OBCS: The Ontology of Biological and Clinical Statistics

Statistics play a critical role in biological and clinical research. To promote logically consistent representation and classification of statistical entities, we have developed the Ontology of Biological and Clinical Statistics (OBCS). OBCS extends the Ontology of Biomedical Investigations (OBI), an OBO Foundry ontology supported by some 20 communities. Currently, OBCS contains 686 terms, including 381 classes imported from OBI and 147 classes specific to OBCS. The goal of this paper is to present OBCS for community critique and to describe a number of use cases designed to illustrate its potential applications. The OBCS project and source code are available at http://obcs.googlecode.com

Non-random mating for selection with restricted rates of inbreeding and overlapping generations

Minimum coancestry mating with a maximum of one offspring per mating pair (MC1) is compared with random mating schemes for populations with overlapping generations. Optimum contribution selection is used, whereby ΔF is restricted. For schemes with ΔF restricted to 0.25% per year, 256 animals born per year and heritability of 0.25, genetic gain increased with 18% compared with random mating. The effect of MC1 on genetic gain decreased for larger schemes and schemes with a less stringent restriction on inbreeding. Breeding schemes hardly changed when omitting the iteration on the generation interval to find an optimum distribution of parents over age-classes, which saves computer time, but inbreeding and genetic merit fluctuated more before the schemes had reached a steady-state. When bulls were progeny tested, these progeny tested bulls were selected instead of the young bulls, which led to increased generation intervals, increased selection intensity of bulls and increased genetic gain (35% compared to a scheme without progeny testing for random mating). The effect of MC1 decreased for schemes with progeny testing. MC1 mating increased genetic gain from 11–18% for overlapping and 1–4% for discrete generations, when comparing schemes with similar genetic gain and size

Immunosuppressive effect and global dysregulation of blood transcriptome in response to psychosocial stress in vervet monkeys (Chlorocebus sabaeus).

Psychosocial stressors - life events that challenge social support and relationships - represent powerful risk factors for human disease; included amongst these events are relocation, isolation and displacement. To evaluate the impact of a controlled psychosocial stressor on physiology and underlying molecular pathways, we longitudinally studied the influence of a 28-day period of quarantine on biomarkers of immune signalling, microbial translocation, glycaemic health and blood transcriptome in the wild-born vervet monkey. This event caused a coordinated, mostly transient, reduction of circulating levels of nine immune signalling molecules. These were paralleled by a massive dysregulation of blood transcriptome, including genes implicated in chronic pathologies and immune functions. Immune and inflammatory functions were enriched among the genes downregulated in response to stress. An upregulation of genes involved in blood coagulation, platelet activation was characteristic of the rapid response to stress induction. Stress also decreased neutrophils and increased CD4 + T cell proportions in blood. This model of psychosocial stress, characterised by an immune dysregulation at the transcriptomic, molecular and cellular levels, creates opportunities to uncover the underlying mechanisms of stress-related diseases with an immune component, including cardiovascular diseases and susceptibility to infections

Suomen puutteellisesti tunnetut maksasammalsuvut: siiransammalet Nardia,rahtusammalet Cephaloziella ja pihtisammalet Cephalozia

Tämä julkaisu on tuotettu osana Ympäristöministeriön rahoittamaa PUTTE-tutkimusohjelmaa (Puutteellisesti tunnettujen ja uhanalaisten metsälajien tutkimusohjelma), josta saimme kaudella 2009-2011 3-vuotisen rahoituksen eräiden puutteellisesti tunnettujen maksasammalten levinneisyyden ja taksonomian nykytilanteen selvittämistä varten. Tutkimusohjelma on osa Etelä-Suomen metsien suojeluohjelmaa (METSO), jonka tavoitteena on lisätä metsälajiston ja metsäisten luontotyyppien suojeluastetta Etelä-Suomessa mm. vahvistamalla lajintuntemuksen tietopohjaa. Julkaisun tavoite on helpottaa pienten, vaikeasti havaittavien ja määritettävien maksasammallajien tunnistamista ja parantaa sukujen siiransammalet Nardia, rahtusammalet Cephaloziella ja pihtisammalet Cephalozia lajintuntemusta. Sukujen lajeista monet kasvavat esimerkiksi lahopuulla. Julkaisussa esitetään näiden sukujen ajantasaiset, suomenkieliset määrityskaavat. Sukuihin liittyy runsaasti taksonomista epäselvyyttä lajitasolla sekä puutteellisia levinneisyystietoja. Tässä esitettävät määrityskaavat koostettiin kirjallisuuden ja omien havaintojemme pohjalta. Lisäksi taustamateriaalina käytettiin Suomen luonnontieteellisten kokoelmien aineistoja. Suomen alueella esiintyvästä muuntelusta saatiin näin kattava aineisto, mikä parantaa kaavojen käytettävyyttä. Suvuista on julkaisussa esitetty kuvaukset, määrityskaavat sekä tarkemmat lajikuvaukset. Kustakin lajista on pyritty esittämään sekä valokuva että piirroskuvat versosta (habitus), lehdestä ja solukosta. Julkaisuun on laadittu piirroskuvat myös muista määrityksen kannalta olennaisista morfologisista yksityiskohdista. Julkaisussa annetaan myös ohjeet sammalnäytteiden keräämistä ja käsittelyä varten. Määrityskaavoista ja julkaisusta tehtiin mahdollisimman selkeät ja helppolukuiset, ja ne soveltuvat niin ammattilais- kuin harrastajakäyttöönkin. Tärkeänä tavoitteenamme on lisätä sammaliin kohdistuvaa mielenkiintoa ja madaltaa kynnystä niihin perehtymisessä. Hankkeemme paljasti myös lisää sukujen taksonomiaan liittyviä tutkimustarpeita

Selection against genetic defects in conservation schemes while controlling inbreeding

We studied different genetic models and evaluation systems to select against a genetic disease with additive, recessive or polygenic inheritance in genetic conservation schemes. When using optimum contribution selection with a restriction on the rate of inbreeding (ΔF) to select against a disease allele, selection directly on DNA-genotypes is, as expected, the most efficient strategy. Selection for BLUP or segregation analysis breeding value estimates both need 1–2 generations more to halve the frequency of the disease allele, while these methods do not require knowledge of the disease mutation at the DNA level. BLUP and segregation analysis methods were equally efficient when selecting against a disease with single gene or complex polygene inheritance, i.e. knowledge about the mode of inheritance of the disease was not needed for efficient selection against the disease. Smaller schemes or schemes with a more stringent restriction on ΔF needed more generations to halve the frequency of the disease alleles or the fraction of diseased animals. Optimum contribution selection maintained ΔF at its predefined level, even when selection of females was at random. It is argued that in the investigated small conservation schemes with selection against a genetic defect, control of ΔF is very important

Association between clinic-level quality of care and patient-level outcomes in multiple sclerosis

Background: Multiple sclerosis (MS) quality of care guidelines are consensus-based. The effectiveness of the recommendations is unknown.// Objective: To determine whether clinic-level quality of care affects clinical and patient-reported outcomes.// Methods: This nationwide observational cohort study included patients with adult-onset MS in the Swedish MS registry with disease onset 2005–2015. Clinic-level quality of care was measured by four indicators: visit density, magnetic resonance imaging (MRI) density, mean time to commencement of disease-modifying therapy, and data completeness. Outcomes were Expanded Disability Status Scale (EDSS) and patient-reported symptoms measured by the Multiple Sclerosis Impact Scale (MSIS-29). Analyses were adjusted for individual patient characteristics and disease-modifying therapy exposure.// Results: In relapsing MS, all quality indicators benefitted EDSS and physical symptoms. Faster treatment, frequent visits, and higher data completeness benefitted psychological symptoms. After controlling for all indicators and individual treatment exposures, faster treatment remained independently associated with lower EDSS (−0.06, 95% confidence interval (CI): −0.01, −0.10) and more frequent visits were associated with milder physical symptoms (MSIS-29 physical score: −16.2%, 95% CI: −1.8%, −29.5%). Clinic-level quality of care did not affect any outcomes in progressive-onset disease.// Conclusion: Certain quality of care indicators correlated to disability and patient-reported outcomes in relapse-onset but not progressive-onset disease. Future guidelines should consider recommendations specific to disease course..

A Generalized Mixing Length Closure for Eddy-Diffusivity Mass-Flux Schemes of Turbulence and Convection

Because of their limited spatial resolution, numerical weather prediction and climate models have to rely on parameterizations to represent atmospheric turbulence and convection. Historically, largely independent approaches have been used to represent boundary layer turbulence and convection, neglecting important interactions at the subgrid scale. Here we build on an eddy‐diffusivity mass‐flux (EDMF) scheme that represents all subgrid‐scale mixing in a unified manner, partitioning subgrid‐scale fluctuations into contributions from local diffusive mixing and coherent advective structures and allowing them to interact within a single framework. The EDMF scheme requires closures for the interaction between the turbulent environment and the plumes and for local mixing. A second‐order equation for turbulence kinetic energy (TKE) provides one ingredient for the diffusive local mixing closure, leaving a mixing length to be parameterized. Here, we propose a new mixing length formulation, based on constraints derived from the TKE balance. It expresses local mixing in terms of the same physical processes in all regimes of boundary layer flow. The formulation is tested at a range of resolutions and across a wide range of boundary layer regimes, including a stably stratified boundary layer, a stratocumulus‐topped marine boundary layer, and dry convection. Comparison with large eddy simulations (LES) shows that the EDMF scheme with this diffusive mixing parameterization accurately captures the structure of the boundary layer and clouds in all cases considered

An Improved Perturbation Pressure Closure for Eddy-Diffusivity Mass-Flux Schemes

Convection parameterizations such as eddy-diffusivity mass-flux (EDMF) schemes require a consistent closure formulation for the perturbation pressure, which arises in the equations for vertical momentum and turbulence kinetic energy (TKE). Here we derive an expression for the perturbation pressure from approximate analytical solutions for 2D and 3D rising thermal bubbles. The new closure combines a modified pressure drag and virtual mass effects with a new momentum advection term. This momentum advection is an important source in the lower half of the thermal bubble and at cloud base levels in convective systems. It represents the essential physics of the perturbation pressure, that is, to ensure the 3D non-divergent properties of the flow. Moreover, the new formulation modifies the pressure drag to be inversely proportional to updraft depth. This is found to significantly improve simulations of the diurnal cycle of deep convection, without compromising simulations of shallow convection. It is thus a key step toward a unified scheme for a range of convective motions. By assuming that the pressure only redistributes TKE between plumes and the environment, rather than vertically, a closure for the velocity pressure-gradient correlation is obtained from the perturbation pressure closure. This novel pressure closure is implemented in an extended EDMF scheme and is shown to successfully simulate a rising bubble test case as well as shallow and deep convection cases in a single column model