Toward optimal implementation of cancer prevention and control programs in public health: A study protocol on mis-implementation

Abstract Background Much of the cancer burden in the USA is preventable, through application of existing knowledge. State-level funders and public health practitioners are in ideal positions to affect programs and policies related to cancer control. Mis-implementation refers to ending effective programs and policies prematurely or continuing ineffective ones. Greater attention to mis-implementation should lead to use of effective interventions and more efficient expenditure of resources, which in the long term, will lead to more positive cancer outcomes. Methods This is a three-phase study that takes a comprehensive approach, leading to the elucidation of tactics for addressing mis-implementation. Phase 1: We assess the extent to which mis-implementation is occurring among state cancer control programs in public health. This initial phase will involve a survey of 800 practitioners representing all states. The programs represented will span the full continuum of cancer control, from primary prevention to survivorship. Phase 2: Using data from phase 1 to identify organizations in which mis-implementation is particularly high or low, the team will conduct eight comparative case studies to get a richer understanding of mis-implementation and to understand contextual differences. These case studies will highlight lessons learned about mis-implementation and identify hypothesized drivers. Phase 3: Agent-based modeling will be used to identify dynamic interactions between individual capacity, organizational capacity, use of evidence, funding, and external factors driving mis-implementation. The team will then translate and disseminate findings from phases 1 to 3 to practitioners and practice-related stakeholders to support the reduction of mis-implementation. Discussion This study is innovative and significant because it will (1) be the first to refine and further develop reliable and valid measures of mis-implementation of public health programs; (2) bring together a strong, transdisciplinary team with significant expertise in practice-based research; (3) use agent-based modeling to address cancer control implementation; and (4) use a participatory, evidence-based, stakeholder-driven approach that will identify key leverage points for addressing mis-implementation among state public health programs. This research is expected to provide replicable computational simulation models that can identify leverage points and public health system dynamics to reduce mis-implementation in cancer control and may be of interest to other health areas

Is group cognitive behaviour therapy for postnatal depression evidence-based practice? A systematic review

Background: There is evidence that psychological therapies including cognitive behaviour therapy (CBT) may be effective in reducing postnatal depression (PND) when offered to individuals. In clinical practice, this is also implemented in a group therapy format, which, although not recommended in guidelines, is seen as a cost-effective alternative. To consider the extent to which group methods can be seen as evidence-based, we systematically review and synthesise the evidence for the efficacy of group CBT compared to currently used packages of care for women with PND, and we discuss further factors which may contribute to clinician confidence in implementing an intervention. Methods: Seventeen electronic databases were searched. All full papers were read by two reviewers and a third reviewer was consulted in the event of a disagreement on inclusion. Selected studies were quality assessed, using the Cochrane Risk of Bias Tool, were data extracted by two reviewers using a standardised data extraction form and statistically synthesised where appropriate using the fixed-effect inverse-variance method. Results: Seven studies met the inclusion criteria. Meta-analyses showed group CBT to be effective in reducing depression compared to routine primary care, usual care or waiting list groups. A pooled effect size of d = 0.57 (95% CI 0.34 to 0.80, p < 0.001) was observed at 10–13 weeks post-randomisation, reducing to d = 0.28 (95% CI 0.03 to 0.53, p = 0.025) at 6 months. The non-randomised comparisons against waiting list controls at 10–13 weeks was associated with a larger effect size of d = 0.94 (95% CI 0.42 to 1.47, p < 0.001). However due to the limitations of the available data, such as ill-specified definitions of the CBT component of the group programmes, these results should be interpreted with caution. Conclusions: Although the evidence available is limited, group CBT was shown to be effective. We argue, therefore, that there is sufficient evidence to implement group CBT, conditional upon routinely collected outcomes being benchmarked against those obtained in trials of individual CBT, and with other important factors such as patient preference, clinical experience, and information from the local context taken into account when making the treatment decision

A Triple Protostar System Formed via Fragmentation of a Gravitationally Unstable Disk

Binary and multiple star systems are a frequent outcome of the star formation process, and as a result, almost half of all sun-like stars have at least one companion star. Theoretical studies indicate that there are two main pathways that can operate concurrently to form binary/multiple star systems: large scale fragmentation of turbulent gas cores and filaments or smaller scale fragmentation of a massive protostellar disk due to gravitational instability. Observational evidence for turbulent fragmentation on scales of $>$1000~AU has recently emerged. Previous evidence for disk fragmentation was limited to inferences based on the separations of more-evolved pre-main sequence and protostellar multiple systems. The triple protostar system L1448 IRS3B is an ideal candidate to search for evidence of disk fragmentation. L1448 IRS3B is in an early phase of the star formation process, likely less than 150,000 years in age, and all protostars in the system are separated by $<$200~AU. Here we report observations of dust and molecular gas emission that reveal a disk with spiral structure surrounding the three protostars. Two protostars near the center of the disk are separated by 61 AU, and a tertiary protostar is coincident with a spiral arm in the outer disk at a 183 AU separation. The inferred mass of the central pair of protostellar objects is $\sim$1 M$_{sun}$, while the disk surrounding the three protostars has a total mass of $\sim$0.30 M_{\sun}. The tertiary protostar itself has a minimum mass of $\sim$0.085 M$_{sun}$. We demonstrate that the disk around L1448 IRS3B appears susceptible to disk fragmentation at radii between 150~AU and 320~AU, overlapping with the location of the tertiary protostar. This is consistent with models for a protostellar disk that has recently undergone gravitational instability, spawning one or two companion stars.Comment: Published in Nature on Oct. 27th. 24 pages, 8 figure

How a Diverse Research Ecosystem Has Generated New Rehabilitation Technologies: Review of NIDILRR’s Rehabilitation Engineering Research Centers

Over 50 million United States citizens (1 in 6 people in the US) have a developmental, acquired, or degenerative disability. The average US citizen can expect to live 20% of his or her life with a disability. Rehabilitation technologies play a major role in improving the quality of life for people with a disability, yet widespread and highly challenging needs remain. Within the US, a major effort aimed at the creation and evaluation of rehabilitation technology has been the Rehabilitation Engineering Research Centers (RERCs) sponsored by the National Institute on Disability, Independent Living, and Rehabilitation Research. As envisioned at their conception by a panel of the National Academy of Science in 1970, these centers were intended to take a “total approach to rehabilitation”, combining medicine, engineering, and related science, to improve the quality of life of individuals with a disability. Here, we review the scope, achievements, and ongoing projects of an unbiased sample of 19 currently active or recently terminated RERCs. Specifically, for each center, we briefly explain the needs it targets, summarize key historical advances, identify emerging innovations, and consider future directions. Our assessment from this review is that the RERC program indeed involves a multidisciplinary approach, with 36 professional fields involved, although 70% of research and development staff are in engineering fields, 23% in clinical fields, and only 7% in basic science fields; significantly, 11% of the professional staff have a disability related to their research. We observe that the RERC program has substantially diversified the scope of its work since the 1970’s, addressing more types of disabilities using more technologies, and, in particular, often now focusing on information technologies. RERC work also now often views users as integrated into an interdependent society through technologies that both people with and without disabilities co-use (such as the internet, wireless communication, and architecture). In addition, RERC research has evolved to view users as able at improving outcomes through learning, exercise, and plasticity (rather than being static), which can be optimally timed. We provide examples of rehabilitation technology innovation produced by the RERCs that illustrate this increasingly diversifying scope and evolving perspective. We conclude by discussing growth opportunities and possible future directions of the RERC program

Results from the dissemination of an evidence-based telephone-delivered intervention for healthy lifestyle and weight loss: the Optimal Health Program

Despite proven efficacy, there are few published evaluations of telephone-delivered interventions targeting physical activity, healthy eating, and weight loss in community dissemination contexts. This study aims to evaluate participant and program outcomes from the Optimal Health Program, a telephone-delivered healthy lifestyle and weight loss program provided by a primary health care organization. Dissemination study used a single-group, repeated measures design; outcomes were assessed at 6-month (mid-program; n = 166) and 12-month (end of program; n = 88) using paired analyses. The program reached a representative sample of at-risk, primary care patients, with 56 % withdrawing before program completion. Among completers, a statistically significant improvement between baseline and end of program was observed for weight [mean change (SE) −5.4 (7.0) kg] and waist circumference [−4.8 (9.7) cm], underpinned by significant physical activity and dietary change. Findings suggest that telephone-delivered weight loss and healthy lifestyle programs can provide an effective model for use in primary care settings, but participant retention remains a challenge

From little things, big things grow: trends and fads in 110 years of Australian ornithology

Publishing histories can reveal changes in ornithological effort, focus or direction through time. This study presents a bibliometric content analysis of Emu (1901&ndash;2011) which revealed 115 trends (long-term changes in publication over time) and 18 fads (temporary increases in publication activity) from the classification of 9,039 articles using 128 codes organised into eight categories (author gender, author affiliation, article type, subject, main focus, main method, geographical scale and geographical location). Across 110 years, private authorship declined, while publications involving universities and multiple institutions increased; from 1960, female authorship increased. Over time, question-driven studies and incidental observations increased and decreased in frequency, respectively. Single species and &lsquo;taxonomic group&rsquo; subjects increased while studies of birds at specific places decreased. The focus of articles shifted from species distribution and activities of the host organisation to breeding, foraging and other biological/ecological topics. Site- and Australian-continental-scales slightly decreased over time; non-Australian studies increased from the 1970s. A wide variety of fads occurred (e.g. articles on bird distribution, 1942&ndash;1951, and using museum specimens, 1906&ndash;1913) though the occurrence of fads decreased over time. Changes over time are correlated with technological, theoretical, social and institutional changes, and suggest ornithological priorities, like those of other scientific disciplines, are temporally labil

Acquired resistance to oxaliplatin is not directly associated with increased resistance to DNA damage in SK-N-ASrOXALI4000, a newly established oxaliplatin-resistant sub-line of the neuroblastoma cell line SK-N-AS

The formation of acquired drug resistance is a major reason for the failure of anti-cancer therapies after initial response. Here, we introduce a novel model of acquired oxaliplatin resistance, a sub-line of the non-MYCN-amplified neuroblastoma cell line SK-N-AS that was adapted to growth in the presence of 4000 ng/mL oxaliplatin (SK-N-ASrOXALI4000). SK-N-ASrOXALI4000 cells displayed enhanced chromosomal aberrations compared to SK-N-AS, as indicated by 24-chromosome fluorescence in situ hybridisation. Moreover, SK-N-ASrOXALI4000 cells were resistant not only to oxaliplatin but also to the two other commonly used anti-cancer platinum agents cisplatin and carboplatin. SK-N-ASrOXALI4000 cells exhibited a stable resistance phenotype that was not affected by culturing the cells for 10 weeks in the absence of oxaliplatin. Interestingly, SK-N-ASrOXALI4000 cells showed no cross resistance to gemcitabine and increased sensitivity to doxorubicin and UVC radiation, alternative treatments that like platinum drugs target DNA integrity. Notably, UVC-induced DNA damage is thought to be predominantly repaired by nucleotide excision repair and nucleotide excision repair has been described as the main oxaliplatin-induced DNA damage repair system. SK-N-ASrOXALI4000 cells were also more sensitive to lysis by influenza A virus, a candidate for oncolytic therapy, than SK-N-AS cells. In conclusion, we introduce a novel oxaliplatin resistance model. The oxaliplatin resistance mechanisms in SK-N-ASrOXALI4000 cells appear to be complex and not to directly depend on enhanced DNA repair capacity. Models of oxaliplatin resistance are of particular relevance since research on platinum drugs has so far predominantly focused on cisplatin and carboplatin

The Inflammatory Kinase MAP4K4 Promotes Reactivation of Kaposi's Sarcoma Herpesvirus and Enhances the Invasiveness of Infected Endothelial Cells

Kaposi's sarcoma (KS) is a mesenchymal tumour, which is caused by Kaposi's sarcoma herpesvirus (KSHV) and develops under inflammatory conditions. KSHV-infected endothelial spindle cells, the neoplastic cells in KS, show increased invasiveness, attributed to the elevated expression of metalloproteinases (MMPs) and cyclooxygenase-2 (COX-2). The majority of these spindle cells harbour latent KSHV genomes, while a minority undergoes lytic reactivation with subsequent production of new virions and viral or cellular chemo- and cytokines, which may promote tumour invasion and dissemination. In order to better understand KSHV pathogenesis, we investigated cellular mechanisms underlying the lytic reactivation of KSHV. Using a combination of small molecule library screening and siRNA silencing we found a STE20 kinase family member, MAP4K4, to be involved in KSHV reactivation from latency and to contribute to the invasive phenotype of KSHV-infected endothelial cells by regulating COX-2, MMP-7, and MMP-13 expression. This kinase is also highly expressed in KS spindle cells in vivo. These findings suggest that MAP4K4, a known mediator of inflammation, is involved in KS aetiology by regulating KSHV lytic reactivation, expression of MMPs and COX-2, and, thereby modulating invasiveness of KSHV-infected endothelial cells. © 2013 Haas et al

Sucrose in the concentrated solution or the supercooled “state” : a review of caramelisation reactions and physical behaviour

Sucrose is probably one of the most studied molecules by food scientists, since it plays an important role as an ingredient or preserving agent in many formulations and technological processes. When sucrose is present in a product with a concentration near or greater than the saturation point—i.e. in the supercooled state—it possesses high potentialities for the food industry in areas as different as pastry industry, dairy and frozen desserts or films and coatings production. This paper presents a review on critical issues and research on highly concentrated sucrose solutions—mainly, on sucrose thermal degradation and relaxation behaviour in such solutions. The reviewed works allow identifying several issues with great potential for contributing to significant advances in Food Science and Technology.Authors are grateful for the valuable discussions with Teresa S. Brandao and Rosiane Lopes da Cunha during this research. Author M. A. C. Quintas acknowledges the financial support of her research by FCT grant SFRH/BPD/41715/2007

‘‘Beet-ing’’ the Mountain: A Review of the Physiological and Performance Effects of Dietary Nitrate Supplementation at Simulated and Terrestrial Altitude

Exposure to altitude results in multiple physiological consequences. These include, but are not limited to, a reduced maximal oxygen consumption, drop in arterial oxygen saturation, and increase in muscle metabolic perturbations at a fixed sub-maximal work rate. Exercise capacity during fixed work rate or incremental exercise and time-trial performance are also impaired at altitude relative to sea-level. Recently, dietary nitrate (NO3-) supplementation has attracted considerable interest as a nutritional aid during altitude exposure. In this review, we summarise and critically evaluate the physiological and performance effects of dietary NO3- supplementation during exposure to simulated and terrestrial altitude. Previous investigations at simulated altitude indicate that NO3- supplementation may reduce the oxygen cost of exercise, elevate arterial and tissue oxygen saturation, improve muscle metabolic function, and enhance exercise capacity/ performance. Conversely, current evidence suggests that NO3- supplementation does not augment the training response at simulated altitude. Few studies have evaluated the effects of NO3- at terrestrial altitude. Current evidence indicates potential improvements in endothelial function at terrestrial altitude following NO3- supplementation. No effects of NO3- supplementation have been observed on oxygen consumption or arterial oxygen saturation at terrestrial altitude, although further research is warranted. Limitations of the present body of literature are discussed, and directions for future research are provided