Structural Insights into Human Peroxisome Proliferator Activated Receptor Delta (PPAR-Delta) Selective Ligand Binding

Peroxisome proliferator activated receptors (PPARs delta, alpha and gamma) are closely related transcription factors that exert distinct effects on fatty acid and glucose metabolism, cardiac disease, inflammatory response and other processes. Several groups developed PPAR subtype specific modulators to trigger desirable effects of particular PPARs without harmful side effects associated with activation of other subtypes. Presently, however, many compounds that bind to one of the PPARs cross-react with others and rational strategies to obtain highly selective PPAR modulators are far from clear. GW0742 is a synthetic ligand that binds PPAR delta more than 300-fold more tightly than PPAR alpha or PPAR gamma but the structural basis of PPAR delta: GW0742 interactions and reasons for strong selectivity are not clear. Here we report the crystal structure of the PPAR delta:GW0742 complex. Comparisons of the PPAR delta:GW0742 complex with published structures of PPARs in complex with alpha and gamma selective agonists and pan agonists suggests that two residues (Val312 and Ile328) in the buried hormone binding pocket play special roles in PPAR delta selective binding and experimental and computational analysis of effects of mutations in these residues confirms this and suggests that bulky substituents that line the PPAR alpha and gamma ligand binding pockets as structural barriers for GW0742 binding. This analysis suggests general strategies for selective PPAR delta ligand design.

A metasynthesis of qualitative studies regarding opinions and perceptions about barriers and determinants of health services’ accessibility in economic migrants

Background: Access to health services is an important health determinant. New research in health equity is required, especially amongst economic migrants from developing countries. Studies conducted on the use of health services by migrant populations highlight existing gaps in understanding which factors affect access to these services from a qualitative perspective. We aim to describe the views of the migrants regarding barriers and determinants of access to health services in the international literature (1997–2011). Methods: A systematic review was conducted for Qualitative research papers (English/Spanish) published in 13 electronic databases. A selection of articles that accomplished the inclusion criteria and a quality evaluation of the studies were carried out. The findings of the selected studies were synthesised by means of metasynthesis using different analysis categories according to Andersen’s conceptual framework of access and use of health services and by incorporating other emergent categories. Results: We located 3,025 titles, 36 studies achieved the inclusion criteria. After quality evaluation, 28 articles were definitively synthesised. 12 studies (46.2%) were carried out in the U.S and 11 studies (42.3%) dealt with primary care services. The participating population varied depending mainly on type of host country. Barriers were described, such as the lack of communication between health services providers and migrants, due to idiomatic difficulties and cultural differences. Other barriers were linked to the economic system, the health service characteristics and the legislation in each country. This situation has consequences for the lack of health control by migrants and their social vulnerability. Conclusions: Economic migrants faced individual and structural barriers to the health services in host countries, especially those with undocumented situation and those experimented idiomatic difficulties. Strategies to improve the structures of health systems and social policies are needed.

Is health a right for all? An umbrella review of the barriers to health care access faced by migrants

Objective. To synthesise the scientific evidence concerning barriers to health care access faced by migrants. We sought to critically analyse this evidence with a view to guiding policies. Design. A systematic review methodology was used to identify systematic and scoping reviews which quantitatively or qualitatively analysed data from primary studies. The main variables analysed were structural and contextual barriers (health system organisation) as well as individual (patients and providers). The quality of evidence from the systematic reviews was critically appraised. From 2674 reviews, 79 were retained for further scrutiny, and finally 9 met the inclusion criteria. Results. The structural barriers identified were the lack of health insurance and the high cost of drugs (non-universal health system) and organisational aspects of health system (social insurance system and national health system). The individual barriers were linguistic and cultural. None of the reviews provided a quality appraisal of the studies. Conclusions. Barriers to health care for migrants range from entitlement in non-universal health systems to accessibility in universal ones, and determinants of access to the respective health services should be analysed within the corresponding national context. Generate social and institutional changes that eliminate barriers to access to health services is essential to ensure health for all.

Use of structural equation modeling to examine the association between breast cancer risk perception and repeat screening mammography among United States women

Breast cancer is the second leading cause of cancer death in United States women, estimated to be diagnosed in 1 out of 8 women in their lifetime. Screening mammography detects breast cancer in its pre-clinical stages when treatment strategies have the greatest chance of success, and is currently the only population-wide prevention method proven to reduce the morbidity and mortality associated with breast cancer. Research has shown that the majority of women are not screened annually, with estimates ranging front 6% - 30% of eligible women receiving all available annual mammograms over a 5-year or greater time frame. Health behavior theorists believe that perception of risk/susceptibility to a disease influences preventive health behavior, in this case, screening mammography The purpose of this dissertation is to examine the association between breast cancer risk perception and repeat screening mammography using a structural equation modeling (SEM) framework. A series of SEM multivariate regressions were conducted using self-reported, nationally representative data from the 2005 National Health Interview Survey. Interaction contrasts were tested to measure the potential moderating effects of variables which have been shown to be predictive of mammography use (physician recommendation, economic barriers, structural barriers, race/ethnicity) on the association between breast cancer risk perception and repeat mammography, while controlling for the covariates of age, income, region, nativity, and educational level. Of the variables tested for moderation, results of the SEM analyses identify physician recommendation as the only moderator of the relationship between risk perception and repeat mammography, thus the potentially most effective point of intervention to increase mammography screening, and decrease the morbidity and mortality associated with breast cancer. These findings expand the role of the physician from recommendation to one of attenuating the effect of risk perception and increasing repeat screening. The long range application of the research is the use of the SEM methodology to identify specific points of intervention most likely to increase preventive behavior in population-wide research, allowing for the most effective use of intervention funds.^

Treatment of suicidal people around the world

Background Suicide is a leading cause of death worldwide; however, little information is available about the treatment of suicidal people, or about barriers to treatment. Aims To examine the receipt of mental health treatment and barriers to care among suicidal people around the world. Method Twenty-one nationally representative samples worldwide (n=55 302; age 18 years and over) from the World Health Organization`s World Mental Health Surveys were interviewed regarding past-year suicidal behaviour and past-year healthcare use. Suicidal respondents who had not used services in the past year were asked why they had not sought care. Results Two-fifths of the suicidal respondents had received treatment (from 17% in low-income countries to 56% in high-income countries), mostly from a general medical practitioner (22%), psychiatrist (15%) or non-psychiatrist (15%). Those who had actually attempted suicide were more likely to receive care. Low perceived need was the most important reason for not seeking help (58%), followed by attitudinal barriers such as the wish to handle the problem alone (40%) and structural barriers such as financial concerns (15%). Only 7% of respondents endorsed stigma as a reason for not seeking treatment. Conclusions Most people with suicide ideation, plans and attempts receive no treatment. This is a consistent and pervasive finding, especially in low-income countries. Improving the receipt of treatment worldwide will have to take into account culture-specific factors that may influence the process of help-seeking.

Participation and older people: Meaning, theory and practice

Increasing older people's participation in society is important in ageing policies worldwide. There is a need to understand the challenges for health professionals of transforming policy on participation into liberating social change practices on the ground. This paper explores the meaning, theory and practice of participation. It uses the example of a work in progress project that has attempted to address structural barriers to older people's participation within an Australian aged care facility, to illustrate theoretical and practice principles surrounding participation.

Consumer resistance to mobile commerce services

Oheinen opinnäytetyö on kvalitatiivinen tutkimus kuluttajavastarinnasta mobiilin kaupankäynnin palveluja kohtaan. Tutkimus kohdistuu läntisiin kulttuureihin, joissa kyseisen innovatiivisen palveluryhmän leviämistä tukevat monet aikaisemmat innovaatiot kuten matkapuhelin, Internet, digitaaliset pankkipalvelut. Tutkimus esittelee innovaatioiden vastarintatekijöitä ihmisen luonnollisena reaktiona tämän vakiintuneita elämäntapoja mullistavia keksintöjä kohtaan nimenomaan läntisissä kulttuureissa, joissa kuluttajat ovat perinteisesti hyvin teknologiamyönteisiä. Toisaalta tutkimusalueella on havaittavissa sosiaalisten ryhmien pirstoutuminen yhä pienemmiksi alaryhmiksi, mikä voi hidastaa sosiaalista oppimista. Tutkimus vastaa todelliseen tutkimusaukkoon. Aihe on samalla sekä ajankohtainen että relevantti vastatessaan nykyisin käytävään utopistiseen keskusteluun digitaalisen informaatioyhteiskunnan kehittymisestä ja merkityksestä modernille ihmiskunnalle. Tutkimuksen teoreettinen eksploratiivinen viitekehys rakentuu valikoiduista uusien tuotteiden ja palvelujen kehittämisen, palvelumarkkinoinnin ja sosiaalisen oppimisen teorioista sekä innovaatio- kommunikaatioteorioista. Empiirisen osan muodostavat kansainvälisten markkinatutkimuslaitosten ja haastateltujen asiantuntijoiden näkemykset alan kehityksestä. Tutkimus osoittaa, että kuluttajat eivät ole valmiita vastaanottamaan kehittyvien teknologioiden mahdollistamia mobiilin kaupankäynnin palveluita ennen kuin ne vastaavat kuluttajien perustarpeisiin ja rakenteelliset vastarintatekijät (alhainen käytettävyys, matala lisäarvo, koetut riskit, perinnevastarinta, palveluryhmän huono mielikuva) on poistettu. Tutkimus esittää, että mobiilin kaupankäynnin alalla toimivien yritysten tulisi työskennellä yhteistyössä keskenään ja kuluttajien kanssa luodakseen kuluttajien tarpeita ja toiveita vastaavia turvallisiksi koettuja mobiilin kaupankäynnin palveluita. Tutkimus ehdottaa, että kyselytutkimusten ohella käytettäisiin havaintomenetelmiä, jotta teknologiat voitaisiin valjastaa kuluttajien tarpeita ja kulutustottumuksia vastaaviksi.

Voices of the Undereducated in Adult Education and Training in Ontario: A Phenomenographic Approach

This doctoral study was an exploration of the qualitatively different ways in which undereducated adults (at or below a high school level of formal education) reported their experiences of participation in adult education and training (AET) programmes offered by publicly funded school boards or their arms-length affiliate in the province of Ontario. In light of a low participation rate in the Canadian AET system by undereducated adults, the rationale was to examine whether or not AET programmes are meeting the needs of undereducated adults beyond a narrow focus on an instrumental approach associated with human capital development. This study was located in a theoretical framework consisting of (a) learning theory, (b) motivations for participation, (c) general barriers to participation, (d) structural barriers to participation, and (e) transformative learning. The purposive sample consisted of 11 participants between the ages of 18-58 who were drawn from service providers in 4 geographic regions of Ontario. Data collection consisted of (a) demographics, (b) voice recordings from face-to-face participant interviews, (c) participant weekly critical incident reports, and (d) researcher reflexive journal notes. Data were analyzed in accordance with a phenomenographic approach within a constructivist/interpretivist research paradigm. Findings revealed 4 qualitatively different ways in which undereducated adult learners reported their experiences of participation in AET and were reported as the voice of (a) security, (b) engagement, (c) relationship, and (d) competency. Implications to theory and practice and to further inquiry were outlined.

Indigenous Language Reclamation: The Learners Perspective

ABSTRACT This study explored the link between learning an Indigenous language and the meanings second language learners attach to their language recovery experiences. The study delves into the factors that motivate, enhance and serve as barriers to individual language revitalization efforts. With the goal of reasserting an Indigenous world view, the traditional teachings of the Ojibwe medicine wheel were combined with the lessons of the seven Grandfathers to provide a methodological basis for conducting ethical research with and for the benefit of First Nations people. Within the context of our relationships with self, community, spirit and environment, the pairing of Indigenous theory with the practical community experiences of Indigenous second language learners, demonstrates how Indigenous systems of thought and ontology lend themselves well to the critical understanding necessary to enhance the recovery our own endangered languages. These research findings indicate that there is a definite link between ancestral language reclamation and increased levels of self-esteem, a sense of grounded cultural identity and resilience, an overall sense of healing and the social responsibility that comes with receiving the gift of language. The barriers associated with learning an ancestral language intersect on multiple and often simultaneous levels making it difficult for the language learners to discover their origin.This research found that it was important for language learners to identify that they often carry a collective sense of shame associated with an internalized attachment to the modality of Indigeneity. Once the origin of this shame was acknowledged – as resulting from settler/assimilation logics, it was often possible for people to move forward in their language recovery journeys, while at the same time considering more broadly the structural barriers that make individual learning so difficult.

Bridging the Conceptualization of Youth with Intellectual Disabilities to Sentencing under the YCJA

The current study examined how disability and the concepts of risk, need and responsivity are understood by criminal justice professionals and inform their perceptions of young offenders with ID at sentencing under the ‘different but equal’ philosophy. Semi-structured interviews were conducted with 11 lawyers and 8 mental health workers across 6 major urban areas in Ontario. Participants primarily perceived ID through a medical discourse, overlooking social and structural barriers that, in some cases, may hinder adherence to sentencing dispositions. Specifically, participants discussed balancing the reduced culpability of offenders (e.g., intent) – justifying lenient sentencing – with public safety concerns (i.e., ID viewed as a barrier to rehabilitation) – justifying increasing the severity of sentences. Participants assessed clients with ID and their risks, needs and responsivity within the context of other legal factors: criminal history, severity of the offence, and YCJA objectives. Participants articulated the importance of tailored courthouse identification programs, services/funding, and education/training.

Smart choices for growth. Bruegel Policy Contribution 2012/21, November 2012

Recovery in Greece, Italy, Portugal and Spain is held back in part by structural barriers. Overcoming these requires structural reform and public investment. Given the limited availability of political and financial capital, prioritising reform efforts and spending is important, but difficult. The different success factors for individual sectors are complementary. Using the example of the high-tech industry, we make the case that only investing in one success factor (eg broadband infrastructure) without having a sufficient endowment of others (eg education) is unlikely to make the sector successful. One consequence of the complementarity of the different success factors is that public investment and reform efforts should be fine-tuned in order to match the endowment of other factors. This might imply an increase in efforts to tackle several structural barriers at the same time, but it might also imply reducing investment in less promising fields. This in turn requires strategic thinking about whether it is worthwhile pursuing development strategies that require investment in many success factors but that do not promise much success. Such a strategic approach to public investment and reform efforts might make the allocation of scarce public financial and political capital more efficient.

Aplicação de extratos enzimáticos fúngicos na ensilagem do milho

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Barreiras à entrada no Setor Siderúrgico Brasileiro no período de 1993 a 2012

This study aims to identify and analyze the barriers to entry in the two technological routes (integrated and semi - integrated mills) , the Brazilian steel industry , specifically in the areas of Plans and Long , in the period 1993-2012 . Thus, the study is characterized as an exploratory - descriptive research, based on data collection from secondary sources. The competitiveness is influenced by structural market factor, among them the threat of new market entrants. The entrants can have their ticket inhibited by entry barriers. In the steel industry, it was identified that the main strong structural barriers are economic, the type of scale economy, highlighting the idle capacity, and sunk costs. Institutional and economic barriers, the diversification and product differentiation type, are considered moderate barriers. Economic barriers, the type absolute cost advantage and initial capital requirements, and strategic price barrier are considered weak. With this, one can consider that the input type which most closely approximates the market for national steel industries is blocked, since their main barriers are the structural type

Il consenso informato come strumento di esercizio del diritto alla salute per i pazienti stranieri?

L’elaborato propone una riflessione rispetto all’atto giuridico del consenso informato quale strumento garante dell’esercizio del diritto alla salute per i migranti. Attraverso una riflessione antropologica rispetto alla natura, alla costruzione e alla logica dei diritti universali, verranno analizzate le normative nazionali, europee ed internazionali a tutela del diritto alla salute per i migranti; l’obiettivo della ricerca è indagare l’eventuale scarto tra normative e politiche garantiste nei confronti della salute migrante e l’esistenza di barriere strutturali che impediscono un pieno esercizio del diritto alla salute. L’ipotesi di ricerca si basa sulla reale capacità performativa del consenso informato, proposto solitamente sia come strumento volto ad assicurare la piena professionalità dell’operatore sanitario nell’informare il paziente circa i rischi e i benefici di un determinato trattamento sanitario, sia come garante del principio di autonomia. La ricerca, attraverso un’analisi quanti-qualitativa, ha interrogato il proprio campo, rappresentato da un reparto di ginecologia ed ostetrica, rispetto alle modalità pratiche di porre in essere la firma nei moduli del consenso informato, con particolare attenzione alle specificità proprie delle pazienti migranti. Attraverso l’osservazione partecipante è stato quindi possibile riflettere su aspetti rilevanti, quali le dinamiche quotidiane che vengono a crearsi tra personale sanitario e pazienti, le caratteristiche e i limiti del servizio di mediazione sanitaria, le azioni pratiche della medicina difensiva. In questo senso il tema del “consenso informato”, indagato facendo interagire discipline quali l’antropologia, la bioetica, la filosofia e la sociologia, si è posto sia come lente di lettura privilegiata per comprendere le dinamiche relazionali ad oggi esistenti tra professionisti sanitari e popolazione migrante, ancora vittima di diseguaglianze strutturali, ma altresì come “innesco potenziale” di nuove modalità di intendere la relazione medico-paziente.

Missed opportunities in the prevention of perinatal human immunodeficiency syndrome virus transmission

Mother to child transmission of human immunodeficiency virus (HIV) has decreased dramatically in the United States since the mid-1990s. Without antiretroviral therapy the risk of perinatal infection is as high as 25%; with treatment the risk drops to <1-2%. However, state surveillance data show a recent rise in the percentage of babies being born with HIV in Texas. No studies of perinatal HIV transmission in Texas have focused on the individual cases and identified what social/institutional barriers stood in the way of the index woman, her support system and her health providers in negotiating access to prenatal care and HIV treatment.^ The Texas Department of State Health Services identifies the babies born in Texas with HIV infection. This two year study will use mixed methods to identify barriers to the diagnosis and treatment of maternal HIV. In-depth interviews and chart reviews will be used to conduct the study. The abstracted medical record will give us demographic data and details of the timing of testing and treatment; interviews will provide information as to the individual and environmental factors that may have delayed testing and treatment. Little research has been done to assess the factors contributing to late prenatal HIV diagnosis and care in Texas and the interventions identified by mothers of affected babies that might overcome these obstacles.^ Conclusions from this study will guide the development of interventions to better educate the public, reduce structural barriers common to the underserved, and/or educate health care professionals. The study will also serve as a model for other states to undertake evaluation of their cases of perinatal infection. ^