Publications by authors named "Katie Powell"

32 Publications

Non-human matter, health disparities and a thousand tiny dis/advantages.

Sociol Health Illn 2021 Mar 15. Epub 2021 Mar 15.

Health Equity and Inclusion Research Group, School of Health and Related Research, University of Sheffield, Sheffield, UK.

The materialist thread within health sociology has observed a clear gradient linking inequalities in health with measures of social class and poverty. More recently, Bourdieu's approach to social class complemented the 'economic capital' of Marxist analysis with 'symbolic' capitals such as 'social' and 'cultural'. However, efforts to assess how symbolic capital interacts with health disparities reveal complex or contradictory effects. In this paper, we re-materialise the study of health and social position via a new materialist focus on the interactions between humans and non-human matter (NHM). We analyse empirical data to disclose the range of human/NHM interactions in daily life, and how these affect people's health status. These interactions establish physical, psychological and social opportunities and constraints on what human bodies can do, contributing to relative advantages and disadvantages. We argue for a revised materialist understanding of sociomaterial position as constituted by a 'thousand tiny dis/advantages', and suggest that health and wellbeing are inextricably linked to dis/advantage.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1467-9566.13265DOI Listing
March 2021

A systems map of the determinants of child health inequalities in England at the local level.

PLoS One 2021 12;16(2):e0245577. Epub 2021 Feb 12.

Department of Population Health Sciences, University of Bristol, Bristol, United Kingdom.

Children and young people in the UK have worse health outcomes than in many similar western countries and child health inequalities are persistent and increasing. Systems thinking has emerged as a promising approach to addressing complex public health issues. We report on a systems approach to mapping the determinants of child health inequalities at the local level in England for young people aged 0-25, and describe the resulting map. Qualitative group concept mapping workshops were held in two contrasting English local authorities with a range of stakeholders: professionals (N = 35); children and young people (N = 33) and carers (N = 5). Initial area maps were developed, and augmented using data from qualitative interviews with professionals (N = 16). The resulting local maps were reviewed and validated by expert stakeholders in each area (N = 9; N = 35). Commonalities between two area-specific system maps (and removal of locality-specific factors) were used to develop a map that could be applied in any English local area. Two rounds of online survey (N = 21; N = 8) experts in public health, local governance and systems science refined the final system map displaying the determinants of child health inequalities. The process created a map of over 150 factors influencing inequalities in health outcomes for children aged 0-25 years at the local area level. The system map has six domains; physical environment, governance, economic, social, service, and personal. To our knowledge this is the first study taking a systems approach to addressing inequalities across all aspects of child health. The study shows how group concept mapping can support systems thinking at the local level. The resulting system map illustrates the complexity of factors influencing child health inequalities, and it may be a useful tool in demonstrating to stakeholders the importance of policies that tackle the systemic drivers of child health inequalities beyond those traditionally associated with public health.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0245577PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880458PMC
February 2021

Cardiovascular risk factor mediation of the effects of education and Genetic Risk Score on cardiovascular disease: a prospective observational cohort study of the Framingham Heart Study.

BMJ Open 2021 01 12;11(1):e045210. Epub 2021 Jan 12.

Clinical Governance, Northern NSW Local Health District, Lismore, New South Wales, Australia

Objectives: Level of education and genetic risk are key predictors of cardiovascular disease (CVD). While several studies have explored the causal mechanisms of education effects, it remains uncertain to what extent genetic risk is mediated by established CVD risk factors. This study sought to investigate this and explored the mediation of education and genetic effects on CVD by established cardiovascular risk factors in the Framingham Heart Study (FHS).

Design: Prospective observational cohort study.

Participants: 7017 participants from the FHS.

Setting: Community-based cohort of adults in Framingham, Massachusetts, USA.

Primary Outcome Measure: Incident CVD. The total effects of education and genetic predisposition using a 63-variant genetic risk score (GRS) on CVD, as well as those mediated by established CVD risk factors, were assessed via mediation analysis based on the counterfactual framework using Cox proportional hazards regression models.

Results: Over a median follow-up time of 12.0 years, 1091 participants experienced a CVD event. Education and GRS displayed significant associations with CVD after adjustment for age and sex and the established risk factors smoking, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), body mass index, systolic blood pressure (SBP) and diabetes. For education effects, smoking, HDL-C and SBP were estimated to mediate 18.8% (95% CI 9.5% to 43%), 11.5% (95% CI 5.7% to 29.0%) and 4.5% (95% CI 1.6% to 13.3%) of the total effect of graduate degree, respectively, with the collective of all risk factors combined mediating 38.5% (95% 24.1% to 64.9%). A much smaller proportion of the effects of GRS were mediated by established risk factors combined (17.6%, 95% CI 2.4% to 35.7%), with HDL-C and TC mediating 11.5% (95% CI 6.2% to 21.5%) and 3.1% (95% CI 0.2% to 8.3%), respectively.

Conclusions: Unlike education inequalities, established risk factors mediated only a fraction of GRS effects on CVD. Further research is required to elucidate the underlying causal mechanisms of genetic contributions to CVD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjopen-2020-045210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7805364PMC
January 2021

Power, control, communities and health inequalities III: participatory spaces-an English case.

Health Promot Int 2020 Dec 31. Epub 2020 Dec 31.

Division of Health Research, Lancaster University, Lancaster LA1 4YG, UK.

This article-third in a series of three-uses theoretical frameworks described in Part 1, and empirical markers reported in Part 2, to present evidence on how power dynamics shifted during the early years of a major English community empowerment initiative. We demonstrate how the capabilities disadvantaged communities require to exercise collective control over decisions/actions impacting on their lives and health (conceptualized as emancipatory power) and the exercise of power over these communities (conceptualized as limiting power) were shaped by the characteristics of participatory spaces created by and/or associated with this initiative. Two main types of participatory spaces were identified: governance and sense-making. Though all forms of emancipatory power emerged in all spaces, some were more evident in particular spaces. In governance spaces, the development and enactment of 'power to' emerged as residents made formal decisions on action, allocated resources and managed accountability. Capabilities for alliance building-power with-were more likely to emerge in these spaces, as was residents' resistance to the exercise of institutional power over them. In contrast, in sense-making spaces residents met informally and 'made sense' of local issues and their ability to influence these. These processes led to the development of power within capabilities and power to resist stigmatizing forms of productive power. The findings highlight the importance of designing community initiatives that: nurture diverse participatory spaces; attend to connectivity between spaces; and identify and act on existing power dynamics undermining capabilities for collective control in disadvantaged communities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/heapro/daaa059DOI Listing
December 2020

Randomized controlled trial comparing Parent Led Therapist Supervised Articulation Therapy (PLAT) with routine intervention for children with speech disorders associated with cleft palate.

Int J Lang Commun Disord 2020 09 29;55(5):639-660. Epub 2020 Jul 29.

Centre for Outcomes and Experience Research in Health, Impairment and Disability (ORCHID), Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.

Background: A total of 68% of pre-school children with cleft palate have speech problems requiring speech therapy. There is a lack of access to regular targeted therapy. Parent training leads to positive outcomes in early communication skills in cleft palate and non-cleft speech disorders. Connected health has been used to address inadequate access to therapy, providing intervention to those who would not otherwise receive therapy.

Aims: To evaluate the speech, activity and participation outcomes of Parent Led, Therapist Supervised, Articulation Therapy (PLAT) compared with routine speech therapy intervention in parent-child dyads.

Methods & Procedures: A total of 44 children, aged 2.9-7.5 years, were included in a two-centre, two-phase randomized controlled trial. Informed consent and assent were obtained. Participants and speech and language therapists (SLTs) were unblinded to the groups. Parents, in the parent-trained group (n = 23), attended 2 days' training, received a detailed speech therapy programme, and undertook intervention over 12 weeks supported by the cleft specialist SLT using FaceTime and one face-to-face session. In the control arm (n = 21), parent-child dyads received six therapy sessions over 12 weeks with a research SLT, comparable with usual care. Speech recordings were undertaken pre- and post-intervention. Percent consonant correct (PCC) was analysed by external SLTs blinded to the time and group. Activity and participation were measured using the Intelligibility in Context Scale (ICS) and Focus on Outcomes for Children Under Six (FOCUS) questionnaire.

Outcomes & Results: There was no evidence of an interaction between Time and Group or an overall statistical difference between groups for PCC scores. There was a statistically significant difference over time for both groups (words: p < 0.002; confidence interval (CI) = 9.38-16.27; d = 0.57; sentences: p < 0.002; CI = 16.04-25.97; d = 0.23). Effect sizes were medium for words and small for sentences. For intelligibility and participation, there was no evidence of an interaction between Time and Group or an overall statistical difference between groups. A statistically significant difference over time was found for intelligibility (F = 29.97, d.f. = 1, 42, p < 0.001, 95 % CI = 1.45-3.15 d = 0.46) and for participation (F = 14.19, d.f. = 1, 41, p < 0.001 95% CI = 7.63-25.03; d = 0.36) with FOCUS results indicating clinically meaningful (parent-led group) and significant (control group) change in participation.

Conclusions & Implications: PLAT can be as effective as routine care in changing speech, activity and participation outcomes for children with cleft palate, when supported by a specialist cleft SLT using connected health. What this paper adds What is already known on this subject Over 50% of children with cleft palate require speech therapy. However, there is a lack of timely, accessible speech therapy services in the UK and Ireland. Previous studies have shown that parents can deliver therapy effectively, and that connected health can support the delivery of speech therapy. This study aims to provide evidence that parent-led therapy with the supervision of a specialist cleft therapist using FaceTime is effective. What this paper adds to existing knowledge This randomized controlled trial indicates that parents can be trained to deliver therapy for children with cleft palate speech disorders, under the supervision of an SLT. This approach results in improved speech, activity and participation outcomes similar to routine care. What are the potential or actual clinical implications of this work? This study indicates that both parent-led articulation therapy and routine care showed meaningful gains in speech, activity and participation, and that parent-led articulation therapy when supported by a cleft SLT using connected health could be an additional service delivery model for children with cleft palate speech disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1460-6984.12542DOI Listing
September 2020

Galectin-3 deficiency in pregnancy increases the risk of fetal growth restriction (FGR) via placental insufficiency.

Cell Death Dis 2020 07 23;11(7):560. Epub 2020 Jul 23.

Experimental and Clinical Research Center, a Cooperation between the Max Delbrück Center for Molecular Medicine in the Helmholtz Association, and Charité - Universitätsmedizin Berlin, Berlin, Germany.

Fetal growth restriction (FGR) is the most common pregnancy complication in developed countries. Pregnancies affected by FGR, frequently concur with complications and high risk of neonatal morbidity and mortality. To date, no approved treatment is available for pregnant women affected with FGR. The objective of this study was to investigate the contribution of galectin-3 (gal-3), a β-galactoside binding protein involved in pregnancy, placental function and fetal growth. We demonstrated that lack of gal-3 during mouse pregnancy leads to placental dysfunction and drives FGR in the absence of a maternal preeclampsia syndrome. Analysis of gal-3 deficient dams revealed placental inflammation and malperfusion, as well as uterine natural killer cell infiltration with aberrant activation. Our results also show that FGR is associated with a failure to increase maternal circulating gal-3 levels during the second and third trimester in human pregnancies. Placentas from human pregnancies affected by FGR displayed lower gal-3 expression, which correlated with placental dysfunction. These data highlight the importance of gal-3 in the promotion of proper placental function, as its absence leads to placental disease and subsequent FGR.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41419-020-02791-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7378206PMC
July 2020

Membrane interactions of the globular domain and the hypervariable region of KRAS4b define its unique diffusion behavior.

Elife 2020 01 20;9. Epub 2020 Jan 20.

NCI RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, United States.

The RAS proteins are GTP-dependent switches that regulate signaling pathways and are frequently mutated in cancer. RAS proteins concentrate in the plasma membrane via lipid-tethers and hypervariable region side-chain interactions in distinct nano-domains. However, little is known about RAS membrane dynamics and the details of RAS activation of downstream signaling. Here, we characterize RAS in live human and mouse cells using single-molecule-tracking methods and estimate RAS mobility parameters. KRAS4b exhibits confined mobility with three diffusive states distinct from the other RAS isoforms (KRAS4a, NRAS, and HRAS); and although most of the amino acid differences between RAS isoforms lie within the hypervariable region, the additional confinement of KRAS4b is largely determined by the protein's globular domain. To understand the altered mobility of an oncogenic KRAS4b, we used complementary experimental and molecular dynamics simulation approaches to reveal a detailed mechanism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7554/eLife.47654DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7060043PMC
January 2020

Acculturation and Food Intake Among Ghanaian Migrants in Europe: Findings From the RODAM Study.

J Nutr Educ Behav 2020 02 7;52(2):114-125. Epub 2019 Oct 7.

Department of Public Health, Amsterdam UMC, University of Amsterdam, Amsterdam Public Health Research Institute, Amsterdam, The Netherlands.

Objective: This study examined the role of migration and acculturation in the diet of Ghanaian migrants in Europe by (1) comparing food intake of Ghanaian migrants in Europe with that of Ghanaians living in Ghana and (2) assessing the association between acculturation and food intake.

Design: Data from the cross-sectional multicenter study Research on Obesity and Diabetes among African Migrants were used. Food intake was assessed using a Ghana-specific food propensity questionnaire (134 items and 14 food groups); foods were grouped based on a model of dietary change proposed by Koctürk-Runefors.

Setting: Ghana, London, Amsterdam, and Berlin.

Participants: A total of 4,534 Ghanaian adults living in Ghana and Europe, with complete dietary data. Of these, 1,773 Ghanaian migrants had complete acculturation data.

Main Outcome Measure: Food intake (the weighted intake frequency per week of food categories).

Analysis: Linear regression.

Results: Food intake differed between Ghanaians living in Ghana and Europe. Among Ghanaian migrants in Europe, there were inconsistent and small associations between acculturation and food intake, except for ethnic identity, which was consistently associated with intake only of traditional staples.

Conclusions And Implications: Findings indicate that migration is associated with dietary changes that cannot be fully explained by ethnic, cultural, and social acculturation. The study provides limited support to the differential changes in diet suggested by the Koctürk-Runefors' model of dietary change.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jneb.2019.09.004DOI Listing
February 2020

A systematic scoping review of asset-based approaches to promote health in communities: development of a framework.

Glob Health Promot 2020 09 18;27(3):15-23. Epub 2019 Jul 18.

School of Health and Related Research (ScHARR), University of Sheffield, United Kingdom.

Asset-based approaches to health promotion have become increasingly popular as a way to tackle health inequalities by empowering people in more disadvantaged communities to use local resources and increase control over health and its determinants. However, questions remain about how they work in practice. This article presents the findings from a systematic scoping review of the empirical literature on asset-based approaches in communities. The aim was to identify the key elements of asset-based approaches, and how they are operationalised in interventions aimed at promoting health and reducing inequalities in local communities. Four databases were searched (Medline, PsycINFO, CINAHL, ASSIA) and papers were included if they described interventions explicitly adopting an asset-based approach but excluded if limited to asset identification. Thirty articles were included in the review. Data were extracted on the type of assets that the intervention built upon, how assets were mobilised, the expected outcomes and evaluation methods. A framework is presented that synthesises the key characteristics of asset-based interventions to promote health in communities. Three main approaches to mobilising assets were identified in the literature: (A) connecting assets, (B) raising awareness of assets and (C) enabling assets to thrive. It is argued that asset-based approaches to health promotion take a wide variety of forms, making it difficult to anticipate outcomes and to evaluate interventions. The framework presented here can be used to better understand the processes through which asset-based approaches work in practice to promote health and reduce inequalities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1757975919848925DOI Listing
September 2020

"I cannot sit here and eat alone when I know a fellow Ghanaian is suffering": Perceptions of food insecurity among Ghanaian migrants.

Appetite 2019 09 17;140:190-196. Epub 2019 May 17.

Public Health Section, School of Health and Related Research-ScHARR, University of Sheffield, Sheffield, UK.

In the UK, ethnic minority groups tend to have higher levels of poverty than the white British population and therefore may be at high risk of food insecurity. Ghanaians, living in Ghana or as migrants are thought to have a high level of social support in their communities, but the role of this resource in relation to food security is unknown. We explored participants' perceptions of social and economic factors influencing food security among Ghanaian migrants in Greater Manchester. Participants aged ≥25 years (n = 31) of Ghanaian ancestry living in Greater Manchester were interviewed using a semi-structured interview guide developed by the researchers. Participants varied in socioeconomic status (SES), gender and migration status. Interviews were transcribed verbatim and analysed thematically using a framework approach. Participants offered similar accounts of the social and economic factors influencing food security. Accounts were based on participants' perceptions and/or personal experiences of food insecurity within the community. Participants indicated that they and their fellow Ghanaians can 'manage' even when they described quite challenging food access environments. This has negative implications on their food choices in the UK. Participants reported food insecure households may be reluctant to make use of food banks for fear of 'gossip' and 'pride'. Paradoxically, this reluctance does not extend to close network. Many participants described the church and other social groups as a trusted base in which people operate; support given through these channels is more acceptable than through the 'official context'. Government assisted food banks could partner with the social groups within this community given that these are more trusted. Keywords: food insecurity; food choice; social networks; Ghanaians; healthy eating; migrants.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.appet.2019.05.018DOI Listing
September 2019

Genome-Wide RNAi Screen Identifies PMPCB as a Therapeutic Vulnerability in EpCAM Hepatocellular Carcinoma.

Cancer Res 2019 05 12;79(9):2379-2391. Epub 2019 Mar 12.

Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland.

Hepatocellular carcinoma (HCC) is a genetically heterogeneous disease for which a dominant actionable molecular driver has not been identified. Patients with the stem cell-like EpCAMAFP HCC subtype have poor prognosis. Here, we performed a genome-wide RNAi screen to identify genes with a synthetic lethal interaction with EpCAM as a potential therapeutic target for the EpCAMAFP HCC subtype. We identified 26 candidate genes linked to EpCAM/Wnt/β-catenin signaling and HCC cell growth. We further characterized the top candidate PMPCB, which plays a role in mitochondrial protein processing, as a target for EpCAM HCC. PMPCB blockage suppressed EpCAM expression and Wnt/β-catenin signaling via mitochondria-related reactive oxygen species production and FOXO activities, resulting in apoptosis and tumor suppression. These results indicate that a synthetic lethality screen is a viable strategy to identify actionable drivers of HCC and identify PMPCB as a therapeutically vulnerable gene in EpCAM HCC subpopulations. SIGNIFICANCE: This study identifies PMPCB as critical to mitochondrial homeostasis and a synthetic lethal candidate that selectively kills highly resistant EpCAM HCC tumors by inactivating the Wnt/β-catenin signaling pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/0008-5472.CAN-18-3015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6497533PMC
May 2019

Reframing "participation" and "inclusion" in public health policy and practice to address health inequalities: Evidence from a major resident-led neighbourhood improvement initiative.

Health Soc Care Community 2019 01 9;27(1):199-206. Epub 2018 Sep 9.

Division of Health Research, Faculty of Health and Medicine, Lancaster University, Lancaster, UK.

There is a need for greater conceptual clarity in place-based initiatives that seek to give residents of disadvantaged neighbourhoods more control over action to address the social determinants of health inequalities at a local level. In this article, we address this issue as it relates to the concepts of participation and inclusion. We draw on qualitative data generated during the first phase of the Communities in Control Study, a longitudinal multisite independent evaluation of the impact of Big Local on the social determinants of health and health inequalities. Big Local is a resident-led area improvement initiative in England, funded by the UK Big Lottery Fund. Initiatives focused on community empowerment are increasingly prominent in public health policy and practice globally. Approaches emphasise the promotion of greater control over decisions and action among individuals, groups, and communities, particularly those living in disadvantaged circumstances. However, when it comes to participation and inclusion in taking action and making decisions, the field is characterised by conceptual confusion. This risks undermining the impact of these initiatives. While participation and inclusion are necessary conditions for empowerment and collective control, they are not necessarily sufficient. Sufficiency requires attention to the breadth of participation (i.e., to inclusion) and to the depth of participation (i.e., the extent to which it is experienced as empowering and ultimately enables the exercise of collective control over decisions and actions). In observing how different Big Local resident-led partnerships across England are tackling the day-to-day challenges of engaging with their communities, we reveal the potential for policy and practice of reframing, and therefore clarifying (to highlight the different roles they have) the concepts of participation and inclusion in terms of depth and breadth.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/hsc.12640DOI Listing
January 2019

Introducing the idea of 'assumed shared food narratives' in the context of social networks: reflections from a qualitative study conducted in Nottingham, England.

Sociol Health Illn 2018 09 19;40(7):1142-1155. Epub 2018 Jun 19.

ScHARR, University of Sheffield, Sheffield, UK.

This study explores the ways in which social networks might shape accounts about food practices. Drawing on insights from the work of Christakis and Fowler () whose claims about the linkages between obesity and social networks have been the subject of vigorous debate in the sociological literature, we present qualitative data from a study of women's' accounts of social networks and food practices, conducted in Nottingham, England. We tentatively suggest that whilst social networks in their broadest sense, might shape what was perceived to be normal and acceptable in relation to food practices (and provide everyday discursive resources which normalise practice), the relationship between the two is more complex than the linear relationship proposed by Christakis and Fowler. Here, we introduce the idea of assumed shared food narratives (ASFNs), which, we propose, sheds light on motive talk about food practices, and which also provide practical and discursive resources to actors seeking to protect and defend against 'untoward' behaviour, in the context of public health messages around food and eating. We suggest that understanding ASFNs and the ways in which they are embedded in social networks represents a novel way of understanding food and eating practices from a sociological perspective.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1467-9566.12746DOI Listing
September 2018

Utility of metabolic profiling of serum in the diagnosis of pregnancy complications.

Placenta 2018 06 10;66:65-73. Epub 2018 Apr 10.

Department of Cardiology, Kolling Institute, Northern Sydney Local Health District, St Leonards, NSW, 2065, Australia; Sydney Medical School Northern, University of Sydney, NSW, 2006, Australia.

Introduction: Currently there are no clinical screening tests available to identify pregnancies at risk of developing preeclampsia (PET) and/or intrauterine growth restriction (IUGR), both of which are associated with abnormal placentation. Metabolic profiling is now a stable analytical platform used in many laboratories and has successfully been used to identify biomarkers associated with various pathological states.

Methods: We used nuclear magnetic resonance spectroscopy (NMR) to metabolically profile serum samples collected from 143 pregnant women at 26-41 weeks gestation with pregnancy outcomes of PET, IUGR, PET IUGR or small for gestational age (SGA) that were age-matched to normal pre/term pregnancies.

Results: Spectral analysis found no difference in the measured metabolites from normal term, pre-term and SGA samples, and of 25 identified metabolites, only glutamate was marginally different between groups. Of the identified metabolites, 3-methylhistidine, creatinine, acetyl groups and acetate, were determined to be independent predictors of PET and produced area under the curves (AUC) = 0.938 and 0.936 for the discovery and validation sets. Only 3-hydroxybutyrate was determined to be an independent predictor of IUGR, however the model had low predictive power (AUC = 0.623 and 0.581 for the discovery and validation sets).

Conclusions: A sub-panel of metabolites had strong predictive power for identifying PET samples in a validation dataset, however prediction of IUGR was more difficult using the identified metabolites. NMR based metabolomics can identify metabolites strongly associated with disease and has the potential to be useful in developing early clinical screening tests for at risk pregnancies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.placenta.2018.04.005DOI Listing
June 2018

Differential Effector Engagement by Oncogenic KRAS.

Cell Rep 2018 02;22(7):1889-1902

Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, 1450 3rd Street, San Francisco, CA 94158, USA; Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., P.O. Box B, Frederick, MD 21702, USA. Electronic address:

KRAS can bind numerous effector proteins, which activate different downstream signaling events. The best known are RAF, phosphatidylinositide (PI)-3' kinase, and RalGDS families, but many additional direct and indirect effectors have been reported. We have assessed how these effectors contribute to several major phenotypes in a quantitative way, using an arrayed combinatorial siRNA screen in which we knocked down 41 KRAS effectors nodes in 92 cell lines. We show that every cell line has a unique combination of effector dependencies, but in spite of this heterogeneity, we were able to identify two major subtypes of KRAS mutant cancers of the lung, pancreas, and large intestine, which reflect different KRAS effector engagement and opportunities for therapeutic intervention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.celrep.2018.01.051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6343826PMC
February 2018

Formyl peptide receptor-2 is decreased in foetal growth restriction and contributes to placental dysfunction.

Mol Hum Reprod 2018 02;24(2):94-109

Department of Maternal-Fetal Medicine Pregnancy Research Centre, The Royal Women's Hospital, Parkville, Victoria 3052, Australia.

Study Question: What is the association between placental formyl peptide receptor 2 (FPR2) and trophoblast and endothelial functions in pregnancies affected by foetal growth restriction (FGR)?

Summary Answer: Reduced FPR2 placental expression in idiopathic FGR results in significantly altered trophoblast differentiation and endothelial function in vitro.

What Is Known Already: FGR is associated with placental insufficiency, where defective trophoblast and endothelial functions contribute to reduced feto-placental growth.

Study Design, Size, Duration: The expression of FPR2 in placental tissues from human pregnancies complicated with FGR was compared to that in gestation-matched uncomplicated control pregnancies (n = 25 from each group). Fpr2 expression was also determined in placental tissues obtained from a murine model of FGR (n = 4). The functional role of FPR2 in primary trophoblasts and endothelial cells in vitro was assessed in diverse assays in a time-dependent manner.

Participants/materials, Setting, Methods: Placentae from third-trimester pregnancies complicated by idiopathic FGR (n = 25) and those from gestation-matched pregnancies with appropriately grown infants as controls (n = 25) were collected at gestation 27-40 weeks. Placental tissues were also collected from a spontaneous CBA/CaH × DBA/2 J murine model of FGR. Placental FPR2/Fpr2 mRNA expression was determined by real-time PCR, while protein expression was examined by immunoblotting and immunohistochemistry. siRNA transfection was used to silence FPR2 expression in primary trophoblasts and in human umbilical vein endothelial cells (HUVEC), and the quantitation of cytokines, chemokines and apoptosis was performed following a cDNA array analyses. Functional effects of trophoblast differentiation were measured using HCGB/β-hCG and syncytin-2 expression as well as markers of apoptosis, tumour protein 53 (TP53), caspase 8, B cell lymphoma 2 (BCL2) and BCL associated X (BAX). Endothelial function was assessed by proliferation, network formation and permeability assays.

Main Results And The Role Of Chance: Placental FPR2/Fpr2 expression was significantly decreased in FGR placentae (n = 25, P < 0.05) as well as in murine FGR placentae compared to controls (n = 4, P < 0.05). FPR2 siRNA (siFPR2) in term trophoblasts significantly increased differentiation markers, HCGB and syncytin-2; cytokines, interleukin (IL)-6, CXCL8; and apoptotic markers, TP53, caspase 8 and BAX, but significantly reduced the expression of the chemokines CXCL12 and its receptors CXCR4 and CXCR7; CXCL16 and its receptor, CXCR6; and cytokine, IL-10, compared with control siRNA (siCONT). Treatment of HUVECs with siFPR2 significantly reduced proliferation and endothelial tube formation, but significantly increased permeability of HUVECs.

Large Scale Data: N/A.

Limitations, Reasons For Caution: Reduced expression of placental FPR2/Fpr2 was observed in the third trimester at delivery after development of FGR, suggesting that FPR2 is associated with FGR pregnancies. However, there is a possibility that the decreased placental FPR2 observed in FGR may be a consequence rather than a cause of FGR, although our in vitro functional analyses using primary trophoblasts and endothelial cells suggest that FPR2 may have a direct or indirect regulatory role on trophoblast differentiation and endothelial function in FGR.

Wider Implications Of The Findings: This is the first study linking placental FPR2 expression with changes in the trophoblast and endothelial functions that may explain the placental insufficiency observed in FGR.

Study Funding/competing Interests: P.M. and P.R.E. received funding from the Australian Institute of Musculoskeletal Science, Western Health, St. Albans, Victoria 3021, Australia. M.L. is supported by a Career Development Fellowship from the National Health and Medical Research Council (NHMRC; Grant no. 1047025). Monash Health is supported by the Victorian Government's Operational Infrastructure Support Programme. The authors declare that there is no conflict of interest in publishing this work.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/molehr/gax067DOI Listing
February 2018

Analyzing Trophoblast Function Using Cell-Based Assays.

Methods Mol Biol 2018 ;1710:233-246

Division of Perinatal Research, Kolling Institute, Northern Sydney Local Health District, St Leonards, NSW, 2065, Australia.

Functional cell-based assays are useful for comparing the effect of a treatment, drug, or condition on cells in culture. Cell lines are a commonly used model to replicate a normal biological process or a pathological condition. Trophoblasts within the placenta are required to perform a variety of functions, which include proliferation, differentiation, migration, and invasion for efficient placentation to occur. These functions are impaired in trophoblasts from preeclamptic pregnancies, and therefore functional cell-based assays can be utilized to measure differences and dissect molecular regulatory pathways.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/978-1-4939-7498-6_18DOI Listing
July 2018

Developing a systems-based framework of the factors influencing dietary and physical activity behaviours in ethnic minority populations living in Europe - a DEDIPAC study.

Int J Behav Nutr Phys Act 2017 11 7;14(1):154. Epub 2017 Nov 7.

Academic Medical Centre, University of Amsterdam, Department of Public Health, Amsterdam Public Health research Institute, Amsterdam, The Netherlands.

Background: Some ethnic minority populations have a higher risk of non-communicable diseases than the majority European population. Diet and physical activity behaviours contribute to this risk, shaped by a system of inter-related factors. This study mapped a systems-based framework of the factors influencing dietary and physical activity behaviours in ethnic minority populations living in Europe, to inform research prioritisation and intervention development.

Methods: A concept mapping approach guided by systems thinking was used: i. Preparation (protocol and terminology); ii. Generating a list of factors influencing dietary and physical activity behaviours in ethnic minority populations living in Europe from evidence (systematic mapping reviews) and 'eminence' (89 participants from 24 academic disciplines via brainstorming, an international symposium and expert review) and; iii. Seeking consensus on structuring, rating and clustering factors, based on how they relate to each other; and iv. Interpreting/utilising the framework for research and interventions. Similar steps were undertaken for frameworks developed for the majority European population.

Results: Seven distinct clusters emerged for dietary behaviour (containing 85 factors) and 8 for physical activity behaviours (containing 183 factors). Four clusters were similar across behaviours: Social and cultural environment; Social and material resources; Psychosocial; and Migration context. Similar clusters of factors emerged in the frameworks for diet and physical activity behaviours of the majority European population, except for 'migration context'. The importance of factors across all clusters was acknowledged, but their relative importance differed for ethnic minority populations compared with the majority population.

Conclusions: This systems-based framework integrates evidence from both expert opinion and published literature, to map the factors influencing dietary and physical activity behaviours in ethnic minority groups. Our findings illustrate that innovative research and complex interventions need to be developed that are sensitive to the needs of ethnic minority populations. A systems approach that encompasses the complexity of the inter-related factors that drive behaviours may inform a more holistic public health paradigm to more effectively reach ethnic minorities living in Europe, as well as the majority host population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12966-017-0608-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5678802PMC
November 2017

A model of how targeted and universal welfare entitlements impact on material, psycho-social and structural determinants of health in older adults.

Soc Sci Med 2017 08 15;187:20-28. Epub 2017 Jun 15.

Institute of Health & Society, Newcastle University, Campus for Ageing and Vitality, Biomedical Sciences Building, Newcastle upon Tyne. NE4 5PL, UK.

A growing body of research attests to the impact of welfare regimes on health and health equity. However, the mechanisms that link different kinds of welfare entitlement to health outcomes are less well understood. This study analysed the accounts of 29 older adults in England to delineate how the form of entitlement to welfare and other resources (specifically, whether this was understood as a universal entitlement or as targeted to those in need) impacts on the determinants of health. Mechanisms directly affecting access to material resources (through deterring uptake of benefits) have been well documented, but those that operate through psychosocial and more structural pathways less so, in part because they are more challenging to identify. Entitlement that was understood collectively, or as arising from financial or other contributions to a social body, had positive impacts on wellbeing beyond material gains, including facilitating access to important health determinants: social contact, recognition and integration. Entitlement understood as targeted in terms of individualised concepts of need or vulnerability deterred access to material resources, but also fostered debate about legitimacy, thus contributing to negative impacts on individual wellbeing and the public health through the erosion of social integration. This has important implications for both policy and evaluation. Calls to target welfare benefits at those in most need emphasise direct material pathways to health impact. We suggest a model for considering policy change and evaluation which also takes into account how psychosocial and structural pathways are affected by the nature of entitlement.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.socscimed.2017.06.015DOI Listing
August 2017

The influence of migration on dietary practices of Ghanaians living in the United Kingdom: a qualitative study.

Ann Hum Biol 2017 Aug 13;44(5):454-463. Epub 2017 Jun 13.

a Public Health Section, School of Health and Related Research-ScHARR , University of Sheffield , Sheffield , UK.

Background: Previous studies have identified a process of dietary acculturation when migrant groups adopt the food patterns of the host country.

Aim: The aim of this study was to explore the influence of migration on dietary practices and the process of dietary acculturation amongst Ghanaians living in the UK.

Subject And Methods: A qualitative study of adults aged ≥25 years (n = 31) of Ghanaian ancestry living in Greater Manchester using face-to-face interviews. Participants varied in socioeconomic status, gender and migration status. Interviews were transcribed verbatim and analysed thematically.

Results: Three distinct dietary practice typologies were discernible that differed in terms of typical meal formats, meal contexts, structure and patterning of meals, food preparation and purchasing behaviours: (i) continuity practices; (ii) flexible practices; and (iii) changed practices. The identified practices were shaped by interrelating factors that fell into four main clusters: social and cultural environment; accessibility of foods; migration context; and food beliefs/perceptions.

Conclusion: Participants retained, to a varying degree, some aspects of Ghanaian dietary practices, whilst adopting key features of UK food culture. This study demonstrates the complexity of dietary change, indicating that it is not a linear process and it is dependent on several factors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/03014460.2017.1333148DOI Listing
August 2017

IFPA meeting 2016 workshop report I: Genomic communication, bioinformatics, trophoblast biology and transport systems.

Placenta 2017 12 11;60 Suppl 1:S5-S9. Epub 2017 Jan 11.

Center for Reproductive Health, MetroHealth Medical Center, Case Western Reserve University, Cleveland, OH, USA. Electronic address:

Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2016 there were twelve themed workshops, four of which are summarized in this report. These workshops covered innovative technologies applied to new and traditional areas of placental research: 1) genomic communication; 2) bioinformatics; 3) trophoblast biology and pathology; 4) placental transport systems.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.placenta.2017.01.103DOI Listing
December 2017

Systematic mapping review of the factors influencing dietary behaviour in ethnic minority groups living in Europe: a DEDIPAC study.

Int J Behav Nutr Phys Act 2016 Jul 28;13:85. Epub 2016 Jul 28.

Public Health Section, School of Health and Related Research-ScHARR, The University of Sheffield, Sheffield, UK.

Background: Europe has a growing population of ethnic minority groups whose dietary behaviours are potentially of public health concern. To promote healthier diets, the factors driving dietary behaviours need to be understood. This review mapped the broad range of factors influencing dietary behaviour among ethnic minority groups living in Europe, in order to identify research gaps in the literature to guide future research.

Methods: A systematic mapping review was conducted (protocol registered with PROSPERO 2014: CRD42014013549). Nine databases were searched for quantitative and qualitative primary research published between 1999 and 2014. Ethnic minority groups were defined as immigrants/populations of immigrant background from low and middle income countries, population groups from former Eastern Bloc countries and minority indigenous populations. In synthesizing the findings, all factors were sorted and structured into emerging clusters according to how they were seen to relate to each other.

Results: Thirty-seven of 2965 studies met the inclusion criteria (n = 18 quantitative; n = 19 qualitative). Most studies were conducted in Northern Europe and were limited to specific European countries, and focused on a selected number of ethnic minority groups, predominantly among populations of South Asian origin. The 63 factors influencing dietary behaviour that emerged were sorted into seven clusters: social and cultural environment (16 factors), food beliefs and perceptions (11 factors), psychosocial (9 factors), social and material resources (5 factors), accessibility of food (10 factors), migration context (7 factors), and the body (5 factors).

Conclusion: This review identified a broad range of factors and clusters influencing dietary behaviour among ethnic minority groups. Gaps in the literature identified a need for researchers to explore the underlying mechanisms that shape dietary behaviours, which can be gleaned from more holistic, systems-based studies exploring relationships between factors and clusters. The dominance of studies exploring 'differences' between ethnic minority groups and the majority population in terms of the socio-cultural environment and food beliefs suggests a need for research exploring 'similarities'. The evidence from this review will feed into developing a framework for the study of factors influencing dietary behaviours in ethnic minority groups in Europe.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12966-016-0412-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4964011PMC
July 2016

Role for the thromboxane A2 receptor β-isoform in the pathogenesis of intrauterine growth restriction.

Sci Rep 2016 07 1;6:28811. Epub 2016 Jul 1.

Division of Perinatal Research, Kolling Institute, Northern Sydney Local Health District, St Leonards, NSW, 2065, Australia.

Intrauterine growth restriction (IUGR) is a pathology of pregnancy that results in failure of the fetus to reach its genetically determined growth potential. In developed nations the most common cause of IUGR is impaired placentation resulting from poor trophoblast function, which reduces blood flow to the fetoplacental unit, promotes hypoxia and enhances production of bioactive lipids (TXA2 and isoprostanes) which act through the thromboxane receptor (TP). TP activation has been implicated as a pathogenic factor in pregnancy complications, including IUGR; however, the role of TP isoforms during pregnancy is poorly defined. We have determined that expression of the human-specific isoform of TP (TPβ) is increased in placentae from IUGR pregnancies, compared to healthy pregnancies. Overexpression of TPα enhanced trophoblast proliferation and syncytialisation. Conversely, TPβ attenuated these functions and inhibited migration. Expression of the TPβ transgene in mice resulted in growth restricted pups and placentae with poor syncytialisation and diminished growth characteristics. Together our data indicate that expression of TPα mediates normal placentation; however, TPβ impairs placentation, and promotes the development of IUGR, and represents an underappreciated pathogenic factor in humans.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/srep28811DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4929481PMC
July 2016

A Gene Expression Signature Associated with Overall Survival in Patients with Hepatocellular Carcinoma Suggests a New Treatment Strategy.

Mol Pharmacol 2016 Feb 14;89(2):263-72. Epub 2015 Dec 14.

Laboratory of Cell Biology (J-P.G., J.P.M., C-P.W., A.M.C., S.V.A., M.M.G.) and Laboratory of Experimental Carcinogenesis (J.B.A., S.S.T.), Center for Cancer Research, National Cancer Institute, and Bioinformatics and Computational Biosciences Branch, Office of Cyber Infrastructure and Computational Biology, Office of Science Management and Operations, National Institute of Allergy and Infectious Diseases (S.V.), National Institutes of Health, Bethesda, Maryland; and the Viral Technologies Group and Molecular Detection Group, Protein Expression Laboratory, Frederick National Laboratory for Cancer Research, National Institutes of Health, Frederick, Marylanld (R.K.B., K.P., W.E.B.)

Despite improvements in the management of liver cancer, the survival rate for patients with hepatocellular carcinoma (HCC) remains dismal. The survival benefit of systemic chemotherapy for the treatment of liver cancer is only marginal. Although the reasons for treatment failure are multifactorial, intrinsic resistance to chemotherapy plays a primary role. Here, we analyzed the expression of 377 multidrug resistance (MDR)-associated genes in two independent cohorts of patients with advanced HCC, with the aim of finding ways to improve survival in this poor-prognosis cancer. Taqman-based quantitative polymerase chain reaction revealed a 45-gene signature that predicts overall survival (OS) in patients with HCC. Using the Connectivity Map Tool, we were able to identify drugs that converted the gene expression profiles of HCC cell lines from ones matching patients with poor OS to profiles associated with good OS. We found three compounds that convert the gene expression profiles of three HCC cell lines to gene expression profiles associated with good OS. These compounds increase histone acetylation, which correlates with the synergistic sensitization of those MDR tumor cells to conventional chemotherapeutic agents, including cisplatin, sorafenib, and 5-fluorouracil. Our results indicate that it is possible to modulate gene expression profiles in HCC cell lines to those associated with better outcome. This approach also increases sensitization of HCC cells toward conventional chemotherapeutic agents. This work suggests new treatment strategies for a disease for which few therapeutic options exist.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1124/mol.115.101360DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4727122PMC
February 2016

The role of social networks in the development of overweight and obesity among adults: a scoping review.

BMC Public Health 2015 Sep 30;15:996. Epub 2015 Sep 30.

School of Health and Related Research (ScHARR), University of Sheffield, 30 Regent Street, Sheffield, S1 4DA, UK.

Background: Although it is increasingly acknowledged that social networks are important to our understanding ofoverweight and obesity, there is limited understanding about the processes by which such networks shapetheir progression. This paper reports the findings of a scoping review of the literature that sought to identify the key processes through which social networks are understood to influence the development of overweight and obesity.

Methods: A scoping review was conducted. Forty five papers were included in the final review, the findings of which were synthesised to provide an overview of the main processes through which networks have been understood to influence the development of overweight and obesity.

Results: Included papers addressed a wide range of research questions framed around six types of networks: a paired network (one's spouse or intimate partner); friends and family (including work colleagues and people within social clubs); ephemeral networks in shared public spaces (such as fellow shoppers in a supermarket or diners in a restaurant); people living within the same geographical region; peers (including co-workers, fellow students, fellow participants in a weight loss programme); and cultural groups (often related toethnicity). As individuals are embedded in many of these different types of social networks at any one time, the pathways of influence from social networks to the development of patterns of overweight and obesity are likely to be complex and interrelated. Included papers addressed a diverse set of issues: body weight trends over time; body size norms or preferences; weight loss and management; physical activity patterns; and dietary patterns.

Discussion: Three inter-related processes were identified: social contagion (whereby the network in which people are embedded influences their weight or weight influencing behaviours), social capital (whereby sense of belonging and social support influence weight or weight influencing behaviours), and social selection (whereby a person's network might develop according to his or her weight).

Conclusions: The findings have important implications for understanding about methods to target the spread of obesity, indicating that much greater attention needs to be paid to the social context in which people make decisions about their weight and weight influencing behaviours.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12889-015-2314-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4589958PMC
September 2015

Exosomes: Mechanisms of Uptake.

J Circ Biomark 2015 Jan-Dec;4. Epub 2015 Jul 17.

Division of Perinatal Medicine, Kolling Institute of Medical Research, University of Sydney at Royal North Shore Hospital, St Leonards, NSW, Australia.

Exosomes are 30-100 nm microvesicles which contain complex cellular signals of RNA, protein and lipids. Because of this, exosomes are implicated as having limitless therapeutic potential for the treatment of cancer, pregnancy complications, infections, and autoimmune diseases. To date we know a considerable amount about exosome biogenesis and secretion, but there is a paucity of data regarding the uptake of exosomes by immune and non-immune cell types (e.g., cancer cells) and the internal signalling pathways by which these exosomes elicit a cellular response. Answering these questions is of paramount importance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5772/61186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5572985PMC
July 2015

Understanding welfare conditionality in the context of a generational habitus: A qualitative study of older citizens in England.

J Aging Stud 2015 Aug 20;34:113-22. Epub 2015 Jun 20.

Department of Health Services Research & Policy, Faculty of Public Health & Policy, London School of Hygiene & Tropical Medicine, 15-17 Tavistock Place, London WC1H 9SH, UK. Electronic address:

In many welfare states, 'austerity' policies have ignited debates about the fairness and cost-effectiveness of universal welfare benefits, with benefits received by older citizens a particular topic of concern. Empirical studies suggest that conditionality generates problems of access and uptake but, to date, there has been little research on how different conditions of entitlement are understood by older citizens. This study drew on interviews with 29 older citizens from three areas of England to explore how eligibility for and uptake of different kinds of welfare benefits were understood. In interviews, current entitlement was understood in relation to a generational habitus, in which 'our generation' was framed as sharing cohort experiences, and moral orientations to self-reliance, hard work and struggle. Entitlement to some welfare benefits was taken for granted as a reward owed by the state to its citizens for hard-earned lives. State transfers such as pensions, free travel and fuel subsidies were congruent with a nationalised generational habitus, and fostered recognition, self-worth and the sense of a generation as a collective. In contrast, transfers contingent on economic or need-based conditionality were more explicitly framed as 'benefits', and negatively associated with vulnerability and moral contestation. Uptake was therefore often incompatible with their generational habitus. Calls for introducing further conditionality to benefits for older adults are often based on claims that this will increase fairness and equality. Our analysis suggests, however, that introducing conditionality has the potential to promote inequality and foster differentiation and division, within the older population and between generations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaging.2015.06.002DOI Listing
August 2015

High maternal serum ferritin in early pregnancy and risk of spontaneous preterm birth.

Br J Nutr 2015 Aug 6;114(3):455-61. Epub 2015 Jul 6.

Clinical and Population Perinatal Health Research, Kolling Institute, University of Sydney, Royal North Shore Hospital,B52, St Leonards,Sydney,NSW2065,Australia.

Previous studies have reported inconsistent associations between maternal serum ferritin concentrations and the risk of spontaneous preterm birth (sPTB). The aim of the present study was to examine the association between Fe biomarkers, including serum ferritin concentrations, and the risk of total ( 75th percentile ( ≥ 43 μg/l) (OR 1.49, 95% CI 1.06, 2.10) and >90th percentile ( ≥ 68 μg/l) (OR 1.92, 95% CI 1.25, 2.96). Increased odds of early and moderate-to-late sPTB were associated with ferritin levels >90th percentile (OR 2.50, 95% CI 1.32, 4.73) and >75th percentile (OR 1.56, 95% CI 1.03, 2.37), respectively. No association was found between the risk of sPTB and elevated sTfR levels or Fe deficiency. In conclusion, elevated maternal serum ferritin levels in early pregnancy are associated with an increased risk of sPTB from 34 weeks of gestation. The usefulness of early pregnancy ferritin levels in identifying women at risk of sPTB warrants further investigation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/S0007114515001932DOI Listing
August 2015

Development of a potent melanoma vaccine capable of stimulating CD8(+) T-cells independently of dendritic cells in a mouse model.

Cancer Immunol Immunother 2015 Jul 19;64(7):861-72. Epub 2015 Apr 19.

School of Medical Science, Griffith University, Gold Coast, QLD, Australia,

At present, there are no vaccines approved for the prevention or treatment of malignant melanoma, despite the amount of time and resources that has been invested. In this study, we aimed to develop a self-contained vaccine capable of directly stimulating anticancer CD8(+) T-cell immune responses. To achieve this, three whole-cell melanoma vaccines were developed expressing 4-1BBL or B7.1 T-cell co-stimulatory molecules individually or in combination. The ability of engineered vaccine cell lines to stimulate potent anticancer immune responses in C57BL/6 mice was assessed. Mice vaccinated with cells overexpressing both 4-1BBL and B7.1 (B16-F10-4-1BBL-B7.1-IFNγ/β anticancer vaccine) displayed the greatest increases in CD8(+) T-cell populations (1.9-fold increase versus control within spleens), which were efficiently activated following antigenic stimulation, resulting in a 10.7-fold increase in cancer cell cytotoxicity relative to control. The enhanced immune responses in B16-F10-4-1BBL-B7.1-IFNγ/β-vaccinated mice translated into highly efficient rejection of live tumour burdens and conferred long-term protection against repeated tumour challenges, which were likely due to enhanced effector memory T-cell populations. Similar results were observed when dendritic cell (DC)-deficient LTα(-/-) mice were treated with the B16-F10-4-1BBL-B7.1-IFNγ/β anticancer vaccine, suggesting that the vaccine can directly stimulate CD8(+) T-cell responses in the context of severely reduced DCs. This study shows that the B16-F10-4-1BBL-B7.1-IFNγ/β anticancer vaccine acted as a highly effective antigen-presenting cell and is likely to be able to directly stimulate CD8(+) T-cells, without requiring co-stimulatory signals from either CD4(+) T-cells or DCs, and warrants translation of this technology into the clinical setting.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00262-015-1695-3DOI Listing
July 2015

Local status and power in area-based health improvement partnerships.

Health (London) 2014 Nov 1;18(6):561-79. Epub 2014 Apr 1.

University of Chester, UK.

Area-based initiatives have formed an important part of public policy towards more socio-economically deprived areas in many countries. Co-ordinating service provision within and across sectors has been a common feature of these initiatives. Despite sustained policy interest in area-based initiatives, little empirical work has explored relations between area-based initiative providers, and partnership development within this context remains under-theorised. This article addresses both of these gaps by exploring partnerships as a social and developmental process, drawing on concepts from figurational sociology to explain how provider relations develop within an area-based initiative. Qualitative methods were used to explore, prospectively, the development of an area-based initiative targeted at a town in the north west of England. A central finding was that although effective delivery of area-based initiatives is premised on a high level of co-ordination between service providers, the pattern of interdependencies between providers limits the frequency and effectiveness of co-operation. In particular, the interdependency of area-based initiative providers with others in their organisation (what is termed here as 'organisational pull') constrained the ways in which they worked with providers outside of their own organisations. 'Local' status, which could be earned over time, enabled some providers to exert greater control over the way in which provider relations developed during the course of the initiative. These findings demonstrate how historically constituted social networks, within which all providers are embedded, shape partnership development. The theoretical insight developed here suggests a need for more realistic expectations among policymakers about how and to what extent provider partnerships can be managed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1363459314524802DOI Listing
November 2014