A novel multilocus sequence typing scheme for the opportunistic pathogen Propionibacterium acnes and characterisation of type 1 cell surface-associated antigens

We have developed a novel multilocus sequence typing (MLST) scheme and database (http://pubmlst.org/pacnes/) for Propionibacterium acnes based on the analysis of seven core housekeeping genes. The scheme, which was validated against previously described antibody, single locus and random amplification of polymorphic DNA typing methods, displayed excellent resolution and differentiated 123 isolates into 37 sequence types (STs). An overall clonal population structure was detected with six eBURST groups representing the major clades I, II and III, along with two singletons. Two highly successful and global clonal lineages, ST6 (type IA) and ST10 (type IB1), representing 64?% of this current MLST isolate collection were identified. The ST6 clone and closely related single locus variants, which comprise a large clonal complex CC6, dominated isolates from patients with acne, and were also significantly associated with ophthalmic infections. Our data therefore support an association between acne and P. acnes strains from the type IA cluster and highlight the role of a widely disseminated clonal genotype in this condition. Characterization of type I cell surface-associated antigens that are not detected in ST10 or strains of type II and III identified two dermatan-sulphate-binding proteins with putative phase/antigenic variation signatures. We propose that the expression of these proteins by type IA organisms contributes to their role in the pathophysiology of acne and helps explain the recurrent nature of the disease. The MLST scheme and database described in this study should provide a valuable platform for future epidemiological and evolutionary studies of P. acnes.

Formation of type 1A fibre Bragg gratings in germanosillicate optical fibre

A report is made that the rate at which type IA fibre Bragg gratings may be inscribed is related to the intensity of the UV inscription laser and that these gratings may be written in only a few minutes. Also presented is the model of the refractive index of type IA gratings.

Fiber grating type dependence of temperature and strain coefficients and application to simultaneous temperature and strain measurement

Although fiber Bragg gratings (FBGs) have been widely used as advanced optical sensors, the cross-sensitivity between temperature and strain has complicated independent measurement procedures for these two measurands. We report here, for the first time to our knowledge, the results of a systematic investigation of the dependence of both temperature and strain sensitivities on the grating type, including the well-known Type I, Type IIA, and a new type which we have designated Type IA, using both hydrogen-free and hydrogenated B/Ge codoped fibers. We have identified distinct sensitivity characteristics for each grating type, and we have utilised them to implement a novel dual-grating, dual-parameter sensor device with performance superior to that of previously reported grating-based structures.

A new phylogenetic group of Propionibacterium acnes

Immunofluorescence microscopy-based identification of presumptive Propionibacterium acnes isolates, using the P. acnes-specific mAb QUBPa3, revealed five organisms with an atypical cellular morphology. Unlike the coryneform morphology seen with P. acnes types I and II, these isolates exhibited long slender filaments (which formed large tangled aggregates) not previously described in P. acnes. No reaction with mAbs that label P. acnes types IA (QUBPa1) and II (QUBPa2) was observed. Nucleotide sequencing of the 16S rRNA gene (1484 bp) revealed the isolates to have between 99.8 and 99.9 % identity to the 16S rRNA gene of the P. acnes type IA, IB and II strains NCTC 737, KPA171202 and NCTC 10390, respectively. Analysis of the recA housekeeping gene (1047 bp) did reveal, however, a greater number of conserved nucleotide polymorphisms between the sequences from these isolates and those from NCTC 737 (98.9 % identity), KPA171202 (98.9 % identity) and NCTC 10390 (99.1 % identity). Phylogenetic investigations demonstrated that the isolates belong to a novel recA cluster or lineage distinct from P. acnes types I and II. We now propose this new grouping as P. acnes type III. The prevalence and clinical importance of this novel recA lineage amongst isolates of P. acnes remains to be determined.

Genotypic and antimicrobial characterisation of Propionibacterium acnes isolates from surgically excised lumbar disc herniations

The anaerobic skin commensal Propionibacterium acnes is an underestimated cause of human infections and clinical conditions. Previous studies have suggested a role for the bacterium in lumbar disc herniation and infection. To further investigate this, five biopsy samples were surgically excised from each of 64 patients with lumbar disc herniation. P. acnes and other bacteria were detected by anaerobic culture, followed by biochemical and PCR-based identification. In total, 24/64 (38%) patients had evidence of P. acnes in their excised herniated disc tissue. Using recA and mAb typing methods, 52% of the isolates were type II (50% of culture-positive patients), while type IA strains accounted for 28% of isolates (42% patients). Type III (11% isolates; 21% patients) and type IB strains (9% isolates; 17% patients) were detected less frequently. The MIC values for all isolates were lowest for amoxicillin, ciprofloxacin, erythromycin, rifampicin, tetracycline, and vancomycin (≤1mg/L). The MIC for fusidic acid was 1-2 mg/L. The MIC for trimethoprim and gentamicin was 2 to ≥4 mg/L. The demonstration that type II and III strains, which are not frequently recovered from skin, predominated within our isolate collection (63%) suggests that the role of P. acnes in lumbar disc herniation should not be readily dismissed. © 2013 Jess Rollason et al.

Use of dual-grating sensors formed by different types of fiber Bragg gratings for simultaneous temperature and strain measurements

We report on a systematic investigation of the dependence of both temperature and strain sensitivities on the fiber Bragg grating type, including the well-known Type I, Type IIA, and a new type that we have designated Type IA, using both hydrogen-free and hydrogenated B/Ge codoped fibres. We have identified distinct sensitivity characteristics for each grating type, and we have used them to implement a novel dual-grating, dual-parameter sensor device. Three dual-grating sensing schemes with different combinations of grating type have been constructed and compared, and that of a Type IA-Type IIA combination exhibits the best performance, which is also superior to that of previously reported grating-based structures. The characteristics of the measurement errors in such dual-grating sensor systems is also presented in detail. © 2004 Optical Society of America.

Advanced UV inscribed fibre grating structures and applications in optical sensing and laser systems

This thesis presents detailed investigation of UV inscribed fibre grating based devices and novel developments in the applications of such devices in optical sensing and fibre laser systems. The major contribution of this PhD programme includes the systematic study on fabrication, spectral characteristics and applications of different types of UV written in-fibre gratings such as Type I and IA Fibre Bragg Gratings (FBGs), Chirped Fibre Bragg Gratings (CFBGs) and Tilted Fibre Gratings (TFGs) with small, large and 45º tilted structures inscribed in normal silica fibre. Three fabrication techniques including holographic, phase-mask and blank beam exposure scanning, which were employed to fabricate a range of gratings in standard single mode fibre, are fully discussed. The thesis reports the creation of smart structures with self-sensing capability by embedding FBG-array sensors in Al matrix composite. In another part of this study, we have demonstrated the particular significant improvements made in sensitising standard FBGs to the chemical surrounding medium by inducing microstructure to the grating by femtosecond (fs) patterning assisted chemical etching technique. Also, a major work is presented for the investigation on the structures, inscription methods and spectral Polarisation Dependent Loss (PDL) and thermal characteristics of different angle TFGs. Finally, a very novel application in realising stable single polarisation and multiwavelength switchable Erbium Doped Fibre Lasers (EDFLs) using intracavity polarisation selective filters based on TFG devices with tilted structures at small, large and exact 45° angles forms another important contribution of this thesis.

The potential use of bio-ultracarbofluids in a standard diesel engine

The replacement of diesel fuel by ultra-carbofluids was perceived to offer the potential to decrease the emissions of environmental pollutants such as carbon dioxide, carbon monoxide, hydrocarbons (HC's) and smoke. Such ultracarbofluids consist of a suspension of coal in fuel oil and water generally in the ratio of 5: 3: 2 plus a small amount of stabilising additive. The literature relating to the economies of coal and fuel oil production, and the production and properties of charcoal and vegetable oils has been critically reviewed. The potential use of charcoal and vegetable oils as replacements for coal and fuel oil are discussed. An experimental investigation was undertaken using novel bio-ultracarbofluid formulations. These differed from an ultracarbofluid by having bio-renewable charcoal and vegetable oil in place of coal and fuel oil. Tests were made with a Lister-Petter 600cc 2-cylinder, 4-stroke diesel engine fitted with a Heenan-Froude DPX 1 water brake dynamometer to measure brake power output, and Mexa-321E and Mexa-211E analysers to measure exhaust pollutants. Measurements were made of engine brake power output, carbon dioxide, carbon monoxide, hydrocarbons and smoke emissions over the speed range 1000 to 3000 rpm at 200 rpm intervals. The results were compared with those obtained with a standard diesel reference fuel. All the bio-ultracarbofluid formulations produced lower brake power outputs (i.e. 5.6% to 20.7% less brake power) but substantially improved exhaust emissions of CO2, CO, HC's and smoke. The major factor in the formulation was found to be the type and amount of charcoal; charcoal with a high volatile content (27.2%) and present at 30% by mass yielded the best results, i.e. only slightly lower brake power output and significantly lower exhaust pollutants.

Education and self-management for people newly diagnosed with type 2 diabetes: a qualitative study of patients' views.

OObjectives: We explored the perceptions, views and experiences of diabetes education in people with type 2 diabetes who were participating in a UK randomized controlled trial of methods of education. The intervention arm of the trial was based on DESMOND, a structured programme of group education sessions aimed at enabling self-management of diabetes, while the standard arm was usual care from general practices. Methods: Individual semi-structured interviews were conducted with 36 adult patients, of whom 19 had attended DESMOND education sessions and 17 had been randomized to receive usual care. Data analysis was based on the constant comparative method. Results: Four principal orientations towards diabetes and its management were identified: `resisters', `identity resisters, consequence accepters', `identity accepters, consequence resisters' and `accepters'. Participants offered varying accounts of the degree of personal responsibility that needed to be assumed in response to the diagnosis. Preferences for different styles of education were also expressed, with many reporting that they enjoyed and benefited from group education, although some reported ambivalence or disappointment with their experiences of education. It was difficult to identify striking thematic differences between accounts of people on different arms of the trial, although there was some very tentative evidence that those who attended DESMOND were more accepting of a changed identity and its implications for their management of diabetes. Discussion: No one single approach to education is likely to suit all people newly diagnosed with diabetes, although structured group education may suit many. This paper identifies varying orientations and preferences of people with diabetes towards forms of both education and self-management, which should be taken into account when planning approaches to education.

SGLT2 inhibitors:glucuretic treatment for type 2 diabetes

Sodium glucose co-transporter-2 (SGLT2) inhibitors offer a novel approach to treat diabetes by reducing hyperglycaemia via increased glucosuria. This approach reduces renal glucose reabsorption in the proximal renal tubules providing an insulin-independent mechanism to lower blood glucose. The glucuretics are advanced in clinical development and dapagliflozin has received most extensive study. Once daily dapaglifolozin as monotherapy or as add-on to metformin for 12-24 weeks in type 2 diabetic patients (baseline HbA 8-9%) reduced HbA by about 0.5-1%, accompanied by weight loss (2-3 kg) and without significant risk of hypoglycaemia. Dapagliflozin has reduced insulin requirement and improved glycaemic control without weight gain in insulin-treated patients. A mild osmotic diuresis associated with glucuretic therapy may account for a small increase in haematocrit (1-2%) and reduced blood pressure (2-5 mmHg). Dehydration and altered electrolyte balance have not been encountered. Urinary tract and genital infections increased in most studies with dapagliflozin, but were typically mild - resolving with selfmedication or standard intervention. Thus glucuretics provide a novel insulin-independent approach for control of hyperglycaemia which does not incur hypoglycaemia, promotes weight loss, may reduce blood pressure and offers compatibility with other glucose-lowering agents. © 2010 The Author(s).

Ethnic differences in health related quality of life for patients with type 2 diabetes

Background - The objective of this study was to investigate the association between ethnicity and health related quality of life (HRQoL) in patients with type 2 diabetes. Methods - The EuroQol EQ-5D measure was administered to 1,978 patients with type 2 diabetes in the UK Asian Diabetes Study (UKADS): 1,486 of south Asian origin (Indian, Pakistani, Bangladeshi or other south Asian) and 492 of white European origin. Multivariate regression using ordinary least square (OLS), Tobit, fractional logit and Censored Least Absolutes Deviations estimators was used to estimate the impact of ethnicity on both visual analogue scale (VAS) and utility scores for the EuroQol EQ-5D. Results - Mean EQ-5D VAS and utility scores were lower among south Asians with diabetes compared to the white European population; the unadjusted effect on the mean EQ-5D VAS score was −7.82 (Standard error [SE] = 1.06, p < 0.01) and on the EQ-5D utility score was −0.06 (SE = 0.02, p < 0.01) (OLS estimator). After controlling for socio-demographic and clinical confounders, the adjusted effect on the EQ-5D VAS score was −9.35 (SE = 2.46, p < 0.01) and on the EQ-5D utility score was 0.06 (SE = 0.04), although the latter was not statistically significant. Conclusions - There was a large and statistically significant association between south Asian ethnicity and lower EQ-5D VAS scores. In contrast, there was no significant difference in EQ-5D utility scores between the south Asian and white European sub-groups. Further research is needed to explain the differences in effects on subjective EQ-5D VAS scores and population-weighted EQ-5D utility scores in this context.

Elevated serum free light chains predict cardiovascular events in type 2 diabetes

OBJECTIVE: Elevated polyclonal serum immunoglobulin free light chains (FLCs; combined FLCκ+FLCλ [cFLC]) are associated with adverse clinical outcomes and increased mortality; we investigated cFLC and cardiovascular disease (CVD) events in type 2 diabetes. RESEARCH DESIGN AND METHODS: In a cohort study of 352 south Asian patients with type 2 diabetes, serum cFLC, high-sensitivity C-reactive protein (hsCRP), and standard biochemistry were measured. CVD events over 2 years were recorded and assessed usingmultiple logistic regression. RESULTS: cFLC levels were elevated significantly in 29 of 352 (8%) patients with CVD events during 2 years of follow-up (50.7 vs. 42.8mg/L; P = 0.004). Inmultivariate analysis, elevated cFLC (>57.2 mg/L) was associated with CVD outcomes (odds ratio 3.3 [95% CI 1.3-8.2]; P = 0.012) and remained significant after adjusting for age, albumin-to-creatinine ratio, diabetes duration, or treatment. CONCLUSIONS: cFLC elevation is a novel marker for CVD outcomes in type 2 diabetes that warrants further investigation. © 2014 by the American Diabetes Association.

Density forecasts of crude-oil prices using option-implied and ARCH-type models

The predictive accuracy of competing crude-oil price forecast densities is investigated for the 1994–2006 period. Moving beyond standard ARCH type models that rely exclusively on past returns, we examine the benefits of utilizing the forward-looking information that is embedded in the prices of derivative contracts. Risk-neutral densities, obtained from panels of crude-oil option prices, are adjusted to reflect real-world risks using either a parametric or a non-parametric calibration approach. The relative performance of the models is evaluated for the entire support of the density, as well as for regions and intervals that are of special interest for the economic agent. We find that non-parametric adjustments of risk-neutral density forecasts perform significantly better than their parametric counterparts. Goodness-of-fit tests and out-of-sample likelihood comparisons favor forecast densities obtained by option prices and non-parametric calibration methods over those constructed using historical returns and simulated ARCH processes. © 2010 Wiley Periodicals, Inc. Jrl Fut Mark 31:727–754, 2011

Metformin - The gold standard:a scientific handbook

Metformin may play in important role in the future in helping to prevent the development of diabetes: it is a strong candidate therapy for delaying the onset of the disease and potentially as part of a treatment programme to correct features of the metabolic syndrome. This book celebrates 50 years of research into metformin and its use in the treatment of diabetes. Metformin is still the drug of choice for managing patients with type 2 diabetes and all new drugs are tested in comparison with this, the gold standard. Comprising seven sections, addressing different aspects of research on metformin and its applications, this book is edited by a world class team of expert diabetologists and beautifully presented in two colour throughout. It also includes a bibliography of all papers published on metformin and a complete list of all authors on those papers.

Sensor and software use for the glycaemic management of insulin-treated type 1 and type 2 diabetes patients

Lowering glucose levels, while avoiding hypoglycaemia, can be challenging in insulin-treated patients with diabetes. We evaluated the role of ambulatory glucose profile in optimising glycaemic control in this population. Insulin-treated patients with type 1 and type 2 diabetes were recruited into a prospective, multicentre, 100-day study and randomised to control (n = 28) or intervention (n = 59) groups. The intervention group used ambulatory glucose profile, generated by continuous glucose monitoring, to assess daily glucose levels, whereas the controls relied on capillary glucose testing. Patients were reviewed at days 30 and 45 by the health care professional to adjust insulin therapy. Comparing first and last 2 weeks of the study, ambulatory glucose profile-monitored type 2 diabetes patients (n = 28) showed increased time in euglycaemia (mean ± standard deviation) by 1.4 ± 3.5 h/day (p = 0.0427) associated with reduction in HbA1c from 77 ± 15 to 67 ± 13 mmol/mol (p = 0.0002) without increased hypoglycaemia. Type 1 diabetes patients (n = 25) showed reduction in hypoglycaemia from 1.4 ± 1.7 to 0.8 ± 0.8 h/day (p = 0.0472) associated with a marginal HbA1c decrease from 75 ± 10 to 72 ± 8 mmol/mol (p = 0.0508). Largely similar findings were observed comparing intervention and control groups at end of study. In conclusion, ambulatory glucose profile helps glycaemic management in insulin-treated diabetes patients by increasing time spent in euglycaemia and decreasing HbA1c in type 2 diabetes patients, while reducing hypoglycaemia in type 1 diabetes patients.