Concurrent validity and test-retest reliability of the Polhemus Liberty for the measurement of spinal range

This paper discusses concurrent validity and test-retest reliability of the Polhemus Liberty for the measurement of spinal range.It was presented at the International Society of Biomechanics, XXII World Congress, in 2009

Combined information from Raman spectroscopy and optical coherence tomography for enhanced diagnostic accuracy in tissue discrimination

We thank the UK EPSRC for funding, the CR-UK/EPSRC/MRC/DoH (England) imaging programme, the European Union project FAMOS (FP7 ICT, contract no. 317744) and the European Union project IIIOS (FP7/2007-2013, contract no. 238802). We thank Tayside Tissue Bank for providing us with the tissue samples under request number TR000289. K.D. is a Royal Society-Wolfson Merit Award Holder.Optical spectroscopy and imaging methods have proved to have potential to discriminate between normal and abnormal tissue types through minimally invasive procedures. Raman spectroscopy and Optical Coherence Tomography (OCT) provides chemical and morphological information of tissues respectively, which are complementary to each other. When used individually they might not be able to obtain high enough sensitivity and specificity that is clinically relevant. In this study we combined Raman spectroscopy information with information obtained from OCT to enhance the sensitivity and specificity in discriminating between Colonic Adenocarcinoma from Normal Colon. OCT being an imaging technique, the information from this technique is conventionally analyzed qualitatively. To combine with Raman spectroscopy information, it was essential to quantify the morphological information obtained from OCT. Texture analysis was used to extract information from OCT images, which in-turn was combined with the information obtained from Raman spectroscopy. The sensitivity and specificity of the classifier was estimated using leave one out cross validation (LOOCV) method where support vector machine (SVM) was used for binary classification of the tissues. The sensitivity obtained using Raman spectroscopy and OCT individually was 89% and 78% respectively and the specificity was 77% and 74% respectively. Combining the information derived using the two techniques increased both sensitivity and specificity to 94% demonstrating that combining complementary optical information enhances diagnostic accuracy. These results demonstrate that a multimodal approach using Raman-OCT would be able to enhance the diagnostic accuracy for identifying normal and cancerous tissue types.Publisher PD

Discrimination of bladder cancer cells from normal urothelial cells with high specificity and sensitivity:combined application of atomic force microscopy and modulated Raman spectroscopy

Atomic force microscopy (AFM) and modulated Raman spectroscopy (MRS) were used to discriminate between living normal human urothelial cells (SV-HUC-1) and bladder tumour cells (MGH-U1) with high specificity and sensitivity. MGH-U1 cells were 1.5-fold smaller, 1.7-fold thicker and 1.4-fold rougher than normal SV-HUC-1 cells. The adhesion energy was 2.6-fold higher in the MGH-U1 cells compared to normal SV-HUC-1 cells, which possibly indicates that bladder tumour cells are more deformable than normal cells. The elastic modulus of MGH-U1 cells was 12-fold lower than SV-HUC-1 cells, suggesting a higher elasticity of the bladder cancer cell membranes. The biochemical fingerprints of cancer cells displayed a higher DNA and lipid content, probably due to an increase in the nuclear to cytoplasm ratio. Normal cells were characterized by higher protein contents. AFM studies revealed a decrease in the lateral dimensions and an increase in thickness of cancer cells compared to normal cells; these studies authenticate the observations from MRS. Nanostructural, nanomechanical and biochemical profiles of bladder cells provide qualitative and quantitative markers to differentiate between normal and cancerous cells at the single cellular level. AFM and MRS allow discrimination between adhesion energy, elasticity and Raman spectra of SV-HUC-1 and MGH-U1 cells with high specificity (83, 98 and 95%) and sensitivity (97, 93 and 98%). Such single-cell-level studies could have a pivotal impact on the development of AFM–Raman combined methodologies for cancer profiling and screening with translational significance

Mapping the methylation status of the miR-145 promoter in saphenous vein smooth muscle cells from individuals with type 2 diabetes

Type 2 diabetes mellitus prevalence is growing globally, and the leading cause of mortality in these patients is cardiovascular disease. Epigenetic mechanisms such as microRNAs (miRs) and DNA methylation may contribute to complications of type 2 diabetes mellitus. We discovered an aberrant type 2 diabetes mellitus–smooth muscle cell phenotype driven by persistent up-regulation of miR-145. This study aimed to determine whether elevated expression was due to changes in methylation at the miR-145 promoter. Smooth muscle cells were cultured from saphenous veins of 22 non-diabetic and 22 type 2 diabetes mellitus donors. DNA was extracted, bisulphite treated and pyrosequencing used to interrogate methylation at 11 CpG sites within the miR-145 promoter. Inter-patient variation was high irrespective of type 2 diabetes mellitus. Differential methylation trends were apparent between non-diabetic and type 2 diabetes mellitus–smooth muscle cells at most sites but were not statistically significant. Methylation at CpGs −112 and −106 was consistently lower than all other sites explored in non-diabetic and type 2 diabetes mellitus–smooth muscle cells. Finally, miR-145 expression per se was not correlated with methylation levels observed at any site. The persistent up-regulation of miR-145 observed in type 2 diabetes mellitus–smooth muscle cells is not related to methylation at the miR-145 promoter. Crucially, miR-145 methylation is highly variable between patients, serving as a cautionary note for future studies of this region in primary human cell types

Struggling for food in a time of crisis: Responsibility and paradox

Responsibility is a useful lens through which to examine the current state of food poverty in the UK in the context of the Covid‐19 crisis, noting that this concept contains several paradoxes. Currently, responsibility involves the voluntary sector, the food industry and the state, a situation which the author has been exploring for the last five years in an ethnographic study of food poverty and food aid in the UK. Food aid organizations, especially food banks, have mushroomed during the period of austerity. This reveals the first paradox: namely, that the existence of food banks conveys the message that ‘something is being done’, but in actuality this is very far from being sufficient to meet the needs of either the ‘old’ or ‘new’ food insecure. The second paradox is that at the onset of the crisis, a government which had been responsible for inflicting austerity on the country for 10 years, dramatically reversed some of its policies. However, predictably, this did not change the situation vis‐à‐vis food insecurity. The third paradox is that the frequent rhetoric invoking the two world wars has not resulted in lessons being learned – notably, the creation of a ministry to deal with food and rationing, as in the Second World War. The final paradox relates to Brexit and its likely deleterious effects on food security, particularly if no ‘deal’ is achieved with the European Union, as seems likely. The voluntary food aid sector, try as it may, cannot possibly assume responsibility for the long‐standing and now hugely increased problems of food insecurity. That belongs to the state

Tensile properties of the transverse carpal ligament and carpal tunnel complex

A new sophisticated method that uses video analysis techniques together with a Maillon Rapide Delta to determine the tensile properties of the transverse carpal ligament–carpal tunnel complex has been developed. Six embalmed cadaveric specimens amputated at the mid-forearm and aged (mean (SD)): 82 (6.29) years were tested. The six hands were from three males (four hands) and one female (two hands). Using trigonometry and geometry the elongation and strain of the transverse carpal ligament and carpal arch were calculated. The cross-sectional area of the transverse carpal ligament was determined. Tensile properties of the transverse carpal ligament–carpal tunnel complex and Load–Displacement data were also obtained. Descriptive statistics, one-way ANOVA together with a post-hoc analysis (Tukey) and t-tests were incorporated. A transverse carpal ligament–carpal tunnel complex novel testing method has been developed. The results suggest that there were no significant differences between the original transverse carpal ligament width and transverse carpal ligament at peak elongation (P= 0.108). There were significant differences between the original carpal arch width and carpal arch width at peak elongation (P=0.002). The transverse carpal ligament failed either at the mid-substance or at their bony attachments. At maximum deformation the peak load and maximum transverse carpal ligament displacements ranged from 285.74 N to 1369.66 N and 7.09 mm to 18.55 mm respectively. The transverse carpal ligament cross-sectional area mean (SD) was 27.21 (3.41)mm2. Using this method the results provide useful biomechanical information and data about the tensile properties of the transverse carpal ligament–carpal tunnel complex

Aberrant phenotype in human endothelial cells of diabetic origin: Implications for saphenous vein graft failure?

Type 2 diabetes (T2DM) confers increased risk of endothelial dysfunction, coronary heart disease, and vulnerability to vein graft failure after bypass grafting, despite glycaemic control. This study explored the concept that endothelial cells (EC) cultured from T2DM and nondiabetic (ND) patients are phenotypically and functionally distinct. Cultured human saphenous vein-(SV-) EC were compared between T2DM and ND patients in parallel. Proliferation, migration, and in vitro angiogenesis assays were performed; western blotting was used to quantify phosphorylation of Akt, ERK, and eNOS. The ability of diabetic stimuli (hyperglycaemia, TNF-α, and palmitate) to modulate angiogenic potential of ND-EC was also explored. T2DM-EC displayed reduced migration (30%) and angiogenesis (40%) compared with ND-EC and a modest, nonsignificant trend to reduced proliferation. Significant inhibition of Akt and eNOS, but not ERK phosphorylation, was observed in T2DM cells. Hyperglycaemia did not modify ND-EC function, but TNF-α and palmitate significantly reduced angiogenic capacity (by 27% and 43%, resp.), effects mimicked by Akt inhibition. Aberrancies of EC function may help to explain the increased risk of SV graft failure in T2DM patients. This study highlights the importance of other potentially contributing factors in addition to hyperglycaemia that may inflict injury and long-term dysfunction to the homeostatic capacity of the endothelium

Impact of controlled vacuum induced surface freezing on the freeze drying of human plasma

During the freezing step of a typical freeze drying process, the temperature at which nucleation is induced is generally stochastically distributed, resulting in undesired within-batch heterogeneity. Controlled nucleation techniques have been developed to address this problem; these make it possible to trigger the formation of ice crystals at the same time and temperature in all the batch. Here, the controlled nucleation technique known as vacuum induced surface freezing is compared to spontaneous freezing for the freeze drying of human plasma, a highly concentrated system commonly stored in a dried state. The potency of Factor VIII (FVIII), a sensitive, labile protein present in plasma, and the reconstitution time of the dried cakes are evaluated immediately after freeze drying, and after 1, 3, 6 or 9 months storage at different degradation temperatures. We show that the application of controlled nucleation significantly reduces the reconstitution time and in addition helps to improve FVIII stability