Establishing an implementation network: lessons learned from community-based participatory research

<p>Abstract</p> <p>Background</p> <p>Implementation of evidence-based mental health assessment and intervention in community public health practice is a high priority for multiple stakeholders. Academic-community partnerships can assist in the implementation of efficacious treatments in community settings; yet, little is known about the processes by which these collaborations are developed. In this paper, we discuss our application of community-based participatory research (CBPR) approach to implementation, and we present six lessons we have learned from the establishment of an academic-community partnership.</p> <p>Methods</p> <p>With older adults with psychosis as a focus, we have developed a partnership between a university research center and a public mental health service system based on CBPR. The long-term goal of the partnership is to collaboratively establish an evidence-based implementation network that is sustainable within the public mental healthcare system.</p> <p>Results</p> <p>In building a sustainable partnership, we found that the following lessons were instrumental: changing attitudes; sharing staff; expecting obstacles and formalizing solutions; monitoring and evaluating; adapting and adjusting; and taking advantage of emerging opportunities. Some of these lessons were previously known principles that were modified as the result of the CBPR process, while some lessons derived directly from the interactive process of forming the partnership.</p> <p>Conclusion</p> <p>The process of forming of academic-public partnerships is challenging and time consuming, yet crucial for the development and implementation of state-of-the-art approaches to assessment and interventions to improve the functioning and quality of life for persons with serious mental illnesses. These partnerships provide necessary organizational support to facilitate the implementation of clinical research findings in community practice benefiting consumers, researchers, and providers.</p

Perturbations of Noise: The origins of Isothermal Flows

We make a detailed analysis of both phenomenological and analytic background for the "Brownian recoil principle" hypothesis (Phys. Rev. A 46, (1992), 4634). A corresponding theory of the isothermal Brownian motion of particle ensembles (Smoluchowski diffusion process approximation), gives account of the environmental recoil effects due to locally induced tiny heat flows. By means of local expectation values we elevate the individually negligible phenomena to a non-negligible (accumulated) recoil effect on the ensemble average. The main technical input is a consequent exploitation of the Hamilton-Jacobi equation as a natural substitute for the local momentum conservation law. Together with the continuity equation (alternatively, Fokker-Planck), it forms a closed system of partial differential equations which uniquely determines an associated Markovian diffusion process. The third Newton law in the mean is utilised to generate diffusion-type processes which are either anomalous (enhanced), or generically non-dispersive.Comment: Latex fil

Diagrammatic analysis of correlations in polymer fluids: Cluster diagrams via Edwards' field theory

A straightforward expansion of Edwards' functional integral representation of the grand partition function for a polymer liquid as an infinite set of Feynman diagrams is shown to yield a cluster expansion that is closely related to the corresponding Mayer cluster expansion developed for flexible molecules by Chandler and coworkers. The procedure initially yields a perturbative cluster expansion in which all free energies and correlation functions are expressed diagrammatically as functionals of single-molecule correlation functions of non-interacting molecules. Topological reduction yields several renormalized expansions for collective correlation functions of all orders as functionals of single-molecule correlation functions in the interacting fluid. Renormalized expansions are also obtained for a generalized Ornstein-Zernicke (OZ) direct correlation function and for intramolecular correlation functions. The application of the formalism to coarse-grained models of polymer fluids is discussed, and a loop expansion about self-consistent field theory is shown to converge for sufficiently coarse-grained models, in which monomers are strongly overlapping. The formalism is used to derive a new expression for the OZ direct correlation function and to recover known results for the 2-point intramolecular correlation function to first order in a loop expansion, for binary blends and diblock copolymer melts.Comment: 98 pages, 13 figures, accepted by Annals of Physic

A novel 4E-interacting protein in Leishmania is involved in stage-specific translation pathways

In eukaryotes, exposure to stress conditions causes a shift from cap-dependent to cap-independent translation. In trypanosomatids, environmental switches are the driving force of a developmental program of gene expression, but it is yet unclear how their translation machinery copes with their constantly changing environment. Trypanosomatids have a unique cap structure (cap-4) and encode four highly diverged paralogs of the cap-binding protein, eIF4E; none were found to genetically complement a yeast mutant failing to express eIF4E. Here we show that in promastigotes, a typical cap-binding complex is anchored through LeishIF4E-4, which associates with components of the cap-binding pre-initiation complex. In axenic amastigotes, expression of LeishIF4E-4 decreases and the protein does not bind the cap, whereas LeishIF4E-1 maintains its expression level and associates with the cap structure and with translation initiation factors. However, LeishIF4E-1 does not interact with eIF4G-like proteins in both life stages, excluding its involvement in cap-dependent translation. Using pull-down assays and mass-spectrometry, we identified a novel, non-conserved 4E-Interacting Protein (Leish4E-IP), which binds to LeishIF4E-1 in promastigotes, but not in amastigotes. Yeast two-hybrid and NMR spectroscopy confirmed the specificity of this interaction. We propose that Leish4E-IP is a translation regulator that is involved in switching between cap-dependent and alternative translation pathways

A novel nonparametric item response theory approach to measuring socioeconomic position: a comparison using household expenditure data from a Vietnam health survey, 2003

BACKGROUND: Measures of household socio-economic position (SEP) are widely used in health research. There exist a number of approaches to their measurement, with Principal Components Analysis (PCA) applied to a basket of household assets being one of the most common. PCA, however, carries a number of assumptions about the distribution of the data which may be untenable, and alternative, non-parametric, approaches may be preferred. Mokken scale analysis is a non-parametric, item response theory approach to scale development which appears never to have been applied to household asset data. A Mokken scale can be used to rank order items (measures of wealth) as well as households. Using data on household asset ownership from a national sample of 4,154 consenting households in the World Health Survey from Vietnam, 2003, we construct two measures of household SEP. Seventeen items asking about assets, and utility and infrastructure use were used. Mokken Scaling and PCA were applied to the data. A single item measure of total household expenditure is used as a point of contrast. RESULTS: An 11 item scale, out of the 17 items, was identified that conformed to the assumptions of a Mokken Scale. All the items in the scale were identified as strong items (Hi > .5). Two PCA measures of SEP were developed as a point of contrast. One PCA measure was developed using all 17 available asset items, the other used the reduced set of 11 items identified in the Mokken scale analaysis. The Mokken Scale measure of SEP and the 17 item PCA measure had a very high correlation (r = .98), and they both correlated moderately with total household expenditure: r = .59 and r = .57 respectively. In contrast the 11 item PCA measure correlated moderately with the Mokken scale (r = .68), and weakly with the total household expenditure (r = .18). CONCLUSION: The Mokken scale measure of household SEP performed at least as well as PCA, and outperformed the PCA measure developed with the 11 items used in the Mokken scale. Unlike PCA, Mokken scaling carries no assumptions about the underlying shape of the distribution of the data, and can be used simultaneous to order household SEP and items. The approach, however, has not been tested with data from other countries and remains an interesting, but under researched approach

The Relevance of Breast Cancer Subtypes in the Outcome of Neoadjuvant Chemotherapy

BACKGROUND: Breast cancer is increasingly considered a heterogeneous disease. The aim of this study was to assess the differences between histological and receptor-based subtypes in breast-conserving surgery and pathological complete response (pCR) after neoadjuvant chemotherapy. METHOD: A consecutive series of 254 patients with operable breast cancer treated with neoadjuvant chemotherapy was analyzed. Tumors were classified according to their receptor status in estrogen receptor (ER)-positive tumors (HER2-negative), triple-negative tumors, and HER2-positive tumors. The type of surgery feasible prior to neoadjuvant chemotherapy was compared with the actual surgery performed. RESULTS: The overall increase in breast-conserving surgery was 37% (73 of 198). In patients with ductal and lobular carcinomas this increase was 41% (63 of 152, 95% confidence interval [95% CI] 0.34-0.49) and 20% (7 of 35, 95% CI 0.10-0.36), respectively (P = 0.02). Half of the patients with lobular carcinoma had to undergo a secondary mastectomy because of incomplete resection margins. In ER-positive, triple-negative and HER2-positive tumors, the increase in breast-conserving surgery was 39% (42 of 109, 95% CI 0.30-0.48), 24% (11 of 45, 95% CI 0.14-0.38), and 45% (20 of 44, 95% CI 0.32-0.60) (P = 0.11). The pCR rate in ductal and lobular carcinomas was 12% (23 of 195) and 2% (1 of 42), respectively (P = 0.09). In ER-positive, triple-negative and HER2-positive tumors the pCR rates were 2% (3 of 138), 28% (16 of 57), and 18% (10 of 56), respectively. Multivariate analysis showed that the receptor-based subtype was the only significant predictor of pCR (P = 0.004). CONCLUSION: In lobular tumors the benefit with regard to breast-conserving surgery of neoadjuvant chemotherapy is questionable. Although in ER-positive tumors the pCR rate is low, the increase in breast-conserving surgery was remarkable in ductal ER-positive tumor

Flavin-Induced Oligomerization in Escherichia coli Adaptive Response Protein AidB

The process known as “adaptive response” allows Escherichia coli to respond to small doses of DNA-methylating agents by upregulating the expression of four proteins. While the role of three of these proteins in mitigating DNA damage is well understood, the function of AidB is less clear. Although AidB is a flavoprotein, no catalytic role has been established for the bound cofactor. Here we investigate the possibility that flavin plays a structural role in the assembly of the AidB tetramer. We report the generation and biophysical characterization of deflavinated AidB and of an AidB mutant that has greatly reduced affinity for flavin adenine dinucleotide (FAD). Using fluorescence quenching and analytical ultracentrifugation, we find that apo AidB has a high affinity for FAD, as indicated by an apparent dissociation constant of 402.1 ± 35.1 nM, and that binding of substoichiometric amounts of FAD triggers a transition in the AidB oligomeric state. In particular, deflavinated AidB is dimeric, whereas the addition of FAD yields a tetramer. We further investigate the dimerization and tetramerization interfaces of AidB by determining a 2.8 Å resolution crystal structure in space group P32 that contains three intact tetramers in the asymmetric unit. Taken together, our findings provide strong evidence that FAD plays a structural role in the formation of tetrameric AidB.National Institutes of Health (U.S.) (grant R01-GM0272663)National Institutes of Health (U.S.) (grant P30-ES002109)National Science Foundation (U.S.) (grant MCB-0543833

Clinical trials update: endocrine and biological therapy combinations in the treatment of breast cancer

A greater understanding of the biological mechanisms responsible for de novo and acquired endocrine resistance has led to the rational design of clinical trials exploring the benefit of combining hormonal therapies with novel biological agents in an effort to enhance the efficacy of ER+ breast cancer treatment. These studies are increasingly including parallel biological analyses to elucidate the molecular characteristics of those tumors that are most likely to respond to specific targeted/endocrine combinations in an effort to develop a tailored approach to the management of individual patients. Unfortunately despite encouraging preclinical data, some of these combinations have yielded disappointing results in the clinical setting. This article will review the results of clinical trials of endocrine/biological combinations conducted in early and advanced breast cancer as well as provide an update on ongoing studies

Systematic review with meta-analysis of the epidemiological evidence relating smoking to COPD, chronic bronchitis and emphysema

<p>Abstract</p> <p>Background</p> <p>Smoking is a known cause of the outcomes COPD, chronic bronchitis (CB) and emphysema, but no previous systematic review exists. We summarize evidence for various smoking indices.</p> <p>Methods</p> <p>Based on MEDLINE searches and other sources we obtained papers published to 2006 describing epidemiological studies relating incidence or prevalence of these outcomes to smoking. Studies in children or adolescents, or in populations at high respiratory disease risk or with co-existing diseases were excluded. Study-specific data were extracted on design, exposures and outcomes considered, and confounder adjustment. For each outcome RRs/ORs and 95% CIs were extracted for ever, current and ex smoking and various dose response indices, and meta-analyses and meta-regressions conducted to determine how relationships were modified by various study and RR characteristics.</p> <p>Results</p> <p>Of 218 studies identified, 133 provide data for COPD, 101 for CB and 28 for emphysema. RR estimates are markedly heterogeneous. Based on random-effects meta-analyses of most-adjusted RR/ORs, estimates are elevated for ever smoking (COPD 2.89, CI 2.63-3.17, n = 129 RRs; CB 2.69, 2.50-2.90, n = 114; emphysema 4.51, 3.38-6.02, n = 28), current smoking (COPD 3.51, 3.08-3.99; CB 3.41, 3.13-3.72; emphysema 4.87, 2.83-8.41) and ex smoking (COPD 2.35, 2.11-2.63; CB 1.63, 1.50-1.78; emphysema 3.52, 2.51-4.94). For COPD, RRs are higher for males, for studies conducted in North America, for cigarette smoking rather than any product smoking, and where the unexposed base is never smoking any product, and are markedly lower when asthma is included in the COPD definition. Variations by sex, continent, smoking product and unexposed group are in the same direction for CB, but less clearly demonstrated. For all outcomes RRs are higher when based on mortality, and for COPD are markedly lower when based on lung function. For all outcomes, risk increases with amount smoked and pack-years. Limited data show risk decreases with increasing starting age for COPD and CB and with increasing quitting duration for COPD. No clear relationship is seen with duration of smoking.</p> <p>Conclusions</p> <p>The results confirm and quantify the causal relationships with smoking.</p