The activity of French Research Ethics Committees and characteristics of biomedical research protocols involving humans: a retrospective cohort study

BACKGROUND: Clinical trials throughout the world must be evaluated by research ethics committees. No one has yet attempted to clearly quantify at the national level the activity of ethics committees and describe the characteristics of the protocols submitted. The objectives of this study were to describe 1) the workload and the activity of Research Ethics Committees in France, and 2) the characteristics of protocols approved on a nation-wide basis. METHODS: Retrospective cohort of 976 protocols approved by a representative sample of 25/48 of French Research Ethics Committees in 1994. Protocols characteristics (design, study size, investigator), number of revisions requested by the ethics committee before approval, time to approval and number of amendments after approval were collected for each protocol by trained research assistant using the committee's files and archives. RESULTS: Thirty-one percent of protocols were approved with no modifications requested in 16 days (95% CI: 14–17). The number of revisions requested by the committee, and amendments submitted by the investigator was on average respectively 39 (95% CI: 25–53) and 37 (95% CI: 27–46), per committee and per year. When revisions were requested, the main reasons were related to information to the patient (28%) and consent modalities (18%). Drugs were the object of research in 68% of the protocols examined. The majority of the research was national (80%) with a predominance of single-centre studies. Workload per protocol has been estimated at twelve and half hours on average for administrative support and at eleven and half hours for expertise. CONCLUSION: The estimated workload justifies specific and independent administrative and financial support for Research Ethics Committees

Ward's Hierarchical Clustering Method: Clustering Criterion and Agglomerative Algorithm

The Ward error sum of squares hierarchical clustering method has been very widely used since its first description by Ward in a 1963 publication. It has also been generalized in various ways. However there are different interpretations in the literature and there are different implementations of the Ward agglomerative algorithm in commonly used software systems, including differing expressions of the agglomerative criterion. Our survey work and case studies will be useful for all those involved in developing software for data analysis using Ward's hierarchical clustering method.Comment: 20 pages, 21 citations, 4 figure

Algorithms for Hierarchical Clustering: An Overview, II

We survey agglomerative hierarchical clustering algorithms and discuss efficient implementations that are available in R and other software environments. We look at hierarchical self-organizing maps, and mixture models. We review grid-based clustering, focusing on hierarchical density-based approaches. Finally we describe a recently developed very efficient (linear time) hierarchical clustering algorithm, which can also be viewed as a hierarchical grid-based algorithm. This review adds to the earlier version, Murtagh and Contreras (2012)

Effect of Age on Variability in the Production of Text-Based Global Inferences

As we age, our differences in cognitive skills become more visible, an effect especially true for memory and problem solving skills (i.e., fluid intelligence). However, by contrast with fluid intelligence, few studies have examined variability in measures that rely on one’s world knowledge (i.e., crystallized intelligence). The current study investigated whether age increased the variability in text based global inference generation–a measure of crystallized intelligence. Global inference generation requires the integration of textual information and world knowledge and can be expressed as a gist or lesson. Variability in generating two global inferences for a single text was examined in young-old (62 to 69 years), middle-old (70 to 76 years) and old-old (77 to 94 years) adults. The older two groups showed greater variability, with the middle elderly group being most variable. These findings suggest that variability may be a characteristic of both fluid and crystallized intelligence in aging

High Differentiation among Eight Villages in a Secluded Area of Sardinia Revealed by Genome-Wide High Density SNPs Analysis

To better design association studies for complex traits in isolated populations it's important to understand how history and isolation moulded the genetic features of different communities. Population isolates should not “a priori” be considered homogeneous, even if the communities are not distant and part of a small region. We studied a particular area of Sardinia called Ogliastra, characterized by the presence of several distinct villages that display different history, immigration events and population size. Cultural and geographic isolation characterized the history of these communities. We determined LD parameters in 8 villages and defined population structure through high density SNPs (about 360 K) on 360 unrelated people (45 selected samples from each village). These isolates showed differences in LD values and LD map length. Five of these villages show high LD values probably due to their reduced population size and extreme isolation. High genetic differentiation among villages was detected. Moreover population structure analysis revealed a high correlation between genetic and geographic distances. Our study indicates that history, geography and biodemography have influenced the genetic features of Ogliastra communities producing differences in LD and population structure. All these data demonstrate that we can consider each village an isolate with specific characteristics. We suggest that, in order to optimize the study design of complex traits, a thorough characterization of genetic features is useful to identify the presence of sub-populations and stratification within genetic isolates

MTV and MGV: Two Criteria for Nonlinear PCA

ized Variance) are popular criteria for PCA with optimal scaling. They are adopted by the SAS-PRINQUAL procedure and OSMOD (Saito and Otsu,1988). MTV is an intuitive generalization of linear PCA criterion. We will show some proper-ties of nonlinear PCA with these criteria in an application to the data of NLSY79 (Zagorsky,1997), a large panel survey in the U.S., conducted over twenty years. We will show the following. (1) The effectiveness of PCA with optimal scaling as a tool for large social research data analysis. We can obtain useful results when it complements analyses by regression models. (2) Features of MTV and MGV, especially their abilities and deficiencies in real data analysis. 1

Structure, Function, and Evolution of the Thiomonas spp. Genome

Bacteria of the Thiomonas genus are ubiquitous in extreme environments, such as arsenic-rich acid mine drainage (AMD). The genome of one of these strains, Thiomonas sp. 3As, was sequenced, annotated, and examined, revealing specific adaptations allowing this bacterium to survive and grow in its highly toxic environment. In order to explore genomic diversity as well as genetic evolution in Thiomonas spp., a comparative genomic hybridization (CGH) approach was used on eight different strains of the Thiomonas genus, including five strains of the same species. Our results suggest that the Thiomonas genome has evolved through the gain or loss of genomic islands and that this evolution is influenced by the specific environmental conditions in which the strains live

The Evolutionary Dynamics of the Lion Panthera leo Revealed by Host and Viral Population Genomics

The lion Panthera leo is one of the world's most charismatic carnivores and is one of Africa's key predators. Here, we used a large dataset from 357 lions comprehending 1.13 megabases of sequence data and genotypes from 22 microsatellite loci to characterize its recent evolutionary history. Patterns of molecular genetic variation in multiple maternal (mtDNA), paternal (Y-chromosome), and biparental nuclear (nDNA) genetic markers were compared with patterns of sequence and subtype variation of the lion feline immunodeficiency virus (FIVPle), a lentivirus analogous to human immunodeficiency virus (HIV). In spite of the ability of lions to disperse long distances, patterns of lion genetic diversity suggest substantial population subdivision (mtDNA ΦST = 0.92; nDNA FST = 0.18), and reduced gene flow, which, along with large differences in sero-prevalence of six distinct FIVPle subtypes among lion populations, refute the hypothesis that African lions consist of a single panmictic population. Our results suggest that extant lion populations derive from several Pleistocene refugia in East and Southern Africa (∼324,000–169,000 years ago), which expanded during the Late Pleistocene (∼100,000 years ago) into Central and North Africa and into Asia. During the Pleistocene/Holocene transition (∼14,000–7,000 years), another expansion occurred from southern refugia northwards towards East Africa, causing population interbreeding. In particular, lion and FIVPle variation affirms that the large, well-studied lion population occupying the greater Serengeti Ecosystem is derived from three distinct populations that admixed recently