What promotes sustainability in Safe Community programmes?

<p>Abstract</p> <p>Background</p> <p>The theory and practice of safety promotion has traditionally focused on the safety of individuals. This study also includes systems, environments, and organizations. Safety promotion programmes are designed to support community health initiatives taking a bottom-up approach. This is a long-term and complex process. The aim of this study was to try to empirically identify factors that promote sustainability in the structures of programmes that are managed and coordinated by the local government.</p> <p>Methods</p> <p>Four focus group sessions with local government politicians and administrators in designated Safe Communities were conducted and analyzed using qualitative content analysis.</p> <p>Results</p> <p>Collaboration was found to be the basis for sustainability. Networks, enabling municipalities to exchange ideas, were reported to positively influence the programmes. Personal contacts rather than organizations themselves, determine whether collaboration is sustained. Participants reported an increase in cross-disciplinary collaboration among staff categories. Administrators and politicians were reported to collaborate well, which was perceived to speed up decision-making and thus to facilitate the programme work. Support from the politicians and the county council was seen as a prerequisite. Participants reported an increased willingness to share information between units, which, in their view, supports sustainability. A structure in which all local authorities' offices were located in close proximity to one another was considered to support collaboration. Appointing a public health coordinator responsible for the programme was seen as a way to strengthen the relational resources of the programme.</p> <p>Conclusion</p> <p>With a public health coordinator, the 'external' negotiating power was concentrated in one person. Also, the 'internal' programme strength increased when the coordination was based on a bureaucratic function rather than on one individual. Increased relational resources facilitated the transfer of information. A regular flow of information to policy-makers, residents, and staff was needed in order to integrate safety programmes into routines. Adopting a bottom-up approach requires that informal and ad hoc activities in information management be replaced by formalized, organizationally sanctioned routines. In contrast to injury prevention, which focuses on technical solutions, safety promotion tries to influence attitudes. Collaboration with the media was an area that could be improved.</p

Genomic variation in myeloma: design, content, and initial application of the Bank On A Cure SNP Panel to detect associations with progression-free survival

<p>Abstract</p> <p>Background</p> <p>We have engaged in an international program designated the <it>Bank On A Cure</it>, which has established DNA banks from multiple cooperative and institutional clinical trials, and a platform for examining the association of genetic variations with disease risk and outcomes in multiple myeloma.</p> <p>We describe the development and content of a novel custom SNP panel that contains 3404 SNPs in 983 genes, representing cellular functions and pathways that may influence disease severity at diagnosis, toxicity, progression or other treatment outcomes. A systematic search of national databases was used to identify non-synonymous coding SNPs and SNPs within transcriptional regulatory regions. To explore SNP associations with PFS we compared SNP profiles of short term (less than 1 year, <it>n </it>= 70) versus long term progression-free survivors (greater than 3 years, <it>n </it>= 73) in two phase III clinical trials.</p> <p>Results</p> <p>Quality controls were established, demonstrating an accurate and robust screening panel for genetic variations, and some initial racial comparisons of allelic variation were done. A variety of analytical approaches, including machine learning tools for data mining and recursive partitioning analyses, demonstrated predictive value of the SNP panel in survival. While the entire SNP panel showed genotype predictive association with PFS, some SNP subsets were identified within drug response, cellular signaling and cell cycle genes.</p> <p>Conclusion</p> <p>A targeted gene approach was undertaken to develop an SNP panel that can test for associations with clinical outcomes in myeloma. The initial analysis provided some predictive power, demonstrating that genetic variations in the myeloma patient population may influence PFS.</p

Azithromycin reduces spontaneous and induced inflammation in ΔF508 cystic fibrosis mice

BACKGROUND: Inflammation plays a critical role in lung disease development and progression in cystic fibrosis. Azithromycin is used for the treatment of cystic fibrosis lung disease, although its mechanisms of action are poorly understood. We tested the hypothesis that azithromycin modulates lung inflammation in cystic fibrosis mice. METHODS: We monitored cellular and molecular inflammatory markers in lungs of cystic fibrosis mutant mice homozygous for the ΔF508 mutation and their littermate controls, either in baseline conditions or after induction of acute inflammation by intratracheal instillation of lipopolysaccharide from Pseudomonas aeruginosa, which would be independent of interactions of bacteria with epithelial cells. The effect of azithromycin pretreatment (10 mg/kg/day) given by oral administration for 4 weeks was evaluated. RESULTS: In naive cystic fibrosis mice, a spontaneous lung inflammation was observed, characterized by macrophage and neutrophil infiltration, and increased intra-luminal content of the pro-inflammatory cytokine macrophage inflammatory protein-2. After induced inflammation, cystic fibrosis mice combined exaggerated cellular infiltration and lower anti-inflammatory interleukin-10 production. In cystic fibrosis mice, azithromycin attenuated cellular infiltration in both baseline and induced inflammatory condition, and inhibited cytokine (tumor necrosis factor-α and macrophage inflammatory protein-2) release in lipopolysaccharide-induced inflammation. CONCLUSION: Our findings further support the concept that inflammatory responses are upregulated in cystic fibrosis. Azithromycin reduces some lung inflammation outcome measures in cystic fibrosis mice. We postulate that some of the benefits of azithromycin treatment in cystic fibrosis patients are due to modulation of lung inflammation

The mechanisms by which polyamines accelerate tumor spread

Increased polyamine concentrations in the blood and urine of cancer patients reflect the enhanced levels of polyamine synthesis in cancer tissues arising from increased activity of enzymes responsible for polyamine synthesis. In addition to their de novo polyamine synthesis, cells can take up polyamines from extracellular sources, such as cancer tissues, food, and intestinal microbiota. Because polyamines are indispensable for cell growth, increased polyamine availability enhances cell growth. However, the malignant potential of cancer is determined by its capability to invade to surrounding tissues and metastasize to distant organs. The mechanisms by which increased polyamine levels enhance the malignant potential of cancer cells and decrease anti-tumor immunity are reviewed. Cancer cells with a greater capability to synthesize polyamines are associated with increased production of proteinases, such as serine proteinase, matrix metalloproteinases, cathepsins, and plasminogen activator, which can degrade surrounding tissues. Although cancer tissues produce vascular growth factors, their deregulated growth induces hypoxia, which in turn enhances polyamine uptake by cancer cells to further augment cell migration and suppress CD44 expression. Increased polyamine uptake by immune cells also results in reduced cytokine production needed for anti-tumor activities and decreases expression of adhesion molecules involved in anti-tumor immunity, such as CD11a and CD56. Immune cells in an environment with increased polyamine levels lose anti-tumor immune functions, such as lymphokine activated killer activities. Recent investigations revealed that increased polyamine availability enhances the capability of cancer cells to invade and metastasize to new tissues while diminishing immune cells' anti-tumor immune functions

All-cis 1,2,3,4,5,6-hexafluorocyclohexane is a facially polarized cyclohexane

This work was generously supported by the Engineering and Physical Sciences Research Council (EPSRC) and the European Research Council (ERC).The highest-energy stereoisomer of 1,2,3,4,5,6-hexafluorocyclohexane, in which all of the fluorines are ‘up’, is prepared in a 12-step protocol. The molecule adopts a classic chair conformation with alternate C–F bonds aligned triaxially, clustering three highly electronegative fluorine atoms in close proximity. This generates a cyclohexane with a high molecular dipole (μ = 6.2 D), unusual in an otherwise aliphatic compound. X-ray analysis indicates that the intramolecular Fax···Fax distances (∼2.77 Å) are longer than the vicinal Fax···Feq­ distances (∼2.73 Å) suggesting a tension stabilizing the chair conformation. In the solid state the molecules pack in an orientation consistent with electrostatic ordering. Our synthesis of this highest-energy isomer demonstrates the properties that accompany the placement of axial fluorines on a cyclohexane and the unusual property of a facially polarized ring in organic chemistry. Derivatives have potential as new motifs for the design of functional organic molecules or for applications in supramolecular chemistry design.PostprintPeer reviewe

Mental Health, and Rural Practice: A Perspective from New Zealand.

This chapter provides an analysis of rural social work in mental health with a particular focus on anti-oppressive practice. The chapter is written within the Aotearoa New Zealand (ANZ) context and as such addresses cultural dimensions essential to practice with tangata whenua (indigenous peoples of New Zealand). The chapter begins by summarising some key facts about rural ANZ followed by identification of organisational initiatives that have been developed outside of the statutory mental health sector to address health and wellbeing. Discussion about Te Whare Tapa Wha (Durie, 1994) follows, a paradigm for understanding the holistic dimensions of Māori. Next, antecedents for modern day social work are explained noting the dual functions of social justice imperatives alongside, case management. Mental health social work using Larson’s (2008) seven principles of anti-oppressive practice discussed next to demonstrate the implications for rural social work practice in Aotearoa New Zealand. The relevance and application of ecological systems theory to rural social work is alluded to throughout. The chapter concludes with a case study to consider and a list of key points about how to foster effective rural mental health social work in an ongoing way

Impact of nutrition on phenotype in CFTR-deficient mice.

To elucidate the impact of nutrition in cystic fibrosis (CF), we compared the phenotypic traits of Cftr -/- mice fed either a lipid-enriched liquid diet (Peptamen) or a standard chow combined with polyethylenglycol osmotic laxative (PEG), two strategies commonly used to prevent intestinal obstruction in CF mice. Survival, growth, liver, and ventilatory status were determined in Cftr -/- and Cftr +/+ mice, followed-up until 120 d. Ventilation was recorded in conscious animals using whole-body plethysmography. We found that the survival rate was similar in Peptamen and PEG Cftr -/- mice. Cftr -/- mice had lower minute ventilation than Cftr +/+ mice, whatever the diet. Both Cftr -/- and Cftr +/+ mice fed Peptamen displayed preadult growth delay compared with PEG-treated animals. Despite subsequent growth catch-up, Cftr -/- mice remained smaller than Cftr +/+ mice, whatever the diet. All Peptamen fed Cftr -/- mice showed hepatomegaly and liver steatosis, which also occurred but to a lesser extent in Peptamen fed Cftr +/+ animals. Therefore, while both treatment strategies are similarly efficient to avoid high mortality at weaning, Peptamen induces preadult growth delay and liver steatosis. These effects of diet are important to consider in future animal studies and also prompt to evaluate high-energy diets in CF patients.Comparative StudyJournal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe