Harmonising and linking biomedical and clinical data across disparate data archives to enable integrative cross-biobank research

A wealth of biospecimen samples are stored in modern globally distributed biobanks. Biomedical researchers worldwide need to be able to combine the available resources to improve the power of large-scale studies. A prerequisite for this effort is to be able to search and access phenotypic, clinical and other information about samples that are currently stored at biobanks in an integrated manner. However, privacy issues together with heterogeneous information systems and the lack of agreed-upon vocabularies have made specimen searching across multiple biobanks extremely challenging. We describe three case studies where we have linked samples and sample descriptions in order to facilitate global searching of available samples for research. The use cases include the ENGAGE (European Network for Genetic and Genomic Epidemiology) consortium comprising at least 39 cohorts, the SUMMIT (surrogate markers for micro- and macro-vascular hard endpoints for innovative diabetes tools) consortium and a pilot for data integration between a Swedish clinical health registry and a biobank. We used the Sample avAILability (SAIL) method for data linking: first, created harmonised variables and then annotated and made searchable information on the number of specimens available in individual biobanks for various phenotypic categories. By operating on this categorised availability data we sidestep many obstacles related to privacy that arise when handling real values and show that harmonised and annotated records about data availability across disparate biomedical archives provide a key methodological advance in pre-analysis exchange of information between biobanks, that is, during the project planning phase

Psychology

The Internet explosion and broad interest in collaborative technology have driven increased interest in the field of computer-supported cooperative work (CSCW). Historically, behavioral research on CSCW applications has reflected a strong influence from ethnomethodology. This article argues that the CSCW community should adopt a stronger orientation to other social science disciplines, particularly psychology. Greater attention to the psychological literature provides three benefits. First, psychologists offer well-validated principles about human behavior in group and organizational contexts that are relevant to CSCW research. Second, psychologists offer reliable and proven measures of human behavior that, if adopted by CSCW researchers, can provide a uniform basis for comparison across studies. Finally, psychologists offer data collection and analysis methods that identify salient and generalizable features of human behavior, which may lead to the development of universal principles of CSCW design.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68835/2/10.1177_089443939801600106.pd

Unimodular bimode gravity and the coherent scalar-graviton field as galaxy dark matter

The explicit violation of the general gauge invariance/relativity is adopted as the origin of dark matter and dark energy of the gravitational nature. The violation of the local scale invariance alone, with the residual unimodular one, is considered. Besides the four-volume preserving deformation mode -- the transverse-tensor graviton -- the metric comprises a compression mode -- the scalar graviton, or the systolon. A unimodular invariant and general covariant metric theory of the bimode/scalar-tensor gravity is consistently worked out. To reduce the primordial ambiguity of the theory a dynamical global symmetry is imposed, with its subsequent spontaneous breaking revealed. The static spherically symmetric case in the empty, but possibly for the origin, space is studied. A three-parameter solution describing a new static space structure -- the dark lacuna -- is constructed. It enjoys the property of gravitational confinement, with the logarithmic potential of gravitational attraction at the periphery, and results in the asymptotically flat rotation curves. Comprising a super-massive dark fracture (a scalar-modified black hole) at the origin surrounded by a cored dark halo, the dark lacunas are proposed as a prototype model of galaxies, implying an ultimate account for the distributed non-gravitational matter and a putative asphericity or rotation.Comment: 38 pages, 10 figures; exposition improved, remarks added, accepted for publicatio

Age at first birth in women is genetically associated with increased risk of schizophrenia

Prof. Paunio on PGC:n jäsenPrevious studies have shown an increased risk for mental health problems in children born to both younger and older parents compared to children of average-aged parents. We previously used a novel design to reveal a latent mechanism of genetic association between schizophrenia and age at first birth in women (AFB). Here, we use independent data from the UK Biobank (N = 38,892) to replicate the finding of an association between predicted genetic risk of schizophrenia and AFB in women, and to estimate the genetic correlation between schizophrenia and AFB in women stratified into younger and older groups. We find evidence for an association between predicted genetic risk of schizophrenia and AFB in women (P-value = 1.12E-05), and we show genetic heterogeneity between younger and older AFB groups (P-value = 3.45E-03). The genetic correlation between schizophrenia and AFB in the younger AFB group is -0.16 (SE = 0.04) while that between schizophrenia and AFB in the older AFB group is 0.14 (SE = 0.08). Our results suggest that early, and perhaps also late, age at first birth in women is associated with increased genetic risk for schizophrenia in the UK Biobank sample. These findings contribute new insights into factors contributing to the complex bio-social risk architecture underpinning the association between parental age and offspring mental health.Peer reviewe

Significance of diet type and diet quality for ecological diversity of African ungulates

1.We test two nutritional hypotheses for the ecological diversity of ungulates, the browser/grazer (diet type) and diet quality models, among free-ranging herbivores in a South African savanna, the Kruger National Park. Tests are based on assessment of relationships between diet type and diet quality with body mass and hypsodonty, two morphological features that have been associated with both elements. 2.We use stable carbon isotope ratios of faeces to reconstruct diet in terms of proportions of C3 plants (browse) and C4 plants (grass) consumed by different species in different seasons. These data are combined with proxies for diet quality (per cent nitrogen, neutral detergent fibre, acid detergent fibre, and acid detergent lignin) from faeces to track changes in diet quality. 3.Two statistical approaches are used in model selection, i.e. tests of significant correlations based on linear regression analyses, and an information-theory approach (Akaike’s Information Criterion) providing insight into strength of evidence for models. 4.Results of both methods show that, contrary to many predictions, body mass and diet type are not related, but these data confirm predictions that diet quality decreases with increasing body size, especially during the dry season. Hypsodonty, as expected, varies with diet type, increasing with increased grass intake. 5.These findings support both a diet type and diet quality model, implying some degree of exclusivity. We propose that congruence between models may be achieved through addition of diet quality proxies not included here, because hypsodonty is more likely a reflection of the abrasive properties of consumed foods, i.e. related to food quality, rather than food type. This implies that adaptation to diets of varying quality, through changes in body size and dental features, has been the primary mechanism for diversification in ungulates. 6. Our interpretation contrasts with several recent studies advocating diet type as the primary factor, exemplifying that further reconciliation between the two models is needed. We discuss the implications of this study for future approaches to achieve a more cohesive understanding of the evolutionary outcomes of herbivore nutrition

Reasons for Premature Closure of a Mentoring Relationship:A Qualitative Study of Mentoring Youth With a Visual Impairment

Preventing mentor-mentee relationships from ending prematurely is important because an early or unanticipated closure could lead to negative youth outcomes. In this study, the reasons for premature closure of a community-based mentoring program for youth with a visual impairment (VI) are studied. Data from 44 prematurely ended mentor-mentee pairs were analyzed; all mentees (M age = 18.5, SD = 1.92) and 23 of the mentors had VI. Logbook data with two types of transcribed semi-structured interviews were thematically coded line-by-line. Frequencies of coded responses provided insight into the most frequently reported reasons and the most frequently reported problems. Chi-square analyses were conducted to study differences between matches in the two conditions (i.e., matches containing mentors with or without VI). Regardless of the condition, premature closure was primarily initiated by mentees, and the most common cause was reported to be due to deficiencies in mentors’ relationship skills. Matches with a mentor with VI experienced more problems within one domain of the International Classification of Functioning (ICF) model. These results show that additional pre-match mentor and supplementary mentee training are needed to increase relationship success in mentoring programs serving youth with VI.</p

Tracing the ecophysiology of ungulates and predator–prey relationships in an early Pleistocene large mammal community

Research into the reconstruction of ancient communities in terms of dietary regimes, habitat preferences and ecological interactions of species has focused predominantly on biogeochemistry or ecomorphology alone and not in combination. The Venta Micena site (Orce, Guadix–Baza basin, SE Spain) has an early Pleistocene vertebrate assemblage with exceptional biomolecular preservation. Collagen was successfully extracted from 77 bone samples of 18 species of large mammals, which allowed analyses of carbon- and nitrogen-isotopes. δ13C, δ15N and δ18O ratios combined with ecomorphological indexes provide interesting clues on the autecology and palaeophysiology of extinct species, which help in deciphering aspects of community trophic structure and predator–prey interactions. Specifically, morphometric ratios (e.g., hypsodonty index and relative length of the lower premolar tooth row; [Palmqvist, P., Gröcke, D.R., Arribas, A., Fariña, R. 2003. Paleoecological reconstruction of a lower Pleistocene large mammals community using biogeochemical (δ13C, δ15N, δ18O, Sr:Zn) and ecomorphological approaches. Paleobiology 29, 204–228.]) allow classifying the ungulates among grazers (Equus altidens, Bison sp., Praeovibos sp., Hemitragus albus, Hippopotamus antiquus, and Mammuthus meridionalis), mized-feeders (Soergelia minor and Pseudodama sp.) and browsers (Stephanorhinus sp. and Praemegaceros cf. verticornis). However, δ13C values reveal that these ungulates consumed exclusively C3 plants and significant differences in isotopic values between perissodactyls (monogastric, hindgut fermenters) and ruminants (foregut fermenters) must reflect physiological differences related to their rates of methane production and digestive efficiency. δ18O ratios allow the interpretation of the dietary water source of these species, suggesting that fallow deer Pseudodama sp., goat H. albus and ovibovine S. minor obtained a significant fraction of their metabolic water from the vegetation consumed. Carnivore species have higher δ15N values than herbivores, which records the isotopic enrichment expected with an increase in trophic level. However, the unexpectedly high δ15N values of hippo H. antiquus and muskoxen Praeovibos sp. suggest that these ungulates predominantly consumed aquatic plants and lichens, respectively. Inferences on predator–prey relationships within this ancient community, derived from the dual linear mixing model, indicate resource partitioning among sympatric predators, suggesting that sabre-tooth Megantereon whitei and jaguar Panthera cf. gombaszoegensis were ambushers of forest environments while sabre-tooth Homotherium latidens and wild dog Lycaon lycaonoides were coursing predators in open habitat. The giant, short-faced hyena Pachycrocuta brevirostris scavenged the prey of these hypercarnivores

Syndromic Ectrodactyly with Severe Limb, Ectodermal, Urogenital, and Palatal Defects Maps to Chromosome 19

SummaryCongenital limb malformations rank behind only congenital heart disease as the most common birth defects observed in infants. Finding genes that cause defects in human limb patterning should be straightforward but has been limited, in part, by the bewildering spectrum of phenotypes, which are difficult to separate into etiologically distinct disorders. One approach to the identification of relevant genes is to take advantage of unique extended kindreds in which a defect in limb patterning is segregating. Recently, a large Dutch family with ectrodactyly, ectodermal dysplasia, cleft palate, and urogenital defects (EEC) was described by Maas et al. We have studied this kindred and localized a gene causing EEC to a locus on chromosome 19, in a region defined by D19S894 and D19S416. A second extended kindred with EEC does not map to this locus, indicating that EEC is a genetically heterogeneous disorder. Growth and patterning of the limbs, teeth, hair, and genitourinary system are mediated in part by epithelial-mesenchyme inductive interactions. The identification of both the gene causing EEC and its mutation may further elucidate the general signals mediating inductive mechanisms