| 1. |
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| 2. |
- Bailey-Wilson, Joan E, et al.
(författare)
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Analysis of Xq27-28 linkage in the international consortium for prostate cancer genetics (ICPCG) families
- 2012
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Ingår i: BMC Medical Genetics. - London : BioMed Central. - 1471-2350. ; 13, s. 46-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Genetic variants are likely to contribute to a portion of prostate cancer risk. Full elucidation of the genetic etiology of prostate cancer is difficult because of incomplete penetrance and genetic and phenotypic heterogeneity. Current evidence suggests that genetic linkage to prostate cancer has been found on several chromosomes including the X; however, identification of causative genes has been elusive.Methods: Parametric and non-parametric linkage analyses were performed using 26 microsatellite markers in each of 11 groups of multiple-case prostate cancer families from the International Consortium for Prostate Cancer Genetics (ICPCG). Meta-analyses of the resultant family-specific linkage statistics across the entire 1,323 families and in several predefined subsets were then performed.Results: Meta-analyses of linkage statistics resulted in a maximum parametric heterogeneity lod score (HLOD) of 1.28, and an allele-sharing lod score (LOD) of 2.0 in favor of linkage to Xq27-q28 at 138 cM. In subset analyses, families with average age at onset less than 65 years exhibited a maximum HLOD of 1.8 (at 138 cM) versus a maximum regional HLOD of only 0.32 in families with average age at onset of 65 years or older. Surprisingly, the subset of families with only 2-3 affected men and some evidence of male-to-male transmission of prostate cancer gave the strongest evidence of linkage to the region (HLOD = 3.24, 134 cM). For this subset, the HLOD was slightly increased (HLOD = 3.47 at 134 cM) when families used in the original published report of linkage to Xq27-28 were excluded.Conclusions: Although there was not strong support for linkage to the Xq27-28 region in the complete set of families, the subset of families with earlier age at onset exhibited more evidence of linkage than families with later onset of disease. A subset of families with 2-3 affected individuals and with some evidence of male to male disease transmission showed stronger linkage signals. Our results suggest that the genetic basis for prostate cancer in our families is much more complex than a single susceptibility locus on the X chromosome, and that future explorations of the Xq27-28 region should focus on the subset of families identified here with the strongest evidence of linkage to this region.
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| 3. |
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| 4. |
- Chen, Baoqing, et al.
(författare)
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The Long Noncoding RNA CCAT2 Induces Chromosomal Instability Through BOP1-AURKB Signaling
- 2020
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Ingår i: Gastroenterology. - : Elsevier BV. - 0016-5085 .- 1528-0012. ; 159:6, s. 2146-2162
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Tidskriftsartikel (refereegranskat)abstract
- Background & AimsChromosomal instability (CIN) is a carcinogenesis event that promotes metastasis and resistance to therapy by unclear mechanisms. Expression of the colon cancer–associated transcript 2 gene (CCAT2), which encodes a long noncoding RNA (lncRNA), associates with CIN, but little is known about how CCAT2 lncRNA regulates this cancer enabling characteristic.MethodsWe performed cytogenetic analysis of colorectal cancer (CRC) cell lines (HCT116, KM12C/SM, and HT29) overexpressing CCAT2 and colon organoids from C57BL/6N mice with the CCAT2 transgene and without (controls). CRC cells were also analyzed by immunofluorescence microscopy, γ-H2AX, and senescence assays. CCAT2 transgene and control mice were given azoxymethane and dextran sulfate sodium to induce colon tumors. We performed gene expression array and mass spectrometry to detect downstream targets of CCAT2 lncRNA. We characterized interactions between CCAT2 with downstream proteins using MS2 pull-down, RNA immunoprecipitation, and selective 2′-hydroxyl acylation analyzed by primer extension analyses. Downstream proteins were overexpressed in CRC cells and analyzed for CIN. Gene expression levels were measured in CRC and non-tumor tissues from 5 cohorts, comprising more than 900 patients.ResultsHigh expression of CCAT2 induced CIN in CRC cell lines and increased resistance to 5-fluorouracil and oxaliplatin. Mice that expressed the CCAT2 transgene developed chromosome abnormalities, and colon organoids derived from crypt cells of these mice had a higher percentage of chromosome abnormalities compared with organoids from control mice. The transgenic mice given azoxymethane and dextran sulfate sodium developed more and larger colon polyps than control mice given these agents. Microarray analysis and mass spectrometry indicated that expression of CCAT2 increased expression of genes involved in ribosome biogenesis and protein synthesis. CCAT2 lncRNA interacted directly with and stabilized BOP1 ribosomal biogenesis factor (BOP1). CCAT2 also increased expression of MYC, which activated expression of BOP1. Overexpression of BOP1 in CRC cell lines resulted in chromosomal missegregation errors, and increased colony formation, and invasiveness, whereas BOP1 knockdown reduced viability. BOP1 promoted CIN by increasing the active form of aurora kinase B, which regulates chromosomal segregation. BOP1 was overexpressed in polyp tissues from CCAT2 transgenic mice compared with healthy tissue. CCAT2 lncRNA and BOP1 mRNA or protein were all increased in microsatellite stable tumors (characterized by CIN), but not in tumors with microsatellite instability compared with nontumor tissues. Increased levels of CCAT2 lncRNA and BOP1 mRNA correlated with each other and with shorter survival times of patients.ConclusionsWe found that overexpression of CCAT2 in colon cells promotes CIN and carcinogenesis by stabilizing and inducing expression of BOP1 an activator of aurora kinase B. Strategies to target this pathway might be developed for treatment of patients with microsatellite stable colorectal tumors.
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| 5. |
- Christensen, G Bryce, et al.
(författare)
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Genome-wide linkage analysis of 1,233 prostate cancer pedigrees from the International Consortium for prostate cancer Genetics using novel sumLINK and sumLOD analyses.
- 2010
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Ingår i: The Prostate. - : Wiley. - 0270-4137 .- 1097-0045. ; 70, s. 735-744
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Prostate cancer (PC) is generally believed to have a strong inherited component, but the search for susceptibility genes has been hindered by the effects of genetic heterogeneity. The recently developed sumLINK and sumLOD statistics are powerful tools for linkage analysis in the presence of heterogeneity. METHODS: We performed a secondary analysis of 1,233 PC pedigrees from the International Consortium for Prostate Cancer Genetics (ICPCG) using two novel statistics, the sumLINK and sumLOD. For both statistics, dominant and recessive genetic models were considered. False discovery rate (FDR) analysis was conducted to assess the effects of multiple testing. RESULTS: Our analysis identified significant linkage evidence at chromosome 22q12, confirming previous findings by the initial conventional analyses of the same ICPCG data. Twelve other regions were identified with genome-wide suggestive evidence for linkage. Seven regions (1q23, 5q11, 5q35, 6p21, 8q12, 11q13, 20p11-q11) are near loci previously identified in the initial ICPCG pooled data analysis or the subset of aggressive PC pedigrees. Three other regions (1p12, 8p23, 19q13) confirm loci reported by others, and two (2p24, 6q27) are novel susceptibility loci. FDR testing indicates that over 70% of these results are likely true positive findings. Statistical recombinant mapping narrowed regions to an average of 9 cM. CONCLUSIONS: Our results represent genomic regions with the greatest consistency of positive linkage evidence across a very large collection of high-risk PC pedigrees using new statistical tests that deal powerfully with heterogeneity. These regions are excellent candidates for further study to identify PC predisposition genes. Prostate (c) 2010 Wiley-Liss, Inc.
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| 6. |
- Colvin, Christopher J, et al.
(författare)
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Understanding careseeking for child illness in sub-Saharan Africa : a systematic review and conceptual framework based on qualitative research of household recognition and response to child diarrhoea, pneumonia and malaria
- 2013
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Ingår i: Social Science and Medicine. - : Elsevier BV. - 0277-9536 .- 1873-5347. ; 86, s. 66-78
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Tidskriftsartikel (refereegranskat)abstract
- Diarrhoea, pneumonia and malaria are the largest contributors to childhood mortality in sub-Saharan Africa. While supply side efforts to deliver effective and affordable interventions are being scaled up, ensuring timely and appropriate use by caregivers remains a challenge. This systematic review synthesises qualitative evidence on the factors that underpin household recognition and response to child diarrhoea, pneumonia and malaria in sub-Saharan Africa. For this review, we searched six electronic databases, hand searched 12 journals from 1980 to 2010 using key search terms, and solicited expert review. We identified 5104 possible studies and included 112. Study quality was appraised using the Critical Appraisal Skills Program (CASP) tool. We followed a meta-ethnographic approach to synthesise findings according to three main themes: how households understand these illnesses, how social relationships affect recognition and response, and how households act to prevent and treat these illnesses. We synthesise these findings into a conceptual model for understanding household pathways to care and decision making. Factors that influence household careseeking include: cultural beliefs and illness perceptions; perceived illness severity and efficacy of treatment; rural location, gender, household income and cost of treatment. Several studies also emphasise the importance of experimentation, previous experience with health services and habit in shaping household choices. Moving beyond well-known barriers to careseeking and linear models of pathways to care, the review suggests that treatment decision making is a dynamic process characterised by uncertainty and debate, experimentation with multiple and simultaneous treatments, and shifting interpretations of the illness and treatment options, with household decision making hinging on social negotiations with a broad variety of actors and influenced by control over financial resources. The review concludes with research recommendations for tackling remaining gaps in knowledge.
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| 7. |
- Ekirapa-Kiracho, Elizabeth, et al.
(författare)
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Effect of a participatory multisectoral maternal and newborn intervention on maternal health service utilization and newborn care practices : a quasi-experimental study in three rural Ugandan districts
- 2017
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Ingår i: Global Health Action. - : Taylor & Francis. - 1654-9716 .- 1654-9880. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Background: The MANIFEST study in eastern Uganda employed a participatory multisectoral approach to reduce barriers to access to maternal and newborn care services.Objectives: This study analyses the effect of the intervention on the utilization of maternal and newborn services and care practices.Methods: The quasi-experimental pre- and post-comparison design had two main components: community mobilization and empowerment, and health provider capacity building. The primary outcomes were utilization of antenatal care (ANC), delivery and postnatal care, and newborn care practices. Baseline (n = 2237) and endline (n = 1946) data were collected from women of reproductive age. The data was analysed using difference in differences (DiD) analysis and logistic regression.Results: The DiD results revealed an 8% difference in early ANC attendance (p < 0.01) and facility delivery (p < 0.01). Facility delivery increased from 66% to 73% in the intervention area, but remained unchanged in the comparison area (64% vs 63%, p < 0.01). The DiD results also demonstrated a 20% difference in clean cord care (p < 0.001) and an 8% difference in delayed bathing (p < 0.001). The intervention elements that predicted facility delivery were attending ANC four times [adjusted odds ratio (aOR) 1.42, 95% confidence interval (CI) 1.171.74] and saving for maternal health (aOR 2.11, 95% CI 1.39-3.21). Facility delivery and village health team (VHT) home visits were key predictors for clean cord care and skin-to-skin care.Conclusions: The multisectoral approach had positive effects on early ANC attendance, facility deliveries and newborn care practices. Community resources such as VHTs and savings are crucial to maternal and newborn outcomes and should be supported. VHT-led health education should incorporate practical measures that enable families to save and access transport services to enhance adequate preparation for birth.
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| 8. |
- Ekirapa-Kiracho, Elizabeth, et al.
(författare)
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Maternal and neonatal implementation for equitable systems : a study design paper
- 2017
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Ingår i: Global Health Action. - : Taylor & Francis. - 1654-9716 .- 1654-9880. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Evidence on effective ways of improving maternal and neonatal health outcomes is widely available. The challenge that most low-income countries grapple with is implementation at scale and sustainability. Objectives: The study aimed at improving access to quality maternal and neonatal health services in a sustainable manner by using a participatory action research approach.Methods: The study consisted of a quasi-experimental design, with a participatory action research approach to implementation in three rural districts (Pallisa, Kibuku and Kamuli) in Eastern Uganda. The intervention had two main components; namely, community empowerment for comprehensive birth preparedness, and health provider and management capacity-building. We collected data using both quantitative and qualitative methods using household and facility-level structured surveys, record reviews, key informant interviews and focus group discussions. We purposively selected the participants for the qualitative data collection, while for the surveys we interviewed all eligible participants in the sampled households and health facilities. Descriptive statistics were used to describe the data, while the difference in difference analysis was used to measure the effect of the intervention. Qualitative data were analysed using thematic analysis.Conclusions: This study was implemented to generate evidence on how to increase access to quality maternal and newborn health services in a sustainable manner using a multisectoral participatory approach.
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| 9. |
- Ekirapa-Kiracho, Elizabeth, et al.
(författare)
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Unlocking community capabilities for improving maternal and newborn health : participatory action research to improve birth preparedness, health facility access, and newborn care in rural Uganda
- 2016
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Ingår i: BMC Health Services Research. - : Springer Science and Business Media LLC. - 1472-6963. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- Background: Community capacities and resources must be harnessed to complement supply side initiatives addressing high maternal and neonatal mortality rates in Uganda. This paper reflects on gains, challenges and lessons learnt from working with communities to improve maternal and newborn health in rural Uganda. Methods: A participatory action research project was supported from 2012 to 2015 in three eastern districts. This project involved working with households, saving groups, sub county and district leaders, transporters and village health teams in diagnosing causes of maternal and neonatal mortality and morbidity, developing action plans to address these issues, taking action and learning from action in a cyclical manner. This paper draws from project experience and documentation, as well as thematic analysis of 20 interviews with community and district stakeholders and 12 focus group discussions with women who had recently delivered and men whose wives had recently delivered. Results: Women and men reported increased awareness about birth preparedness, improved newborn care practices and more male involvement in maternal and newborn health. However, additional direct communication strategies were required to reach more men beyond the minority who attended community dialogues and home visits. Saving groups and other saving modalities were strengthened, with money saved used to meet transport costs, purchase other items needed for birth and other routine household needs. However saving groups required significant support to improve income generation, management and trust among members. Linkages between savings groups and transport providers improved women's access to health facilities at reduced cost. Although village health teams were a key resource for providing information, their efforts were constrained by low levels of education, inadequate financial compensation and transportation challenges. Ensuring that the village health teams and savings groups functioned required regular supervision, review meetings and payment for supervisors to visit. Conclusions: This participatory program, which focused on building the capacity of community stakeholders, was able to improve local awareness of maternal and newborn health practices and instigate local action to improve access to healthcare. Collaborative problem solving among diverse stakeholders, continuous support and a participatory approach that allowed flexibility were essential project characteristics that enabled overcoming of challenges faced.
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| 10. |
- Kamal-Eldin, Afaf, et al.
(författare)
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Dietary fiber components, microstructure, and texture of date fruits (Phoenix dactylifera, L.)
- 2020
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 10:1, s. 1-11
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Tidskriftsartikel (refereegranskat)abstract
- Date fruits vary widely in the hardness of their edible parts and they are classified accordingly into soft, semi-dry, and dry varieties. Fruit texture, a significant parameter in determining consumer acceptance, is related to the tissue structure and chemical composition of the fruit, mainly the ratio of sucrose to reducing sugars. This study aimed to understand the relationship between the chemical composition, microstructure, and texture profile of 10 major Emirati date fruits. The soluble sugars, glucose and fructose, represent ca 80 g/100 g of the fruits on the basis of dry weight (DW) while the dietary fiber contents varied 5.2-7.4 g/100 dg D.W. with lignin being the main determinant of the variability. The textures of the samples were studied using instrumental texture profile analysis. While no correlation was found between the soluble sugar and texture parameters in this study, the different fiber constituents correlated variably with the different parameters of date fruit texture. Lignin, arabinoxylan, galactomannan, and pectin were found to correlate significantly with fruit hardness and the related parameters, gumminess and chewiness. Both lignin and arabinoxylan correlated with resilience, and arabinoxylan exhibited a strong correlation with cohesiveness.
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| 11. |
- McGorman, Laura, et al.
(författare)
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A Health Systems Approach to Integrated Community Case Management of Childhood Illness : Methods and Tools
- 2012
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Ingår i: American Journal of Tropical Medicine and Hygiene. - : American Society of Tropical Medicine and Hygiene. - 0002-9637 .- 1476-1645. ; 87:suppl 5, s. 69-76
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Tidskriftsartikel (refereegranskat)abstract
- Integrated community case management (iCCM) of childhood illness is an increasingly popular strategy to expand life-saving health services to underserved communities. However, community health approaches vary widely across countries and do not always distribute resources evenly across local health systems. We present a harmonized framework, developed through interagency consultation and review, which supports the design of CCM by using a systems approach. To verify that the framework produces results, we also suggest a list of complementary indicators, including nine global metrics, and a menu of 39 country-specific measures. When used by program managers and evaluators, we propose that the framework and indicators can facilitate the design, implementation, and evaluation of community case management.
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| 12. |
- Paina, Ligia, et al.
(författare)
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Using Theories of Change to inform implementation of health systems research and innovation : experiences of Future Health Systems consortium partners in Bangladesh, India and Uganda
- 2017
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Ingår i: Health Research Policy and Systems. - : BioMed Central. - 1478-4505. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- Background: The Theory of Change (ToC) is a management and evaluation too ! supporting critical thinking in the design, implementation and evaluation of development programmes. We document the experience of Future Health Systems (FHS) Consortium research teams in Bangladesh, India and Uganda with using ToC. We seek to understand how and why ToCs were applied and to clarify how they facilitate the implementation of iterative intervention designs and stakeholder engagement in health systems research and strengthening.Methods: This paper combines literature on ToC, with a summary of reflections by FHS research members on the motivation, development, revision and use of the ToC, as well as on the benefits and challenges of the process. We describe three FHS teams' experiences along four potential uses of ToCs, namely planning, communication, learning and. accountability.Results: The three teams developed ToCs for planning and. evaluation purposes as required for their initial plans for FHS in 2011 and. revised, them half-way through the project, based on assumptions informed, by and adjusted, through the teams' experiences during the previous 2 years of implementation. All teams found that the revised ToCs and their accompanying narratives recognised greater feedback among intervention components and among key stakeholders. The ToC development and. revision fostered, channels for both internal and external communication, among research team members and. with key stakeholders, respectively. The process of revising the ToCs challenged the teams' initial assumptions based on new evidence and experience. In contrast, the ToCs were only minimally used for accountability purposes.Conclusions: The ToC development and revision process helped FHS research teams, and occasionally key local stakeholders, to reflect on and make their assumptions and mental models about their respective interventions explicit. Other projects using the ToC should allow time for revising and reflecting upon the ToCs, to recognise and document the adaptive nature of health systems, and to foster the time, space and flexibility that health systems strengthening programmes must have to learn from implementation and stakeholder engagement.
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| 13. |
- Schneider, Helen, et al.
(författare)
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The Multiple Lenses on the Community Health System : Implications for Policy, Practice and Research
- 2022
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Ingår i: International Journal of Health Policy and Management. - : Kerman University of Medical Science. - 2322-5939. ; 11:1, s. 9-16
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Tidskriftsartikel (refereegranskat)abstract
- Community health systems (CHSs) have historically been approached from multiple perspectives, with different purposes and methodological and disciplinary orientations. The terrain is, on the one hand, vast and diverse. On the other hand, under the banner of universal health coverage (UHC) and the Sustainable Development Goals (SDGs), a streamlined version of 'community health' is increasingly being consolidated in global health and donor communities. With the view to informing debate and practice, this paper seeks to synthesise approaches to the CHS into a set of 'lenses,' drawing on the collective and multi-disciplinary knowledge (both formal and experiential) of the authors, a collaborative network of 23 researchers from seven institutions across six countries (spanning low, middle and high income). With a common view of the CHS as a complex adaptive system, we propose four key lenses, referred to as programmatic, relational, collective action and critical lenses. The lenses represent different positionalities in community health, encompassing macro-level policy-maker, front-line and community vantage points, and purposes ranging from social justice to instrumental goals. We define and describe the main elements of each lens and their implications for thinking about policy, practice and research. Distilling a set of key lenses offers a way to make sense of a complex terrain, but also counters what may emerge as a dominant, single narrative on the CHS in global health. By making explicit and bringing together different lenses on the CHS, the limits and possibilities of each may be better appreciated, while promoting integrative, systems thinking in policy, practice and research.
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| 14. |
- Tetui, Moses, et al.
(författare)
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A participatory action research approach to strengthening health managers' capacity at district level in Eastern Uganda
- 2017
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Ingår i: Health Research Policy and Systems. - : BioMed Central. - 1478-4505. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- Background: Many approaches to improving health managers' capacity in poor countries, particularly those pursued by external agencies, employ non-participatory approaches and often seek to circumvent (rather than strengthen) weak public management structures. This limits opportunities for strengthening local health managers' capacity, improving resource utilisation and enhancing service delivery. This study explored the contribution of a participatory action research approach to strengthening health managers' capacity in Eastern Uganda.Methods: This was a qualitative study that used open-ended key informant interviews, combined with review of meeting minutes and observations to collect data. Both inductive and deductive thematic analysis was undertaken. The Competing Values Framework of organisational management functions guided the deductive process of analysis and the interpretation of the findings. The framework builds on four earlier models of management and regards them as complementary rather than conflicting, and identifies four managers' capacities (collaborate, create, compete and control) by categorising them along two axes, one contrasting flexibility versus control and the other internal versus external organisational focus.Results: The findings indicate that the participatory action research approach enhanced health managers' capacity to collaborate with others, be creative, attain goals and review progress. The enablers included expanded interaction spaces, encouragement of flexibility, empowerment of local managers, and the promotion of reflection and accountability. Tension and conflict across different management functions was apparent; for example, while there was a need to collaborate, maintaining control over processes was also needed. These tensions meant that managers needed to learn to simultaneously draw upon and use different capacities as reflected by the Competing Values Framework in order to maximise their effectiveness.Conclusions: Improved health manager capacity is essential if sustained improvements in health outcomes in low-income countries are to be attained. The expansion of interaction spaces, encouragement of flexibility, empowerment of local managers, and the promotion of reflection and accountability were the key means by which participatory action research strengthened health managers' capacity. The participatory approach to implementation therefore created opportunities to strengthen health managers' capacity.
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| 15. |
- Zulu, Joseph M., et al.
(författare)
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Integrating community health assistant-driven sexual and reproductive health services in the community health system in Nyimba district in Zambia : mapping key actors, points of integration, and conditions shaping the process
- 2019
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Ingår i: Reproductive Health. - : BioMed Central. - 1742-4755. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Although large scale public sector community health worker programs have been key in providing sexual and reproductive health (SRH) services in low- and middle-income countries, their integration process into community health systems is not well understood. This study aimed to identify the conditions and strategies through which Community Health Assistants (CHAs) gained entry and acceptability into community health systems to provide SRH services to youth in Zambia. The country's CHA program was launched in 2010.Methodology: A phenomenological design was conducted in Nyimba district. All nine CHAs deployed in Nyimba district were interviewed in-depth on their experiences of navigating the introduction of SRH services for youth in community settings, and the data obtained analyzed thematically.Results: In delivering SRH services targeting youth, CHAs worked with a range of community actors, including other health workers, safe motherhood action groups, community health workers, neighborhood health committees, teachers, as well as political, traditional and religious leaders. CHAs delivered SRH education and services in health facilities, schools, police stations, home settings, and community spaces. They used their health facility service delivery role to gain trust and entry into the community, and they also worked to build relationships with other community level actors by holding regular joint meetings, and acting as brokers between the volunteer health workers and the Ministry of Health. CHAs used their existing social networks to deliver SRH services to adolescents. By embedding the provision of information about SRH into general life skills at community level, the topic's sensitivity was reduced and its acceptability was enhanced. Further, support from community leaders towards CHA-driven services promoted the legitimacy of providing SRH for youth. Factors limiting the acceptability of CHA services included the taboo of discussing sexuality issues, a gender discriminatory environment, competition with other providers, and challenges in conducting household visits.Conclusion: Strengthening CHAs' ability to negotiate and navigate and gain acceptability in the community health system as they deliver SRH, requires support from both the formal health system and community networks. Limitations to the acceptability of CHA-driven SRH services are a product of challenges both in the community and in the formal health system.
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