Biomechanical comparison of the track start and the modified one-handed track start in competitive swimming: an intervention study

This study compared the conventional track and a new one-handed track start in elite age group swimmers to determine if the new technique had biomechanical implications on dive performance. Five male and seven female GB national qualifiers participated (mean ± SD: age 16.7 ± 1.9 years, stretched stature 1.76 ± 0.8 m, body mass 67.4 ± 7.9 kg) and were assigned to a control group (n = 6) or an intervention group (n = 6) that learned the new onehanded dive technique. All swimmers underwent a 4-week intervention comprising 12 ± 3 thirty-minute training sessions. Video cameras synchronized with an audible signal and timing suite captured temporal and kinematic data. A portable force plate and load cell handrail mounted to a swim starting block collected force data over 3 trials of each technique. A MANCOVA identified Block Time (BT), Flight Time (FT), Peak Horizontal Force of the lower limbs (PHF) and Horizontal Velocity at Take-off (Vx) as covariates. During the 10-m swim trial, significant differences were found in Time to 10 m (TT10m), Total Time (TT), Peak Vertical Force (PVF), Flight Distance (FD), and Horizontal Velocity at Take-off (Vx) (p < .05). Results indicated that the conventional track start method was faster over 10 m, and therefore may be seen as a superior start after a short intervention. During training, swimmers and coaches should focus on the most statistically significant dive performance variables: peak horizontal force and velocity at take-off, block and flight time

Multivariate ToF-SIMS image analysis of polymer microarrays and protein adsorption

The complexity of hyperspectral time of flight secondary ion mass spectrometry (ToF-SIMS) datasets makes their subsequent analysis and interpretation challenging, and is often an impasse to the identification of trends and differences within large sample-sets. The application of multivariate data analysis has become a routine method to successfully deconvolute and analyze objectively these datasets. The advent of high-resolution large area ToF-SIMS imaging capability has enlarged further the data handling challenges. In this work, a modified multivariate curve resolution image analysis of a polymer microarray containing 70 different poly(meth)acrylate type spots (over a 9.2 × 9.2 mm area) is presented. This analysis distinguished key differences within the polymer library such as the differentiation between acrylate and methacrylate polymers and variance specific to side groups. Partial least squares (PLS) regression analysis was performed to identify correlations between the ToF-SIMS surface chemistry and the protein adsorption. PLS analysis identified a number of chemical moieties correlating with high or low protein adsorption, including ions derived from the polymer backbone and polyethylene glycol side-groups. The retrospective validation of the findings from the PLS analysis was also performed using the secondary ion images for those ions found to significantly contribute to high or low protein adsorption

Continuing to enhance the quality of case study methodology in health services research.

Case study methodology has grown in popularity within Health Services Research (HSR). However, its use and merit as a methodology are frequently criticized due to its flexible approach and inconsistent application. Nevertheless, case study methodology is well suited to HSR because it can track and examine complex relationships, contexts, and systems as they evolve. Applied appropriately, it can help generate information on how multiple forms of knowledge come together to inform decision-making within healthcare contexts. In this article, we aim to demystify case study methodology by outlining its philosophical underpinnings and three foundational approaches. We provide literature-based guidance to decision-makers, policy-makers, and health leaders on how to engage in and critically appraise case study design. We advocate that researchers work in collaboration with health leaders to detail their research process with an aim of strengthening the validity and integrity of case study for its continued and advanced use in HSR

Targeting the Insulin-Like Growth Factor 1 Receptor in Ewing's Sarcoma: Reality and Expectations

Ewing's sarcoma family of tumours comprises a group of very aggressive diseases that are potentially curable with multimodality treatment. Despite the undoubted success of current treatment, approximately 30% of patients will relapse and ultimately die of disease. The insulin-like growth factor 1 receptor (IGF-1R) has been implicated in the genesis, growth, proliferation, and the development of metastatic disease in Ewing's sarcoma. In addition, IGF1-R has been validated, both in vitro and in vivo, as a potential therapeutic target in Ewing's sarcoma. Phase I studies of IGF-1R monoclonal antibodies reported several radiological and clinical responses in Ewing's sarcoma patients, and initial reports of several Phase II studies suggest that about a fourth of the patients would benefit from IGF-1R monoclonal antibodies as single therapy, with approximately 10% of patients achieving objective responses. Furthermore, these therapies are well tolerated, and thus far severe toxicity has been rare. Other studies assessing IGF-1R monoclonal antibodies in combination with traditional cytotoxics or other targeted therapies are expected. Despite, the initial promising results, not all patients benefit from IGF-1R inhibition, and consequently, there is an urgent need for the identification of predictive markers of response

Imaging of crystalline and amorphous surface regions using time-of-flight secondary-ion mass spectrometry (ToF-SIMS): application to pharmaceutical materials

The structure of a material, in particular the extremes of crystalline and amorphous forms, significantly impacts material performance in numerous sectors such as semiconductors, energy storage, and pharmaceutical products, which are investigated in this paper. To characterize the spatial distribution for crystalline−amorphous forms at the uppermost molecular surface layer, we performed time-of-flight secondary-ion mass spectroscopy (ToF-SIMS) measurements for quench-cooled amorphous and recrystallized samples of the drugs indomethacin, felodipine, and acetaminophen. Polarized light microscopy was used to localize crystallinity induced in the samples under controlled conditions. Principal component analysis was used to identify the subtle changes in the ToF-SIMS spectra indicative of the amorphous and crystalline forms for each drug. The indicators of amorphous and crystalline surfaces were common in type across the three drugs, and could be explained in general terms of crystal packing and intermolecular bonding, leading to intramolecular chain scission in the formation of secondary ions. Less intramolecular scission occurred in the amorphous form, resulting in a greater intensity of molecular and dimer secondary ions. To test the generality of amorphous−crystalline differentiation using ToF-SIMS, a different recrystallization method was investigated where acetaminophen single crystals were recrystallized from supersaturated solutions. The findings indicated that the ability to assign the crystalline/amorphous state of the sample using ToF-SIMS was insensitive to the recrystallization method. This demonstrates ToF-SIMS capabilities of detecting and mapping ordered crystalline and disordered amorphous molecular materials forms at micron spatial resolution in the uppermost surface of a material

Oncogenic B-RAFV600E Promotes Anchorage-Independent Survival of Human Melanocytes

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High throughput discovery of thermo-responsive materials using water contact angle measurements and time-of-flight secondary ion mass spectrometry

Switchable materials that alter their chemical or physical properties in response to external stimuli allow for temporal control of material-biological interactions, thus, are of interest for many biomaterial applications. Our interest is the discovery of new materials suitable to the specific requirements of certain biological systems. A high throughput methodology has been developed to screen a library of polymers for thermo-responsiveness, which has resulted in the identification of novel switchable materials. To elucidate the mechanism by which the materials switch, time-of-flight secondary ion mass spectrometry has been employed to analyse the top 2 nm of the polymer samples at different temperatures. The surface enrichment of certain molecular fragments has been identified by time-of-flight secondary ion mass spectrometry analysis at different temperatures, suggesting an altered molecular conformation. In one example, a switch between an extended and collapsed conformation is inferred

High throughput discovery of thermo-responsive materials using water contact angle measurements and time-of-flight secondary ion mass spectrometry

Switchable materials that alter their chemical or physical properties in response to external stimuli allow for temporal control of material-biological interactions, thus, are of interest for many biomaterial applications. Our interest is the discovery of new materials suitable to the specific requirements of certain biological systems. A high throughput methodology has been developed to screen a library of polymers for thermo-responsiveness, which has resulted in the identification of novel switchable materials. To elucidate the mechanism by which the materials switch, time-of-flight secondary ion mass spectrometry has been employed to analyse the top 2 nm of the polymer samples at different temperatures. The surface enrichment of certain molecular fragments has been identified by time-of-flight secondary ion mass spectrometry analysis at different temperatures, suggesting an altered molecular conformation. In one example, a switch between an extended and collapsed conformation is inferred

Analysis and prediction of defects in UV photo-initiated polymer microarrays

Polymer microarrays are a key enabling technology for the discovery of novel materials. This technology can be further enhanced by expanding the combinatorial space represented on an array. However, not all materials are compatible with the microarray format and materials must be screened to assess their suitability with the microarray manufacturing methodology prior to their inclusion in a materials discovery investigation. In this study a library of materials expressed on the microarray format are assessed by light microscopy, atomic force microscopy and time-of-flight secondary ion mass spectrometry to identify compositions with defects that cause a polymer spot to exhibit surface properties significantly different from a smooth, round, chemically homogeneous ‘normal’ spot. It was demonstrated that the presence of these defects could be predicted in 85% of cases using a partial least square regression model based upon molecular descriptors of the monomer components of the polymeric materials. This may allow for potentially defective materials to be identified prior to their formation. Analysis of the PLS regression model highlighted some chemical properties that influenced the formation of defects, and in particular suggested that mixing a methacrylate and an acrylate monomer and/or mixing monomers with long and linear or short and bulky pendant groups will prevent the formation of defects. These results are of interest for the formation of polymer microarrays and may also inform the formulation of printed polymer materials generally.Burroughs Wellcome Fund (grant number 085245)Royal Society (Great Britain) (Wolfson Research Merit Award

Strategies for MCR image analysis of large hyperspectral data-sets

Polymer microarrays are a key enabling technology for high throughput materials discovery. In this study, multivariate image analysis, specifically multivariate curve resolution (MCR), is applied to the hyperspectral time of flight secondary ion mass spectroscopy (ToF-SIMS) data from eight individual microarray spots. Rather than analysing the data individually, the data-sets are collated and analysed as a single large data-set. Desktop computing is not a practical method for undertaking MCR analysis of such large data-sets due to the constraints of memory and computational overhead. Here, a distributed memory High-Performance Computing facility (HPC) is used. Similar to what is achieved using MCR analysis of individual samples, the results from this consolidated data-set allow clear identification of the substrate material; furthermore, specific chemistries common to different spots are also identified. The application of the HPC facility to the MCR analysis of ToF-SIMS hyperspectral data-sets demonstrates a potential methodology for the analysis of macro-scale data without compromising spatial resolution (data ‘binning’