Le diabète de type 2 est-il uniquement une affaire d'hyperglycémie? Entre science, humanisme et economie [Type 2 diabetes, is it just a case of hyperglycemia? Confusion between the interests of science, humanity and the economy]

The recommendations for the treatment of type 2 diabetic patients are often centered on the glycemia. These clinical trials based on this approach show only a beneficial effects on the prevention of microangiopathy. The coronary artery disease which is the main cause of mortality among these patients, is not reduced. These data should be interpreted with a systemic prospect. The diabetes vascular complications have multifactorial causes and these clinical trials are motivated for the promotion of hypoglycemic agents. Fortunately, the STENO study offers another glance on the treatment of the diabetes, associating multirisk approach and patients' accompaniment. It obliges to have a critical glance on the research often moved by economic issues and gives to the center a humanistic approach based on the therapeutic relation.

CSF1R mutations link POLD and HDLS as a single disease entity.

OBJECTIVE: Pigmented orthochromatic leukodystrophy (POLD) and hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) are rare neurodegenerative disorders characterized by cerebral white matter abnormalities, myelin loss, and axonal swellings. The striking overlap of clinical and pathologic features of these disorders suggested a common pathogenesis; however, no genetic or mechanistic link between POLD and HDLS has been established. Recently, we reported that mutations in the colony-stimulating factor 1 receptor (CSF1R) gene cause HDLS. In this study, we determined whether CSF1R mutations are also a cause of POLD. METHODS: We performed sequencing of CSF1R in 2 pathologically confirmed POLD families. For the largest family (FTD368), a detailed case report was provided and brain samples from 2 affected family members previously diagnosed with POLD were re-evaluated to determine whether they had HDLS features. In vitro functional characterization of wild-type and mutant CSF1R was also performed. RESULTS: We identified CSF1R mutations in both POLD families: in family 5901, we found c.2297T>C (p.M766T), previously reported by us in HDLS family CA1, and in family FTD368, we identified c.2345G>A (p.R782H), recently reported in a biopsy-proven HDLS case. Immunohistochemical examination in family FTD368 showed the typical neuronal and glial findings of HDLS. Functional analyses of CSF1R mutant p.R782H (identified in this study) and p.M875T (previously observed in HDLS), showed a similar loss of CSF1R autophosphorylation of selected tyrosine residues in the kinase domain for both mutations when compared with wild-type CSF1R. CONCLUSIONS: We provide the first genetic and mechanistic evidence that POLD and HDLS are a single clinicopathologic entity.

Can Soil Penetration Resistance and Bulk Density Be Determined in a Single Undisturbed Sample?

Soil quality indicators such as penetration resistance (PR) and bulk density (BD) are traditionally determined in a single undisturbed soil sample. The aim of this study was to assess the effect of PR measurements of undisturbed samples on the determination of BD in the same sample of two soils differing in clay contents. To this end, samples were collected from the 0.00-0.10 and 0.10-0.20 m layers of two soils of clayey and very clayey texture. Volumetric rings were used to collect a total of 120 undisturbed soil samples from each soil layer that were divided into two subsets containing 60 units each. One sample set, designated “perforated samples”, was used to determine PR and BD in the same undisturbed sample; the other, named “intact samples”, was used to determine BD only. Bulk density values for perforated and intact samples were compared by analysis of variance, using a completely randomized experimental design. Means were compared by the t-test at 5 %. The BD values for the clayey soil were similar in perforated and intact samples from the two layers. However, BD of the very clayey soil was lower in the perforated than in the intact samples at both depths. Therefore, PR and BD in clayey soils can be accurately determined in the same undisturbed sample whereas in very clayey soils, different samples are required for this purpose.

A multicenter phase II trial (SAKK 36/06) of single-agent everolimus (RAD001) in patients with relapsed or refractory mantle cell lymphoma.

BACKGROUND: Mantle cell lymphoma accounts for 6% of all B-cell lymphomas and is generally incurable. It is characterized by the translocation t(11;14) leading to cyclin D1 over-expression. Cyclin D1 is downstream of the mammalian target of rapamycin threonine kinase and can be effectively blocked by mammalian target of rapamycin inhibitors. We set out to examine the single agent activity of the orally available mammalian target of rapamycin inhibitor everolimus in a prospective, multicenter trial in patients with relapsed or refractory mantle cell lymphoma (NCT00516412). DESIGN AND METHODS: Eligible patients who had received a maximum of three prior lines of chemotherapy were given everolimus 10 mg for 28 days (one cycle) for a total of six cycles or until disease progression. The primary endpoint was the best objective response. Adverse reactions, progression-free survival and molecular response were secondary endpoints. RESULTS: Thirty-six patients (35 evaluable) were enrolled and treatment was generally well tolerated with Common Terminology Criteria grade ≥ 3 adverse events (>5%) including anemia (11%), thrombocytopenia (11%) and neutropenia (8%). The overall response rate was 20% (95% CI: 8-37%) with two complete remissions and five partial responses; 49% of the patients had stable disease. At a median follow-up of 6 months, the median progression-free survival was 5.5 months (95% CI: 2.8-8.2) overall and 17.0 (6.4-23.3) months for 18 patients who received six or more cycles of treatment. Three patients achieved a lasting complete molecular response, as assessed by polymerase chain reaction analysis of peripheral blood. CONCLUSIONS: Everolimus as a single agent is well tolerated and has anti-lymphoma activity in relapsed or refractory mantle cell lymphoma. Further studies of everolimus in combination with chemotherapy or as a single agent for maintenance treatment are warranted.

Feasibility Study of Strengthening Existing Single Span Steel Beam Concrete Deck Bridges, June 1961

Iowa has the same problem that confronts most states in the United States: many bridges constructed more than 20 years ago either have deteriorated to the point that they are inadequate for original design loads or have been rendered inadequate by changes in design/maintenance standards or design loads. Inadequate bridges require either strengthening or posting for reduced loads. A sizeable number of single span, composite concrete deck - steel I beam bridges in Iowa currently cannot be rated to carry today's design loads. Various methods for strengthening the unsafe bridges have been proposed and some methods have been tried. No method appears to be as economical and promising as strengthening by post-tensioning of the steel beams. At the time this research study was begun, the feasibility of posttensioning existing composite bridges was unknown. As one would expect, the design of a bridge-strengthening scheme utilizing post-tensioning is quite complex. The design involves composite construction stressed in an abnormal manner (possible tension in the deck slab), consideration of different sizes of exterior and interior beams, cover-plated beams already designed for maximum moment at midspan and at plate cut-off points, complex live load distribution, and distribution of post-tensioningforces and moments among the bridge beams. Although information is available on many of these topics, there is miminal information on several of them and no information available on the total design problem. This study, therefore, is an effort to gather some of the missing information, primarily through testing a half-size bridge model and thus determining the feasibility of strengthening composite bridges by post-tensioning. Based on the results of this study, the authors anticipate that a second phase of the study will be undertaken and directed toward strengthening of one or more prototype bridges in Iowa.

Single-valued solutions for the Böhm-Bawerk horse market game

Single-valued solutions for the case of two-sided market games without product differentiation, also known as Böhm-Bawerk horse market games, are analyzed. The nucleolus is proved to coincide with the tau-value, and is thus the midpoint of the core. Moreover a characterization of this setof games in terms of the assignment matrix is provided.

Organisational reforms in active welfare states: A comparative analysis of the turn to 'single gateways' in Western Europe

Based on the case of reforms aimed at integrating the provision of income protection and employment services for jobless people in Europe, this thesis seeks to understand the reasons which may prompt governments to engage in large-scale organisational reforms. Over the last 20 years, several European countries have indeed radically redesigned the organisational structure of their welfare state by merging or bundling existing front-line offices in charge of benefit payment and employment services together into 'one-stop' agencies. Whereas in academic and political debates, these reforms are generally presented as a necessary and rational response to the problems and inconsistencies induced by fragmentation in a context of the reorientation of welfare states towards labour market activation, this thesis shows that the agenda setting of these reforms is in fact the result of multidimensional political dynamics. More specifically, the main argument of this thesis is that these reforms are best understood not so such from the problems induced by organisational compartmentalism, whose political recognition is often controversial, but from the various goals that governments may simultaneously achieve by means of their adoption. This argument is tested by comparing agenda-setting processes of large-scale reforms of coordination in the United Kingdom (Jobcentre Plus), Germany (Hartz IV reform) and Denmark (2005 Jobcentre reform), and contrasting them with the Swiss case where the government has so far rejected any coordination initiative involving organisational redesign. This comparison brings to light the importance, for the rise of organisational reforms, of the possibility to couple them with the following three goals: first, goals related to the strengthening of activation policies; second, institutional goals seeking to redefine the balance of responsibilities between the central state and non-state actors, and finally electoral goals for governments eager to maintain political credibility. The decisive role of electoral goals in the three countries suggests that these reforms are less bound by partisan politics than by the particular pressures facing governments arrived in office after long periods in opposition.

How single-trial electrical neuroimaging contributes to multisensory research.

This study details a method to statistically determine, on a millisecond scale and for individual subjects, those brain areas whose activity differs between experimental conditions, using single-trial scalp-recorded EEG data. To do this, we non-invasively estimated local field potentials (LFPs) using the ELECTRA distributed inverse solution and applied non-parametric statistical tests at each brain voxel and for each time point. This yields a spatio-temporal activation pattern of differential brain responses. The method is illustrated here in the analysis of auditory-somatosensory (AS) multisensory interactions in four subjects. Differential multisensory responses were temporally and spatially consistent across individuals, with onset at approximately 50 ms and superposition within areas of the posterior superior temporal cortex that have traditionally been considered auditory in their function. The close agreement of these results with previous investigations of AS multisensory interactions suggests that the present approach constitutes a reliable method for studying multisensory processing with the temporal and spatial resolution required to elucidate several existing questions in this field. In particular, the present analyses permit a more direct comparison between human and animal studies of multisensory interactions and can be extended to examine correlation between electrophysiological phenomena and behavior.

Supporting interdisciplinary case studies: development and implementation of a joint learning environment for students in forensic science and criminal law

Scientific reporting and communication is a challenging topic for which traditional study programs do not offer structured learning activities on a regular basis. This paper reports on the development and implementation of a web application and associated learning activities that intend to raise the awareness of reporting and communication issues among students in forensic science and law. The project covers interdisciplinary case studies based on a library of written reports about forensic examinations. Special features of the web framework, in particular a report annotation tool, support the design of various individual and group learning activities that focus on the development of knowledge and competence in dealing with reporting and communication challenges in the students' future areas of professional activity.

The stomach cancer pooling (StoP) project: study design and presentation.

Gastric cancer affects about one million people per year worldwide, being the second leading cause of cancer mortality. The study of its etiology remains therefore a global issue as it may allow the identification of major targets, besides eradication of Helicobacter pylori infection, for primary prevention. It has however received little attention, given its comparatively low incidence in most high-income countries. We introduce a consortium of epidemiological investigations named the 'Stomach cancer Pooling (StoP) Project'. Twenty-two studies agreed to participate, for a total of over 9000 cases and 23 000 controls. Twenty studies have already shared the original data set. Of the patients, 40% are from Asia, 43% from Europe, and 17% from North America; 34% are women and 66% men; the median age is 61 years; 56% are from population-based case-control studies, 41% from hospital-based ones, and 3% from nested case-control studies derived from cohort investigations. Biological samples are available from 12 studies. The aim of the StoP Project is to analyze the role of lifestyle and genetic determinants in the etiology of gastric cancer through pooled analyses of individual-level data. The uniquely large data set will allow us to define and quantify the main effects of each risk factor of interest, including a number of infrequent habits, and to adequately address associations in subgroups of the population, as well as interaction within and between environmental and genetic factors. Further, we will carry out separate analyses according to different histotypes and subsites of gastric cancer, to identify potential different risk patterns and etiological characteristics.

Can we disentangle predator-prey interactions from species distributions at a macro-scale? A case study with a raptor species.

There is a debate on whether an influence of biotic interactions on species distributions can be reflected at macro-scale levels. Whereas the influence of biotic interactions on spatial arrangements is beginning to be studied at local scales, similar studies at macro-scale levels are scarce. There is no example disentangling, from other similarities with related species, the influence of predator-prey interactions on species distributions at macro-scale levels. In this study we aimed to disentangle predator-prey interactions from species distribution data following an experimental approach including a factorial design. As a case of study we selected the short-toed eagle because of its known specialization on certain prey reptiles. We used presence-absence data at a 100 Km2 spatial resolution to extract the explanatory capacity of different environmental predictors (five abiotic and two biotic predictors) on the short-toed eagle species distribution in Peninsular Spain. Abiotic predictors were relevant climatic and topographic variables, and relevant biotic predictors were prey richness and forest density. In addition to the short-toed eagle, we also obtained the predictor's explanatory capacities for i) species of the same family Accipitridae (as a reference), ii) for other birds of different families (as controls) and iii) species with randomly selected presences (as null models). We run 650 models to test for similarities of the short-toed eagle, controls and null models with reference species, assessed by regressions of explanatory capacities. We found higher similarities between the short-toed eagle and other species of the family Accipitridae than for the other two groups. Once corrected by the family effect, our analyses revealed a signal of predator-prey interaction embedded in species distribution data. This result was corroborated with additional analyses testing for differences in the concordance between the distributions of different bird categories and the distributions of either prey or non-prey species of the short-toed eagle. Our analyses were useful to disentangle a signal of predator-prey interactions from species distribution data at a macro-scale. This study highlights the importance of disentangling specific features from the variation shared with a given taxonomic level.

Rockfall monitoring by Terrestrial Laser Scanning ¿ case study of the basaltic rock face at Castellfollit de la Roca (Catalonia, Spain)

This case study deals with a rock face monitoring in urban areas using a Terrestrial Laser Scanner. The pilot study area is an almost vertical, fifty meter high cliff, on top of which the village of Castellfollit de la Roca is located. Rockfall activity is currently causing a retreat of the rock face, which may endanger the houses located at its edge. TLS datasets consist of high density 3-D point clouds acquired from five stations, nine times in a time span of 22 months (from March 2006 to January 2008). The change detection, i.e. rockfalls, was performed through a sequential comparison of datasets. Two types of mass movement were detected in the monitoring period: (a) detachment of single basaltic columns, with magnitudes below 1.5 m3 and (b) detachment of groups of columns, with magnitudes of 1.5 to 150 m3. Furthermore, the historical record revealed (c) the occurrence of slab failures with magnitudes higher than 150 m3. Displacements of a likely slab failure were measured, suggesting an apparent stationary stage. Even failures are clearly episodic, our results, together with the study of the historical record, enabled us to estimate a mean detachment of material from 46 to 91.5 m3 year¿1. The application of TLS considerably improved our understanding of rockfall phenomena in the study area.

Rockfall induced seismic signals: case study in Montserrat, Catalonia

After a rockfall event, a usual post event survey includes qualitative volume estimation, trajectory mapping and determination of departing zones. However, quantitative measurements are not usually made. Additional relevant quantitative information could be useful in determining the spatial occurrence of rockfall events and help us in quantifying their size. Seismic measurements could be suitable for detection purposes since they are non invasive methods and are relatively inexpensive. Moreover, seismic techniques could provide important information on rockfall size and location of impacts. On 14 February 2007 the Avalanche Group of the University of Barcelona obtained the seismic data generated by an artificially triggered rockfall event at the Montserrat massif (near Barcelona, Spain) carried out in order to purge a slope. Two 3 component seismic stations were deployed in the area about 200 m from the explosion point that triggered the rockfall. Seismic signals and video images were simultaneously obtained. The initial volume of the rockfall was estimated to be 75 m3 by laser scanner data analysis. After the explosion, dozens of boulders ranging from 10¿4 to 5 m3 in volume impacted on the ground at different locations. The blocks fell down onto a terrace, 120 m below the release zone. The impact generated a small continuous mass movement composed of a mixture of rocks, sand and dust that ran down the slope and impacted on the road 60 m below. Time, time-frequency evolution and particle motion analysis of the seismic records and seismic energy estimation were performed. The results are as follows: 1 ¿ A rockfall event generates seismic signals with specific characteristics in the time domain; 2 ¿ the seismic signals generated by the mass movement show a time-frequency evolution different from that of other seismogenic sources (e.g. earthquakes, explosions or a single rock impact). This feature could be used for detection purposes; 3 ¿ particle motion plot analysis shows that the procedure to locate the rock impact using two stations is feasible; 4 ¿ The feasibility and validity of seismic methods for the detection of rockfall events, their localization and size determination are comfirmed.

Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.

OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved β-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis.

Development of a New Process for Determining Design Year Traffic Demands, TR-528, 2007

Researchers should continuously ask how to improve the models we rely on to make financial decisions in terms of the planning, design, construction, and maintenance of roadways. This project presents an alternative tool that will supplement local decision making but maintain a full appreciation of the complexity and sophistication of today’s regional model and local traffic impact study methodologies. This alternative method is tailored to the desires of local agencies, which requested a better, faster, and easier way to evaluate land uses and their impact on future traffic demands at the sub-area or project corridor levels. A particular emphasis was placed on scenario planning for currently undeveloped areas. The scenario planning tool was developed using actual land use and roadway information for the communities of Johnston and West Des Moines, Iowa. Both communities used the output from this process to make regular decisions regarding infrastructure investment, design, and land use planning. The City of Johnston case study included forecasting future traffic for the western portion of the city within a 2,600-acre area, which included 42 intersections. The City of West Des Moines case study included forecasting future traffic for the city’s western growth area covering over 30,000 acres and 331 intersections. Both studies included forecasting a.m. and p.m. peak-hour traffic volumes based upon a variety of different land use scenarios. The tool developed took goegraphic information system (GIS)-based parcel and roadway information, converted the data into a graphical spreadsheet tool, allowed the user to conduct trip generation, distribution, and assignment, and then to automatically convert the data into a Synchro roadway network which allows for capacity analysis and visualization. The operational delay outputs were converted back into a GIS thematic format for contrast and further scenario planning. This project has laid the groundwork for improving both planning and civil transportation decision making at the sub-regional, super-project level.