Semiconservative quasispecies equations for polysomic genomes: The general case

This paper develops a formulation of the quasispecies equations appropriate for polysomic, semiconservatively replicating genomes. This paper is an extension of previous work on the subject, which considered the case of haploid genomes. Here, we develop a more general formulation of the quasispecies equations that is applicable to diploid and even polyploid genomes. Interestingly, with an appropriate classification of population fractions, we obtain a system of equations that is formally identical to the haploid case. As with the work for haploid genomes, we consider both random and immortal DNA strand chromosome segregation mechanisms. However, in contrast to the haploid case, we have found that an analytical solution for the mean fitness is considerably more difficult to obtain for the polyploid case. Accordingly, whereas for the haploid case we obtained expressions for the mean fitness for the case of an analogue of the single-fitness-peak landscape for arbitrary lesion repair probabilities (thereby allowing for non-complementary genomes), here we solve for the mean fitness for the restricted case of perfect lesion repair.Comment: 16 pages, 3 figure

Efficiency of using community organisations as catalysts for recruitment to continence promotion trials

This article is available open access through the publisher’s website from the link below. Copyright @ 2012 The Authors.Background - A major challenge for determining the effectiveness of community-based continence promotion campaigns is recruitment of a representative sample of incontinent participants who have not previously sought care. Purpose - To evaluate the efficiency of engaging community organisations as catalysts for recruitment of community-dwelling older women with incontinence to the ‘Continence across Continents’ randomised controlled trial. Methods - Seniors’ and women’s community-based organisations throughout the United Kingdom were solicited by telephone or email to assist recruitment for an open-label cluster randomised controlled trial testing three experimental continence promotion interventions and a control intervention for incontinent older women. Women aged 60 years and older who experienced at least weekly urinary incontinence and who had never sought treatment were eligible to participate. The response rate of the organisations and enrolment rate of eligible participants attending the continence promotion workshops were recorded. Differences in recruitment efficiency by intervention group were ascertained using analysis of variance statistics. Results - We contacted 408 community organisations over a 1-year period. Seventy organisations (17%) agreed to host a workshop, 249 (61%) did not provide a response, and 89 (22%) refused. Workshops were administered in a group format to 61 organisations (15%); 667 women attended, 583 (87%) submitted the screening questionnaire, and 437 (66%) met eligibility criteria for inclusion. A total of 192 women consented to participate in the trial, yielding a 44% recruitment efficiency among workshop attendees known to be eligible, with no significant difference in enrolment rates between groups. However, the mean participant recruitment rate per number of attendees at each workshop was only 29%, varying substantially between groups from 19% to 37%, with the lowest rate observed for the control group. The mean annual recruitment rate expressed as the number of enrolled participants per community organisation contacted was 0.5. Limitations - Reasons for women’s non-response were not collected. The findings may be country specific. Conclusions - The recruitment rate for a continence promotion trial among older women known to be eligible and attending workshops hosted by local community organisations was high (44%). Strategies are needed to bolster community organisations’ involvement in health promotion trials in general and for continence issues in particular

From the ISR to RHIC--measurements of hard-scattering and jets using inclusive single particle production and 2-particle correlations

Hard scattering in p-p collisions, discovered at the CERN ISR in 1972 by the method of leading particles, proved that the partons of Deeply Inelastic Scattering strongly interacted with each other. Further ISR measurements utilizing inclusive single or pairs of hadrons established that high pT particles are produced from states with two roughly back-to-back jets which are the result of scattering of constituents of the nucleons as desribed by Quantum Chromodynamics (QCD), which was developed during the course of these measurements. These techniques, which are the only practical method to study hard-scattering and jet phenomena in Au+Au central collisions at RHIC energies, are reviewed, as an introduction to present RHIC measurements.Comment: To appear in the proceedings of the workshop on Correlations and Fluctuations in Relativistic Nuclear Collisions, MIT, Cambridge, MA, April 21-23, 2005, 10 pages, 9 figures, Journal of Physics: Conference Proceeding

Affine Registration of label maps in Label Space

Two key aspects of coupled multi-object shape\ud analysis and atlas generation are the choice of representation\ud and subsequent registration methods used to align the sample\ud set. For example, a typical brain image can be labeled into\ud three structures: grey matter, white matter and cerebrospinal\ud fluid. Many manipulations such as interpolation, transformation,\ud smoothing, or registration need to be performed on these images\ud before they can be used in further analysis. Current techniques\ud for such analysis tend to trade off performance between the two\ud tasks, performing well for one task but developing problems when\ud used for the other.\ud This article proposes to use a representation that is both\ud flexible and well suited for both tasks. We propose to map object\ud labels to vertices of a regular simplex, e.g. the unit interval for\ud two labels, a triangle for three labels, a tetrahedron for four\ud labels, etc. This representation, which is routinely used in fuzzy\ud classification, is ideally suited for representing and registering\ud multiple shapes. On closer examination, this representation\ud reveals several desirable properties: algebraic operations may\ud be done directly, label uncertainty is expressed as a weighted\ud mixture of labels (probabilistic interpretation), interpolation is\ud unbiased toward any label or the background, and registration\ud may be performed directly.\ud We demonstrate these properties by using label space in a gradient\ud descent based registration scheme to obtain a probabilistic\ud atlas. While straightforward, this iterative method is very slow,\ud could get stuck in local minima, and depends heavily on the initial\ud conditions. To address these issues, two fast methods are proposed\ud which serve as coarse registration schemes following which the\ud iterative descent method can be used to refine the results. Further,\ud we derive an analytical formulation for direct computation of the\ud "group mean" from the parameters of pairwise registration of all\ud the images in the sample set. We show results on richly labeled\ud 2D and 3D data sets

Effectiveness of continence promotion for older women via community organisations: A cluster randomised trial

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/Objectives: The primary objective of this cluster randomised controlled trial was to compare the effectiveness of the three experimental continence promotion interventions against a control intervention on urinary symptom improvement in older women with untreated incontinence recruited from community organisations. A second objective was to determine whether changes in incontinence-related knowledge and new uptake of risk-modifying behaviours explain these improvements. Setting: 71 community organisations across the UK. Participants: 259 women aged 60 years and older with untreated incontinence entered the trial; 88% completed the 3-month follow-up. Interventions: The three active interventions consisted of a single 60 min group workshop on (1) continence education (20 clusters, 64 women); (2) evidence-based self-management (17 clusters, 70 women); or (3) combined continence education and self-management (17 clusters, 61 women). The control intervention was a single 60 min educational group workshop on memory loss, polypharmacy and osteoporosis (17 clusters, 64 women). Primary and secondary outcome measures: The primary outcome was self-reported improvement in incontinence 3 months postintervention at the level of the individual. The secondary outcome was change in the International Consultation on Incontinence Questionnaire (ICIQ) from baseline to 3-month follow-up. Changes in incontinence-related knowledge and behaviours were also assessed. Results: The highest rate of urinary symptom improvement occurred in the combined intervention group (66% vs 11% of the control group, prevalence difference 55%, 95% CI 43% to 67%, intracluster correlation 0). 30% versus 6% of participants reported significant improvement respectively (prevalence difference 23%, 95% CI 10% to 36%, intracluster correlation 0). The number-needed-to-treat was 2 to achieve any improvement in incontinence symptoms, and 5 to attain significant improvement. Compared to controls, participants in the combined intervention reported an adjusted mean 2.05 point (95% CI 0.87 to 3.24) greater improvement on the ICIQ from baseline to 3-month follow-up. Changes in knowledge and self-reported risk-reduction behaviours paralleled rates of improvement in all intervention arms. Conclusions: Continence education combined with evidence-based self-management improves symptoms of incontinence among untreated older women. Community organisations represent an untapped vector for delivering effective continence promotion interventions.Canadian Institutes of Health Research – Institute on Aging and the Economic and Social Research Council (UK

Pilot study for a sperm quality-based reproductive assessment scheme for deer

Ecological risk assessments (ERAs) for mammals at chemically contaminated terrestrial sites conventionally apply a food-chain model to draw inferences about a population’s reproductive condition. Very recently though, the ERA field was advanced beyond the desktop level with the introduction of Rodent Sperm Analysis (RSA), a direct health status assessment method for the actual chemically exposed site receptor. Here, the sperm parameters of rodents (count, motility, morphology) of contaminated sites and their habitat-matched non-contaminated reference locations are comparatively reviewed for a technically supported indication of reproductive capability, ERA’s toxicological endpoint of greatest concern. With the extent to which sperm parameters need to be impaired in order to compromise reproduction being known, more definitive determinations are possible than with the food-chain model approach. We sought to adapt the RSA method to the white-tailed deer (Odocoileus virginianus), recognizing that this commonly evaluated mammalian species of ERAs is one of a very few species that avails itself to regularly being removed (through hunting) from the field. We conclude that the adaptation is viable, although sperm motility and a few other measures routinely compiled in RSA applications cannot be collected. In the pilot application, the deer population we assessed, with exposures to Superfund and other sites of known contamination, was not found to have compromised reproduction. This finding is consistent with RSA’s supporting theory as well as population census information. The outcomes of so-called deer sperm analysis applications for herds exposed to one or more environmental stressors, have the potential to serve as reliable indicators of reproductive status. Such outcomes also provide further weight-of-evidence that suspected contamination is not associated with adverse ecological effects

The Influence of Individual Characteristics and the Work Environment on Varying Levels of Training Outcomes

This study tested a model in which pretraining self-efficacy and motivation were hypothesized to mediate the relationship between job involvement, organizational commitment, perceptions of the work environment, and training reactions and knowledge acquisition. It also proposed hierarchical relationships between levels of training effectiveness criteria. A series of analyses demonstrated support for the model. Future research should incorporate a multilevel framework and consider the multidimensional nature of training outcomes

Физиотерапия (лечебная физкультура и кинезитерапия) у больных муковисцидозом

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Multivariate Modeling Identifies Neutrophil- and Th17-Related Factors as Differential Serum Biomarkers of Chronic Murine Colitis

Background: Diagnosis of chronic intestinal inflammation, which characterizes inflammatory bowel disease (IBD), along with prediction of disease state is hindered by the availability of predictive serum biomarker. Serum biomarkers predictive of disease state will improve trials for therapeutic intervention, and disease monitoring, particularly in genetically susceptible individuals. Chronic inflammation during IBD is considered distinct from infectious intestinal inflammation thereby requiring biomarkers to provide differential diagnosis. To address whether differential serum biomarkers could be identified in murine models of colitis, immunological profiles from both chronic spontaneous and acute infectious colitis were compared and predictive serum biomarkers identified via multivariate modeling.Methodology/Principal Findings: Discriminatory multivariate modeling of 23 cytokines plus chlorotyrosine and nitrotyrosine (protein adducts from reactive nitrogen species and hypochlorite) in serum and tissue from two murine models of colitis was performed to identify disease-associated biomarkers. Acute C. rodentium-induced colitis in C57BL/6J mice and chronic spontaneous Helicobacter-dependent colitis in TLR4−/− x IL-10−/− mice were utilized for evaluation. Colon profiles of both colitis models were nearly identical with chemokines, neutrophil- and Th17-related factors highly associated with intestinal disease. In acute colitis, discriminatory disease-associated serum factors were not those identified in the colon. In contrast, the discriminatory predictive serum factors for chronic colitis were neutrophil- and Th17-related factors (KC, IL-12/23p40, IL-17, G-CSF, and chlorotyrosine) that were also elevated in colon tissue. Chronic colitis serum biomarkers were specific to chronic colitis as they were not discriminatory for acute colitis.Conclusions/Significance: Immunological profiling revealed strikingly similar colon profiles, yet distinctly different serum profiles for acute and chronic colitis. Neutrophil- and Th17-related factors were identified as predictive serum biomarkers of chronic colitis, but not acute colitis, despite their presence in colitic tissue of both diseases thereby demonstrating the utility of mathematical modeling for identifying disease-associated serum biomarkers.</p