Evolution of the Pelagonian carbonate platform complex and the adjacent oceanic realm in response to plate tectonic forcing (Late Triassic and Jurassic), Evvoia, Greece

The Late Triassic and Jurassic platform and the oceanic complexes in Evvoia, Greece, share a complementary plate-tectonic evolution. Shallow marine carbonate deposition responded to changing rates of subsidence and uplift, whilst the adjacent ocean underwent spreading, and then convergence, collision and finally obduction over the platform complex. Late Triassic ocean spreading correlated with platform subsidence and the formation of a long-persisting peritidal passive-margin platform. Incipient drowning occurred from the Sinemurian to the late Middle Jurassic. This subsidence correlated with intra-oceanic subduction and plate convergence that led to supra-subduction calc-alkaline magmatism and the formation of a primitive volcanic arc. During the Middle Jurassic, plate collision caused arc uplift above the carbonate compensation depth (CCD) in the oceanic realm, and related thrust-faulting, on the platform, led to sub-aerial exposures. Patch-reefs developed there during the Late Oxfordian to Kimmeridgian. Advanced oceanic nappe-loading caused platform drowning below the CCD during the Tithonian, which is documented by intercalations of reefal turbidites with non-carbonate radiolarites. Radiolarites and bypass-turbidites, consisting of siliciclastic greywacke, terminate the platform succession beneath the emplaced oceanic nappe during late Tithonian to Valanginian time.

Rapid fluidic exchange microsystem for recording of fast ion channel kinetics in Xenopus oocytes.

We present a new lab-on-a-chip system for electrophysiological measurements on Xenopus oocytes. Xenopus oocytes are widely used host cells in the field of pharmacological studies and drug development. We developed a novel non-invasive technique using immobilized non-devitellinized cells that replaces the traditional "two-electrode voltage-clamp" (TEVC) method. In particular, rapid fluidic exchange was implemented on-chip to allow recording of fast kinetic events of exogenous ion channels expressed in the cell membrane. Reducing fluidic exchange times of extracellular reagent solutions is a great challenge with these large millimetre-sized cells. Fluidic switching is obtained by shifting the laminar flow interface in a perfusion channel under the cell by means of integrated poly-dimethylsiloxane (PDMS) microvalves. Reagent solution exchange times down to 20 ms have been achieved. An on-chip purging system allows to perform complex pharmacological protocols, making the system suitable for screening of ion channel ligand libraries. The performance of the integrated rapid fluidic exchange system was demonstrated by investigating the self-inhibition of human epithelial sodium channels (ENaC). Our results show that the response time of this ion channel to a specific reactant is about an order of magnitude faster than could be estimated with the traditional TEVC technique.

Combination of carbon isotope ratio with hydrogen isotope ratio determinations in sports drug testing.

Carbon isotope ratio (CIR) analysis has been routinely and successfully applied to doping control analysis for many years to uncover the misuse of endogenous steroids such as testosterone. Over the years, several challenges and limitations of this approach became apparent, e.g., the influence of inadequate chromatographic separation on CIR values or the emergence of steroid preparations comprising identical CIRs as endogenous steroids. While the latter has been addressed recently by the implementation of hydrogen isotope ratios (HIR), an improved sample preparation for CIR avoiding co-eluting compounds is presented herein together with newly established reference values of those endogenous steroids being relevant for doping controls. From the fraction of glucuronidated steroids 5β-pregnane-3α,20α-diol, 5α-androst-16-en-3α-ol, 3α-Hydroxy-5β-androstane-11,17-dione, 3α-hydroxy-5α-androstan-17-one (ANDRO), 3α-hydroxy-5β-androstan-17-one (ETIO), 3β-hydroxy-androst-5-en-17-one (DHEA), 5α- and 5β-androstane-3α,17β-diol (5aDIOL and 5bDIOL), 17β-hydroxy-androst-4-en-3-one and 17α-hydroxy-androst-4-en-3-one were included. In addition, sulfate conjugates of ANDRO, ETIO, DHEA, 3β-hydroxy-5α-androstan-17-one plus 17α- and androst-5-ene-3β,17β-diol were considered and analyzed after acidic solvolysis. The results obtained for the reference population encompassing n = 67 males and females confirmed earlier findings regarding factors influencing endogenous CIR. Variations in sample preparation influenced CIR measurements especially for 5aDIOL and 5bDIOL, the most valuable steroidal analytes for the detection of testosterone misuse. Earlier investigations on the HIR of the same reference population enabled the evaluation of combined measurements of CIR and HIR and its usefulness regarding both steroid metabolism studies and doping control analysis. The combination of both stable isotopes would allow for lower reference limits providing the same statistical power and certainty to distinguish between the endo- or exogenous origin of a urinary steroid.

Optical probing of sodium dynamics in neurons and astrocytes.

Changes in intracellular Na(+) concentration underlie essential neurobiological processes, but few reliable tools exist for their measurement. Here we characterize a new synthetic Na(+)-sensitive fluorescent dye, Asante Natrium Green (ANG), with unique properties. This indicator was excitable in the visible spectrum and by two-photon illumination, suffered little photobleaching and located to the cytosol were it remained for long durations without noticeable unwanted effects on basic cell properties. When used in brain tissue, ANG yielded a bright fluorescent signal during physiological Na(+) responses both in neurons and astrocytes. Synchronous electrophysiological and fluorometric recordings showed that ANG produced accurate Na(+) measurement in situ. This new Na(+) indicator opens innovative ways of probing neuronal circuits.

Rockfall characterisation and structural protection: A review

Rockfall is an extremely rapid process involving long travel distances. Due to these features, when an event occurs, the ability to take evasive action is practically zero and, thus, the risk of injury or loss of life is high. Damage to buildings and infrastructure is quite likely. In many cases, therefore, suitable protection measures are necessary. This contribution provides an overview of previous and current research on the main topics related to rockfall. It covers the onset of rockfall and runout modelling approaches, as well as hazard zoning and protection measures. It is the aim of this article to provide an in-depth knowledge base for researchers and practitioners involved in projects dealing with the rockfall protection of infrastructures, who may work in the fields of civil or environmental engineering, risk and safety, the earth and natural sciences.

No variation of physical performance and perceived exertion after adrenal gland stimulation by synthetic ACTH (Synacthen) in cyclists.

There is anecdotal evidence that athletes use the banned substance Synacthen because of its perceived benefit with its associated rise in cortisol. To test the performance-enhancing effects of Synacthen, eight trained cyclists completed two, 2-day exercise sessions separated by 7-10 days. On the first day of each 2-day exercise session, subjects received either Synacthen (0.25 mg, TX) or placebo (PLA) injection. Performance was assessed by a 20-km time trial (TT) after a 90-min fatigue period on day 1 and without the fatiguing protocol on day 2. Plasma androgens and ACTH concentrations were measured during the exercise bouts as well as the rate of perceived exertion (RPE). Spot urines were analyzed for androgens and glucocorticoids quantification. Basal plasma hormones did not differ significantly between PLA and TX groups before and 24 h after the IM injection (P > 0.05). After TX injection, ACTH peaked at 30 min and hormone profiles were significantly different compared to the PLA trial (P < 0.001). RPE increased significantly in both groups as the exercise sessions progressed (P < 0.001) but was not influenced by treatment. The time to completion of the TT was not affected on both days by Synacthen treatment. In the present study, a single IM injection of synthetic ACTH did not improve either acute or subsequent cycling performance and did not influence perceived exertion. The investigated urinary hormones did not vary after treatment, reinforcing the difficulty for ACTH abuse detection.

Estradiol levels in men with congenital hypogonadotropic hypogonadism and the effects of different modalities of hormonal treatment.

Objective: To evaluate the degree of E-2 deficiency in male congenital hypogonadotropic hypogonadism (CHH), and its response to different hormonal treatments.Design: Retrospective and prospective studies.Setting: Academic institution.Patient(s): Untreated or treated CHH, healthy men, untreated men with Klinefelter syndrome (KS). Intervention(s): Serum sex hormone-binding globulin (SHBG) and total E-2 (TE2) as well as bioavailable (BE2) and free (FE2) levels were measured and determined.Main Outcome Measure(s): Total, bioavailable, and free testosterone, TE2, BE2, FE2 were compared in normal men, untreated and treated CHH and in untreated KS.Result(s): TE2, BE2, and FE2 levels were very significantly lower in untreated patients with CHH (n = 91) than in controls (n = 63) and in patients with KS (n = 45). The TE2 correlated positively with serum total T in patients with CHH. The TE2 also correlated very positively with serum LH in the combined population of patients with CHH and healthy men, suggesting that low E-2 levels in CHH are due to severe LH-driven T deficiency. All fractions of circulating E-2 were very significantly higher in patients with CHH receiving T enanthate (n = 101) or the FSH-hCG combination (n = 88) than in untreated patients with CHH. Contrary to dihydrotestosterone (DHT), both T enanthate and combined FSH-hCGtherapy significantly and prospectively increased TE2 levels in patients with CHH.Conclusion(s): Contrary to KS, the male hypogonadism observed in CHH is associated with profound E-2 deficiency, which can be overcome by aromatizable androgen or combined gonadotropin therapy. (Fertil Steril (R) 2011; 95: 2324-29. (C) 2011 by American Society for Reproductive Medicine.)

Acute life-threatening extrinsic allergic alveolitis in a paint controller.

BACKGROUND: Occupational diisocyanate-induced extrinsic allergic alveolitis (EAA) is a rare and probably underestimated diagnosis. Two acute occupational EAA cases have been described in this context, but neither of them concerned hexamethylene diisocyanate (HDI) exposure. AIMS: To investigate the cause of a life-threatening EAA arising at work in a healthy 30-year-old female paint quality controller. METHODS: Occupational medical assessment, workplace evaluation, airborne and biological monitoring and immunodermatological tests. RESULTS: Diagnosis of EAA relied on congruent clinical and radiological information, confirmed occupational HDI exposure and positive IgG antibodies and patch tests. The patient worked in a small laboratory for 7 years, only occasionally using HDI-containing hardeners. While working with HDI for 6 h, she developed breathlessness, rapidly progressing to severe respiratory failure. Workplace HDI airborne exposure values ranged from undetectable levels to 4.25 p.p.b. Biological monitoring of urinary hexamethylene diamine in co-workers ranged from <1.0 to 15.4 μg/g creatinine. Patch tests 8 months later showed delayed skin reaction to HDI at 48 h. Subsequent skin biopsy showed spongiotic dermatitis with infiltration of CD4(+) and CD8(+) T cells. CONCLUSIONS: We believe this is the first reported case of acute life-threatening EAA following exposure to HDI. Low concentrations of airborne HDI and relatively high urinary hexamethylene diamine suggest significant skin absorption of HDI could have significantly contributed to the development of this acute occupational EAA.

Production endogène de Nortestostérone chez l'homme et influence de l'activité physique et du régime alimentaire

RESUME Depuis les années 1980, les stéroïdes androgéniques anabolisants (SAA) sont restés les produits dopants les plus utilisés par les sportifs. Les propriétés principales attribuées à ces substances sont une augmentation de la masse et de la force musculaire ainsi qu'une agressivité supérieure pouvant s'avérer bénéfique lors des entraînements ou des compétitions. En plus de cette "tradition" liée à la consommation des SAA, une autre problématique est apparue dans le monde antidopage suite à la fulgurante expansion de l'utilisation des compléments alimentaires par les athlètes professionnels et amateurs. Dès la fin des années 1990, une recrudescence de cas positifs de dopage aux SAA a été attribuée à la contamination des compléments alimentaires par des composés anabolisants tels que la testostérone ou la nandrolone ou par des prohormones se situant en amont dans le métabolisme de certains SAA et conduisant à la présence, dans les urines, de traces de substances interdites par l'Agence Mondiale Antidopage (AMA). Afin de mettre en garde les autorités antidopage ainsi que les athlètes quant aux problèmes liés aux compléments alimentaires, le Laboratoire Suisse d'Analyse du Dopage (LAD) a décidé d'étudier de manière plus précise la composition d'une centaine de produits accessibles en Suisse par l'intermédiaire d'internet. Cette étude a permis de mettre en évidence un taux de non conformité des produits avoisinant les 20%, avec une contamination plus importante des produits contenant des hormones ou des prohormones. La consommation de doses journalières recommandées des produits contaminés a mené à la détection dans les urines de la présence de substances interdites par l'AMA. Ces résultats confirment ainsi que l'usage de compléments alimentaires peut s'avérer dangereuse dans le cadre de contrôles antidopage et que les effets sur l'état physique et mental des athlètes peuvent dépasser les effets désirés et être dramatiques pour la poursuite d'une carrière sportive. D'autre part, cela démontre que l'alimentation peut mener à la présence urinaire de substances proscrites telles que les métabolites de la nandrolone, la 19-norandrostéreone (19-NA) et la 19-norétiocholanolone (19-NE). Afin de démontrer un effet potentiel de l'exercice physique sur l'excrétion urinaire des métabolites de la nandrolone, une première étude clinique a été réalisée avec 34 volontaires. Deux doses orales de nandrolone marquée avec deux atomes de C13 ont été administrées aux sujets. Les urines ont été récoltées durant les 5 jours suivant les prises orales (études d'excrétion) ainsi qu'avant et après les 8 séances d'entraînements du protocole. Les analyses des études d'excrétion ont permis d'établir une variabilité intra- et inter-individuelle du métabolisme et de la pharmacocinétique de la 19-NA et de la 19-NE. En dépit de la rapide élimination urinaire des métabolites de la nandrolone C13, les analyses des échantillons prélevés avant et après les différents efforts n'ont pas révélé une influence nette de l'exercice physique sur les concentrations urinaires de la 19-NA et 19-NE. Une seconde étude clinique a été effectuée, avec la participation de 30 volontaires. Il s'agissait de déterminer si la consommation de multiples doses orales d'un décanoate de testostérone, de 19-norandrostenedione (un précurseur de la nandrolone) ou de placebo durant un mois, pouvait avoir des effets bénéfiques sur la récupération et la performance physique. En parallèle, les sujets étaient soumis à un entrainement d'endurance intense et individualisé. Divers paramètres physiologiques ont été étudiés dans le sérum et les urines afin de mettre en évidence une meilleure récupération de l'organisme. Aucun de ses paramètres n'a permis de conclure que la consommation orale de SAA est favorable pour optimaliser les capacités de récupération des athlètes. De plus, les performances physiques ont été évaluées avant et après l'entraînement et le traitement. Aucune différence significative n'a été démontrée entre les trois groupes de volontaires. L'état psychologique des volontaires a été évalué à l'aide de questionnaires (short Profile of Mood State, sPOMS) remplis à trois reprises au cours du protocole. De manière générale, l'évolution observée est une augmentation de la fatigue avec une diminution de la vigueur. Des analyses statistiques ont révélé que des prises orales de testostérone, et dans une moindre mesure de 19-norandrostenedione, ont une légère influence sur cette évolution générale en diminuant les effets de l'entrainement sur le profil psychologique. Les urines récoltées durant le protocole ont été analysées par GC/C/IRMS et GCMS afin de détecter les variations des concentrations des hormones liées au métabolisme de la testostérone. Les résultats ont démontré une variabilité interindividuelle du métabolisme de la testostérone qui implique que les critères de positivité imposés par l'AMA ne sont pas forcément valables pour tous les individus. La détection de la 19-NA et de la 19-NE, issus du métabolisme in vivo de la 19norandrostenedione, a confirmé les résultats obtenus sur la pharmacocinétique et le métabolisme de la nandrolone C13 obtenus lors de la première étude clinique. Ce travail a permis de clarifier certains points en lien avec l'abus de la nandrolone dans le sport et notamment par rapport à la consommation de compléments alimentaires. Les deux études cliniques n'ont pas véritablement apporté les réponses souhaitées aux hypothèses de départ. Cependant certains aspects intéressants en relation avec le métabolisme des SAA ont été découverts et pourront peut-être permettre à la lutte antidopage d'évoluer vers une meilleure efficacité. SUMMARY Since 1980's, anabolic androgenic steroids (AAS) are still the most used doping agents in sports. The main properties attributed to these substances are an increase of muscle mass and strength and also a higher aggressiveness that could be beneficial during trainings and competitions. In addition to this "tradition" linked to the AAS intake, another problematics has raised in the antidoping field. Indeed, nutritional supplements have been more and more used by professional and amateur athletes. Since the end of the 1990's, an outburst of positive doping cases with AAS has been attributed to nutritional supplements contaminations with anabolic compounds like testosterone or nandrolone or with prohormones located above in the metabolism of some AAS and prompting urinary traces of forbidden compounds by the World Antidoping Agency (WADA). In order to inform the antidoping authorities and the athletes about the problems linked to the nutritional supplements, the Swiss Laboratory for Doping Analyses (LAD) decided to investigate more precisely the composition of about hundred products accessible in Switzerland through different web sites. This study showed that about 20% of the products were not conformed to the composition announced by the manufacturers. The oral intake of daily recommended doses of the contaminated products revealed the presence in urines of forbidden substances by the WADA. Hence, these results confirm that the use of nutritional supplements can lead to adverse analytical findings in antidoping controls and that the effects on athletes' physical and mental state could be different from the ones desired and could be dramatic for the continuation of an athlete's career. Moreover, this demonstrates that the diet can lead to the presence in urines of proscribed substances like nandrolone metabolites, i.e. 19-norandrosterone (19-NA) and 19-noretiocholanolone (19-NE). To put forward a potential effect of physical exercise on urinary nandrolone metabolites excretion rate, a first clinical study was done with 34 volunteers. Two oral doses of nandrolone labelled with two C13 atoms were administered to the subjects. The urines were collected during the 5 days following the treatment (excretion studies) and before and after the 8 exercise sessions of the protocol. The analyses of excretion studies revealed an intra- and inter-individual variability of the metabolism and the pharmacokinetics of 19-NA and 19-NE. In spite of the rapid urinary elimination of the nandrolone C13 metabolites, the analyses of the urine samples gathered before and after efforts did not show a clear influence of physical exercise on the urinary 19-NA and 19-NE concentrations. A second clinical study was done with the participation of 30 volunteers. The main aim was to determine if multiple oral doses of testosterone undecanoate, 19-norandrostenedione (a nandrolone precursor) or placebo during one month, could have beneficial effects on recovery and physical performance. Meanwhile, the individuals had to follow an intense and personalized endurance training program. Several physiological parameters were investigated in serum and urines in order to demonstrate a better organism's recovery. None of these parameters lead to the conclusion that oral intake of AAS is useful to optimise the recovery capacities of athletes. In addition, physical performances were evaluated before and after the training and treatment month. No significant difference was shown between the three volunteers groups. The psychological state of the volunteers was assessed through questionnaires (short Profile of Mood State, sP4MS) filled three times during the protocol. The global evolution is an increase of fatigue with an decrease of vigour. Statistical analyses revealed that the oral intake of testosterone, and to a lesser extent of 19= norandrostenedione, have a small influence on this general evolution in decreasing the effect of training on the psychological profile. The urines collected during the protocol were analysed by GC/C/IRMS and GCMS to detect concentrations variations of hormones related to the testosterone metabolism. The results revealed an interindividual variability of testosterone metabolism which implies that the guidance concerning endogenous steroids prescribed by the WADA are not uniformly valid for all individuals. Detection of 19-NA and 19-NE, coming from the in vivo metabolism of 19norandrostenedione, confirmed the results previously obtained on the pharamcokinetics and metabolism of the nandrolone C13 in the first clinical study. This work allowed to clarify some aspects linked to nandrolone abuse in sports and noteworthy related to nutritional supplements intake. The two clinical studies did not really bring plain answers to the basal hypotheses but some interesting aspects in relation with AAS metabolism were put forth and would perhaps allow an evolution of a more effective fight against doping.

Wide resection of the lateral malleolus and adjacent tibial, talar and calcanear bones with ankle fusion and allograft reconstruction for an osteosarcoma.

Introduction: Primary bone sarcomas around the ankle are rare. Due to the proximity of neurovascular structures and limited soft tissue reserves, limb salvage is often not possible. Case report: A 19 yo male presented with pain and a progressive swelling of his ankle. X-rays revealed cortical erosions and an extensive periosteal reaction (sunburst) of the distal fibula. MRI showed a large mass of the fibula invading adjacent soft tissue. The lesion appeared close to the ankle joint, but with the articular cartilage as a barrier and without joint effusion. Core-needle biopsy revealed a high-grade chondroblastic osteosarcoma. No metastases were detected. After presentation at our multidisciplinary sarcoma board, the patient was subjected to neo-adjuvant chemotherapy (AOST 03-331). Without any sign of intra-articular contamination of the ankle joint, surgical treatment consisted of wide resection of the lateral malleolus including a large skin patch, the distal third of the fibula, the lateral surfaces of the tibia and talus as well as the insertion of the lateral ligament on the calcaneus. The distal parts of the anterior, peroneal, and posterior muscular compartments were resected en bloc with the tumor. The defect was reconstructed with tibio-talar and talo-calcanear fusion, bony allograft and a plate. Soft-tissue coverage was achieved with a free fascio-cutaneous flap from the controlateral thigh. Histological analysis revealed clear margins and 50% of tumor necrosis. The oncologic treatment was completed with adjuvant chemotherapy. Conclusion: Wide resection and reconstruction of the lateral malleolus is technically demanding but possible in selected cases. Despite some important functional loss, limb salvage is superior to an amputation.

Model development for capercaillie (Tetrao urogallus) habitat in the Jura Mountains (Western Switzerland)

Capercaillie, Tetrao urogallus, is a threatened species in central Europe, and Swiss populations declined 40 to 50 % between 1970 and 1985. Capercaillie are sensitive to forest structure, and loss of habitat is a major cause of their decline. Knowledge of habitat characteristics is therefore essential for capercaillie conservation. Here, we present models predicting capercaillie probability of occurrence, based on relevant structural habitat variables. Models were built using multiple logistic regression analyses on capercaillie presence/absence data. Vegetation survey was carried out in July 1999 in a 170-km2 forested area (Jura mountains, canton de Vaud, western Switzerland) inhabited by capercaillie and presence/absence of the species was assessed according to dropping presence/absence. The survey was based on 10-m-radius sample plots each in a 1-km2 forest patch (n = 76 with capercaillie droppings, n = 80 without). A first model included seven out of 27 measured habitat variables and a second model only four. The latter model best represents practical needs. It includes three variables which had a negative impact on capercaillie presence: tree and shrub covers and spruce, Picea excelsa, shrub cover, and one which had a positive effect: bilberry, Vaccinium myrtillus, cover, highlighting that capaercaillie selected open forest with high bilberry abundance. The model can be used to map potential capercaillie habitat distribution and to manage the habitat in favour of capercaillie (protection and adapted forestry practices) in the Swiss Jura mountains.

The co-evolution of social institutions, demography, and large-scale human cooperation.

Human cooperation is typically coordinated by institutions, which determine the outcome structure of the social interactions individuals engage in. Explaining the Neolithic transition from small- to large-scale societies involves understanding how these institutions co-evolve with demography. We study this using a demographically explicit model of institution formation in a patch-structured population. Each patch supports both social and asocial niches. Social individuals create an institution, at a cost to themselves, by negotiating how much of the costly public good provided by cooperators is invested into sanctioning defectors. The remainder of their public good is invested in technology that increases carrying capacity, such as irrigation systems. We show that social individuals can invade a population of asocials, and form institutions that support high levels of cooperation. We then demonstrate conditions where the co-evolution of cooperation, institutions, and demographic carrying capacity creates a transition from small- to large-scale social groups.

ConnectomeViewer - Multi-Modal Multi-Level Network Visualization and Analysis.

Introduction: The field of Connectomic research is growing rapidly, resulting from methodological advances in structural neuroimaging on many spatial scales. Especially progress in Diffusion MRI data acquisition and processing made available macroscopic structural connectivity maps in vivo through Connectome Mapping Pipelines (Hagmann et al, 2008) into so-called Connectomes (Hagmann 2005, Sporns et al, 2005). They exhibit both spatial and topological information that constrain functional imaging studies and are relevant in their interpretation. The need for a special-purpose software tool for both clinical researchers and neuroscientists to support investigations of such connectome data has grown. Methods: We developed the ConnectomeViewer, a powerful, extensible software tool for visualization and analysis in connectomic research. It uses the novel defined container-like Connectome File Format, specifying networks (GraphML), surfaces (Gifti), volumes (Nifti), track data (TrackVis) and metadata. Usage of Python as programming language allows it to by cross-platform and have access to a multitude of scientific libraries. Results: Using a flexible plugin architecture, it is possible to enhance functionality for specific purposes easily. Following features are already implemented: * Ready usage of libraries, e.g. for complex network analysis (NetworkX) and data plotting (Matplotlib). More brain connectivity measures will be implemented in a future release (Rubinov et al, 2009). * 3D View of networks with node positioning based on corresponding ROI surface patch. Other layouts possible. * Picking functionality to select nodes, select edges, get more node information (ConnectomeWiki), toggle surface representations * Interactive thresholding and modality selection of edge properties using filters * Arbitrary metadata can be stored for networks, thereby allowing e.g. group-based analysis or meta-analysis. * Python Shell for scripting. Application data is exposed and can be modified or used for further post-processing. * Visualization pipelines using filters and modules can be composed with Mayavi (Ramachandran et al, 2008). * Interface to TrackVis to visualize track data. Selected nodes are converted to ROIs for fiber filtering The Connectome Mapping Pipeline (Hagmann et al, 2008) processed 20 healthy subjects into an average Connectome dataset. The Figures show the ConnectomeViewer user interface using this dataset. Connections are shown that occur in all 20 subjects. The dataset is freely available from the homepage (connectomeviewer.org). Conclusions: The ConnectomeViewer is a cross-platform, open-source software tool that provides extensive visualization and analysis capabilities for connectomic research. It has a modular architecture, integrates relevant datatypes and is completely scriptable. Visit www.connectomics.org to get involved as user or developer.

The cost effectiveness of pharmacological smoking cessation therapies in developing countries: a case study in the Seychelles

OBJECTIVE: To examine the incremental cost effectiveness of the five first line pharmacological smoking cessation therapies in the Seychelles and other developing countries. DESIGN: A Markov chain cohort simulation. SUBJECTS: Two simulated cohorts of smokers: (1) a reference cohort given physician counselling only; (2) a treatment cohort given counselling plus cessation therapy. INTERVENTION: Addition of each of the five pharmacological cessation therapies to physician provided smoking cessation counselling. MAIN OUTCOME MEASURES: Cost per life-year saved (LYS) associated with the five pharmacotherapies. Effectiveness expressed as odds ratios for quitting associated with pharmacotherapies. Costs based on the additional physician time required and retail prices of the medications. RESULTS: Based on prices for currently available generic medications on the global market, the incremental cost per LYS for a 45 year old in the Seychelles was 599 US dollars for gum and 227 dollars for bupropion. Assuming US treatment prices as a conservative estimate, the incremental cost per LYS was significantly higher, though still favourable in comparison to other common medical interventions: 3712 dollars for nicotine gum, 1982 dollars for nicotine patch, 4597 dollars for nicotine spray, 4291 dollars for nicotine inhaler, and 1324 dollars for bupropion. Cost per LYS increased significantly upon application of higher discount rates, which may be used to reflect relatively high opportunity costs for health expenditures in developing countries with highly constrained resources and high overall mortality. CONCLUSION: Pharmacological cessation therapy can be highly cost effective as compared to other common medical interventions in low mortality, middle income countries, particularly if medications can be procured at low prices.

Determinants of maternal sex steroids during the first half of pregnancy.

OBJECTIVE: To examine the associations of maternal and child characteristics with early pregnancy maternal concentrations of testosterone, androstenedione, progesterone, 17-hydroxyprogesterone, and estradiol (E2). METHODS: We analyzed these hormones among 1,343 women with singleton pregnancies who donated serum samples to the Finnish Maternity Cohort from 1986 to 2006 during the first half of pregnancy (median 11 weeks). The associations of maternal and child characteristics with hormone concentrations were investigated by correlation and multivariable regression. RESULTS: Women older than age 30 years had lower androgen and E2 but higher progesterone concentrations than women younger than that age. Multiparous women had 14% lower testosterone, 11% lower androstenedione and 17-hydroxyprogesterone, 9% lower progesterone, and 16% lower E2 concentrations compared with nulliparous women (all P<.05). Smoking mothers had 11%, 18%, and 8% higher testosterone, androstenedione, and 17-hydroxyprogesterone levels, respectively, but 10% lower progesterone compared with nonsmoking women (all P<.05). E2 concentrations were 9% higher (P<.05) among women with a female fetus compared with those with a male fetus. CONCLUSION: Parity, smoking, and, to a lesser extent, maternal age and child sex are associated with sex steroid levels during the first half of a singleton pregnancy. The effects of smoking on the maternal hormonal environment and the possible long-term deleterious consequences on the fetus deserve further evaluation. LEVEL OF EVIDENCE: II.