Argumentation schemes for collaborative planning

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Valproic Acid Teratogenicity: A Toxicogenomics Approach

Embryonic development is a highly coordinated set of processes that depend on hierarchies of signaling and gene regulatory networks, and the disruption of such networks may underlie many cases of chemically induced birth defects. The antiepileptic drug valproic acid (VPA) is a potent inducer of neural tube defects (NTDs) in human and mouse embryos. As with many other developmental toxicants however, the mechanism of VPA teratogenicity is unknown. Using microarray analysis, we compared the global gene expression responses to VPA in mouse embryos during the critical stages of teratogen action in vivo with those in cultured P19 embryocarcinoma cells in vitro. Among the identified VPA-responsive genes, some have been associated previously with NTDs or VPA effects [vinculin, metallothioneins 1 and 2 (Mt1, Mt2), keratin 1-18 (Krt1-18)], whereas others provide novel putative VPA targets, some of which are associated with processes relevant to neural tube formation and closure [transgelin 2 (Tagln2), thyroid hormone receptor interacting protein 6, galectin-1 (Lgals1), inhibitor of DNA binding 1 (Idb1), fatty acid synthase (Fasn), annexins A5 and A11 (Anxa5, Anxa11)], or with VPA effects or known molecular actions of VPA (Lgals1, Mt1, Mt2, Id1, Fasn, Anxa5, Anxa11, Krt1-18). A subset of genes with a transcriptional response to VPA that is similar in embryos and the cell model can be evaluated as potential biomarkers for VPA-induced teratogenicity that could be exploited directly in P19 cell–based in vitro assays. As several of the identified genes may be activated or repressed through a pathway of histone deacetylase (HDAC) inhibition and specificity protein 1 activation, our data support a role of HDAC as an important molecular target of VPA action in vivo

Patient-Powered Research Networks of the Autoimmune Research Collaborative: Rationale, Capacity, and Future Directions

Patient-Powered Research Networks (PPRNs) are US-based registry infrastructures co-created by advocacy groups, patient research partners, academic investigators, and other healthcare stakeholders. Patient-Powered Research Networks collect information directly from patients to conduct and disseminate the results of patient-centered/powered research that helps patients make more informed decisions about their healthcare. Patient-Powered Research Networks gather and utilize real-world data and patient-reported outcomes to conduct comparative effectiveness, safety, and other research, and leverage the Internet to accomplish this effectively and efficiently. Four PPRNs focused on autoimmune and immune-mediated conditions formed the Autoimmune Research Collaborative: ArthritisPower (rheumatoid arthritis, spondyloarthritis, and other rheumatic and musculoskeletal diseases), IBD Partners (inflammatory bowel disease), iConquerMS (multiple sclerosis), and the Vasculitis PPRN (vasculitis). The Autoimmune Research Collaborative aims to inform the healthcare decision making of patients, care partners, and other stakeholders, such as clinicians, regulators, and payers. Illustrated by practical applications from the Autoimmune Research Collaborative and its constituent PPRNs, this article discusses the shared capacities and challenges of the PPRN model, and the opportunities presented by collaborating across autoimmune conditions to design, conduct, and disseminate patient-centered outcomes research

Effect of Pulsed or Continuous Delivery of Salt on Sensory Perception Over Short Time Intervals

Salt in the human diet is a major risk factor for hypertension and many countries have set targets to reduce salt consumption. Technological solutions are being sought to lower the salt content of processed foods without altering their taste. In this study, the approach was to deliver salt solutions in pulses of different concentrations to determine whether a pulsed delivery profile affected sensory perception of salt. Nine different salt profiles were delivered by a Dynataste device and a trained panel assessed their saltiness using time–intensity and single-score sensory techniques. The profile duration (15 s) was designed to match eating conditions and the effects of intensity and duration of the pulses on sensory perception were investigated. Sensory results from the profiles delivered in either water or in a bouillon base were not statistically different. Maximum perceived salt intensities and the area under the time– intensity curves correlated well with the overall perceived saltiness intensity despite the stimulus being delivered as several pulses. The overall saltiness scores for profiles delivering the same overall amount of sodium were statistically not different from one another suggesting that, in this system, pulsed delivery did not enhance salt perception but the overall amount of salt delivered in each profile did affect sensory perception

Tnni3k Modifies Disease Progression in Murine Models of Cardiomyopathy

The Calsequestrin (Csq) transgenic mouse model of cardiomyopathy exhibits wide variation in phenotypic progression dependent on genetic background. Seven heart failure modifier (Hrtfm) loci modify disease progression and outcome. Here we report Tnni3k (cardiac Troponin I-interacting kinase) as the gene underlying Hrtfm2. Strains with the more susceptible phenotype exhibit high transcript levels while less susceptible strains show dramatically reduced transcript levels. This decrease is caused by an intronic SNP in low-transcript strains that activates a cryptic splice site leading to a frameshifted transcript, followed by nonsense-mediated decay of message and an absence of detectable protein. A transgenic animal overexpressing human TNNI3K alone exhibits no cardiac phenotype. However, TNNI3K/Csq double transgenics display severely impaired systolic function and reduced survival, indicating that TNNI3K expression modifies disease progression. TNNI3K expression also accelerates disease progression in a pressure-overload model of heart failure. These combined data demonstrate that Tnni3k plays a critical role in the modulation of different forms of heart disease, and this protein may provide a novel target for therapeutic intervention

A collaborative approach to forecasting product–service systems (PSS)

Copyright @ Springer-Verlag London Limited 2010. The final version of this article may be viewed at the link below.This paper examines the forecasting implications for product–service systems (PSS) applications in manufacturing firms. The approach taken is to identify the scope of operations for PSS applications by identifying all the activities associated with the service deployment in the telecom sector. The paper then develops a revenue model for manufacturing firms providing PSS applications. The revenue model identifies three generic revenue streams that provide the basis for discussion on the differences in forecasting approaches, including collaborative approaches based on PSS staff being geographically co-located

Psychosocial factors during the first year after a coronary heart disease event in cases and referents. Secondary Prevention in Uppsala Primary Health Care Project (SUPRIM)

<p>Abstract</p> <p>Background</p> <p>A large number of studies have reported on the psychosocial risk factor pattern prior to coronary heart disease events, but few have investigated the situation during the first year after an event, and none has been controlled. We therefore performed a case-referent study in which the prevalence of a number of psychosocial factors was evaluated.</p> <p>Methods</p> <p>Three hundred and forty-six coronary heart disease male and female cases no more than 75 years of age, discharged from hospital within the past 12 months, and 1038 referents from the general population, matched to the cases by age, sex and place of living, received a postal questionnaire in which information on lifestyle, psychosocial and quality of life measures were sought.</p> <p>Results</p> <p>The cases were, as expected, on sick leave to a larger extent than the referents, reported poorer fitness, poorer perceived health, fewer leisure time activities, but unexpectedly reported better social support, and more optimistic views of the future than the referents. There were no significant case-referent differences in everyday life stress, stressful life events, vital exhaustion, depressive mood, coping or life orientation test. However, women reported less favourable situations than men regarding stressful life events affecting others, vital exhaustion, depressive mood, coping, self-esteem, sleep, and symptom reporting, and female cases reported the most unfavourable situation of all groups.</p> <p>Conclusion</p> <p>In this first controlled study of the situation during the first year after a CHD event disease and gender status both appeared to be determinants of psychological well-being, with gender status apparently the strongest. This may have implications for cardiac rehabilitation programmes.</p

Human pluripotent embryonal carcinoma NTERA2 cl.D1 cells maintain their typical morphology in an angiomyogenic medium

BACKGROUND: Pluripotent embryonal carcinomas are good potential models, to study, "in vitro," the mechanisms that control differentiation during embryogenesis. The NTERA2cl.D1 (NT2/D1) cell line is a well known system of ectodermal differentiation. Retinoic acid (RA) induces a dorsal pattern of differentiation (essentially neurons) and bone morphogenetic protein (BMP) or hexamethylenebisacetamide (HMBA) induces a more ventral (epidermal) pattern of differentiation. However, whether these human cells could give rise to mesoderm derivatives as their counterpart in mouse remained elusive. We analyzed the morphological characteristics and transcriptional activation of genes pertinent in cardiac muscle and endothelium differentiation, during the growth of NT2/D1 cells in an inductive angiomyogenic medium with or without Bone Morphogenetic Protein 2 (BMP2). RESULTS: Our experiments showed that NT2/D1 maintains their typical actin organization in angiomyogenic medium. Although the beta myosin heavy chain gene was never detected, all the other 15 genes analyzed maintained their expression throughout the time course of the experiment. Among them were early and late cardiac, endothelial, neuronal and teratocarcinoma genes. CONCLUSION: Our results suggest that despite the NT2/D1 cells natural tendency to differentiate into neuroectodermal lineages, they can activate genes of mesodermal lineages. Therefore, we believe that these pluripotent cells might still be a good model to study biological development of mesodermal derivatives, provided the right culture conditions are met

Engaging Multistakeholder Perspectives to Identify Patient-Centered Research Priorities Regarding Vaccine Uptake Among Adults With Autoimmune Conditions

Objective: The study objective was to prioritize topics for future patient-centered research to increase uptake of common vaccines, such as for pneumococcal pneumonia, influenza, herpes zoster, human papillomavirus, and severe acute respiratory syndrome coronavirus 2, among adults living with autoimmune conditions. Methods: A steering committee (SC) was formed that included clinicians, patients, patient advocates, and researchers associated with rheumatic diseases (psoriatic arthritis, rheumatoid arthritis, vasculitis), inflammatory bowel disease, and multiple sclerosis. Through a scoping review and discussions, SC members identified research topics regarding vaccine uptake and/or hesitancy for prioritization. A larger multistakeholder alliance that included patients and patient advocates, clinicians, researchers, policy makers, regulators, and vaccine manufacturers conducted a modified Delphi exercise online with three rating rounds and one ranking round. Frequency analysis and comparisons across stakeholder groups were conducted. A weighted ranking score was generated for each item in the ranking round for final prioritization. Results: Through the Delphi process, 33 research topics were identified, of which 13 topics were rated as critical by more than 70% of all stakeholders (n = 31). The two highest ranked critical topics per the full stakeholder group were “How well a vaccine works for adults with autoimmune conditions” and “How beliefs about vaccine safety affect vaccine uptake.”. Conclusion: A multistakeholder group identified key topics as critically important priorities for future research to decrease vaccine hesitancy and improve uptake of vaccines for adults with autoimmune conditions

A systematic review of methods for increasing vegetable consumption in early childhood

PURPOSE OF REVIEW: This study aims to synthesise the body of research investigating methods for increasing vegetable consumption in 2- to 5-year-old children, while offering advice for practitioners. RECENT FINDINGS: Repeated exposure is a well-supported method for increasing vegetable consumption in early childhood and may be enhanced with the inclusion of non-food rewards to incentivise tasting. Peer models appear particularly effective for increasing 2-5-year-olds' vegetable consumption. There is little evidence for the effectiveness of food adaptations (e.g. flavour-nutrient learning) for increasing general vegetable intake among this age group, although they show some promise with bitter vegetables. SUMMARY: This review suggests that practitioners may want to focus their advice to parents around strategies such as repeated exposure, as well as the potential benefits of modelling and incentivising tasting with non-food rewards. Intervention duration varies greatly, and considerations need to be made for how this impacts on success