Evaluation of N (epsilon)-(3-formyl-3,4-dehydropiperidino)lysine as a novel biomarker for the severity of diabetic retinopathy.

AIMS/HYPOTHESIS: Recent studies suggest that oxidative stress should be monitored alongside HbA(1c) to identify subgroups of diabetic patients at high risk of initiation or progression of retinopathy. The acrolein-derived advanced lipoxidation end-product (ALE), [Formula: see text]-(3-formyl-3,4-dehydropiperidino)lysine (FDP-lysine), is a useful biomarker that reflects the cumulative burden of oxidative stress over long periods of time. The purpose of the present study was to investigate whether serum and haemoglobin levels of FDP-lysine are associated with the severity of diabetic retinopathy in type 1 and type 2 diabetic patients.

METHODS: Serum and haemoglobin levels of FDP-lysine were measured by competitive ELISA in 59 type 1 and 76 type 2 diabetic patients with no retinopathy, non-proliferative retinopathy or proliferative retinopathy (mean age [+/-SEM] 54.3 +/- 1.3 years), and in 47 non-diabetic control individuals (mean age 51.9 +/- 2.1 years).

RESULTS: Serum and haemoglobin levels of FDP-lysine were significantly increased in diabetic patients compared with control individuals (p = 0.04 and p = 0.002, respectively). However, no significant association was found between levels of serum FDP-lysine and the severity of diabetic retinopathy (p = 0.97). In contrast, increased haemoglobin FDP-lysine levels were observed in patients with proliferative retinopathy compared with patients without retinopathy and with non-proliferative retinopathy (p = 0.04). The relationship of FDP-lysine with proliferative retinopathy was unaltered after adjustment for HbA(1c), or other clinical parameters.

CONCLUSIONS/INTERPRETATION: Our data suggest that haemoglobin FDP-lysine may provide a useful risk marker for the development of proliferative diabetic retinopathy independently of HbA(1c), and that elevated intracellular ALE formation may be involved in the pathogenesis of this sight-threatening complication of diabetes.

Gemini observations of Wolf-Rayet stars in the Local Group starburst galaxy IC 10

We present Gemini-N GMOS and CFHT MOS spectroscopy of Wolf-Rayet candidates in the Local Group dwarf galaxy IC 10 that were previously identified by Massey et al. and Royer et al. From the present spectroscopic survey, the WC/WN ratio for IC 10 remains unusually high, given its low metallicity, although none of the WC9 stars suspected from narrow-band imaging are confirmed. Our spectroscopy confirms 9 newly discovered Wolf-Rayet candidates from Royer et al., whilst spectral types of 14 Wolf-Rayet stars previously observed by Massey & Armandroff are refined here. In total, there are 26 spectroscopically confirmed Wolf-Rayet stars in IC 10. All but one of the fourteen WC stars are WC4-6 stars, the exception being # 10 from Massey et al., a broad-lined, apparently single WC7 star. There are a total of eleven WN stars, which are predominantly early WN3-4 stars, but include a rare WN10 star, # 8 from Royer et al. # 5 from Massey et al. is newly identified as a transition WN/C star. Consequently, the WC/WN ratio for IC10 is 14/11similar to1.3, unusually high for a metal-poor galaxy. Re-evaluating recent photometric data of Massey & Holmes, we suggest that the true WC/WN ratio may not be as low as similar to0.3. Finally, we present ground-based finding charts for all confirmed WR stars, plus HST/WFPC2 charts for twelve cases.

Haloalkane degradation and assimilation by Rhodococcus rhodochrous NCIMB -13064

The bacterium Rhodococcus rhodochrous NCIMB 13064, isolated from an industrial site, could use a wide range of 1-haloalkanes as sole carbon source but apparently utilized several different mechanisms simultaneously for assimilation of substrate. Catabolism of 1-chlorobutane occurred mainly by attack at the C-1 atom by a hydrolytic dehalogenase with the formation of butanol which was metabolized via butyric acid. The detection of small amounts of gamma-butyrolactone in the medium suggested that some oxygenase attack at C-4 also occurred, leading to the formation of 4-chlorobutyric acid which subsequently lactonized chemically to gamma-butyrolactone. Although 1-chlorobutane-grown cells exhibited little dehalogenase activity on 1-chloroalkanes with chain lengths above C-10, the organism utilized such compounds as growth substrates with the release of chloride. Concomitantly, gamma-butyrolactone accumulated to 1 mM in the culture medium with 1-chlorohexadecane as substrate. Traces of 4-hydroxybutyric acid were also detected. It is suggested that attack on the long-chain chloroalkane is initiated by an oxygenase at the non-halogenated end of the molecule leading to the formation of an omega-chlorofatty acid. This is degraded by beta-oxidation to 4-chlorobutyric acid which is chemically lactonized to gamma-butyrolactone which is only slowly further catabolized via 4-hydroxybutyric acid and succinic acid. However, release of chloride into the medium during growth on long-chain chloroalkanes was insufficient to account for all the halogen present in the substrate. Analysis of the fatty acid composition of 1-chlorohexadecane-grown cells indicated that chlorofatty acids comprised 75% of the total fatty acid content with C-14:0, C-16:0, C-16:1, and C-18:1 acids predominating. Thus the incorporation of 16-chlorohexadecanoic acid, the product of oxygenase attack directly into cellular lipid represents a third route of chloroalkane assimilation. This pathway accounts at least in part for the incomplete mineralization of long-chain chloroalkane substrates. This is the first report of the coexistence of a dehalogenase and the ability to incorporate long-chain haloalkanes into the lipid fraction within a single organism and raises important questions regarding the biological treatment of haloalkane containing effluents.

The global pharmacy workforce: a systematic review of the literature.

Hawthorne N, Anderson C. (2009) The global pharmacy workforce: a systematic review of the literature. Human Resources for Health, 7:48.

Novel Generic Bounds on the Sum Rate of MIMO ZF Receivers

This paper introduces some novel upper and lower bounds on the achievable sum rate of multiple-input multiple-output (MIMO) systems with zero-forcing (ZF) receivers. The presented bounds are not only tractable but also generic since they apply for different fading models of interest, such as uncorrelated/ correlated Rayleigh fading and Ricean fading. We further formulate a new relationship between the sum rate and the first negative moment of the unordered eigenvalue of the instantaneous correlation matrix. The derived expressions are explicitly compared with some existing results on MIMO systems operating with optimal and minimum mean-squared error (MMSE) receivers. Based on our analytical results, we gain valuable insights into the implications of the model parameters, such as the number of antennas, spatial correlation and Ricean-K factor, on the sum rate of MIMO ZF receivers. © 2011 IEEE.

A lesson in business: cost-effectiveness analysis of a novel financial incentive intervention for increasing physical activity in the workplace

Background: Recently both the UK and US governments have advocated the use of financial incentives to encourage healthier lifestyle choices but evidence for the cost-effectiveness of such interventions is lacking. Our aim was to perform a cost-effectiveness analysis (CEA) of a quasi-experimental trial, exploring the use of financial incentives to increase employee physical activity levels, from a healthcare and employer’s perspective.

Methods: Employees used a ‘loyalty card’ to objectively monitor their physical activity at work over 12 weeks. The Incentive Group (n=199) collected points and received rewards for minutes of physical activity completed. The No Incentive Group (n=207) self-monitored their physical activity only. Quality of life (QOL) and absenteeism were assessed at baseline and 6 months follow-up. QOL scores were also converted into productivity estimates using a validated algorithm. The additional costs of the Incentive Group were divided by the additional quality adjusted life years (QALYs) or productivity gained to calculate incremental cost effectiveness ratios (ICERs). Cost-effectiveness acceptability curves (CEACs) and population expected value of perfect information (EVPI) was used to characterize and value the uncertainty in our estimates.

Results: The Incentive Group performed more physical activity over 12 weeks and by 6 months had achieved greater gains in QOL and productivity, although these mean differences were not statistically significant. The ICERs were £2,900/QALY and £2,700 per percentage increase in overall employee productivity. Whilst the confidence intervals surrounding these ICERs were wide, CEACs showed a high chance of the intervention being cost-effective at low willingness-to-pay (WTP) thresholds.

Conclusions: The Physical Activity Loyalty card (PAL) scheme is potentially cost-effective from both a healthcare and employer’s perspective but further research is warranted to reduce uncertainty in our results. It is based on a sustainable “business model” which should become more cost-effective as it is delivered to more participants and can be adapted to suit other health behaviors and settings. This comes at a time when both UK and US governments are encouraging business involvement in tackling public health challenges.

Massive MIMO with Non-Ideal Arbitrary Arrays: Hardware Scaling Laws and Circuit-Aware Design

Massive multiple-input multiple-output (MIMO) systems are cellular networks where the base stations (BSs) are equipped with unconventionally many antennas, deployed on colocated or distributed arrays. Huge spatial degrees-of-freedom are achieved by coherent processing over these massive arrays, which provide strong signal gains, resilience to imperfect channel knowledge, and low interference. This comes at the price of more infrastructure; the hardware cost and circuit power consumption scale linearly/affinely with the number of BS antennas N. Hence, the key to cost-efficient deployment of large arrays is low-cost antenna branches with low circuit power, in contrast to today’s conventional expensive and power-hungry BS antenna branches. Such low-cost transceivers are prone to hardware imperfections, but it has been conjectured that the huge degrees-of-freedom would bring robustness to such imperfections. We prove this claim for a generalized uplink system with multiplicative phasedrifts, additive distortion noise, and noise amplification. Specifically, we derive closed-form expressions for the user rates and a scaling law that shows how fast the hardware imperfections can increase with N while maintaining high rates. The connection between this scaling law and the power consumption of different transceiver circuits is rigorously exemplified. This reveals that one can make the circuit power increase as p N, instead of linearly, by careful circuit-aware system design.

Organising EU non-discrimination law around the nodes of ‘race’ gender and disability?

EU non-discrimination law has seen a proliferation of discrimination grounds from 2000. Dis-crimination on grounds of gender (in the field of equal pay) and on grounds of nationality (generally within the scope of application of EU law) were the only prohibited forms of discrimination in EU law, until the Treaty of Amsterdam empowered the Community to legislate in order to combat discrimination on grounds of sex, racial or ethnic origin, religion or belief, disability, age or sexual orientation (Article 13 EC). Proliferation of non-discrimination grounds is also characteristic for international and national non-discrimination law. As such, proliferation of grounds results in an increase in potential cases of “multiple discrimination” and the danger of diluting the demands of equality law by ever more multiplication of grounds. The hierarchy of equality, which has been so widely criticised in EU law, is a signifier of the latter danger.
This chapter proposes to structure the confusing field of non-discrimination grounds by organising them around nodes of discrimination fields. It will first reflect different ways of establishing hierarchies between grounds. This will be followed by a recount of different (narrow and wide) reading of grounds. A comprehensive reading of the grounds gender, ‘race’ and disability as establishing overlapping fields of discrimination grounds will be mapped out, with some examples for practical uses.

Sharing services, saving money? Five risks to cost saving when organizations share administrative services

Shared services are a popular reform for governments under financial pressure. The hope is to reduce overheads and increase efficiency by providing support services like HR, finance and procurement once to multiple agencies. Drawing on insights from organization theory and political science, we identify five risks that shared services won’t live up to current expectations. We illustrate each with empirical evidence from the UK, Ireland and further afield, and conclude with suggestions on how to manage these risks.

Time-lapse Monitoring of the Slopes of a Heritage Earthwork by Means of Near-surface Seismic Techniques

A significant portion of UK’s infrastructures earthworks was built more than 100 years ago, without modern construction standards: poor maintenance and the change of precipitations pattern experienced in the past decades are currently compromising their stability, leading to an increasing number of failures. To address the need for a reliable and time-efficient monitoring of earthworks at risk of failure we propose here the use of two established seismic techniques for the characterization of the near surface, MASW and P-wave refraction. We have regularly collected MASW and P-wave refraction data, from March 2014 to February 2015, along 4 reduced-scale seismic lines located on the flanks of a heritage railway embankment located in Broadway, SW of England. We have observed a definite temporal variability in terms of phase velocities of SW dispersion curves and of P-wave travel times. The accurate choice of ad-hoc inversion strategies has allowed to reconstruct reliable VP and VS models through which it is potentially possible to track the temporal variations of geo-mechanical properties of the embankment slopes. The variability over time of seismic data and seismic velocities seems to correlate well with rainfall data recorded in the days immediately preceding the date of acquisition.

‘Disability and HIV in Africa: Breaking the barriers to sexual health care’

Three decades in to the HIV pandemic, the issues affecting people with disabilities remains less known. Increasing attention has been given to this overlooked population when it comes to HIV prevention, treatment and care. This is related to the significant unmet sexual and reproductive health care needs facing people with disabilities worldwide. This article discusses the barriers to sexual health for people with disabilities in Africa, and presents an argument about how mainstream HIV prevention work and research does not adequately attend to the sorts of systemic barriers that exclude people with disabilities, which a more targeted, and critical approach could.