprint. As NNE/SSW directions occur as well below (mean direction << B >> : 5 degrees /58 degrees) as above the debris flow (PDMb : 200 degrees/-58 degrees). the NNW directions (<< C >> : 337 degrees /64 degrees) associated with the debris flow volcanism may be interpreted as resulting from a magnetic field excursion. According to the polarity scale of Cande and Kent [1992, 1995] and the radiometric age of MDF, the directions with normal polarity (TV, TVB, TVD, SPM85. SPM86a. MDF. DFC) may represent the period 5En. while the directions with reversed polarity PDMb and SPM86b were likely acquired during the period 5Dr. Using the mean << Al >> direction, the mean << B >>, or the PDM direction (tab. I). the deviation in declination with the direction of stable Europe 6.4 degrees /58.7 degrees (alpha (95) = 8 degrees) for a selection of 4 middle Tertiary poles by Besse et Courtillot [1991] or 7 degrees /56 degrees (alpha (95) = 3 degrees) for 19 poles listed by Edel [1980] can be considered as negligible. Using the results from the uppermost ignimbritic layer of Anglona also emplaced around 18.3 Ma [Odin rt al.. 1994]. the mean direction << E >> (3 degrees /51.5 degrees) leads to the same conclusion. On the contrary, when taking into account all dated results available for the period 5En (mean direction << D >> 353 degrees /56 degrees for 45 sites) (tab. II). the deviation 13 degrees is much more significant. As the rotation of Sardinia started around 21-20.5 Ma. the assumption of a constant velocity of rotation and the deviations of the Sardinia directions with respect to the stable Europe direction locate the end of the motion between 18.3 and 17.2 or 16.7 Ma (fig. 4). During the interval 18.35-17.5 Ma, the marine transgression took place. At the same period a NE-SW shortening interpreted as resulting from the collision of Sardinia with Apulia affected different parts of the island [Letouzey et al., 1982]. Consequently, the new paleomagnetic results and the tectono-sedimentary evolution are in favour of an end of the rotation at 17.5-18 Ma.

Profiles of drug users in Switzerland and effects of early-onset intensive use of alcohol, tobacco and cannabis on other illicit drug use.

QUESTIONS UNDER STUDY / PRINCIPLES: The main aim of this study was to investigate profiles of drug users, with a particular focus on illicit drugs other than cannabis, and to explore the effect of early-onset intensive use (drunkenness, daily smoking, high on cannabis) on profiles of illicit drug use. METHODS: Baseline data from a representative sample of 5,831 young Swiss men in the ongoing Cohort Study on Substance Use Risk Factors were used. Substance use (alcohol, tobacco, cannabis and 15 types of other illicit drug) and age of onset of intensive use were assessed. The Item Response Theory (IRT) and prevalence rates at different ages of onset were used to reveal different profiles of illicit drug use. RESULTS: In addition to cannabis, there were two profiles of other illicit drug use: (a) "softer" drug users (uppers, hallucinogens and inhaled drugs), among which ecstasy had the highest discriminatory potential (IRT slope = 4.68, standard error (SE) = 0.48; p <0.001); and (b) "harder" drug users (heroin, ketamine, gamma-hydroxybutyrate/gamma-hydroxylactone, research chemicals, crystal meth and spice), among which ketamine had the highest discriminatory potential (slope = 4.05; SE = 0.63; p <0.001). Onset of intensive use at the age of 12 years or younger also discriminated between these two profiles. CONCLUSION: Both the IRT model and the effect of onset of intensive use enabled two groups of illicit drugs to be identified. In particular, very early onset (at 12 years or younger) intensive use of any substance was a marker for later use of the second group of drugs.

The Exotic Palaeo-Thethys Terrane in Central Iran: New geological data from Anarak, Jandaq and Posht-e-Badam areas

Résumé Le « terrane » d'Anarak-Jandak occupe une position géologique clé au nord-ouest du Microcontinent Centre-East Iranien (CE1M), connecté avec le Bloc du Grand Kavir et la ceinture métamorphique de Sanandaj-Sirjan. Nous discutons ici l'origine de ces différentes unités, reliées jusqu'à présent à des épisodes orogéniques d'âge Précambrien à Paléozoïque inférieur, pour conclure finalement de leur affinité paléotéthysienne. Leur histoire commence par un épisode de rifting d'âge Ordovicien supérieur-Dévonien inférieur, pour se terminer au Trias par la collision des blocs Cimmériens dérivé du Gondwana avec le Bloc du Turan d'affinité asiatique (événement Eocimmérien). La plus importante unité métamorphique affleurant au sud-ouest de la région de Jandak-Anarak-Kaboudan est une épaisse séquence silicoclastique à grains fins contenant des blocs ophiolitiques (marginal-sea-type), et des associations basalte-gabbro à signatures géochimiques de type supra-subduction. Dans la région de Nakhlak, nous avons daté ces gabbros par la méthode U-Pb à 387f0.11 Ma ; les roches métamorphiques pélitiques ont donné des âges de refroidissement Ar-Ar pour la muscovite de 320 à 333 Ma. Ce complexe d'accrétion "varisque" a été métamorphisé dans le faciès schiste vert-amphibolite au cours de l'accrétion de la ceinture granitique d'Airekan, d'âge Cambrien inférieur (549±15 Ma par la méthode U/Pb), qui affleure aujourd'hui à l'extrémité nord-ouest du terrane d'Anarak-Jandak . La subduction vers le nord de l'océan Paléotéthys depuis le Paléazoïque supérieur jusqu'au Trias, a permis l'accumulation de grandes quantités de matériel océanique dans la zone de subduction. Par exemple, une succession de guyots (Anarak, Kaboudan, et Meraji Seamounts) et de hauts sous-marins, entrés en collision oblique avec le prisme d'accrétion, est à l'origine d'un léger métamorphisme de type HP qui affecte ces séries {âges Ar-Ar de 280 à 230 Ma). De plus, le magmatisme bimodal de Chah Gorbeh est caractérisé d'une part par des roches de type trondjémite-gabbros (262 Ma), d'autre part par des laves en coussin de type basaltes alcalins-rhyolites; ces roches magmatiques ont recoupé l'ophiolite d'Anarak lors de la mise en place de cette dernière dans la fosse interne de subduction. Quant au prisme d'accrétion de Doshakh, d'âge essentiellement Permien supérieur, i1 a été accrété le long de la marge continentale et métamorphisé dans le faciès schiste vert. La fermeture de la Paléotéthys s'enregistre finalement par la sédimentation dans le bassin d'avant pays du flysch de Bayazeh, d'âge probable Triasique. Le matériel issu de l'arc magmatique de la Paléotéthys est très bien préservé dans les dépôts infra-arc Dévonien supérieur-Carbonifère de Godar-e-Siah, ainsi que dans la succession d'avant-arc de Nakhlak. Pendant l'intervalle Paléozoïque supérieur-Trias, la région de Jandak a été soumise à un régime extensif de type bassin d'arrière-arc, dont un témoin pourrait être la ceinture ophiolitique d'Arusan, elle-même comparable aux écailles ophiolitiques d'Aghdarband au nord-est de l'Iran. Cet ensemble métamorphique est recoupé par des granites d'arc à collisionnel datés à 215±15 Ma. Dans la région de Yazd, témoin de la marge passive Cimmérienne, la sédimentation syn-rift Silurienne à Dévonienne inférieure a été interrompue pendant l'intervalle Trias moyen-Trias supérieur; il en a été de même pour les dépôts de plate-forme Paléozoïque supérieur. L'érosion, qui dans ce dernier cas a atteint le Permien, pourrait être liée au bombement flexural de la marge passive. La collision finale n'a pas induit de déformations trop importantes, et se caractérise par la mise en place de nappes sur la marge passive. Cet événement est scellé par des dépôts molassique du Lias. D'un point de vue régional, la zone s'étendant actuellement de la Mer Noire au Pamir a été soumise à six épisodes d'extension-compression du Jurassique inférieur (début du l'ouverture en position arrière-arc de la Néotéthys) à l'Eocène moyen. Par exemple, le terrane d'AnarakJandak, probablement situé entre le Kopeh Dagh et la plate-forme nord Afghane, s'est complètement détaché de sa patrie d'origine au début du Crétacé supérieur. Des preuves de cet événement se retrouvent dans les séries de plate-forme de Khur (préservation de séries syn-rift puis de marge passive). Les ophiolites de Nain et de Sabzevar sont de plus interprétée comme un témoin de l'existence de ce bassin d'arrière-arc. Dans l'intervalle Eocène-Oligocène, l'indentation par la plaque indienne de l'Eurasie a été contemporaine de la rotation horaire de fragments de l'ancien microcontinent Iranien et de la formation du CEIM. Cette rotation est responsable du transport du terrane d'Anarak-Jandak vers sa position actuelle en Iran Central, et de la dislocation de Terranes de moindre importance, comme le bloc de Posht-e Badam. Depuis le Miocène supérieur, et à la suite de la collision entre l'Arabie et l'Iran, le ternane d'Anarak-Jandak a subi des déformations liées à l'activité d'une zone de cisaillement dextre parallèle à la suture du Zagros, à l'arrière de l'arc magmatique d'Uromieh-Dokhtar. Résumé large public Le Microcontinent Centre-Est Iranien occupe une position géologique clé au centre de l'Iran. Les différentes unités qui le composent, reliées jusqu'à présent à des épisodes orogéniques d'âge Précambrien à Paléozoïque inférieur, sont maintenant rajeunies et liés à la fermeture de l'océean Paléotéthys. Leur histoire commence par un épisode de rifting d'âge Ordovicien supérieur à Dévonien inférieur, pour se terminer au Trias par la collision des- blocs Cimmériens, dérivés du Gondwana, avec le Bloc du Turan d'affinité asiatique. Dans la marge active asiatique de la Paléotéthys, nous avons daté les restes d'un océan marginal à 387±0.11 Ma. Ce complexe d'accrétion a été métamorphisé au cours de la réaccrétion de la ceinture granitique d'Airekan, d'âge Cambrien inférieur (549±15 Ma), qui affleure aujourd'hui à l'extrémité nord-ouest du « terrane » d'Anarak-Jandak correspondant à la plus grande partie de la région étudiée. Le matériel issu de l'arc magmatique de la Paléotéthys est très bien préservé et daté du Dévonien supérieur-Carbonifère. Pendant l'intervalle Paléozoïque supérieur-Trias, la région a été soumise à un régime extensif de type bassin d'arrière-arc, dont un témoin pourrait être la ceinture ophiolitique d'Arusan, comparable aux écailles ophiolitiques d'Aghdarband au nord-est de l'Iran. Cet ensemble métamorphique est recoupé par des granites datés à 215±15 Ma. La subduction vers le nord de l'océan Paléotéthys depuis le Paléozoïque supérieur jusqu'au Trias, a permis l'accumulation de grandes quantités de matériel océanique dans la zone de subduction. Par exemple, une succession de volcans sous-marins, entrés en collision avec le prisme d'accrétion, est à l'origine d'un léger métamorphisme de type HP qui affecte ces séries (280 à 230 Ma). Quant au prisme d'accrétion de Doshakh, d'âge essentiellement Permien supérieur, il a été mis en place le long de la marge continentale et métamorphisé dans le faciès schiste vert. La fermeture de la Paléotéthys s'enregistre finalement par la sédimentation dans le bassin d'avant pays du flysch de Bayazeh, d'âge Triasique. Dans la région de Yazd, on trouve les témoins de la marge passive Cimmérienne, la sédimentation syn-rift Silurienne à Dévonienne inférieure a été interrompue pendant l'intervalle Trias moyen-Trias supérieur, marqué par la flexuration de la marge passive lorsqu'elle rentra en collision avec la marge active asiatique. Cet événement est scellé par des dépôts molassique à charbon du Lias. Le «terrane» d'Anarak-Jandak, probablement situé à l'origine entre le Kopeh Dagh et la plate-forme nord Afghane, s'est complètement détaché de cette région au début du Crétacé supérieur lors de l'ouverture d'un bassin d'arrière-arc, engendré, cette fois, par la subduction de l'océan Néotéthys situé au sud des blocs cimmériens. Des preuves de cet événement se retrouvent dans les séries syn-rift, puis de marge passive de Khour. Les ophiolites de Nain et de Sabzevar sont interprétées comme un témoin de l'existence de ce bassin d'arrière-arc. Dans l'intervalle Eocène-Oligocène, l'indentation de l'Eurasie par la plaque indienne a été contemporaine de la rotation horaire de fragments de l'ancien microcontinent centre-Iranien. Cette rotation de près de 90° est responsable du transport du « terrane » d'Anarak-Jandak vers sa position actuelle. Abstract The Anarak-Jandaq terrane occupies a strategic geological situation at the north-western part of the Central-East Iranian Microcontinent (CEIM) and in connection with the Great Kavir Block and Sanandaj-Sirjan metamorphic belt. Our recent findings redefine the origin of these mentioned areas so far attributed to the Precambrian-Early Palaeozoic orogenic episodes, to be now directly related to the tectonic evolution of the Palaeo-Tethys Ocean, commenced by Late Ordovician-Early Devonian rifting events and terminated in the Triassic by the Eocimmerian tectonic event due to the collision of the Cimmerian blocks with the Asiatic Turan block. The most distributed metamorphic unit that is exposed from the south-west of Jandaq to the Anarak and Kaboudan areas is a thick and fine grain siliciclastic sequence accompanied by marginal-sea-basin ophiolitic blocks including basalt-gabbro association with supra-subduction-geochemical signature. These gabbros in the Nakhlak area were dated by U/Pb method at 387.6 ± 0.11 Ma and the metamorphic pelitic rocks yielded a range of 320 to 333 Ma muscovite-cooling ages based on 40Ar/39 Ar method. This "Variscan" accretionary complex was metamorphosed in greenschist-amphibolite facies during accretion to the Lower Cambrian Airekan granitic belt (549 ± 15 Ma by U/Pb method) that crops out at the northwestern edge of the Anarak-Jandaq terrane. Continued northward subduction of the Palaeo-Tethys Ocean during the entire Late Palaeozoic-Middle Triassic brought huge amount of oceanic material to the subduction zone. One chain of Carboniferous-Triassic oceanic rises and seamounts (the Anarak, Kaboudan, and Meraji Seamounts) obliquely collided with the accretionary wedge and created a mild HP metamorphic event (280-230 Ma based on 40Ar/39Ar results). Bimodal magmatism of the Chah Gorbeh area is characterized by a 262 Ma trondjemite-gabbro as well as pillow alkalibasalts-rhyolites which intruded the Anarak ophiolite when it was being emplaced within the inner-wall trench. The mainly Late Permian-Triassic Doshakh wedge was accreted along the continent and metamorphosed under lower greenschist facies and the probable Triassic Bayazeh flysch filled the foreland basin during the final closure. The Palaeo-Tethys magmatic arc products have been well preserved in the Late Devonian-Carboniferous Godar-e-Siah intra-arc deposits and the Triassic Nakhlak fore-arc succession. During the Late Palaeozoic-Triassic times, the Jandaq area has been affected by back-arc extension and probably the Arusan ophiolitic belt is the remnant of this narrow basin comparable to the Aqdarband ophiolitic remnant in north-east Iran. This metamorphic belt was intruded by 215 ± 15 Ma arc to collisional granites. In the passive margin of the Cimmerian block, on the Yazd region, the Silurian-Early Devonian syn-rift succession as well as the nearly continuous Upper Palaeozoic platform-type deposition was interrupted during the Middle to Late Triassic time, local erosion down to Devonian levels may be related to flexural bulge erosion. The collision event was not so strong to generate intensive deformation but was accompanied by some nappe thrusting onto the passive margin. It is finally unconformably covered by Liassic continental molassic deposits. Related to the onset of Neo-Tethyan back-arc opening in Early Jurassic to Mid-Eocene times, six periods of extensional-compressional events have differently influenced an elongated area, extending from the West Black Sea to Pamir. The Anarak-Jandaq terrane which was situated somewhere in this affected area, probably between the Kopeh Dagh and North Afghan platform, was completely detached from its source at the beginning of the Late Cretaceous

Appropriateness of early management of newly diagnosed Crohn's disease in a European population-based cohort.

OBJECTIVE: The European Panel on the Appropriateness of Crohn's disease Therapy (EPACT) has developed appropriateness criteria. We have applied these criteria retrospectively to the population-based inception cohort of Crohn's disease (CD) patients of the European Collaborative Study Group on Inflammatory Bowel Disease (EC-IBD). MATERIAL AND METHODS: A total of 426 diagnosed CD patients from 13 European centers were enrolled at the time of diagnosis (first flare, naive patients). We used the EPACT definitions to identify 247 patients with active luminal CD. We then assessed the appropriateness of the initial drug prescription according to the EPACT criteria. RESULTS: Among the cohort patients 163 suffered from mild-to-moderate CD and 84 from severe CD. Among the mild-to-moderate disease group, 96 patients (59%) received an appropriate treatment, whereas for 66 patients (40%) the treatment was uncertain and in one case (1%) inappropriate. Among the severe disease group, 86% were treated medically and 14% required surgery. 59 (70%) were appropriately treated, whereas for one patient (1%) the procedure was considered uncertain and for 24 patients (29%) inappropriate. CONCLUSION: Initial treatment was appropriate in the majority of cases for non-complicated luminal CD. Inappropriate or uncertain treatment was given in a significant minority of patients, with an increased potential risk of adverse events.

Modelling the effect of minor orthopaedic day surgery on patient mood at the early post-operative period: a prospective population-based cohort study.

OBJECTIVE: The effect of minor orthopaedic day surgery (MiODS) on patient's mood. METHODS: A prospective population-based cohort study of 148 consecutive patients with age above 18 and less than 65, an American Society of Anaesthesiology (ASA) score of 1, and the requirement of general anaesthesia (GA) were included. The Medical Outcomes Study - Short Form 36 (SF-36), Beck Anxiety Inventory (BAI) and Beck Depression Inventory (BDI) were used pre- and post-operatively. RESULTS: The mean physical component score of SF-36 before surgery was 45.3 (SD=+/-10.1) and 8 weeks following surgery was 44.9 (SD=+/-11.04) [n=148, p=0.51, 95% CI=(-1.03 to 1.52)]. For the measurement of the changes in mood using BDI, BAI and SF-36, latent construct modelling was employed to increase validity. The covariance between mood pre- and post-operatively (cov=69.44) corresponded to a correlation coefficient, r=0.88 indicating that patients suffering a greater number of mood symptoms before surgery continue to have a greater number of symptoms following surgery. When the latent mood constructs were permitted to have different means the model fitted well with chi(2) (df=1)=0.86 for which p=0.77, thus the null hypothesis that MiODS has no effect on patient mood was rejected. CONCLUSIONS: MiODS affects patient mood which deteriorates at 8 weeks post-operatively regardless of the pre-operative patient mood state. More importantly patients suffering a greater number of mood symptoms before MiODS continue to have a greater number of symptoms following surgery.

Lessons learned from developing a national NCD programme in low- and middle-income countries (Seychelles)

This paper identifies selected issues and lessons learned from the implementation of a national program of prevention and control of non-communicable diseases (NCD) during the past 20 years in the Seychelles, a small island state in the African region. As early as in 1989, population-based surveys demonstrated high levels of several cardiovascular risk factors, which prompted an organized response by the government. The early creation of a NCD unit within the Ministry of Health, coupled with cooperation with international partners, enabled incremental capacity building and coherent development of NCD programs and policy. Information campaigns and screening for hypertension and diabetes in work/public places raised awareness and rallied increasingly broad awareness and support to NCD prevention and control. A variety of interventions were organized for tobacco control and comprehensive tobacco control legislation was enacted in 2009 (including total bans on tobacco advertising and on smoking in all enclosed public and work places). A recent School Nutrition Policy prohibits the sale of soft drinks in schools. At primary health care level, guidelines were developed for the management of hypertension and diabetes (these conditions are managed in all health centers within a national health system); regular interactive education sessions were organized for groups of high risk patients ("heart health club"); and specialized "NCD nurses" were trained. Decreasing prevalence of smoking is evidence of success, but the raising "diabesity epidemic" calls for strengthened health care to high-risk patients and broader multisectoral policy to mould an environment conducive to healthy behaviors. Key components of NCD prevention and control in Seychelles include effective surveillance mechanisms supplemented by focused research; generating broad interest and consensus on the need for prevention and control of NCD; mobilizing leadership and commitment at all levels; involving local and international expertise; building on existing efforts; and seeking integrated, multi-disciplinary and multisectoral approaches.

Large-scale evolutionary trends of Acrochordiceratidae Arthaber, 1911 (Ammonoidea, Middle Triassic) and Cope's rule

Directed evolution of life through millions of years, such as increasing adult body size, is one of the most intriguing patterns displayed by fossil lineages. Processes and causes of such evolutionary trends are still poorly understood. Ammonoids (externally shelled marine cephalopods) are well known to have experienced repetitive morphological evolutionary trends of their adult size, shell geometry and ornamentation. This study analyses the evolutionary trends of the family Acrochordiceratidae Arthaber, 1911 from the Early to Middle Triassic (251228 Ma). Exceptionally large and bed-rock-controlled collections of this ammonoid family were obtained from strata of Anisian age (Middle Triassic) in north-west Nevada and north-east British Columbia. They enable quantitative and statistical analyses of its morphological evolutionary trends. This study demonstrates that the monophyletic clade Acrochordiceratidae underwent the classical evolute to involute evolutionary trend (i.e. increasing coiling of the shell), an increase in its shell adult size (conch diameter) and an increase in the indentation of its shell suture shape. These evolutionary trends are statistically robust and seem more or less gradual. Furthermore, they are nonrandom with the sustained shift in the mean, the minimum and the maximum of studied shell characters. These results can be classically interpreted as being constrained by the persistence and common selection pressure on this mostly anagenetic lineage characterized by relatively moderate evolutionary rates. Increasing involution of ammonites is traditionally interpreted by increasing adaptation mostly in terms of improved hydrodynamics. However, this trend in ammonoid geometry can also be explained as a case of Copes rule (increasing adult body size) instead of functional explanation of coiling, because both shell diameter and shell involution are two possible paths for ammonoids to accommodate size increase.

The Anarak, Jandaq and Posht-e-Badam metamorphic complexes in central Iran: New geological data, relationships and tectonic implications

The Anarak, Jandaq and Posht-e-Badam metamorphic complexes occupy the NW part of the Central-East Iranian Microcontinent and are juxtaposed with the Great Kavir block and Sanandaj-Sirjan zone. Our recent findings redefine the origin of these complexes, so far attributed to the Precambrian-Early Paleozoic orogenic episodes, and now directly related to the tectonic evolution of the Paleo-Tethys Ocean. This tectonic evolution was initiated by Late Ordovician-Early Devonian rifting events and terminated in the Triassic by the Eocimmerian collision event due to the docking of the Cimmerian blocks with the Asiatic Turan block. The ``Variscan accretionary complex'' is a new name we proposed for the most widely distributed metamorphic rocks connected to the Anarak and Jandaq complexes. This accretionary complex exposed from SW of Jandaq to the Anarak and Kabudan areas is a thick and fine grain siliciclastic sequence accompanied by marginal-sea ophiolitic remnants, including gabbro-basalts with a supra-subduction-geochemical signature. New Ar-40/Ar-39 ages are obtained as 333-320 Ma for the metamorphism of this sequence under greenschist to amphibolite facies. Moreover, the limy intercalations in the volcano-sedimentary part of this complex in Godar-e-Siah yielded Upper Devonian-Tournaisian conodonts. The northeastern part of this complex in the Jandaq area was intruded by 215 +/- 15 Ma arc to collisional granite and pegmatites dated by ID-TIMS and its metamorphic rocks are characterized by Some Ar-40/Ar-39 radiometric ages of 163-156 Ma. The ``Variscan'' accretionary complex was northwardly accreted to the Airekan granitic terrane dated at 549 +/- 15 Ma. Later, from the Late Carboniferous to Triassic, huge amounts of oceanic material were accreted to its southern side and penetrated by several seamounts such as the Anarak and Kabudan. This new period of accretion is supported by the 280-230 Ma Ar-40/Ar-39 ages for the Anarak mild high-pressure metamorphic rocks and a 262 Ma U-Pb age for the trondhjemite-rhyolite association of that area. The Triassic Bayazeh flysch filled the foreland basin during the final closure of the Paleo-Tethys Ocean and was partly deposited and/or thrusted onto the Cimmerian Yazd block. The Paleo-Tethys magmatic arc products have been well-preserved in the Late Devonian-Carboniferous Godar-e-Siah intra-arc deposits and the Triassic Nakhlak fore-arc succession. On the passive margin of the Cimmerian block, in the Yazd region, the nearly continuous Upper Paleozoic platform-type deposition was totally interrupted during the Middle to Late Triassic. Local erosion, down to Lower Paleozoic levels, may be related to flexural bulge erosion. The platform was finally unconformably covered by Liassic continental molassic deposits of the Shemshak. One of the extensional periods related to Neo-Tethyan back-arc rifting in Late Cretaceous time finally separated parts of the Eocimmerian collisional domain from the Eurasian Turan domain. The opening and closing of this new ocean, characterized by the Nain and Sabzevar ophiolitic melanges, finally transported the Anarak-Jandaq composite terrane to Central Iran, accompanied by large scale rotation of the Central-East Iranian Microcontinent (CEIM). Due to many similarities between the Posht-e-Badam metamorphic complex and the Anarak-Jandaq composite terrane, the former could be part of the latter, if it was transported further south during Tertiary time. (C) 2007 Elsevier B.V. All rights reserved.