: To describe the use and reporting of Health Impact Assessment (HIA) in Australia and New Zealand between 2005 and 2009.
: We identified 115 HIAs undertaken in Australia and New Zealand between 2005 and 2009. We reviewed 55 HIAs meeting the study's inclusion criteria to identify characteristics and appraise the quality of the reports.
: Of the 55 HIAs, 31 were undertaken in Australia and 24 in New Zealand. The HIAs were undertaken on plans (31), projects (12), programs (6) and policies (6). Compared to Australia, a higher proportion of New Zealand HIAs were on policies and plans and were rapid assessments done voluntarily to support decision-making. In both countries, most HIAs were on land use planning proposals. Overall, 65% of HIA reports were judged to be adequate.
: This study is the first attempt to empirically investigate the nature of the broad range of HIAs done in Australia and New Zealand and has highlighted the emergence of HIA as a growing area of public health practice. It identifies areas where current practice could be improved and provides a baseline against which future HIA developments can be assessed.
There is evidence that HIA is becoming a part of public health practice in Australia and New Zealand across a wide range of policies, plans and projects. The assessment of quality of reports allows the development of practical suggestions on ways current practice may be improved. The growth of HIA will depend on ongoing organisation and workforce development in both countries.
Health Impact Assessment; Australia; New Zealand; audit
We evaluate the effect of pre-Katrina housing tenure and post-disaster financial resources on the odds of housing displacement after Hurricane Katrina for a sample of low-income African-American mothers.
Using longitudinal data from a sample of low-income African-American mothers with pre-Katrina measures of housing tenure and individual characteristics and post-Katrina indicators of disaster impacts, we estimate a multinomial logistic regression model predicting post-Katrina housing outcomes.
Among low-income African-American mothers, homeowners’ odds of being in their pre-Katrina home rather than a new home are greater than those of renters, while renters’ odds of being in a pre-Katrina home are greater than those of subsidized housing residents, ceteris paribus. The difference in homeowners’ and renters’ odds is reduced to insignificance when access to private insurance is added to the model, although the difference for subsidized housing residents remains.
Homeownership and disaster assistance protect against housing displacement. Renters, especially those in subsidized housing, were more vulnerable to housing loss after this disaster.
Supplemental Digital Content is available in the text.
A polymorphism in the receptor for the Fc region of IgG, Fc γ-receptor IIIa (FcγRIIIa, FCGR3A rs396991), has been inconsistently shown in the literature to have an effect on response to monoclonal antibody therapy in several indications. The rs396991 (T/G) polymorphism leads to an F176V substitution and increased affinity for IgG. This variant has proven difficult to genotype accurately, primarily because of extensive homology between the FCGR3A and FCGR3B genes. We have shown that rs396991 can be genotyped by PCR amplification, followed by direct Sanger sequencing of the product, without coamplification of FCGR3B, and that the rs396991 TaqMan assay (C__25815666_10) agrees with Sanger sequencing results in 100% of European and Asian samples tested, but it has a small error rate in African and American populations. C__25815666_10 is therefore suitable to interrogate rs396991 in studies involving Europeans and Asians; however for other populations, the default genotyping method should be PCR followed by Sanger sequencing.
F176V; Fc gamma receptor IIIa; TaqMan; FCGR3A; FCGR3B; genotyping; rs396991
While many guidelines explain how to conduct Health Impact Assessments (HIAs), less is known about the factors that determine the extent to which HIAs affect health considerations in the decision making process. We investigated which factors are associated with increased or reduced effectiveness of HIAs in changing decisions and in the implementation of policies, programs or projects. This study builds on and tests the Harris and Harris-Roxas’ conceptual framework for evaluating HIA effectiveness, which emphasises context, process and output as key domains.
We reviewed 55 HIA reports in Australia and New Zealand from 2005 to 2009 and conducted surveys and interviews for 48 of these HIAs. Eleven detailed case studies were undertaken using document review and stakeholder interviews. Case study participants were selected through purposeful and snowball sampling. The data were analysed by thematic content analysis. Findings were synthesised and mapped against the conceptual framework. A stakeholder forum was utilised to test face validity and practical adequacy of the findings.
We found that some features of HIA are essential, such as the stepwise but flexible process, and evidence based approach. Non-essential features that can enhance the impact of HIAs include capacity and experience; ‘right person right level’; involvement of decision-makers and communities; and relationships and partnerships. There are contextual factors outside of HIA such as fit with planning and decision making context, broader global context and unanticipated events, and shared values and goals that may influence a HIA. Crosscutting factors include proactive positioning, and time and timeliness. These all operate within complex open systems, involving multiple decision-makers, levels of decision-making, and points of influence. The Harris and Harris-Roxas framework was generally supported.
We have confirmed previously identified factors influencing effectiveness of HIA and identified new factors such as proactive positioning. Our findings challenge some presumptions about ‘right’ timing for HIA and the rationality and linearity of decision-making processes. The influence of right timing on decision making needs to be seen within the context of other factors such as proactive positioning. This research can help HIA practitioners and researchers understand and identify what can be enhanced within the HIA process. Practitioners can adapt the flexible HIA process to accommodate the external contextual factors identified in this report.
Electronic supplementary material
The online version of this article (doi:10.1186/s12889-015-2319-8) contains supplementary material, which is available to authorized users.
Health impact assessment; Effectiveness; Australia; New Zealand; Case studies
The green alga Chlamydomonas reinhardtii is a popular unicellular organism for studying photosynthesis, cilia biogenesis and micronutrient homeostasis. Ten years since its genome project was initiated, an iterative process of improvements to the genome and gene predictions has propelled this organism to the forefront of the “omics” era. Housed at Phytozome, the Joint Genome Institute’s (JGI) plant genomics portal, the most up-to-date genomic data include a genome arranged on chromosomes and high-quality gene models with alternative splice forms supported by an abundance of RNA-Seq data. Here, we present the past, present and future of Chlamydomonas genomics. Specifically, we detail progress on genome assembly and gene model refinement, discuss resources for gene annotations, functional predictions and locus ID mapping between versions and, importantly, outline a standardized framework for naming genes.
Chlamydomonas; algae; nomenclature; gene symbols; Phytozome; annotation
Supplementation with vitamins, minerals and phytonutrients may be beneficial for cognition, especially in older adults. The aim of this study was to assess the effects of multivitamin supplementation in older adults on cognitive function and associated blood biomarkers. In a randomised, double blind, placebo-controlled trial, healthy women (n = 68) and men (n = 48) aged 55–65 years were supplemented daily for 16 weeks with women’s and men’s formula multivitamin supplements. Assessments at baseline and post-supplementation included computerised cognitive tasks and blood biomarkers relevant to cognitive aging. No cognitive improvements were observed after supplementation with either formula; however, several significant improvements were observed in blood biomarkers including increased levels of vitamins B6 and B12 in women and men; reduced C-reactive protein in women; reduced homocysteine and marginally reduced oxidative stress in men; as well as improvements to the lipid profile in men. In healthy older people, multivitamin supplementation improved a number of blood biomarkers that are relevant to cognition, but these biomarker changes were not accompanied by improved cognitive function.
multivitamins; vitamins; cognition; biomarkers
There is a lack of research investigating long-term effects of exercise training upon the body composition and muscle function in HIV-infected patients (PHIV). The study investigated the influence of a 2-year supervised exercise program on body composition and strength of PHIV under highly active antiretroviral therapy (HAART).
A training program including aerobic, strength and flexibility exercises was performed by 27 PHIV (17 men/ 10 women; age: 48.7±7.0 years; HAART: 150.7±65.3 months) during 1 year and 18 PHIV (10 men/ 8 women; age: 50.6±5.2 years; HAART: 176.6±53.1 months) during 2 years. Body composition and knee isokinetic strength were assessed at baseline and at the end of each year of intervention.
Body composition remained stable along the whole experiment vs baseline (1-year - total muscle mass: Δ men=1.1%, P=0.21; Δ women=1.4%, P=0.06; trunk fat: Δ men=-0.1%, P=0.65; Δ women=-1.5%, P=0.45; 2 years - total muscle mass: Δ men=2.7%, P=0.54; Δ women=-1.9%, P=0.71; trunk fat: Δ men=4.4%, P=0.96; Δ women=10.0%, P=0.30). After 1-year, peak torque increased in men (Δ extension=4.2%, P=0.01; Δ flexion=12.2%, P=0.04) and total work reduced in women (Δ extension=-15.4%, P=0.01, Δ flexion=-17.5%, P=0.05). All strength markers remained stable vs baseline after 2 years of intervention (P>0.05). Only men showed significant reduction in the risk of disability due to sarcopenia (P=0.05) after 1 year of intervention, which remained stable after 2 years.
Long-term exercise training preserved strength and muscle mass in PHIV under HAART. Exercise programs should be part of HIV therapy to prevent sarcopenia of this population along the years.
Trial Registration :
ACTRN12610000683033; UTN U1111-1116-4416.
AIDS; fitness; HAART; health; muscle mass; physical activity; strength
Policy decisions made within all sectors have the potential to influence population health and equity. Recognition of this provides impetus for the health sector to engage with other sectors to facilitate the development of policies that recognise, and aim to improve, population outcomes. This paper compares the approaches implemented to facilitate such engagement in two Australian jurisdictions. These are Health Impact Assessment (HIA) in New South Wales (NSW) and Health in All Policies (HiAP) in South Australia (SA).
The comparisons presented in this paper emerged through collaborative activities between stakeholders in both jurisdictions, including critical reflection on HIA and HiAP practice, joint participation in a workshop, and the preparation of a discussion paper written to inform a conference plenary session. The plenary provided an opportunity for the incorporation of additional insights from policy practitioners and academics.
Comparison of the approaches indicates that their overall intent is similar. Differences exist, however, in the underpinning principles, technical processes and tactical strategies applied. These differences appear to stem mainly from the organisational positioning of the work in each state and the extent to which each approach is linked to government systems.
The alignment of the HiAP approach with the systems of the SA Government increases the likelihood of influence within the policy cycle. However, the political priorities and sensitivities of the SA Government limit the scope of HiAP work. The implementation of the HIA approach from outside government in NSW means greater freedom to collaborate with a range of partners and to assess policy issues in any area, regardless of government priorities. However, the comparative distance of HIA from NSW Government systems may reduce the potential for impact on government policy. The diversity in the technical and tactical strategies that are applied within each approach provides insight into how the approaches have been tailored to suit the particular contexts in which they have been implemented.
Health in all policies; Health impact assessment; Healthy public policy
Health Impact Assessment (HIA) involves assessing how proposals may alter the determinants of health prior to implementation and recommends changes to enhance positive and mitigate negative impacts. HIAs growing use needs to be supported by a strong evidence base, both to validate the value of its application and to make its application more robust. We have carried out the first systematic empirical study of the influence of HIA on decision-making and implementation of proposals in Australia and New Zealand. This paper focuses on identifying whether and how HIAs changed decision-making and implementation and impacts that participants report following involvement in HIAs.
We used a two-step process first surveying 55 HIAs followed by 11 in-depth case studies. Data gathering methods included questionnaires with follow-up interview, semi-structured interviews and document collation. We carried out deductive and inductive qualitative content analyses of interview transcripts and documents as well as simple descriptive statistics.
We found that most HIAs are effective in some way. HIAs are often directly effective in changing, influencing, broadening areas considered and in some cases having immediate impact on decisions. Even when HIAs are reported to have no direct effect on a decision they are often still effective in influencing decision-making processes and the stakeholders involved in them. HIA participants identify changes in relationships, improved understanding of the determinants of health and positive working relationships as major and sustainable impacts of their involvement.
This study clearly demonstrates direct and indirect effectiveness of HIA influencing decision making in Australia and New Zealand. We recommend that public health leaders and policy makers should be confident in promoting the use of HIA and investing in building capacity to undertake high quality HIAs. New findings about the value HIA stakeholders put on indirect impacts such as learning and relationship building suggest HIA has a role both as a technical tool that makes predictions of potential impacts of a policy, program or project and as a mechanism for developing relationships with and influencing other sectors. Accordingly when evaluating the effectiveness of HIAs we need to look beyond the direct impacts on decisions.
Health impact assessment; Effectiveness; Evaluation
Advances in the molecular characterisation of genetic muscle disease has been rapid, as demonstrated by a recent analysis of these conditions in the north of England by Norwood et al (2009), in which a genetic diagnosis was achieved for 75.7% of patients. However, there remain many patients with suspected genetic muscle disease in who a diagnosis is not obtained, often despite considerable diagnostic effort, and these patients are now being considered for the application of new technologies such as next generation sequencing. This study aimed to provide an in-depth phenotype analysis of undiagnosed patients referred to the Northern region muscle clinic with suspected genetic muscle disease, with the intention of gaining insight into these conditions, identifing cases with a shared phenotype who may be amenable to collective diagnostic testing or research, and evaluating the strengths and limitations of our current diagnostic strategy. We used two approaches: a review of clinical findings in patients with undiagnosed muscle disease, and a hierarchical cluster analysis to provide an unbiased interpretation of the phenotype data. These joint approaches identified a correlation of phenotypic features according to the age of disease onset and also delineated several interesting groups of patients, as well as highlighting areas of frequent diagnostic difficulty that could benefit from the use of new high-throughput diagnostic techniques.
Correspondence to: firstname.lastname@example.org
The formation and function of eukaryotic cilia/flagella require the action of a large array of dynein microtubule motor complexes. Due to genetic, biochemical, and microscopic tractability, Chlamydomonas reinhardtii has become the premier model system in which to dissect the role of dyneins in flagellar assembly, motility, and signaling. Currently, fifty-four proteins have been described as components of various Chlamydomonas flagellar dyneins or as factors required for their assembly in the cytoplasm and/or transport into the flagellum; orthologues of nearly all these components are present in other ciliated organisms including humans. For historical reasons, the nomenclature of these diverse dynein components and their corresponding genes, mutant alleles and orthologues has become extraordinarily confusing. Here, we unify Chlamydomonas dynein gene nomenclature and establish a systematic classification scheme based on structural properties of the encoded proteins. Furthermore, we provide detailed tabulations of the various mutant alleles and protein aliases that have been used and explicitly define the correspondence with orthologous components in other model organisms and humans.
Chlamydomonas; Cilia; Dynein; Flagella; Microtubule
There is little data on the impact of office-based buprenorphine therapy on criminal activity. The goal of this study was to determine the impact of primary care clinic-based buprenorphine maintenance therapy on rates of criminal charges and the factors associated with criminal charges in the 2 years after initiation of treatment.
We collected demographic and outcome data on 252 patients who were given at least one prescription for buprenorphine. We searched a public database of criminal charges and recorded criminal charges prior to and after enrollment. We compared the total number of criminal cases and drug cases 2 years before versus 2 years after initiation of treatment.
There was at least one criminal charge made against 38% of the subjects in the 2 years after initiation of treatment; these subjects were more likely to have used heroin, to have injected drugs, to have had any prior criminal charges, and recent criminal charges. There was no significant difference in the number of subjects with any criminal charge or a drug charge before and after initiation of treatment. Likewise, the mean number of all cases and drug cases was not significantly different between the two periods. However, among those who were opioid-negative for 6 or more months in the first year of treatment, there was a significant decline in criminal cases. On multivariable analysis, having recent criminal charges was significantly associated with criminal charges after initiation of treatment (adjusted odds ratio 3.92); subjects who were on opioid maintenance treatment prior to enrollment were significantly less likely to have subsequent criminal charges (adjusted odds ratio 0.52).
Among subjects with prior criminal charges, initiation of office-based buprenorphine treatment did not appear to have a significant impact on subsequent criminal charges.
Opioid-related disorders; Crime; Primary health care; Buprenorphine
To investigate pediatric chief residents' responsibilities and determine
how chief residents and program directors view the scope of the chief
We distributed a 20-item survey to program directors and chief residents at
all US pediatric residency programs. Questions pertained to activities
performed and the level of importance of administrative, clinical, and
educational activities. The survey also investigated motivating factors to
become chief resident, future career plans, and level of job
We received responses from 127 program directors and 101 chief residents. Of
the chief residents, 98% (99/101) felt administrative tasks were
very/somewhat important, followed by education, service, and research.
Significantly more program directors than chief residents felt chiefs'
overall workload was well balanced. Program directors gave higher ratings
than chief residents on chief's ability to develop clinical skills
(79% [95/121] versus 61% [61/100]) and
manage stress and burnout (86% [104/121] versus 72%
[72/100]). Future career plans for chief residents in decreasing
order included fellowship, outpatient practice, academic practice, and
working as a hospitalist. The most significant problems reported by the
chief residents were lack of administrative support and lack of time spent
in educational/clinical activities.
The chief resident role is primarily administrative, but program directors
and chiefs feel teaching and clinical responsibilities also are important.
Although the 2 groups agreed in many areas, program directors underestimated
the administrative demands placed on the chief residents, and our findings
suggest the chief resident role may be more fulfilling if the balance was
shifted somewhat toward teaching and clinical responsibilities.
The role of primary care in addressing lifestyle behaviours associated with chronic disease has developed incrementally over the past decade, and has led to greater calls for collaboration with population health.
Major obstacles exist at the practice, local area, state and national levels to strengthen collaboration; strategies to address these obstacles have been identified as part of a joint public health and general practice framework.
These obstacles have been especially evident for disadvantaged groups who receive ‘inverse preventive care’ from poorly resourced primary care and public health services in local disadvantaged areas.
Health reform has created opportunities for extensive change. This requires not only good will, but also a mechanism to increase joint planning with the aim of preventing chronic diseases, improving population health and reducing inequities.
Why this matters to us
We have a commitment to achieving improved public health and health equity through primary care. Mark chaired the joint committee which brought together the key organisations for general practice and public health between 2001 and 2004 and has conducted research on and contributed to development of guidelines for the prevention of chronic diseases in primary care. Elizabeth co-led the primary health care committee of the National Health Inequalities Research Collaboration and initiatives to improve primary health care as a strategy to implement health equity policy at state government levels.
In Australia, partnership working between public health and primary healthcare for the prevention and management of chronic disease has been developing incrementally since the 2003 consensus statement developed by the Joint Advisory Group of the General Practice Partnership Advisory Council and the National Public Health Partnership Group.
Australia's first national primary healthcare strategy (2010) provides a new opportunity to further develop this partnership, including multidisciplinary team-working in general practice for chronic disease prevention, and a new primary care organisation to oversee population health planning and health promotion. The needs of vulnerable and disadvantaged groups will be a central focus of the new planning structures. However, major barriers continue to frustrate collaborative population based planning and service development.
Conclusion The jury is still out on how effective the partnership between state funded public health service and the new nationally funded primary care organisations will be. There is significant overlap in their functions, but few formal mechanisms for collaboration have been as yet established.
chronic disease; preventive medicine; primary health care; public health
Actin-dependent finger-like protrusions such as filopodia and microvilli are widespread in eukaryotes, but their assembly mechanisms are poorly understood. Filopodia assembly requires at least three biochemical activities on actin: actin filament nucleation, prolonged actin filament elongation, and actin filament bundling. These activities are shared by several mammalian formin proteins, including mDia2, FRL1 (also called FMNL1), and FRL2 (FMNL3). In this paper, we compare the abilities of constructs from these three formins to induce filopodia. FH1-FH2 constructs of both FRL2 and mDia2 stimulate potent filopodia assembly in multiple cell types, and enrich strongly at filopodia tips. In contrast, FRL1 FH1-FH2 lacks this activity, despite possessing similar biochemical activities and being highly homologous to FRL2. Chimeric FH1-FH2 experiments between FRL1 and FRL2 show that, while both an FH1 and an FH2 are needed, either FH1 domain supports filopodia assembly but only FRL2’s FH2 domain allows this activity. A mutation that compromises FRL2’s barbed end binding ability abolishes filopodia assembly. FRL2’s ability to stimulate filopodia assembly is not altered by additional domains (GBD, DID, DAD), but is significantly reduced in the full-length construct, suggesting that FRL2 is subject to inhibitory regulation. The data suggest that the FH2 domain of FRL2 possesses properties not shared by FRL1 that allow it to generate filopodia.
microvilli; FMNL3; mDia2; FH2 domain; bundling; FRL1
Endothelial cells form cell-cell adhesive structures, called adherens and tight junctions, which maintain tissue integrity, but must be dynamic for leukocyte transmigration during the inflammatory response and cellular remodeling during angiogenesis. This review will focus on Vascular Endothelial (VE)-cadherin, an endothelial-specific cell-cell adhesion protein of the adherens junction complex. VE-cadherin plays a key role in endothelial barrier function and angiogenesis, and consequently VE-cadherin availability and function are tightly regulated. VE-cadherin also participates directly and indirectly in intracellular signaling pathways that control cell dynamics and cell cycle progression. Here we highlight recent work that has advanced our understanding of multiple regulatory and signaling mechanisms that converge on VE-cadherin and have consequences for endothelial barrier function and angiogenic remodeling.
Equity focused health impact assessments (EFHIAs), or health equity impact assessments, are being increasingly promoted internationally as a mechanism for enhancing the consideration of health equity in the development of policies, programs and projects. Despite this there are relatively few examples of examples of completed EFHIAs available. This paper presents a case study of a rapid EFHIA that was conducted in Australia on a health promotion policy implementation plan. It briefly describes the process and findings of the EFHIA and evaluates the impact on decision-making and implementation.
The rapid EFHIA was undertaken in four days, drawing on an expert panel and limited review of the literature. A process evaluation was undertaken by email one month after the EFHIA was completed. An impact evaluation was undertaken two years later based on five semi-structured interviews with members of the EFHIA working group and policy officers and managers responsible for implementing the plan. A cost estimation was conducted by the EFHIA working group.
The EFHIA made both general and specific recommendations about how the health equity impacts of the policy implementation plan could be improved. The impact evaluation identified changes to development and implementation that occurred as a result of the EFHIA, though there was disagreement about the extent to which changes could be attributed solely to the EFHIA. Those responsible considered the recommendations of the EFHIA in the next versions of their ABHI implementation plans. Factors that influenced the impact of the EFHIA included consolidating understandings of equity, enabling discussion of alternatives, and differing understandings of the purpose of the EFHIA. The EFHIA cost US$4,036 to undertake.
This EFHIA was conducted in a short timeframe using relatively few resources. It had some reported impacts on the development of the implementation plan and enhanced overall consideration of health equity. This case highlights some of the factors and preconditions that may maximise the impact of future EFHIAs on decision-making and implementation.
Adenomatous polyposis coli is a cytoskeletal organizer and a scaffold for mediating degradation of the Wnt effector β-catenin. We uncouple these different APC functions and show that GSK3β/CKI phosphorylation regulates APC clusters and cell migration independently of cell–cell adhesion and β-catenin transcriptional activity.
Adenomatous polyposis coli (APC), a tumor suppressor commonly mutated in cancer, is a cytoskeletal organizer for cell migration and a scaffold for GSK3β/CKI-mediated phosphorylation and degradation of the Wnt effector β-catenin. It remains unclear whether these different APC functions are coupled, or independently regulated and localized. In primary endothelial cells, we show that GSK3β/CKI-phosphorylated APC localizes to microtubule-dependent clusters at the tips of membrane extensions. Loss of GSK3β/CKI-phosphorylated APC from these clusters correlates with a decrease in cell migration. GSK3β/CKI-phosphorylated APC and β-catenin at clusters is degraded rapidly by the proteasome, but inhibition of GSK3β/CKI does not increase β-catenin–mediated transcription. GSK3β/CKI-phosphorylated and -nonphosphorylated APC also localize along adherens junctions, which requires actin and cell–cell adhesion. Significantly, inhibition of cell–cell adhesion results in loss of lateral membrane APC and a concomitant increase in GSK3β/CKI-phosphorylated APC in clusters. These results uncouple different APC functions and show that GSK3β/CKI phosphorylation regulates APC clusters and cell migration independently of cell–cell adhesion and β-catenin transcriptional activity.
Chlamydomonas reinhardtii is a unicellular green alga whose lineage diverged from land plants over 1 billion years ago. It is a model system for studying chloroplast-based photosynthesis, as well as the structure, assembly, and function of eukaryotic flagella (cilia), which were inherited from the common ancestor of plants and animals, but lost in land plants. We sequenced the ∼120-megabase nuclear genome of Chlamydomonas and performed comparative phylogenomic analyses, identifying genes encoding uncharacterized proteins that are likely associated with the function and biogenesis of chloroplasts or eukaryotic flagella. Analyses of the Chlamydomonas genome advance our understanding of the ancestral eukaryotic cell, reveal previously unknown genes associated with photosynthetic and flagellar functions, and establish links between ciliopathy and the composition and function of flagella.
Chronic gastritis induced by Helicobacter pylori is the strongest known risk factor for gastric adenocarcinoma, yet the effects of bacterial eradication on carcinogenesis remain unclear. Animal models provide important insights into factors that are involved in gastric carcinogenesis, and we previously utilized such a model to demonstrate that an in vivo adapted H. pylori strain, 7.13, rapidly and reproducibly induces inflammation-mediated gastric carcinoma. In the current study, we used this bacterial strain as a prototype to define the role of targeted antimicrobial therapy in gastric carcinogenesis. Mongolian gerbils were infected with H. pylori for 4 or 8 weeks, treated with antimicrobial agents or vehicle, and then euthanized at 8 weeks after the completion of therapy. All infected gerbils developed gastritis; however, inflammation was significantly attenuated in animals receiving antimicrobial therapy. Gastric dysplasia or cancer developed in > 60% of the gerbils that remained persistently colonized with H. pylori, but in none of the animals treated with antibiotics following 4 weeks of infection. Infection with H. pylori for 8 weeks prior to therapy resulted in an attenuation, but not complete prevention, of pre-malignant and malignant lesions. Similarly, antibiotic therapy initiated at 4, but not 8, weeks after H. pylori challenge significantly reduced expression of the Th1 pro-inflammatory cytokine interferon-γ within colonized gastric mucosa. These results indicate that treatment of H. pylori in this model decreases the incidence and severity of lesions with carcinogenic potential. The effectiveness of eradication is dependent upon the timing of intervention, providing insights into mechanisms that may regulate the development of malignancies arising within the context of inflammatory states.
inflammation; cytokine; dysplasia; gastric cancer; antibiotics
Organic anion transporting polypeptide 1B3 (OATP1B3, SLCO1B3) is normally expressed in hepatocytes. In this study, we demonstrated frequent overexpression of OATP1B3 in colorectal adenocarcinomas. Quantitative RT-PCR analysis of 17 colon tumors indicated tumoral overexpression of OATP1B3 by ~100 fold, compared to 20 normal colon samples (p<0.0001). Using immunohistochemistry on a tissue microarray containing 93 evaluable colon tumor specimens, we detected immunostaining of OATP1B3 in 75 colon adenocarcinomas (81%) and no immunostaining in normal samples. To determine the functional effects of OATP1B3 expression on drug-induced apoptosis, we used camptothecin and oxaliplatin on a panel of colorectal cancer cell lines stably overexpressing OATP1B3. The results indicated that OATP1B3 overexpression enhanced cell survival in RKO, HCT-8 and HCT116p53+/+ cells that harbor wildtype p53 but not in Caco-2 and HCT116p53-/- cells that lack p53, compared to the respective empty vector controls (p<0.01). The TUNEL assay confirmed that HCT116p53+/+ cells overexpressing OATP1B3 had significantly lower apoptotic levels compared to empty vector control (P<0.001). The overexpression of OATP1B3 reduced the transcriptional activity of p53, with subsequent reductions in transcript and protein levels of its downstream transcription targets (P21WAF1 and PUMA). Overexpression of a point mutation (G583E) variant of OATP1B3 lacking transport activity did not confer an antiapoptotic effect or affect p53 transcriptional activity, suggesting that the antiapoptotic effect of OATP1B3 may be associated with its transport activity. Taken together, our results suggest that OATP1B3 overexpression in colorectal cancer cells may provide a survival advantage by altering p53-dependent pathways.
Residents of socioeconomically disadvantaged locations are more likely to have poor health than residents of socioeconomically advantaged locations and this has been comprehensively mapped in Australian cities. These inequalities present a challenge for the public health workers based in or responsible for improving the health of people living in disadvantaged localities. The purpose of this study was to develop a generic workforce needs assessment tool and to use it to identify the competencies needed by the public health workforce to work effectively in disadvantaged communities.
A two-step mixed method process was used to identify the workforce needs. In step 1 a generic workforce needs assessment tool was developed and applied in three NSW Area Health Services using focus groups, key stakeholder interviews and a staff survey. In step 2 the findings of this needs assessment process were mapped against the existing National Health Training Package (HLT07) competencies, gaps were identified, additional competencies described and modules of training developed to fill identified gaps.
There was a high level of agreement among the AHS staff on the nature of the problems to be addressed but less confidence indentifying the work to be done. Processes for needs assessments, community consultations and adapting mainstream programs to local needs were frequently mentioned as points of intervention. Recruiting and retaining experienced staff to work in these communities and ensuring their safety were major concerns. Workforce skill development needs were seen in two ways: higher order planning/epidemiological skills and more effective working relationships with communities and other sectors. Organisational barriers to effective practice were high levels of annual compulsory training, balancing state and national priorities with local needs and giving equal attention to the population groups that are easy to reach and to those that are difficult to engage. A number of additional competency areas were identified and three training modules developed.
The generic workforce needs assessment tool was easy to use and interpret. It appears that the public health workforce involved in this study has a high level of understanding of the relationship between the social determinants and health. However there is a skill gap in identifying and undertaking effective intervention.
Home visiting programs comprising intensive and sustained visits by professionals (usually nurses) over the first two years of life show promise in promoting child health and family functioning, and ameliorating disadvantage. Australian evidence of the effectiveness of sustained nurse home visiting in early childhood is limited. This paper describes the method and cohort characteristics of the first Australian study of sustained home visiting commencing antenatally and continuing to child-age two years for at-risk mothers in a disadvantaged community (the Miller Early Childhood Sustained Home-visiting trial).
Methods and design
Mothers reporting risks for poorer parenting outcomes residing in an area of socioeconomic disadvantage were recruited between February 2003 and March 2005. Mothers randomised to the intervention group received a standardised program of nurse home visiting. Interviews and observations covering child, maternal, family and environmental issues were undertaken with mothers antenatally and at 1, 12 and 24 months postpartum. Standardised tests of child development and maternal-child interaction were undertaken at 18 and 30 months postpartum. Information from hospital and community heath records was also obtained.
A total of 338 women were identified and invited to participate, and 208 were recruited to the study. Rates of active follow-up were 86% at 12 months, 74% at 24 months and 63% at 30 months postpartum. Participation in particular data points ranged from 66% at 1 month to 51% at 24 months postpartum. Rates of active follow-up and data point participation were not significantly different for the intervention or comparison group at any data point. Mothers who presented for antenatal care prior to 20 weeks pregnant, those with household income from full-time employment and those who reported being abused themselves as a child were more likely to be retained in the study. The Miller Early Childhood Sustained Home-visiting trial will provide Australian evidence of the effectiveness of sustained nurse home visiting for children at risk of poorer health and developmental outcomes.