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Fiber clustering methods are typically used in brain research to study the organization of white matter bundles from large diffusion MRI tractography datasets. These methods enable exploratory bundle inspection using visualization and other methods that require identifying brain white matter structures in individuals or a population. Some applications, such as real-time visualization and inter-subject clustering, need fast and high-quality intra-subject clustering algorithms. This work proposes a parallel algorithm using a General Purpose Graphics Processing Unit (GPGPU) for fiber clustering based on the FFClust algorithm. The proposed GPGPU implementation exploits data parallelism using both multicore and GPU fine-grained parallelism present in commodity architectures, including current laptops and desktop computers. Our approach implements all FFClust steps in parallel, improving execution times in all of them. In addition, our parallel approach includes a parallel Kmeans++ algorithm implementation and defines a new variant of Kmeans++ to reduce the impact of choosing outliers as initial centroids. The results show that our approach provides clustering quality results very similar to FFClust, and it requires an execution time of 3.5 s for processing about a million fibers, achieving a speedup of 11.5 times compared to FFClust.

Introduction Subjects with type 2 diabetes have an excess risk of cancer. The potential role of advanced glycation end products (AGEs) accumulated during long-term hyperglycemia in cancer development has been suggested by biological studies but clinical data are missing. AGEs can be estimated by measuring the skin autofluorescence. We searched whether the skin autofluorescence could predict new cancers in persons with type 2 diabetes.Research design and methods From 2009 to 2015, we measured the skin autofluorescence of 413 subjects hospitalized for uncontrolled or complicated type 2 diabetes, without any history of cancer. The participants were followed for at least 1 year and the occurrences of new cancers were compared according to their initial skin autofluorescences.Results The participants were mainly men (57.9%), with poorly controlled (HbA1c 72±14 mmol/mol or 8.7%±1.8%) and/or complicated type 2 diabetes. Their median skin autofluorescence was 2.6 (2.2–3.0) arbitrary units. Forty-five new cancer cases (10.9%) were registered during 4.8±2.3 years of follow-up: 75.6% of these subjects had skin autofluorescence higher than the median (χ2: p=0.001). By Cox regression analysis adjusted for age, gender, body mass index, history of smoking and renal parameters, skin autofluorescence >2.6 predicted a 2.57-fold higher risk of cancer (95% CI 1.28 to 5.19, p=0.008). This association remained significant after excluding the eight cancers that occurred in the 4 years after inclusion (OR 2.95, 95% CI 1.36 to 6.38, p=0.006). As a continuous variable, skin autofluorescence was also related to new cancers (OR 1.05, 95% CI 1.01 to 1.10, p=0.045).Conclusions Skin autofluorescence, a potential marker of glycemic memory, predicts the occurrence of cancer in subjects with type 2 diabetes. This relation provides a new clinical argument for the role of AGEs in cancer. Their estimation by measuring the skin autofluorescence may help select subjects with diabetes in cancer screening programs.

Carried out in 2006, the excavation of 33, rue du Rio in Saint-Marcel/Argentomagus (Indre) identified several series of quadrangular ditched enclosures, oriented along the cardinal points. The overlaps are frequent and difficult to discern. The most complete plans are close to square or rectangular and delimit surfaces of 3.7 to 14.4 m2. The irregular excavations are shallow and reveal, in a carbonaceous sediment, mostly burnt material attributable to the first half of the 1st century AD (ceramics, glass, small items of furniture, etc.) (ceramics, glass, small furniture, human and animal bones, carporest). In the absence of a grave in the centre, the nature of the residues collected suggests that these were pyre enclosures. Their spatial organisation suggests that these enclosures were part of plots whose orientations and boundaries may have varied somewhat. Nearby, or intersecting their lines, there are eight burials of infants and one of a child under ten years old. Two ossuary cremation deposits, one adult and one immature individual, are identified at either end of the right-of-way, near what appears to be a circulation space. In terms of the material, enclosures, cremation deposits and burials are contemporary and similar to those found in the Ripottes necropolis, 50m to the south. The abandonment of this burial space after the middle of the 1st century is probably related to the development of the agglomeration outside the limits of the ancient oppidum and the construction of the amphitheatre 50 m to the west.

Introduction: A nuclear-powered ballistic missile submarine (SSBN) is a singular professional environment, exposing personnel to isolation and confinement amidst sophisticated technology for the duration of a mission. Submariners see their mood and cognition deteriorate as their mission progresses. With regard to the benefits of physical activity (PA) on mental health, this study evaluates the impact of regular PA on the maintenance of thymia and sensory functioning during patrols.Method: This pragmatic exploratory cohort follow-up study included 29 volunteer submariners before, during and 1 month after return from patrol. PA practice was evaluated by a daily self-questionnaire. This allowed submariners to be classified into two groups according to the median of the total duration in minutes of a sport practiced during the patrol (PA practicing submariners and non-practicing). Changes in mood and psychological activation, health (including sleep), unipodal stability, and accommodation distances were compared between the two groups over the period of the patrol.Results: Overall thymic functioning deteriorated during the patrol. Submariners who practice PA maintain a stable level of activation unlike non-practicing PA submariners, but they exhibited both worse general health and sleep at recovery. For these personnel, postural control is better at the end of the patrol and far visual accommodation tends to be preserved.Conclusion: PA during patrol alone is not sufficient to compensate for the thymic dysregulation induced by the SSBN environment. Nevertheless, it seems to help in maintaining an exteroceptive functioning. This exploratory study suggests directions for possible future research on physical activity associated with sensory stimulation amongst submariners, and more generally amongst people working in isolated and confined environments.

Diffusion Magnetic Resonance Imaging tractography is a non-invasive technique that produces a collection of streamlines representing the main white matter bundle trajectories. Methods, such as fiber clustering algorithms, are important in computational neuroscience and have been the basis of several white matter analysis methods and studies. Nevertheless, these clustering methods face the challenge of the absence of ground truth of white matter fibers, making their evaluation difficult. As an alternative solution, we present an innovative brain fiber bundle simulator that uses spline curves for fiber representation. The methodology uses a tubular model for the bundle simulation based on a bundle centroid and five radii along the bundle. The algorithm was tested by simulating 28 Deep White Matter atlas bundles, leading to low inter-bundle distances and high intersection percentages between the original and simulated bundles. To prove the utility of the simulator, we created three whole-brain datasets containing different numbers of fiber bundles to assess the quality performance of QuickBundles and Fast Fiber Clustering algorithms using five clustering metrics. Our results indicate that QuickBundles tends to split less and Fast Fiber Clustering tends to merge less, which is consistent with their expected behavior. The performance of both algorithms decreases when the number of bundles is increased due to higher bundle crossings. Additionally, the two algorithms exhibit robust behavior with input data permutation. To our knowledge, this is the first whole-brain fiber bundle simulator capable of assessing fiber clustering algorithms with realistic data. [ABSTRACT FROM AUTHOR]

Summary: Primary biliary cholangitis (PBC) is an autoimmune, cholestatic, chronic liver disease that ultimately progresses towards cirrhosis and liver failure if untreated. While ursodeoxycholic acid has been established as standard of care for PBC in the last few decades, significant advances in second-line treatment options have recently been made and new therapeutic developments are currently under evaluation. The purpose of this article is to provide the clinician with an overview of the current treatment options and future opportunities for patients with PBC. Keywords: PBC, ursodeoxycholic acid, obeticholic acid, fibrates, FXR, PPAR, cholestasis, inflammation, liver disease

Héloïse Rouzé1,2, Marie Viprey1,2, Samuel Allemann2, Alexandra L Dima2, Pascal Caillet3, Angélique Denis1, Stéphanie Poupon-Bourdy1, Boubou Camara4, Catherine Llerena5, Philippe Reix6, Isabelle Durieu2,7, Quitterie Reynaud2,7, Sandrine Touzet1,2 1Public Health Department, Hospices Civils de Lyon, Lyon, France; 2HESPER Lab-EA 7425, Université de Lyon-Université Claude Bernard Lyon 1, Lyon, France; 3Department of Clinical Pharmacology, CHU de Nantes, Nantes, France; 4Pulmonary Department, Adult CF Center, CHU de Grenoble, Grenoble, France; 5Pediatric Pulmonology Department, Pediatric CF Center, CHU de Grenoble, Grenoble, France; 6Pediatric Pulmonology Department, Pediatric CF Center, Hôpital Femme-Mère-Enfant, Hospices Civils de Lyon, Lyon, France; 7Department of Internal Medicine, Adult Cystic Fibrosis Care Center, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Lyon, FranceCorrespondence: Héloïse RouzéHospices Civils de Lyon, Pôle de Santé Publique, Bâtiment A, 6ème étage, 162 Avenue Lacassagne 69003 Lyon, FranceTel +33 47 211 5132Email heloise.rouze@chu-lyon.frBackground: Cystic fibrosis (CF) is a life-shortening genetic condition that usually affects several organs and involves significant treatment burden. Adherence to medication is important for successful CF management.Objective: To describe medication adherence according to age, therapeutic class, and pharmaceutical form in adults and children followed in four regional CF centers in France.Methods: We conducted a cross-sectional study with non-transplanted patients followed in two adult and two pediatric centers during 2015 who were covered by the French National Health Insurance (NHI). Sociodemographic, clinical, hospitalization, and prescription data were collected from patient medical records. Medication dispensations were extracted from the regional French NHI database. Adherence was calculated over 12 months using continuous medication availability (CMA) accounting for dose adjustments and hospitalizations. Drug-specific CMA was computed in R with the AdhereR package for each medication prescribed more than 3 months, which was averaged to obtain a composite CMA score (cCMA) for all treatments and per therapeutic class as well as pharmaceutical form for each patient.Results: A total of 228 patients were included. The number of chronic medications increased with age (r=0.50, p

Abstract Cystic fibrosis (CF)-related diabetes is associated with increased mortality. We analysed the clinical and glycemic profiles of two cohorts of patients treated according to the same guidelines in France and Canada. To investigate incidence differences in phenotypic and glucose abnormalities and to explore the evolution over a 4-year follow-up period, two cohorts of 224 Canadian and 147 French adult CF patients (≥18 years) without treated CF-related diabetes (CFRD) were followed over a 4 year period. In each of these groups, we investigated the longitudinal relationship between glucose tolerance and pulmonary function. An annual 2-hour oral glucose tolerance test was performed: fasting blood glucose (G0) and 2-h blood glucose (G2) were measured. Patients were classified at inclusion according to their glucose tolerance status: Normal glucose tolerant, abnormal glucose tolerant or de novo CFRD. Age, sex ratio and proportion of F508del homozygous patients were not statistically different between both cohorts. Canadian patients had better pulmonary function (median %FEV1 (IQR): 71.0 (55.0–82.0) vs. 64.0 (40.0–78.0), p

Abstract Background Triple-negative breast cancer (TNBC) treatment is currently restricted to chemotherapy. Hence, tumor-specific molecular targets and/or alternative therapeutic strategies for TNBC are urgently needed. Immunotherapy is emerging as an exciting treatment option for TNBC patients. The aspartic protease cathepsin D (cath-D), a marker of poor prognosis in breast cancer (BC), is overproduced and hypersecreted by human BC cells. This study explores whether cath-D is a tumor cell-associated extracellular biomarker and a potent target for antibody-based therapy in TNBC. Methods Cath-D prognostic value and localization was evaluated by transcriptomics, proteomics and immunohistochemistry in TNBC. First-in-class anti-cath-D human scFv fragments binding to both human and mouse cath-D were generated using phage display and cloned in the human IgG1 λ format (F1 and E2). Anti-cath-D antibody biodistribution, antitumor efficacy and in vivo underlying mechanisms were investigated in TNBC MDA-MB-231 tumor xenografts in nude mice. Antitumor effect was further assessed in TNBC patient-derived xenografts (PDXs). Results High CTSD mRNA levels correlated with shorter recurrence-free survival in TNBC, and extracellular cath-D was detected in the tumor microenvironment, but not in matched normal breast stroma. Anti-cath-D F1 and E2 antibodies accumulated in TNBC MDA-MB-231 tumor xenografts, inhibited tumor growth and improved mice survival without apparent toxicity. The Fc function of F1, the best antibody candidate, was essential for maximal tumor inhibition in the MDA-MB-231 model. Mechanistically, F1 antitumor response was triggered through natural killer cell activation via IL-15 upregulation, associated with granzyme B and perforin production, and the release of antitumor IFNγ cytokine. The F1 antibody also prevented the tumor recruitment of immunosuppressive tumor-associated macrophages M2 and myeloid-derived suppressor cells, a specific effect associated with a less immunosuppressive tumor microenvironment highlighted by TGFβ decrease. Finally, the antibody F1 inhibited tumor growth of two TNBC PDXs, isolated from patients resistant or not to neo-adjuvant chemotherapy. Conclusion Cath-D is a tumor-specific extracellular target in TNBC suitable for antibody-based therapy. Immunomodulatory antibody-based strategy against cath-D is a promising immunotherapy to treat patients with TNBC.