A randomised controlled trial of total hip arthroplasty versus resurfacing arthroplasty in the treatment of young patients with arthritis of the hip joint

Background: Hip replacement (arthroplasty) surgery is a highly successful treatment for patients with severe symptomatic arthritis of the hip joint. For older patients, several designs of Total Hip Arthroplasty have shown excellent results in terms of both function and value for money. However, in younger more active patients, there is approximately a 50% failure rate at 25 years for traditional implants. Hip resurfacing is a relatively new arthroplasty technique. In a recent review of the literature on resurfacing arthroplasty it was concluded that the short-term functional results appear promising but some potential early disadvantages were identified, including the risk of femoral neck fracture and collapse of the head of the femur. The aim of the current study is to assess whether there is a difference in functional hip scores at one year post-operation between Total Hip Arthroplasty and Resurfacing Arthroplasty. Secondary aims include assessment of complication rates for both procedures as well cost effectiveness. Methods/design: All patients medically fit for surgery and deemed suitable for a resurfacing arthroplasty are eligible to take part in this study. A randomisation sequence will be produced and administered independently. After consenting, all patients will be clinically reviewed and hip function, quality of life and physical activity level will be assessed through questionnaires. The allocated surgery will then be performed with the preferred technique of the surgeon. Six weeks post-operation hip function will be assessed and complications recorded. Three, six and 12 months post-operation hip function, quality of life and physical activity level will be assessed. Additional information about patients' out-of-pocket expenses will also be collected

Adaptive clinical trials incorporating treatment selection and evaluation: methodology and application in progressive multiple sclerosis

In progressive multiple sclerosis (MS) irreversible disability often takes many years to accumulate as a result prolonged trials are required to assess the benefits of therapies. There is a need to understand the relationship between short-term outcome measures such as MRI endpoints and long-term clinical outcomes in progression to determine the evolution of the disease early on. Thus, the common phase I-II-III paradigm for clinical trial design with separate trials for each phase may not be appropriate

Application of digital particle image velocimetry to insect aerodynamics: measurement of the leading-edge vortex and near wake of a Hawkmoth.

Some insects use leading-edge vortices to generate high lift forces, as has been inferred from qualitative smoke visualisations of the flow around their wings. Here we present the first Digital Particle Image Velocimetry (DPIV) data and quantitative analysis of an insect’s leading-edge vortex and near wake at two flight speeds. This allows us to describe objectively 2D slices through the flow field of a tethered Tobacco Hawkmoth (Manduca sexta). The near-field vortex wake appears to braodly resemble elliptical vortex loops. The presence of a leading-edge vortex towards the end of the downstroke is found to coincide with peak upward force production measured by a six-component force–moment balance. The topology of Manduca’s leading-edge vortex differs from that previously described because late in the downstroke, the structure extends continuously from wingtip across the thorax to the other wingtip

An evaluation of the quality of statistical design and analysis of published medical research : results from a systematic survey of general orthopaedic journals

Background: The application of statistics in reported research in trauma and orthopaedic surgery has become ever more important and complex. Despite the extensive use of statistical analysis, it is still a subject which is often not conceptually well understood, resulting in clear methodological flaws and inadequate reporting in many papers. Methods: A detailed statistical survey sampled 100 representative orthopaedic papers using a validated questionnaire that assessed the quality of the trial design and statistical analysis methods. Results: The survey found evidence of failings in study design, statistical methodology and presentation of the results. Overall, in 17% (95% confidence interval; 10–26%) of the studies investigated the conclusions were not clearly justified by the results, in 39% (30–49%) of studies a different analysis should have been undertaken and in 17% (10–26%) a different analysis could have made a difference to the overall conclusions. Conclusion: It is only by an improved dialogue between statistician, clinician, reviewer and journal editor that the failings in design methodology and analysis highlighted by this survey can be addressed

Unconventional machine learning of genome-wide human cancer data

Recent advances in high-throughput genomic technologies coupled with exponential increases in computer processing and memory have allowed us to interrogate the complex aberrant molecular underpinnings of human disease from a genome-wide perspective. While the deluge of genomic information is expected to increase, a bottleneck in conventional high-performance computing is rapidly approaching. Inspired in part by recent advances in physical quantum processors, we evaluated several unconventional machine learning (ML) strategies on actual human tumor data. Here we show for the first time the efficacy of multiple annealing-based ML algorithms for classification of high-dimensional, multi-omics human cancer data from the Cancer Genome Atlas. To assess algorithm performance, we compared these classifiers to a variety of standard ML methods. Our results indicate the feasibility of using annealing-based ML to provide competitive classification of human cancer types and associated molecular subtypes and superior performance with smaller training datasets, thus providing compelling empirical evidence for the potential future application of unconventional computing architectures in the biomedical sciences

Flexibility in the receptor-binding domain of the enzymatic colicin E9 is required for toxicity against Escherichia coli cells

The events that occur after the binding of the enzymatic E colicins to Escherichia coli BtuB receptors that lead to translocation of the cytotoxic domain into the periplasmic space and, ultimately, cell killing are poorly understood. It has been suggested that unfolding of the coiled-coil Mull receptor binding domain of the E colicins may be an essential step that leads to the loss of immunity protein from the colicin and immunity protein complex and then triggers the events of translocation. We introduced pairs of cysteine mutations into the receptor binding domain of colicin E9 (ColE9) that resulted in the formation of a disulfide bond located near the middle or the top of the R domain. After dithiothreitol reduction, the ColE9 protein with the mutations L359C and F412C (ColE9 L359C-F412C) and the ColE9 protein with the mutations Y324C and L447C (ColE9 Y324C-L447C) were slightly less active than equivalent concentrations of ColE9. On oxidation with diamide, no significant biological activity was seen with the ColE9 L359C-F412C and the ColE9 Y324C-L447C mutant proteins; however diamide had no effect on the activity of ColE9. The presence of a disulfide bond was confirmed in both of the oxidized, mutant proteins by matrix-assisted laser desorption ionization-time of flight mass spectrometry. The loss of biological activity of the disulfide-containing mutant proteins was not due to an indirect effect on the properties of the translocation or DNase domains of the mutant colicins. The data are consistent with a requirement for the flexibility of the coiled-coil R domain after binding to BtuB