Divergent and convergent margins in the north-western Alps - Confrontation to actualistic models

Divergent and convergent margins actualistic models are reviewed and applied to the history of the western Alps. Tethyan rifting history and geometry are analyzed: the northern European margin is considered as an upper plate whereas the southern Apulian margin is a lower plate; the Breche basin is regarded as the former break-away trough; the internal Brianconnais domain represents the northern rift shoulder whilst the more external domains are regarded as the infill of a complex rim basin locally affected by important extension (Valaisan and Vocontain trough). The Schistes lustres and ophiolites of the Tsate nappe are compared to an accretionary prism: the imbrication of this nappe elements is regarded as a direct consequence of the accretionary phenomena already active in early Cretaceous; the Gets/Simme complex could orginate from a more internal part of the accretionary prism. Some eclogitic basements represent the former Apulian margin substratum (Sesia) others (Mont-Rose) are interpreted as the former edge of the European margin. The history of the closing Tethyan domain is analyzed and the remaining problems concerning the cinematics, the presence/absence of a volcanic arc and the eoalpine metamorphism are discussed.

Soft tissue sarcomas with complex genomic profiles.

Soft tissue sarcomas (STS) with complex genomic profiles (50% of all STS) are predominantly composed of spindle cell/pleomorphic sarcomas, including leiomyosarcoma, myxofibrosarcoma, pleomorphic liposarcoma, pleomorphic rhabdomyosarcoma, malignant peripheral nerve sheath tumor, angiosarcoma, extraskeletal osteosarcoma, and spindle cell/pleomorphic unclassified sarcoma (previously called spindle cell/pleomorphic malignant fibrous histiocytoma). These neoplasms show, characteristically, gains and losses of numerous chromosomes or chromosome regions, as well as amplifications. Many of them share recurrent aberrations (e.g., gain of 5p13-p15) that seem to play a significant role in tumor progression and/or metastatic dissemination. In this paper, we review the cytogenetic, molecular genetic, and clinicopathologic characteristics of the most common STS displaying complex genomic profiles. Features of diagnostic or prognostic relevance will be discussed when needed.

Objective analysis of gait coordination for total knee arthroplasty outcome

Introduction: Coordination is a strategy chosen by the central nervous system to control the movements and maintain stability during gait. Coordinated multi-joint movements require a complex interaction between nervous outputs, biomechanical constraints, and pro-prioception. Quantitatively understanding and modeling gait coordination still remain a challenge. Surgeons lack a way to model and appreciate the coordination of patients before and after surgery of the lower limbs. Patients alter their gait patterns and their kinematic synergies when they walk faster or slower than normal speed to maintain their stability and minimize the energy cost of locomotion. The goal of this study was to provide a dynamical system approach to quantitatively describe human gait coordination and apply it to patients before and after total knee arthroplasty. Methods: A new method of quantitative analysis of interjoint coordination during gait was designed, providing a general model to capture the whole dynamics and showing the kinematic synergies at various walking speeds. The proposed model imposed a relationship among lower limb joint angles (hips and knees) to parameterize the dynamics of locomotion of each individual. An integration of different analysis tools such as Harmonic analysis, Principal Component Analysis, and Artificial Neural Network helped overcome high-dimensionality, temporal dependence, and non-linear relationships of the gait patterns. Ten patients were studied using an ambulatory gait device (Physilog®). Each participant was asked to perform two walking trials of 30m long at 3 different speeds and to complete an EQ-5D questionnaire, a WOMAC and Knee Society Score. Lower limbs rotations were measured by four miniature angular rate sensors mounted respectively, on each shank and thigh. The outcomes of the eight patients undergoing total knee arthroplasty, recorded pre-operatively and post-operatively at 6 weeks, 3 months, 6 months and 1 year were compared to 2 age-matched healthy subjects. Results: The new method provided coordination scores at various walking speeds, ranged between 0 and 10. It determined the overall coordination of the lower limbs as well as the contribution of each joint to the total coordination. The difference between the pre-operative and post-operative coordination values were correlated with the improvements of the subjective outcome scores. Although the study group was small, the results showed a new way to objectively quantify gait coordination of patients undergoing total knee arthroplasty, using only portable body-fixed sensors. Conclusion: A new method for objective gait coordination analysis has been developed with very encouraging results regarding the objective outcome of lower limb surgery.

Evaluating sampling strategies and logistic regression methods for modelling complex land cover changes

The role of land cover change as a significant component of global change has become increasingly recognized in recent decades. Large databases measuring land cover change, and the data which can potentially be used to explain the observed changes, are also becoming more commonly available. When developing statistical models to investigate observed changes, it is important to be aware that the chosen sampling strategy and modelling techniques can influence results. We present a comparison of three sampling strategies and two forms of grouped logistic regression models (multinomial and ordinal) in the investigation of patterns of successional change after agricultural land abandonment in Switzerland. Results indicated that both ordinal and nominal transitional change occurs in the landscape and that the use of different sampling regimes and modelling techniques as investigative tools yield different results. Synthesis and applications. Our multimodel inference identified successfully a set of consistently selected indicators of land cover change, which can be used to predict further change, including annual average temperature, the number of already overgrown neighbouring areas of land and distance to historically destructive avalanche sites. This allows for more reliable decision making and planning with respect to landscape management. Although both model approaches gave similar results, ordinal regression yielded more parsimonious models that identified the important predictors of land cover change more efficiently. Thus, this approach is favourable where land cover change pattern can be interpreted as an ordinal process. Otherwise, multinomial logistic regression is a viable alternative.

Shallow-level migmatization of gabbros in a metamorphic contact aureole, Fuerteventura Basal Complex, Canary Islands

Migmatization of gabbroic rocks at 2-3 kbar has occurred in the metamorphic contact aureole of a mafic pluton in the Fuerteventura Basal Complex (Canary Island;). Migmatites are characterized by a dense network: of closely spaced millimetre-wide leucocratic veins with perfectly preserved igneous textures. They are all relatively enriched in Al, Na I: Sr Ba, Nb, Y and the rare earth elements compared with the unaffected country rock beyond the aureole. Migmatization under such low-pressure conditions war possible because of the unusual tectonic and magmatic contact in which ii occurred. Multiple basic intrusions associated with extrusive volcanic activity created high heat flow in a small area. Alkaline and metasomatized rocks present in the country rock of the intruding pluton were leached by high-temperature fluids during contact metamorphism. These enriched fluids then favoured partial melting of the host gabbroic rocks, and contaminated both the leucosomes and melanosomes. A transpressive tectonic setting at the time of intrusion created shearing along the contact between the intrusion and its host rock. This shearing enhanced circulation of the fluids and allowed segregation of the nea-formed melts from their restite by opening tension veins into which the melts migrated. Depending on the relative timing of melt segregation and recrystallization leucosomes range in composition from a 40-60% mixture of clinopyroxene (+/- amphibole) and plagioclase to almost pure feldspathic veins. Comparable occurrences of gabbros migmatized at low pressure are expected only at a snail scale in localized areas of high heat flow in the presence of fluids, such as in. mid-ocean ridges or ocean-islands.

Chondrodysplasia and Abnormal Joint Development Associated with Mutations in IMPAD1, Encoding the Golgi-Resident Nucleotide Phosphatase, gPAPP.

We used whole-exome sequencing to study three individuals with a distinct condition characterized by short stature, chondrodysplasia with brachydactyly, congenital joint dislocations, cleft palate, and facial dysmorphism. Affected individuals carried homozygous missense mutations in IMPAD1, the gene coding for gPAPP, a Golgi-resident nucleotide phosphatase that hydrolyzes phosphoadenosine phosphate (PAP), the byproduct of sulfotransferase reactions, to AMP. The mutations affected residues in or adjacent to the phosphatase active site and are predicted to impair enzyme activity. A fourth unrelated patient was subsequently found to be homozygous for a premature termination codon in IMPAD1. Impad1 inactivation in mice has previously been shown to produce chondrodysplasia with abnormal joint formation and impaired proteoglycan sulfation. The human chondrodysplasia associated with gPAPP deficiency joins a growing number of skeletoarticular conditions associated with defective synthesis of sulfated proteoglycans, highlighting the importance of proteoglycans in the development of skeletal elements and joints.

The mouse Lyt-2/3 antigen complex--II. Structural analysis of the subunits.

Surface- or biosynthetically labeled Lyt-2/3 antigens were isolated from cell lysates by immunoprecipitation and affinity chromatography with a monoclonal antibody. Tryptic digests of the individual subunits of 37,000, 32,000 and 28,000 apparent mol. wts were analysed by reverse-phase high-performance liquid chromatography and by two-dimensional peptide mapping. The results indicate that the 37,000 and 32,000 mol. wt components are structurally very similar whereas the 28,000 mol. wt component appears as a different molecule.

Pets as the main source of two zoonotic species of the Trichophyton mentagrophytes complex in Switzerland, Arthroderma vanbreuseghemii and Arthroderma benhamiae

In cases of highly inflammatory dermatophytosis in humans, it is important to identify the possible source of animal transmission in order to prevent recurrence, family outbreaks or rapidly progressing epidemics. A survey of dermatophytes in pets during a 14-month period in Switzerland revealed, in addition to Microsporum canis, two different species of the Trichophyton mentagrophytes complex, Arthroderma benhamiae and Arthroderma vanbreuseghemii, all causing inflammatory dermatophytoses. Arthroderma benhamiae was only and frequently isolated from guinea pigs. Arthroderma vanbreuseghemii was isolated mainly from European short hair cats, but also from dogs and in one case from a pure-bred cat. Ninety-three percent of the cats carrying A. vanbreuseghemii were hunters and all had skin lesions. In contrast, cats with skin lesions that were strictly indoors were found to be almost exclusively infected by M. canis. Therefore, it can be suspected that infection with A. vanbreuseghemii occurred during hunting and that the natural source of this dermatophyte is either soil or an animal other than the cat, most probably a rodent.

Structure of a multisubunit complex that promotes DNA branch migration.

The RuvA and RuvB proteins of Escherichia coli, which are induced in response to DNA damage, are important in the formation of heteroduplex DNA during genetic recombination and related recombinational repair processes. In vitro studies show that RuvA binds Holiday junctions and acts as a specificity factor that targets the RuvB ATPase, a hexameric ring protein, to the junction. Together, RuvA and RuvB promote branch migration, an ATP-dependent reaction that increases the length of the heteroduplex DNA. Electron microscopic visualization of RuvAB now provides a new insight into the mechanism of this process. We observe the formation of a tripartite protein complex in which RuvA binds the crossover and is sandwiched between two hexameric rings of RuvB. The Holliday junction within this complex adopts a square-planar structure. We propose a molecular model for branch migration, a unique feature of which is the role played by the two oppositely oriented RuvB ring motors.

Developments in the scientific and clinical understanding of gout.

Gout is the most common form of inflammatory arthritis in the elderly. In the last two decades, both hyperuricemia and gout have increased markedly and similar trends in the epidemiology of the metabolic syndrome have been observed. Recent studies provide new insights into the transporters that handle uric acid in the kidney as well as possible links between these transporters, hyperuricemia, and hypertension. The treatment of established hyperuricemia has also seen new developments. Febuxostat and PEG-uricase are two novel treatments that have been evaluated and shown to be highly effective in the management of hyperuricemia, thus enlarging the therapeutic options available to lower uric acid levels. Monosodium urate (MSU) crystals are potent inducers of inflammation. Within the joint, they trigger a local inflammatory reaction, neutrophil recruitment, and the production of pro-inflammatory cytokines as well as other inflammatory mediators. Experimentally, the uptake of MSU crystals by monocytes involves interactions with components of the innate immune system, namely Toll-like receptor (TLR)-2, TLR-4, and CD14. Intracellularly, MSU crystals activate multiple processes that lead to the formation of the NALP-3 (NACHT, LRR, and pyrin domain-containing-3) inflammasome complex that in turn processes pro-interleukin (IL)-1 to yield mature IL-1 beta, which is then secreted. The inflammatory effects of MSU are IL-1-dependent and can be blocked by IL-1 inhibitors. These advances in the understanding of hyperuricemia and gout provide new therapeutic targets for the future.

Disseminated M. avium complex infection in the Swiss HIV Cohort Study: declining incidence, improved prognosis and discontinuation of maintenance therapy.

Introduction of potent antiretroviral combination therapy (ART) has reduced overall morbidity and mortality amongst HIV-infected adults. Some prophylactic regimes against opportunistic infections can be discontinued in patients under successful ART. (1) The influence of the availability of ART on incidence and mortality of disseminated M. avium Complex infection (MAC). (2) The safety of discontinuation of maintenance therapy against MAC in patients on ART. The Swiss HIV-Cohort Study, a prospective multicentre study of HIV-infected adults. Patients with a nadir CD4 count below 50 cells/mm3 were considered at risk for MAC and contributed to total follow-up time for calculating the incidence. Survival analysis was performed by using Kaplan Meier and Cox proportional hazards methods. Safety of discontinuation of maintenance therapy was evaluated by review of the medical notes. 398 patients were diagnosed with MAC from 1990 to 1999. 350 had a previous CD4 count below 50 cells/mm3. A total of 3208 patients had a nadir CD4 count of less than 50 cells/mm3 during the study period and contributed to a total follow-up of 6004 person-years. The incidence over the whole study period was 5.8 events per 100 person-years. In the time period of available ART the incidence of MAC was significantly reduced (1.4 versus 8.8 events per 100 person-years, p < 0.001). Being diagnosed after 1995 was the most powerful predictor of better survival (adjusted hazard ratio for death: 0.27; p < 0.001). None of 24 patients discontinuing maintenance therapy while on ART experienced recurrence of MAC during a total follow-up of 56.6 person-years (upper 95% confidence limit 5.3 per 100 person-years). Introducing ART has markedly reduced the risk of MAC for HIV-infected individuals with a history of very low CD4 counts. Survival after diagnosis of MAC has improved after ART became available. In patients responding to ART, discontinuation of maintenance therapy against M. avium may be safe.

Complex landslide behaviour and structural controlled by the structures: A 3D conceptual model example of Åknes rockslide, Norway

Åknes is an active complex large rockslide of approximately 30?40 Mm3 located within the Proterozoic gneisses of western Norway. The observed surface displacements indicate that this rockslide is divided into several blocks moving in different directions at velocities of between 3 and 10 cm year?1. Because of regional safety issues and economic interests this rockslide has been extensively monitored since 2004. The understanding of the deformation mechanism is crucial for the implementation of a viable monitoring system. Detailed field investigations and the analysis of a digital elevation model (DEM) indicate that the movements and the block geometry are controlled by the main schistosity (S1) in gneisses, folds, joints and regional faults. Such complex slope deformations use pre-existing structures, but also result in new failure surfaces and deformation zones, like preferential rupture in fold-hinge zones. Our interpretation provides a consistent conceptual three-dimensional (3D) model for the movements measured by various methods that is crucial for numerical stability modelling. In addition, this reinterpretation of the morphology confirms that in the past several rockslides occurred from the Åknes slope. They may be related to scars propagating along the vertical foliation in folds hinges. Finally, a model of the evolution of the Åknes slope is presented.

Selective abrogation of major histocompatibility complex class II expression on extrahematopoietic cells in mice lacking promoter IV of the class II transactivator gene.

MHC class II (MHCII) molecules play a pivotal role in the induction and regulation of immune responses. The transcriptional coactivator class II transactivator (CIITA) controls MHCII expression. The CIITA gene is regulated by three independent promoters (pI, pIII, pIV). We have generated pIV knockout mice. These mice exhibit selective abrogation of interferon (IFN)-gamma-induced MHCII expression on a wide variety of non-bone marrow-derived cells, including endothelia, epithelia, astrocytes, and fibroblasts. Constitutive MHCII expression on cortical thymic epithelial cells, and thus positive selection of CD4(+) T cells, is also abolished. In contrast, constitutive and inducible MHCII expression is unaffected on professional antigen-presenting cells, including B cells, dendritic cells, and IFN-gamma-activated cells of the macrophage lineage. pIV(-/-) mice have thus allowed precise definition of CIITA pIV usage in vivo. Moreover, they represent a unique animal model for studying the significance and contribution of MHCII-mediated antigen presentation by nonprofessional antigen-presenting cells in health and disease.