High-throughput identification of genotype-specific cancer vulnerabilities in mixtures of barcoded tumor cell lines.

Hundreds of genetically characterized cell lines are available for the discovery of genotype-specific cancer vulnerabilities. However, screening large numbers of compounds against large numbers of cell lines is currently impractical, and such experiments are often difficult to control. Here we report a method called PRISM that allows pooled screening of mixtures of cancer cell lines by labeling each cell line with 24-nucleotide barcodes. PRISM revealed the expected patterns of cell killing seen in conventional (unpooled) assays. In a screen of 102 cell lines across 8,400 compounds, PRISM led to the identification of BRD-7880 as a potent and highly specific inhibitor of aurora kinases B and C. Cell line pools also efficiently formed tumors as xenografts, and PRISM recapitulated the expected pattern of erlotinib sensitivity in vivo

A pragmatic cluster randomised trial evaluating three implementation interventions

Background Implementation research is concerned with bridging the gap between evidence and practice through the study of methods to promote the uptake of research into routine practice. Good quality evidence has been summarised into guideline recommendations to show that peri-operative fasting times could be considerably shorter than patients currently experience. The objective of this trial was to evaluate the effectiveness of three strategies for the implementation of recommendations about peri-operative fasting. Methods A pragmatic cluster randomised trial underpinned by the PARIHS framework was conducted during 2006 to 2009 with a national sample of UK hospitals using time series with mixed methods process evaluation and cost analysis. Hospitals were randomised to one of three interventions: standard dissemination (SD) of a guideline package, SD plus a web-based resource championed by an opinion leader, and SD plus plan-do-study-act (PDSA). The primary outcome was duration of fluid fast prior to induction of anaesthesia. Secondary outcomes included duration of food fast, patients' experiences, and stakeholders' experiences of implementation, including influences. ANOVA was used to test differences over time and interventions. Results Nineteen acute NHS hospitals participated. Across timepoints, 3,505 duration of fasting observations were recorded. No significant effect of the interventions was observed for either fluid or food fasting times. The effect size was 0.33 for the web-based intervention compared to SD alone for the change in fluid fasting and was 0.12 for PDSA compared to SD alone. The process evaluation showed different types of impact, including changes to practices, policies, and attitudes. A rich picture of the implementation challenges emerged, including inter-professional tensions and a lack of clarity for decision-making authority and responsibility. Conclusions This was a large, complex study and one of the first national randomised controlled trials conducted within acute care in implementation research. The evidence base for fasting practice was accepted by those participating in this study and the messages from it simple; however, implementation and practical challenges influenced the interventions' impact. A set of conditions for implementation emerges from the findings of this study, which are presented as theoretically transferable propositions that have international relevance. Trial registration ISRCTN18046709 - Peri-operative Implementation Study Evaluation (POISE

Muscle Oxygen Changes following Sprint Interval Cycling Training in Elite Field Hockey Players

This study examined the effects of Sprint Interval Cycling (SIT) on muscle oxygenation kinetics and performance during the 30-15 intermittent fitness test (IFT). Twenty-five women hockey players of Olympic standard were randomly selected into an experimental group (EXP) and a control group (CON). The EXP group performed six additional SIT sessions over six weeks in addition to their normal training program. To explore the potential training-induced change, EXP subjects additionally completed 5 x 30s maximal intensity cycle testing before and after training. During these tests near-infrared spectroscopy (NIRS) measured parameters; oxyhaemoglobin + oxymyoglobin (HbO2+ MbO2), tissue deoxyhaemoglobin + deoxymyoglobin (HHb+HMb), total tissue haemoglobin (tHb) and tissue oxygenation (TSI %) were taken. In the EXP group (5.34±0.14 to 5.50±0.14m.s-1) but not the CON group (pre = 5.37± 0.27 to 5.39±0.30m.s-1) significant changes were seen in the 30-15IFTperformance. EXP group also displayed significant post-training increases during the sprint cycling: ΔTSI (-7.59±0.91 to -12.16±2.70%); ΔHHb+HMb (35.68±6.67 to 69.44 ±26.48μM.cm); and ΔHbO2+ MbO2 (-74.29±13.82 to -109.36±22.61μM.cm). No significant differences were seen in ΔtHb (-45.81±15.23 to -42.93±16.24). NIRS is able to detect positive peripheral muscle oxygenation changes when used during a SIT protocol which has been shown to be an effective training modality within elite athletes

Transfemoral amputee recovery strategies following trips to their sound and prosthesis sides throughout swing phase

BACKGROUND: Recovering from trips is challenging for transfemoral amputees, and attempts often result in falls. Better understanding of the effects of the sensory-motor deficits brought by amputation and the functional limitations of prosthetic devices could help guide therapy and fall prevention mechanisms in prostheses. However, how transfemoral amputees attempt to recover from trips on the sound and prosthesis sides throughout swing phase is poorly understood. METHODS: We tripped eight able-bodied subjects and eight unilateral transfemoral amputees wearing their prescribed prostheses. The protocol consisted of six repetitions of 6 and 4 points throughout swing phase, respectively. We compared recovery strategies in able-bodied, sound side and prosthesis side limbs. The number of kinematic recovery strategies used, when they were used throughout swing phase, and kinematic characteristics (tripped limb joint angles, bilateral trochanter height and time from foot arrest to foot strike) of each strategy were compared across limb groups. Non-parametric statistical tests with corrections for post-hoc tests were used. RESULTS: Amputees used the same recovery strategies as able-bodied subjects on both sound and prosthesis sides, although not all subjects used all strategies. Compared to able-bodied subjects, amputees used delayed-lowering strategies less often from 30-60 % of swing phase on the sound side, and from 45-60 % of swing phase on the prosthesis side. Within-strategy kinematic differences occurred across limbs; however, these differences were not consistent across all strategies. Amputee-specific recovery strategies—that are not used by control subjects—occurred following trips on both the sound and prosthesis sides in mid- to late swing. CONCLUSIONS: Collectively, these results suggest that sensory input from the distal tripped leg is not necessary to trigger able-bodied trip recovery strategies. In addition, the differences between sound and prosthesis side recoveries indicate that the ability of the support leg might be more critical than that of the tripped leg when determining the response to a trip. The outcomes of this study have implications for prosthesis control, suggesting that providing correct and intuitive real-time selection of typical able-bodied recovery strategies by a prosthetic device when it is the tripped and the support limb could better enable balance recovery and avoid falls. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12984-015-0067-8) contains supplementary material, which is available to authorized users

Exploring how Chinese primary school psychological counsellors understand and use therapeutic stories

Psychological counsellors in western countries have used stories and storytelling for therapeutic purposes for decades. However, the development of the profession of school counselling in China is at an early stage and little research has been done on using therapeutic stories in Chinese primary school settings. This exploratory study presents qualitative data on using therapeutic stories collected from interviews with Chinese psychological counsellors who work with primary school students. Findings from a grounded theory analysis revealed that therapeutic stories were used by the participants in various therapeutic approaches. A spectrum of therapist directiveness was developed to integrate different ways of using therapeutic stories