Zeroth-order finite similitude and scaling of complex geometries in biomechanical experimentation

Scaled experimentation provides an alternative approach to full-scale biomechanical (and biological) testing but is known to suffer from scale effects, where the underlying system behaviour changes with scale. This phenomenon is arguably the overriding principal obstacle to the many advantages that scaled experimentation provides. These include reduced costs, materials and time, along with the eschewal of ethical compliance concerns with the application of substitute artificial materials as opposed to the use of hazardous biological agents. This paper examines the role scale effects play in biomechanical experimentation involving strain measurement and introduces a formulation that overtly captures scale dependencies arising from geometrical change. The basic idea underpinning the new scaling approach is the concept of space scaling, where a biomechanical experiment is scaled by the metaphysical mechanism of space contraction. The scaling approach is verified and validated with finite-element (FE) models and actual physical-trial experimentation using digital image correlation software applied to synthetic composite bone. The experimental design aspect of the approach allows for the selection of three-dimensional printing materials for trial-space analysis in a complex pelvis geometry. This aspect takes advantage of recent advancements in additive manufacturing technologies with the objective of countering behavioural distorting scale effects. Analysis is carried out using a laser confocal microscope to compare the trial and physical space materials and subsequently measured using surface roughness parameters. FE models were constructed for the left hemipelvis and results show similar strain patterns (average percentage error less than 10%) for two of the three trial-space material combinations. A Bland–Altman statistical analysis shows a good agreement between the FE models and physical experimentation and a good agreement between the physical-trial experimentation, providing good supporting evidence of the applicability of the new scaling approach in a wider range of experiments

Soft Photoproduction Physics

Several topics of interest in soft photoproduction physics are discussed. These include jet universality issues (particle flavour composition), the subdivision into event classes, the buildup of the total photoproduction cross section and the effects of multiple interactions.Comment: 10 pages, LaTeX2e, no figures, to appear in the proceedings of the Durham Workshop on HERA Physics, ``Proton, Photon and Pomeron Structure'', 17--23 September 1995, Durham, U.

Genome-wide association study of nevirapine hypersensitivity in a sub-Saharan African HIV-infected population

The initial GWAS was funded by the International Serious Adverse Events Consortium (iSAEC). The iSAEC is a non-profit organization dedicated to identifying and validating DNA variants useful in predicting the risk of drug-related serious adverse events. The Consortium brings together the pharmaceutical industry, regulatory authorities and academic centres to address clinical and scientific issues associated with the genetics of drug-related serious adverse events. The iSAEC’s current funding members include: Abbott, Amgen, AstraZeneca, Daiichi Sankyo, GlaxoSmithKline, Merck, Novartis, Pfizer, Takeda and the Wellcome Trust. Mas Chaponda was funded by a 3 year Wellcome Trust training fellowship WT078857MA administered through the University of Liverpool. Malawi-Liverpool-Wellcome Trust Clinical Research Programme is funded through a Core Programme Grant award from the Wellcome Trust. Munir Pirmohamed is a National Institute for Health Research Senior Investigator, and also wishes to thank the MRC Centre for Drug Safety Science for support. The DART study was supported by the UK Medical Research Council (grant number G0600344), the UK Department for International Development and the Rockefeller Foundation. Andrew P. Morris is a Wellcome Trust Senior Research Fellow in Basic Biomedical Science (grant number WT098017). Louise Y. Takeshita is funded by a PhD fellowship from CNPq (National Council for Scientific and Technological Development, Brazil). Panos Deloukas’ work forms part of the research themes contributing to the translational research portfolio of Barts Cardiovascular Biomedical Research Unit which is supported and funded by the National Institute for Health Research

Antimicrobial resistance (AMR) nanomachines: mechanisms for fluoroquinolone and glycopeptide recognition, efflux and/or deactivation

In this review, we discuss mechanisms of resistance identified in bacterial agents Staphylococcus aureus and the enterococci towards two priority classes of antibiotics—the fluoroquinolones and the glycopeptides. Members of both classes interact with a number of components in the cells of these bacteria, so the cellular targets are also considered. Fluoroquinolone resistance mechanisms include efflux pumps (MepA, NorA, NorB, NorC, MdeA, LmrS or SdrM in S. aureus and EfmA or EfrAB in the enterococci) for removal of fluoroquinolone from the intracellular environment of bacterial cells and/or protection of the gyrase and topoisomerase IV target sites in Enterococcus faecalis by Qnr-like proteins. Expression of efflux systems is regulated by GntR-like (S. aureus NorG), MarR-like (MgrA, MepR) regulators or a two-component signal transduction system (TCS) (S. aureus ArlSR). Resistance to the glycopeptide antibiotic teicoplanin occurs via efflux regulated by the TcaR regulator in S. aureus. Resistance to vancomycin occurs through modification of the D-Ala-D-Ala target in the cell wall peptidoglycan and removal of high affinity precursors, or by target protection via cell wall thickening. Of the six Van resistance types (VanA-E, VanG), the VanA resistance type is considered in this review, including its regulation by the VanSR TCS. We describe the recent application of biophysical approaches such as the hydrodynamic technique of analytical ultracentrifugation and circular dichroism spectroscopy to identify the possible molecular effector of the VanS receptor that activates expression of the Van resistance genes; both approaches demonstrated that vancomycin interacts with VanS, suggesting that vancomycin itself (or vancomycin with an accessory factor) may be an effector of vancomycin resistance. With 16 and 19 proteins or protein complexes involved in fluoroquinolone and glycopeptide resistances, respectively, and the complexities of bacterial sensing mechanisms that trigger and regulate a wide variety of possible resistance mechanisms, we propose that these antimicrobial resistance mechanisms might be considered complex ‘nanomachines’ that drive survival of bacterial cells in antibiotic environments

Brain Imaging of Pain

The brain is the principal processor of internal and external sensory experiences including pain. Pain is a multidimensional experience influenced by complex interactions among multiple processes including nociception (the afferent neural activity transmitting sensory information about noxious stimuli), cognitive appraisals (expectation, attention), and emotional aspects (affect)