Can Action Research Strengthen District Health Management and Improve Health Workforce Performance? A Research Protocol.

The single biggest barrier for countries in sub-Saharan Africa (SSA) to scale up the necessary health services for addressing the three health-related Millennium Development Goals and achieving Universal Health Coverage is the lack of an adequate and well-performing health workforce. This deficit needs to be addressed both by training more new health personnel and by improving the performance of the existing and future health workforce. However, efforts have mostly been focused on training new staff and less on improving the performance of the existing health workforce. The purpose of this paper is to disseminate the protocol for the PERFORM project and reflect on the key challenges encountered during the development of this methodology and how they are being overcome. The overall aim of the PERFORM project is to identify ways of strengthening district management in order to address health workforce inadequacies by improving health workforce performance in SSA. The study will take place in three districts each in Ghana, Tanzania and Uganda using an action research approach. With the support of the country research teams, the district health management teams (DHMTs) will lead on planning, implementation, observation, reflection and redefinition of the activities in the study. Taking into account the national and local human resource (HR) and health systems (HS) policies and practices already in place, 'bundles' of HR/HS strategies that are feasible within the context and affordable within the districts' budget will be developed by the DHMTs to strengthen priority areas of health workforce performance. A comparative analysis of the findings from the three districts in each country will add new knowledge on the effects of these HR/HS bundles on DHMT management and workforce performance and the impact of an action research approach on improving the effectiveness of the DHMTs in implementing these interventions. Different challenges were faced during the development of the methodology. These include the changing context in the study districts, competing with other projects and duties for the time of district managers, complexity of the study design, maintaining the anonymity and confidentiality of study participants as well as how to record the processes during the study. We also discuss how these challenges are being addressed. The dissemination of this research protocol is intended to generate interest in the PERFORM project and also stimulate discussion on the use of action research in complex studies such as this on strengthening district health management to improve health workforce performance

Exploring what lies behind public preferences for avoiding health losses caused by lapses in healthcare safety and patient lifestyle choices

© 2013 Singh et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0),which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.This article has been made available through the Brunel Open Access Publishing Fund.Background: Although many studies have identified public preferences for prioritising health care interventions based on characteristics of recipient or care, very few of them have examined the reasons for the stated preferences. We conducted an on-line person trade-off (PTO) study (N=1030) to investigate whether the public attach a premium to the avoidance of ill health associated with alternative types of responsibilities: lapses in healthcare safety, those caused by individual action or lifestyle choice; or genetic conditions. We found that the public gave higher priority to prevention of harm in a hospital setting such as preventing hospital associated infections than genetic disorder but drug administration errors were valued similar to genetic disorders. Prevention of staff injuries, lifestyle diseases and sports injuries, were given lower priority. In this paper we aim to understand the reasoning behind the responses by analysing comments provided by respondents to the PTO questions. Method: A majority of the respondents who participated in the survey provided brief comments explaining preferences in free text responses following PTO questions. This qualitative data was transformed into explicit codes conveying similar meanings. An overall coding framework was developed and a reliability test was carried out. Recurrent patterns were identified in each preference group. Comments which challenged the assumptions of hypothetical scenarios were also investigated. Results: NHS causation of illness and a duty of care were the most cited reasons to prioritise lapses in healthcare safety. Personal responsibility dominated responses for lifestyle related contexts, and many respondents mentioned that health loss was the result of the individual’s choice to engage in risky behaviour. A small proportion of responses questioned the assumptions underlying the PTO questions. However excluding these from the main analysis did not affect the conclusions. Conclusion: Although some responses indicated misunderstanding or rejection of assumptions we put forward, the results were still robust. The reasons put forward for responses differed between comparisons but responsibility was the most frequently cited. Most preference elicitation studies only focus on eliciting numerical valuations but allowing for qualitative data can augment understanding of preferences as well as verifying results.EPSRC through the MATCH programme(EP/F063822/1 and EP/G012393/1) and HERG within Brunel University

Inhibition of Aβ42 aggregation using peptides selected from combinatorial libraries

Increasing evidence suggests that the aggregation of the small peptide Aβ42 plays an important role in the development of Alzheimer’s disease. Inhibiting the initial aggregation of Aβ42 may be an effective treatment for preventing, or slowing, the onset of the disease. Using an in vivo screen based on the enzyme EGFP, we have searched through two combinatorially diverse peptide libraries to identify peptides capable of inhibiting Aβ42 aggregation. From this initial screen, three candidate peptides were selected and characterized. ThT studies indicated that the selected peptides were capable of inhibiting amyloid aggregation. Additional ThT studies showed that one of the selected peptides was capable of disaggregating preformed Aβ42 fibers

Enhancement of Cardiac Store Operated Calcium Entry (SOCE) within Novel Intercalated Disk Microdomains in Arrhythmic Disease

Store-operated Ca2+ entry (SOCE), a major Ca2+ signaling mechanism in non-myocyte cells, has recently emerged as a component of Ca2+ signaling in cardiac myocytes. Though it has been reported to play a role in cardiac arrhythmias and to be upregulated in cardiac disease, little is known about the fundamental properties of cardiac SOCE, its structural underpinnings or effector targets. An even greater question is how SOCE interacts with canonical excitation-contraction coupling (ECC). We undertook a multiscale structural and functional investigation of SOCE in cardiac myocytes from healthy mice (wild type; WT) and from a genetic murine model of arrhythmic disease (catecholaminergic ventricular tachycardia; CPVT). Here we provide the first demonstration of local, transient Ca2+ entry (LoCE) events, which comprise cardiac SOCE. Although infrequent in WT myocytes, LoCEs occurred with greater frequency and amplitude in CPVT myocytes. CPVT myocytes also evidenced characteristic arrhythmogenic spontaneous Ca2+ waves under cholinergic stress, which were effectively prevented by SOCE inhibition. In a surprising finding, we report that both LoCEs and their underlying protein machinery are concentrated at the intercalated disk (ID). Therefore, localization of cardiac SOCE in the ID compartment has important implications for SOCE-mediated signaling, arrhythmogenesis and intercellular mechanical and electrical coupling in health and disease

Mucin (Muc) expression during pancreatic cancer progression in spontaneous mouse model: potential implications for diagnosis and therapy.

BACKGROUND: Pancreatic cancer (PC) is a lethal malignancy primarily driven by activated Kras mutations and characterized by the deregulation of several genes including mucins. Previous studies on mucins have identified their significant role in both benign and malignant human diseases including PC progression and metastasis. However, the initiation of MUC expression during PC remains unknown because of lack of early stage tumor tissues from PC patients. METHODS: In the present study, we have evaluated stage specific expression patterns of mucins during mouse PC progression in (Kras(G12D);Pdx1-Cre (KC)) murine PC model from pancreatic intraepithelial neoplasia (PanIN) to pancreatic ductal adenocarcinoma (PDAC) by immunohistochemistry and quantitative real-time PCR. RESULTS: In agreement with previous studies on human PC, we observed a progressive increase in the expression of mucins particularly Muc1, Muc4 and Muc5AC in the pancreas of KC (as early as PanIN I) mice with advancement of PanIN lesions and PDAC both at mRNA and protein levels. Additionally, mucin expression correlated with the increased expression of inflammatory cytokines IFN-γ (p \u3c 0.0062), CXCL1 (p \u3c 0.00014) and CXCL2 (p \u3c 0.08) in the pancreas of KC mice, which are known to induce mucin expression. Further, we also observed progressive increase in inflammation in pancreas of KC mice from 10 to 50 weeks of age as indicated by the increase in the macrophage infiltration. Overall, this study corroborates with previous human studies that indicated the aberrant overexpression of MUC1, MUC4 and MUC5AC mucins during the progression of PC. CONCLUSIONS: Our study reinforces the potential utility of the KC murine model for determining the functional role of mucins in PC pathogenesis by crossing KC mice with corresponding mucin knockout mice and evaluating mucin based diagnostic and therapeutic approaches for lethal PC

Artificial reefs: from ecological processes to fishing enhancement tools

info:eu-repo/semantics/publishedVersio

Smoking accelerates pancreatic cancer progression by promoting differentiation of MDSCs and inducing HB-EGF expression in macrophages

Smoking is an established risk factor for pancreatic cancer (PC), but late diagnosis limits the evaluation of its mechanistic role in the progression of PC. We used a well-established genetically engineered mouse model (LSL-K-rasG12D) of PC to elucidate the role of smoking during initiation and development of pancreatic intraepithelial neoplasia (PanIN). The 10-week-old floxed mice (K-rasG12D; Pdx-1cre) and their control unfloxed (LSL-K-rasG12D) littermates were exposed to cigarette smoke (total suspended particles: 150 mg/m3) for 20 weeks. Smoke exposure significantly accelerated the development of PanIN lesions in the floxed mice, which correlated with tenfold increase in the expression of cytokeratin19. The systemic accumulation of myeloid-derived suppressor cells (MDSCs) decreased significantly in floxed mice compared with unfloxed controls (P\u3c0.01) after the smoke exposure with the concurrent increase in the macrophage (P\u3c0.05) and dendritic cell (DCs) (P\u3c0.01) population. Further, smoking-induced inflammation (IFN-γ, CXCL2; P\u3c0.05) was accompanied by enhanced activation of pancreatic stellate cells and elevated levels of serum retinoic acid-binding protein 4, indicating increased bioavailability of retinoic acid which contributes to differentiation of MDSCs to tumor-associated macrophages (TAMs) and DCs. TAMs predominantly contribute to the increased expression of heparin-binding epidermal growth factor-like growth factor (EGFR ligand) in pre-neoplastic lesions in smoke-exposed floxed mice that facilitate acinar-to-ductal metaplasia (ADM). Further, smoke exposure also resulted in partial suppression of the immune system early during PC progression. Overall, the present study provides a novel mechanism of smoking-induced increase in ADM in the presence of constitutively active K-ras mutation

Application of Acoustic Telemetry to Assess Residency and Movements of Rockfish and Lingcod at Created and Natural Habitats in Prince William Sound

Loss and/or degradation of nearshore habitats have led to increased efforts to restore or enhance many of these habitats, particularly those that are deemed essential for marine fishes. Copper rockfish (Sebastes caurinus) and lingcod (Ophiodon enlongatus) are dominant members of the typical reef fish community that inhabit rocky and high-relief substrates along the Pacific Northwest. We used acoustic telemetry to document their residency and movements in the nearshore waters of Prince William Sound, Alaska in order to assess use of created reef habitat in an individual-based manner. A total of 57 fish were surgically implanted with acoustic transmitters. Forty-five fish were captured and monitored in three habitats: artificial reef, low-relief natural reef, and patchy high-relief natural reef. Within each habitat, both rockfish and lingcod exhibited long periods of residency with limited movements. Twelve rockfish were captured at the natural reefs and displaced a distance of 4.0 km to the artificial reef. Five of the 12 rockfish returned within 10 d of their release to their initial capture site. Another five of the 12 displaced fish established residency at the artificial reef through the duration of our study. Our results suggest the potential for artificial reefs to provide rockfish habitat in the event of disturbances to natural habitat

Sex differences in the impact of ozone on survival and alveolar macrophage function of mice after Klebsiella pneumoniae infection

<p>Abstract</p> <p>Background</p> <p>Sex differences have been described in a number of pulmonary diseases. However, the impact of ozone exposure followed by pneumonia infection on sex-related survival and macrophage function have not been reported. The purpose of this study was to determine whether ozone exposure differentially affects: 1) survival of male and female mice infected with <it>Klebsiella pneumoniae</it>, and 2) the phagocytic ability of macrophages from these mice.</p> <p>Methods</p> <p>Male and female C57BL/6 mice were exposed to O₃or to filtered air (FA) (control) and then infected intratracheally with <it>K. pneumoniae </it>bacteria. Survival was monitored over a 14-day period, and the ability of alveolar macrophages to phagocytize the pathogen <it>in vivo </it>was investigated after 1 h.</p> <p>Results</p> <p>1) Both male and female mice exposed to O₃are significantly more susceptible to <it>K. pneumoniae </it>infection than mice treated with FA; 2) although females appeared to be more resistant to <it>K. pneumoniae </it>than males, O₃exposure significantly increased the susceptibility of females to <it>K. pneumoniae </it>infection to a greater degree than males; 3) alveolar macrophages from O₃-exposed male and female mice have impaired phagocytic ability compared to macrophages from FA-exposed mice; and 4) the O₃-dependent reduction in phagocytic ability is greater in female mice.</p> <p>Conclusion</p> <p>O₃exposure reduces the ability of mice to survive <it>K. pneumoniae </it>infection and the reduced phagocytic ability of alveolar macrophages may be one of the contributing factors. Both events are significantly more pronounced in female mice following exposure to the environmental pollutant, ozone.</p