Transcriptomic response to differentiation induction

BACKGROUND: Microarrays used for gene expression studies yield large amounts of data. The processing of such data typically leads to lists of differentially-regulated genes. A common terminal data analysis step is to map pathways of potentially interrelated genes. METHODS: We applied a transcriptomics analysis tool to elucidate the underlying pathways of leukocyte maturation at the genomic level in an established cellular model of leukemia by examining time-course data in two subclones of U-937 cells. Leukemias such as Acute Promyelocytic Leukemia (APL) are characterized by a block in the hematopoietic stem cell maturation program at a point when expansion of clones which should be destined to mature into terminally-differentiated effector cells get locked into endless proliferation with few cells reaching maturation. Treatment with retinoic acid, depending on the precise genomic abnormality, often releases the responsible promyelocytes from this blockade but clinically can yield adverse sequellae in terms of potentially lethal side effects, referred to as retinoic acid syndrome. RESULTS: Briefly, the list of genes for temporal patterns of expression was pasted into the ABCC GRID Promoter TFSite Comparison Page website tool and the outputs for each pattern were examined for possible coordinated regulation by shared regelems (regulatory elements). We found it informative to use this novel web tool for identifying, on a genomic scale, genes regulated by drug treatment. CONCLUSION: Improvement is needed in understanding the nature of the mutations responsible for controlling the maturation process and how these genes regulate downstream effects if there is to be better targeting of chemical interventions. Expanded implementation of the techniques and results reported here may better direct future efforts to improve treatment for diseases not restricted to APL

Book Reviews : Social Experiments: Method for Design and Evaluation, Leonard Saxe, and Michelle Fine, with introduction by Donald T. Campbell. Beverly Hills, California, Sage Pub lications, 1981, 266 pp

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68123/2/10.1177_109019818601300109.pd

Low infection rates after 34,361 intramedullary nail operations in 55 low- and middle-income countries: Validation of the Surgical Implant Generation Network (SIGN) Online Surgical Database

Background: The Surgical Implant Generation Network (SIGN) supplies intramedullary (IM) nails for the treatment of long bone fractures free of charge to hospitals in low- and middle-income countries (LMICs). Most operations are reported to the SIGN Online Surgical Database (SOSD). Follow-up has been reported to be low, however. We wanted to examine the pattern of follow-up and to assess whether infection rates could be trusted. Patients and methods: The SOSD contained 36,454 IM nail surgeries in 55 LMICs. We excluded humerus and hip fractures, and fractures without a registered surgical approach. This left 34,361 IM nails for analysis. A generalized additive regression model (gam) was used to explore the association between follow-up rates and infection rates. Results: The overall follow-up rate in the SOSD was 18.1% (95% CI: 17.7–18.5) and national follow-up rates ranged from 0% to 74.2%. The overall infection rate was 0.7% (CI: 0.6–0.8) for femoral fractures and 1.2% (CI: 1.0–1.4) for tibial fractures. If only nails with a registered follow-up visit were included (n = 6,224), infection rates were 3.5% (CI: 3.0–4.1) for femoral fractures and 7.3% (CI: 6.2–8.4) for tibial fractures. We found an increase in infection rates with increasing follow-up rates up to a level of 5%. Follow-up above 5% did not result in increased infection rates. Interpretation: Reported infection rates after IM nailing in the SOSD appear to be reliable and could be used for further research. The low infection rates suggest that IM nailing is a safe procedure also in low- and middle-income countries.publishedVersio

Modelling the Service Quality of Public Bicycle Schemes Considering User Heterogeneity

This article proposes a methodology for studying the quality of service perceived by users of a public bicycle scheme. The public are involved from the first phases of the research through their presence in focus groups to identify the relevant variables asked about in the survey. Ordered probit models have been calibrated which consider systematic variations in preference and random parameters. The results highlight the importance of safety and available information above other service variables, as well as the adjustment in perception of overall quality after considering each of the characteristics of the service, as it is proposed in this methodology

Second chances: Investigating athletes’ experiences of talent transfer

Talent transfer initiatives seek to transfer talented, mature individuals from one sport to another. Unfortunately talent transfer initiatives seem to lack an evidence-based direction and a rigorous exploration of the mechanisms underpinning the approach. The purpose of this exploratory study was to identify the factors which successfully transferring athletes cite as facilitative of talent transfer. In contrast to the anthropometric and performance variables that underpin current talent transfer initiatives, participants identified a range of psychobehavioral and environmental factors as key to successful transfer. We argue that further research into the mechanisms of talent transfer is needed in order to provide a strong evidence base for the methodologies employed in these initiatives

Comparison of (18)F SPECT with PET in myocardial imaging: A realistic thorax-cardiac phantom study

BACKGROUND: Positron emission tomography (PET) imaging with fluorine-18 ((18)F) Fluorodeoxyglucose (FDG) and flow tracer such as Rubidium-82 ((82)Rb) is an established method for evaluating an ischemic but viable myocardium. However, the high cost of PET imaging restricts its wider clinical use. Therefore, less expensive (18)F FDG single photon emission computed tomography (SPECT) imaging has been considered as an alternative to (18)F FDG PET imaging. The purpose of the work is to compare SPECT with PET in myocardial perfusion/viability imaging. METHODS: A nonuniform RH-2 thorax-heart phantom was used in the SPECT and PET acquisitions. Three inserts, 3 cm, 2 cm and 1 cm in diameter, were placed in the left ventricular (LV) wall to simulate infarcts. The phantom acquisition was performed sequentially with 7.4 MBq of (18)F and 22.2 MBq of Technetium-99m ((99m)Tc) in the SPECT study and with 7.4 MBq of (18)F and 370 MBq of (82)Rb in the PET study. SPECT and PET data were processed using standard reconstruction software provided by vendors. Circumferential profiles of the short-axis slices, the contrast and viability of the inserts were used to evaluate the SPECT and PET images. RESULTS: The contrast for 3 cm, 2 cm and 1 cm inserts were for (18)F PET data, 1.0 ± 0.01, 0.67 ± 0.02 and 0.25 ± 0.01, respectively. For (82)Rb PET data, the corresponding contrast values were 0.61 ± 0.02, 0.37 ± 0.02 and 0.19 ± 0.01, respectively. For (18)F SPECT the contrast values were, 0.31 ± 0.03 and 0.20 ± 0.05 for 3 cm and 2 cm inserts, respectively. For (99m)Tc SPECT the contrast values were, 0.63 ± 0.04 and 0.24 ± 0.05 for 3 cm and 2 cm inserts respectively. In SPECT, the 1 cm insert was not detectable. In the SPECT study, all three inserts were falsely diagnosed as "viable", while in the PET study, only the 1 cm insert was diagnosed falsely "viable". CONCLUSION: For smaller defects the (99m)Tc/(18)F SPECT imaging cannot entirely replace the more expensive (82)Rb/(18)F PET for myocardial perfusion/viability imaging, due to poorer image spatial resolution and poorer defect contrast

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

"That never would have occurred to me": a qualitative study of medical students' views of a cultural competence curriculum

BACKGROUND: The evidence is mixed regarding the efficacy of cultural competence curricula in developing learners' knowledge, attitudes and skills. More research is needed to better understand both the strengths and shortcomings of existing curricula from the perspective of learners in order to improve training. METHODS: We conducted three focus groups with medical students in their first year of clinical training to assess their perceptions of the cultural competence curriculum at a public university school of medicine. RESULTS: Students evaluated the informal curriculum as a more important source of learning about cultural competence than the formal curriculum. In terms of bias in both self and others, the cultural competence curriculum increased awareness, but was less effective in teaching specific interventional skills. Students also noted that the cultural competence curriculum did not always sufficiently help them find a balance between group-specific knowledge and respect for individual differences. Despite some concerns as to whether political correctness characterized the cultural competence curriculum, it was also seen as a way to rehumanize the medical education experience. CONCLUSION: Future research needs to pay attention to issues such as perceived relevance, stereotyping, and political correctness in developing cross-cultural training programs

Chedoke Arm and Hand Activity Inventory-9 (CAHAI-9): Perceived clinical utility within 14 days of stroke

Purpose: The Chedoke Arm and Hand Activity Inventory-9 (CAHAI-9) is an activity-based assessment developed to include relevant functional tasks and to be sensitive to clinically important changes in upper limb function. The aim of this study was to explore both therapists' and clients' views on the clinical utility of CAHAI-9 within 14 days of stroke. Method: Twenty-one occupational therapists actively working in stroke settings were recruited by convenience sampling from 8 hospitals and participated in semistructured focus groups. Five clients within 14 days of stroke were recruited by consecutive sampling from 1 metropolitan hospital and participated in structured individual interviews. The transcripts were analyzed thematically. Results: Six themes emerged from the focus groups and interviews: collecting information, decisions regarding client suitability, administration and scoring, organizational demands, raising awareness, and clients' perceptions of CAHAI-9 utility. All therapists agreed CAHAI-9 was suited for the stroke population and assisted identification of client abilities or difficulties within functional contexts. Opinions varied as to whether CAHAI-9 should be routinely administered with clients who had mild and severe upper limb deficits, but therapists agreed it was appropriate for clients with moderate deficits. Therapists made suggestions regarding refinement of the scoring and training to increase utility. All clients with stroke felt that the assessment provided reassurance regarding their recovery. Conclusion: The findings indicate that CAHAI-9 shows promise as an upper limb ability assessment for clients within 14 days of stroke