Catastrophic senescence and semelparity in the Penna aging model

The catastrophic senescence of the Pacific salmon is among the initial tests used to validate the Penna aging model. Based on the mutation accumulation theory, the sudden decrease in fitness following reproduction may be solely attributed to the semelparity of the species. In this work, we report other consequences of mutation accumulation. Contrary to earlier findings, such dramatic manifestation of aging depends not only on the choice of breeding strategy but also on the value of the reproduction age, R, and the mutation threshold, T. Senescence is catastrophic when $T \leq R$. As the organism's tolerance for harmful genetic mutations increases, the aging process becomes more gradual. We observe senescence that is threshold dependent whenever T>R. That is, the sudden drop in survival rate occurs at age equal to the mutation threshold value

Autoimmune alternating hyper- and hypo-thyroidism: a rare condition in pediatrics

Alternating between hyper- and hypo-thyroidism may be explained by the simultaneous presence of both types of TSH receptor autoantibodies (TRAbs) - thyroid stimulating autoantibodies (TSAbs) and TSH blocking autoantibodies (TBAbs). It is a very rare condition, particulary in the pediatric age. The clinical state of these patients is determined by the balance between TSAbs and TBAbs and can change over time. Many mechanisms may be involved in fluctuating thyroid function: hormonal supplementation, antithyroid drugs and levels of TSAbs and TBAbs. Frequent dose adjustments are needed in order to achieve euthyroidism. A definitive therapy may be necessary to avoid switches in thyroid function and frequent need of therapeutic changes. We describe an immune-mediated case of oscillating thyroid function in a 13-year-old adolescent. After a short period of levothyroxine treatment, the patient switched to a hyperthyroid state that was only controlled by adding an antithyroid drug. LEARNING POINTS: Autoimmune alternating hypo- and hyper-thyroidism is a highly uncommon condition in the pediatric age.It may be due to the simultaneous presence of both TSAbs and TBAbs, whose activity may be estimated in vitro through bioassays.The clinical state of these patients is determined by the balance between TSAbs and TBAbs and can change over time.The management of this condition is challenging, and three therapeutic options could be considered: I-131 ablation, thyroidectomy or pharmacological treatment (single or double therapy).Therapeutic decisions should be taken according to clinical manifestations and thyroid function tests, independent of the bioassays results.A definitive treatment might be considered due to the frequent switches in thyroid function and the need for close monitoring of pharmacological treatment. A definitive treatment might be considered due to the frequent switches in thyroid function and the need for close monitoring of pharmacological treatment.info:eu-repo/semantics/publishedVersio

Sex, Body Image, and Relationships: A BRIGHTLIGHT Workshop on Information and Support Needs of Adolescents and Young Adults

PURPOSE: Discovering sexuality and romantic relationships are important development milestones in adolescence and young adulthood. A cancer diagnosis imposes obstacles for young people such as changes in their sexual function due to the disease and/or side effects of treatment, body image concerns, and interpersonal relationship difficulties. This can cause psychological distress and can impact on quality of life. We aimed to explore sexual health information and support needs of adolescents and young adults with cancer. METHODS: Five young people aged 16-24 years, with a previous cancer diagnosis when aged 13-22 years, attended an in-depth 4-hour workshop. The framework approach was used to analyze workshop transcripts. RESULTS: Three overarching themes emerged: (i) information sharing; (ii) contexts and relationships (influencing factors); and (iii) information sharing preferences. Information shared by healthcare professionals was focused on a medicalized view of sex with symptoms, infection control, and protected sex at its core. Young people had unanswered questions related to sexual function, the impact of cancer and how to manage it, and about pleasure, body image, and relationships. Parents' presence at clinical consultations inhibited discussions about sex. Young people wanted professionals who were comfortable to talk about sex with them. CONCLUSION: Young people exhibited significant unmet needs around information provision on sex, body image, and relationships. They wanted information to be given by professionals and access to online resources. Development of training for professionals and resources to support young people requires further work

Qualitative study to understand the barriers to recruiting young people with cancer to BRIGHTLIGHT: a national cohort study in England

Objectives: BRIGHTLIGHT is a national evaluation of cancer services for teenagers and young adults in England. Following challenges with recruitment, our aim was to understand more fully healthcare professionals’ perspectives of the challenges of recruiting young people to a low-risk observational study, and to provide guidance for future recruitment processes. / Design: Qualitative. / Setting: National Health Service (NHS) hospitals in England. / Methods: Semistructured telephone interviews with a convenience sample of 23 healthcare professionals. Participants included principal investigators/other staff recruiting into the BRIGHTLIGHT study. Data were analysed using framework analysis. / Results: The emergent themes were linked to levels of research organisational management, described using the levels of social network analysis: micro-level (the individual; in this case the target population to be recruited—young people with cancer); meso-level (the organisation; refers to place of recruitment and people responsible for recruitment); and macro-level (the large-scale or global structure; refers to the wider research function of the NHS and associated policies). Study-related issues occurred across all three levels, which were influenced by the context of the study. At the meso-level, professionals’ perceptions of young people and communication between professionals generated age/cancer type silos, resulting in recruitment of either children or adults, but not both by the same team, and only in the cancer type the recruiting professional was aligned to. At the macro-level the main barrier was discordant configuration of a research service with a clinical service. / Conclusions: This study has identified significant barriers to recruitment mainly at the meso-level and macro-level, which are more challenging for research teams to influence. We suggest that interconnected whole-system changes are required to facilitate the success of interventions designed to improve recruitment. Interventions targeted at study design/management and the micro-level only may be less successful. We offer solutions to be considered by those involved at all levels of research for this population

Determinants of health care utilisation: The case of Timor-Leste

© The Author(s) 2018. Background: Health financing and delivery reforms designed to achieve universal health coverage (UHC) need to be informed by an understanding of factors that both promote access to health care and undermine it. This study examines the level of health care utilisation in Timor-Leste and the factors that drive it. Methods: Data from a nationally representative cross-sectional survey of health care utilisation in 1712 households were used to develop multilevel models exploring how need and predisposing and enabling factors explain health care utilisation at both primary and secondary care facilities. Results: Need was found to be the key driver in seeking both primary care and hospital services. Rural households were less likely to go to hospital (odds ratio 0.7) than urban households. The poorest quintile was also less likely to use more expensive hospital services than other socio-economic groups. Conclusions: Understanding the determinants of seeking health care in Timor-Leste is of considerable policy significance, because health care is free at the point of use. Our findings indicate that the public resources for health care are subsidising the rich more than the poor. Health care reforms in Timor-Leste need to reduce the 'other' costs of health care, such as distance barriers, to address these inequities

A feature selection approach for identification of signature genes from SAGE data

<p>Abstract</p> <p>Background</p> <p>One goal of gene expression profiling is to identify signature genes that robustly distinguish different types or grades of tumors. Several tumor classifiers based on expression profiling have been proposed using microarray technique. Due to important differences in the probabilistic models of microarray and SAGE technologies, it is important to develop suitable techniques to select specific genes from SAGE measurements.</p> <p>Results</p> <p>A new framework to select specific genes that distinguish different biological states based on the analysis of SAGE data is proposed. The new framework applies the bolstered error for the identification of strong genes that separate the biological states in a feature space defined by the gene expression of a training set. Credibility intervals defined from a probabilistic model of SAGE measurements are used to identify the genes that distinguish the different states with more reliability among all gene groups selected by the strong genes method. A score taking into account the credibility and the bolstered error values in order to rank the groups of considered genes is proposed. Results obtained using SAGE data from gliomas are presented, thus corroborating the introduced methodology.</p> <p>Conclusion</p> <p>The model representing counting data, such as SAGE, provides additional statistical information that allows a more robust analysis. The additional statistical information provided by the probabilistic model is incorporated in the methodology described in the paper. The introduced method is suitable to identify signature genes that lead to a good separation of the biological states using SAGE and may be adapted for other counting methods such as Massive Parallel Signature Sequencing (MPSS) or the recent Sequencing-By-Synthesis (SBS) technique. Some of such genes identified by the proposed method may be useful to generate classifiers.</p

Nanostructured 3D Constructs Based on Chitosan and Chondroitin Sulphate Multilayers for Cartilage Tissue Engineering

Nanostructured three-dimensional constructs combining layer-by-layer technology (LbL) and template leaching were processed and evaluated as possible support structures for cartilage tissue engineering. Multilayered constructs were formed by depositing the polyelectrolytes chitosan (CHT) and chondroitin sulphate (CS) on either bidimensional glass surfaces or 3D packet of paraffin spheres. 2D CHT/CS multi-layered constructs proved to support the attachment and proliferation of bovine chondrocytes (BCH). The technology was transposed to 3D level and CHT/CS multi-layered hierarchical scaffolds were retrieved after paraffin leaching. The obtained nanostructured 3D constructs had a high porosity and water uptake capacity of about 300%. Dynamical mechanical analysis (DMA) showed the viscoelastic nature of the scaffolds. Cellular tests were performed with the culture of BCH and multipotent bone marrow derived stromal cells (hMSCs) up to 21 days in chondrogenic differentiation media. Together with scanning electronic microscopy analysis, viability tests and DNA quantification, our results clearly showed that cells attached, proliferated and were metabolically active over the entire scaffold. Cartilaginous extracellular matrix (ECM) formation was further assessed and results showed that GAG secretion occurred indicating the maintenance of the chondrogenic phenotype and the chondrogenic differentiation of hMSCs

Thyroid Hormones within the Normal Range and Cardiac Function in the General Population: The EPIPorto Study

Background: Hypothyroidism and hyperthyroidism are associated with marked changes in cardiac structure and function. However, the association of thyroid function within the normal range with cardiac structure and function in the general population remains uncertain. Methods: Eight hundred thirty-five subjects aged ≥45 years from the EPIPorto cohort (evaluation between 2006 and 2008) were cross-sectionally analyzed. We excluded participants with TSH, free T4 (FT4), or free T3 (FT3) outside of the reference range or with self-reported cardiovascular or thyroid disease. Cardiac structure and function were evaluated by echocardiography. We used linear regression models unadjusted and adjusted for sex and age (model 1), and sex, age, BMI, diabetes, hypertension, and smoking (model 2). Nonlinear associations were assessed using restricted cubic splines. Results: The mean age was 61.5 years (SD 10.5); 61.1% of the patients were women. In the adjusted model 2, heart rate was positively associated with FT3; diastolic blood pressure was positively associated with TSH; LV end-diastolic and end-systolic volumes were inversely associated with TSH, and ejection fraction was nonlinearly associated with FT3, with higher ejection fractions near the limits of the reference range. Left ventricle (LV) posterior wall thickness was nonlinearly associated with FT4 in the adjusted model 1, with a greater thickness near the limits of the reference range. Regarding diastolic function, no significant associations were observed in adjusted models. Conclusions: Thyroid function within the reference range was associated with heart rate, blood pressure, cardiac structure, and function. Increasing thyroid function (lower TSH, higher FT4, or higher FT3) was associated with a higher heart rate, a lower diastolic blood pressure, and larger LV volumes. LV wall thickness and ejection fraction had a U-shaped association with thyroid hormones.This work was supported by the DOCnet project (NORTE-01-0145-FEDER-000003), supported by Norte Portugal Regional Operational Program (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF), and the NETDIAMOND project (POCI-01-0145-FEDER-016385), supported by European Structural and Investment Funds, Lisbon’s Regional Operational Program 2020, and national funds from the Portuguese Foundation for Science and Technology – both projects through the Cardiovascular Research Center (UnIC, FCT 51/94) – and by the Portuguese Foundation for Science and Technology (grant POCI/SAU-ESP/61492/2004) and the Unidade de Investigação em Epidemiologia – Instituto de Saúde Pública da Universidade do Porto (EPIUnit) (POCI-01-0145-FEDER-006862, ref. info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID/DTP/04750/2013/PT)

Peristomal Skin Complications Are Common, Expensive, and Difficult to Manage: A Population Based Cost Modeling Study

BACKGROUND: Peristomal skin complications (PSCs) are the most common post-operative complications following creation of a stoma. Living with a stoma is a challenge, not only for the patient and their carers, but also for society as a whole. Due to methodological problems of PSC assessment, the associated health-economic burden of medium to longterm complications has been poorly described. AIM: The aim of the present study was to create a model to estimate treatment costs of PSCs using the standardized assessment Ostomy Skin Tool as a reference. The resultant model was applied to a real-life global data set of stoma patients (n = 3017) to determine the prevalence and financial burden of PSCs. METHODS: Eleven experienced stoma care nurses were interviewed to get a global understanding of a treatment algorithm that formed the basis of the cost analysis. The estimated costs were based on a seven week treatment period. PSC costs were estimated for five underlying diagnostic categories and three levels of severity. The estimated treatment costs of severe cases of PSCs were increased 2-5 fold for the different diagnostic categories of PSCs compared with mild cases. French unit costs were applied to the global data set. RESULTS: The estimated total average cost for a seven week treatment period (including appliances and accessories) was 263€ for those with PSCs (n = 1742) compared to 215€ for those without PSCs (n = 1172). A co-variance analysis showed that leakage level had a significant impact on PSC cost from 'rarely/never' to 'always/often' p<0.00001 and from 'rarely/never' to 'sometimes' p = 0.0115. CONCLUSION: PSCs are common and troublesome and the consequences are substantial, both for the patient and from a health economic viewpoint. PSCs should be diagnosed and treated at an early stage to prevent long term, debilitating and expensive complications