Adiabatic reduction near a bifurcation in stochastically modulated systems

We re-examine the procedure of adiabatic elimination of fast relaxing variables near a bifurcation point when some of the parameters of the system are stochastically modulated. Approximate stationary solutions of the Fokker-Planck equation are obtained near threshold for the pitchfork and transcritical bifurcations. Stochastic resonance between fast variables and random modulation may shift the effective bifurcation point by an amount proportional to the intensity of the fluctuations. We also find that fluctuations of the fast variables above threshold are not always Gaussian and centered around the (deterministic) center manifold as was previously believed. Numerical solutions obtained for a few illustrative examples support these conclusions.Comment: RevTeX, 19 pages and 16 figure

Vaccinating Girls and Boys with Different Human Papillomavirus Vaccines: Can It Optimise Population-Level Effectiveness?

<label>BACKGROUND</label>Decision-makers may consider vaccinating girls and boys with different HPV vaccines to benefit from their respective strengths; the quadrivalent (HPV4) prevents anogenital warts (AGW) whilst the bivalent (HPV2) may confer greater cross-protection. We compared, to a girls-only vaccination program with HPV4, the impact of vaccinating: 1) both genders with HPV4, and 2) boys with HPV4 and girls with HPV2.<label>METHODS</label>We used an individual-based transmission-dynamic model of heterosexual HPV infection and diseases. Our base-case scenario assumed lifelong efficacy of 100% against vaccine types, and 46,29,8,18,6% and 77,43,79,8,0% efficacy against HPV-31,-33,-45,-52,-58 for HPV4 and HPV2, respectively.<label>RESULTS</label>Assuming 70% vaccination coverage and lifelong cross-protection, vaccinating boys has little additional benefit on AGW prevention, irrespective of the vaccine used for girls. Furthermore, using HPV4 for boys and HPV2 for girls produces greater incremental reductions in SCC incidence than using HPV4 for both genders (12 vs 7 percentage points). At 50% vaccination coverage, vaccinating boys produces incremental reductions in AGW of 17 percentage points if both genders are vaccinated with HPV4, but increases female incidence by 16 percentage points if girls are switched to HPV2 (heterosexual male incidence is incrementally reduced by 24 percentage points in both scenarios). Higher incremental reductions in SCC incidence are predicted when vaccinating boys with HPV4 and girls with HPV2 versus vaccinating both genders with HPV4 (16 vs 12 percentage points). Results are sensitive to vaccination coverage and the relative duration of protection of the vaccines.<label>CONCLUSION</label>Vaccinating girls with HPV2 and boys with HPV4 can optimize SCC prevention if HPV2 has higher/longer cross-protection, but can increase AGW incidence if vaccination coverage is low among boys

La bioéthique selon Van Rensselaer Potter : une perspective pertinente à la réflexion ergothérapique contemporaine

Ce commentaire présente trois arguments de la pensée potterienne à partir de la lunette ergothérapique afin de soutenir les réflexions relatives au développement des pratiques durables en ergothérapie. Il permet ainsi d’initier les ergothérapeutes à une perspective de bioéthique globale susceptible de les soutenir dans l’actualisation d’une approche écosystémique respectueuse de l’environnement. This commentary presents three arguments of Potterian thought from an occupational therapy perspective in order to support reflections on the development of sustainable practices in occupational therapy. In this way, it introduces occupational therapists to a global bioethical perspective that can support them in implementing an ecosystemic approach that respects the environment

Assortative mixing as a source of bias in epidemiological studies of sexually transmitted infections: the case of smoking and human papillomavirus

For studies examining risk factors of sexually transmitted infections (STIs), confounding can stem from characteristics of partners of study subjects, and persist after adjustment for the subjects’ individual-level characteristics. Two conditions that can result in confounding by the subjects’ partners are: (C1) partner choice is assortative by the risk factor examined and, (C2) sexual activity is associated with the risk factor. The objective of this paper is to illustrate the potential impact of the assortativity bias in studies examining STI risk factors, using smoking and human papillomavirus (HPV) as an example. We developed an HPV transmission-dynamic mathematical model in which we nested a cross-sectional study assessing the smoking–HPV association. In our base case, we assumed (1) no effect of smoking on HPV, and (2) conditions C1–C2 hold for smoking (based on empirical data). The assortativity bias caused an overestimation of the odds ratio (OR) in the simulated study after perfect adjustment for the subjects’ individual-level characteristics (adjusted OR 1·51 instead of 1·00). The bias was amplified by a lower basic reproductive number (R(0)), greater mixing assortativity and stronger association of smoking with sexual activity. Adjustment for characteristics of partners is needed to mitigate assortativity bias

Women rebuilding lives post-disaster: innovative community practices for building resilience and promoting sustainable development

Disasters result in devastating human, economic, and environmental effects. The paper highlights women's active participation in community-based disaster recovery efforts drawing from the results of the ‘Rebuilding Lives Post-disaster: Innovative Community Practices for Sustainable Development’ by an international research partnership. Two case studies are presented from Pakistan and the USA to demonstrate how women contribute to building resilience and promoting sustainable development in diverse post-disaster contexts. The policy and practice implications are relevant for discussions regarding the post-2015 Sustainable Development Goals and framework

Wage losses in the year after breast cancer: Extent and determinants among Canadian women

This article is available open access through the publisher’s website at the link below. © The Author 2008.Background - Wage losses after breast cancer may result in considerable financial burden. Their assessment is made more urgent because more women now participate in the workforce and because breast cancer is managed using multiple treatment modalities that could lead to long work absences. We evaluated wage losses, their determinants, and the associations between wage losses and changes for the worse in the family's financial situation among Canadian women over the first 12 months after diagnosis of early breast cancer. Methods - We conducted a prospective cohort study among women with breast cancer from eight hospitals throughout the province of Quebec. Information that permitted the calculation of wage losses and information on potential determinants of wage losses were collected by three pretested telephone interviews conducted over the year following the start of treatment. Information on medical characteristics was obtained from medical records. The main outcome was the proportion of annual wages lost because of breast cancer. Multivariable analysis of variance using the general linear model was used to identify personal, medical, and employment characteristics associated with the proportion of wages lost. All statistical tests were two-sided. Results - Among 962 eligible breast cancer patients, 800 completed all three interviews. Of these, 459 had a paying job during the month before diagnosis. On average, these working women lost 27% of their projected usual annual wages (median = 19%) after compensation received had been taken into account. Multivariable analysis showed that a higher percentage of lost wages was statistically significantly associated with a lower level of education (Ptrend = .0018), living 50 km or more from the hospital where surgery was performed (P = .070), lower social support (P = .012), having invasive disease (P = .086), receipt of chemotherapy (P < .001), self-employment (P < .001), shorter tenure in the job (Ptrend < .001), and part-time work (P < .001). Conclusion - Wage losses and their effects on financial situation constitute an important adverse consequence of breast cancer in Canada.The Canadian Breast Cancer Research Alliance, Canadian Institutes of Health Research, and Fondation de l’Université Laval

Soutenir les valeurs d’écoresponsabilité et de justice occupationnelle intergénérationnelle dans un contexte clinique : un devoir pour l’ergothérapeute ?

Cet article questionne la pertinence de soutenir la valeur qu’est l’écoresponsabilité et, plus largement, la justice occupationnelle intergénérationnelle dans le contexte de la pratique clinique de l’ergothérapeute. Au moment d’adopter des pratiques professionnelles respectueuses de ces valeurs, l’ergothérapeute peut être amené à vivre un dilemme éthique opposant celles-ci à l’approche centrée sur le client qui est grandement valorisée au sein de la profession. Cet article développe une réflexion éthique sur un des résultats d’une recherche qui a été menée sur les pratiques durables ou écoresponsables en ergothérapie. Plus précisément, nous développons une réflexion éthique sur la légitimité pour l’ergothérapeute de défendre les valeurs que sont l’écoresponsabilité et la justice occupationnelle intergénérationnelle dans un contexte clinique. Pour ce faire, le Cadre éthique quadripartite (CÉQ) – un cadre d’analyse éthique qui a été développé pour soutenir l’ergothérapeute dans ses réflexions éthiques – est mobilisé. Sans apporter une réponse claire ni définitive quant à la pertinence éthique de défendre ces valeurs en clinique, la réflexion ici développée met en lumière des éléments qui pourraient être considérés par l’ergothérapeute qui vit ce dilemme éthique. This article questions the relevance of supporting the value of eco-responsibility and, more broadly, intergenerational occupational justice in the context of the clinical practice of the occupational therapy. When adopting professional practices that are respectful of these values, occupational therapists may be faced with an ethical dilemma that opposes these values to the client-centred approach that is highly valued within the profession. This article develops an ethical reflection on one of the results of a research study conducted on sustainable or eco-responsible practices in occupational therapy. More specifically, we develop an ethical reflection on the legitimacy for occupational therapists to defend the values of eco-responsibility and intergenerational occupational justice in a clinical context. To do so, we mobilize the Quadripartite Ethical Framework (QEF), an ethical analysis framework that was developed to support occupational therapists in their ethical reflections. Without providing a clear or definitive answer as to the ethical relevance of defending these values in a clinical setting, the reflection developed here highlights elements that could be considered by occupational therapists experiencing such an ethical dilemma

Potential population-level effectiveness of one-dose HPV vaccination in low-income and middle-income countries: a mathematical modelling analysis

BACKGROUND: Given the accumulating evidence that one-dose vaccination could provide high and sustained protection against human papillomavirus (HPV) infection and related diseases, we examined the population-level effectiveness and efficiency of one-dose HPV vaccination of girls compared with two-dose vaccination, using mathematical modelling. METHODS: In this mathematical modelling study, we used HPV-ADVISE LMIC, an individual-based transmission-dynamic model independently calibrated to four epidemiologically diverse low-income and middle-income countries (LMICs; India, Nigeria, Uganda, and Viet Nam). We parameterised and calibrated the model using sexual behaviour and epidemiological data identified from international population-based datasets and the literature. All base-case vaccination scenarios start in 2023 with the nonavalent vaccine and assumed 80% vaccination coverage with one or two doses. We assumed that two doses of vaccine provide 100% efficacy against vaccine-type infections and a lifelong duration of protection. We examined a non-inferior vaccination scenario for one dose compared with two doses, pessimistic scenarios of lower one-dose vaccine efficacy (85%) or a shorter duration of protection (ie, 20 or 30 years), and the effectiveness of a mitigation scenario in which schedules would switch from one dose to two doses. We also did sensitivity analyses by varying vaccination coverage. We used three outcomes: the relative reduction in cervical cancer incidence, the number of cervical cancers averted, and the number of vaccine doses needed to prevent one cervical cancer. FINDINGS: Assuming non-inferior vaccine characteristics for one dose compared with two doses, the model projections show that two-dose or one-dose routine vaccination of girls aged 9 years (with a multi-age cohort vaccination of girls aged 10-14 years) would avert 12·0 million (80% UI 9·5-14·5) cervical cancers in India, 4·7 million (3·4-5·8) in Nigeria, 2·3 million (1·9-2·6) in Uganda, and 0·4 million (0·2-0·5) in Viet Nam over 100 years. Under pessimistic assumptions of lower one-dose efficacy (85%) or a shorter duration of protection (ie, 30 years), one-dose routine vaccination would avert 69% (61-80) to 94% (92-96) of the cervical cancers averted with two-dose routine vaccination. However, when assuming a duration of protection of 20 years, one-dose routine vaccination would avert substantially fewer cervical cancers (ie, 35% [26-44] to 69% [65-71] of the cervical cancers averted with two-dose routine vaccination). A switch from one-dose to two-dose routine vaccination of girls aged 9 years, with a one-dose catch-up of girls aged 10-14 years, 5 years after the start of the vaccination programme, could mitigate potential losses in cervical cancer prevention from a short one-dose duration of protection (averting 92% [83-98] to 99% [97-100]) of the cervical cancers averted with two-dose routine vaccination). One-dose routine vaccination would result in fewer doses needed to prevent one cervical cancer than two-dose routine vaccination, even if the duration of protection is as low as 20 years. Finally, for countries with two-dose routine vaccination, adding one-dose multi-age cohort vaccination in the first year would provide similar benefits as a two-dose multi-age cohort vaccination, and would be more efficient even under the pessimistic assumptions of lower one-dose vaccine efficacy or duration of protection. INTERPRETATION: One-dose routine vaccination could avert most of the cervical cancers averted with two-dose vaccination while being more efficient, provided the duration of one-dose protection is greater than 20-30 years (depending on the LMIC). The doses saved by introducing one-dose routine vaccination could offer the opportunity to vaccinate girls before they age out of the vaccination window of 9-14 years and, potentially, to vaccinate boys or older age groups. FUNDING: Fonds de recherche du Québec-Santé, Digital Research Alliance of Canada, Bill & Melinda Gates Foundation

PITUITARY ONTOGENY OF THE SNELL DWARF MOUSE REVEALS PIT-1-INDEPENDENT AND PIT-1-DEPENDENT ORIGINS OF THE THYROTROPE

The anterior pituitary provides a model to study the molecular mechanisms responsible for emergence of distinct cell types within an organ. Dwarf mice (Snell) that express a mutant form of the tissue-specific POU-domain transcription factor Pit-1 fail to generate three cell types, including the thyrotrope (S. Li, E. B. Crenshaw, E. J. Rawson, D. S. Simmons, L. Swanson and M. G. Rosenfeld (1990), Nature 347, 528-533). Analyses of wild-type and Pit-1-defective mice, presented here, have revealed that thyrotropes unexpectedly arise from two independent cell populations. The first population is Pit-1-independent and appears on e12 in the rostral tip of the developing gland, but phenotypically disappears by the day of birth. The second is Pit-1-dependent and arises subsequently in the caudomedial portion of the developing gland (e15.5), following the initial expression of Pit-1 in this region. The failure of caudomedial thyrotrope cells to appear in the Snell dwarf, and the observation that Pit-1 can bind to and transactivate the TSH beta promoter, apparently enhanced by its phosphorylation, suggests that Pit-1 is directly required for the appearance of this distinct population that serves as the precursors of the mature thyrotrope cell type. These data suggest that different molecular mechanisms, based on the actions of distinct transcription factors, can serve to independently generate a specific cell phenotype during mammalian organogenesis

Grain boundary pinning and glassy dynamics in stripe phases

We study numerically and analytically the coarsening of stripe phases in two spatial dimensions, and show that transient configurations do not achieve long ranged orientational order but rather evolve into glassy configurations with very slow dynamics. In the absence of thermal fluctuations, defects such as grain boundaries become pinned in an effective periodic potential that is induced by the underlying periodicity of the stripe pattern itself. Pinning arises without quenched disorder from the non-adiabatic coupling between the slowly varying envelope of the order parameter around a defect, and its fast variation over the stripe wavelength. The characteristic size of ordered domains asymptotes to a finite value $R_g \sim \lambda_0\ \epsilon^{-1/2}\exp(|a|/\sqrt{\epsilon})$, where$\epsilon\ll 1$is the dimensionless distance away from threshold,$\lambda_0$the stripe wavelength, and$a$ a constant of order unity. Random fluctuations allow defect motion to resume until a new characteristic scale is reached, function of the intensity of the fluctuations. We finally discuss the relationship between defect pinning and the coarsening laws obtained in the intermediate time regime.Comment: 17 pages, 8 figures. Corrected version with one new figur