Aims Nucleic acids, particularly antibiotic resistance genes, are commonly found on surfaces within healthcare environments, with levels not reducing following cleaning. Within the UK, there are no regulations for testing disinfectants against nucleic acids.Methods and results A series of commonplace in vitro methods were used to determine disinfectant-induced physical and functional damage to various nucleic acids; RNA (10 mu g), genomic DNA (2 mu g), and plasmids (1 mu g). Using these methods, the optimal residence time (10 minutes) and working concentration (10%) were determined for a new disinfectant. Furthermore, comparison of disinfectants with different active ingredients including lactic acid (LA), sodium hydroxide (NaOH), chloroxylenol (PCMX), and quaternary ammonium compounds (QACs), were compared to controls. All disinfectants showed greater degradation by gel electrophoresis of genomic DNA and RNA than of purified plasmids. Functional analysis using quantitative polymerase chain reaction (qPCR) and polymerase chain reaction (PCR) demonstrated that no disinfectant tested (apart from control) could damage DNA to the level where PCR amplification was not possible, and only the NaOH reagent could achieve this for RNA.Conclusions The set of methods described herein provides a platform for future standardization and potential regulation regarding monitoring cleaning solutions for their activity against nucleic acids.

IntroductionThrombosis is a severe and frequent complication of heparin-induced thrombocytopenia (HIT). However, there is currently no knowledge of the effects of HIT-like antibodies on the resulting microstructure of the formed clot, despite such information being linked to thrombotic events. We evaluate the effect of the addition of pathogenic HIT-like antibodies to blood on the resulting microstructure of the formed clot.Materials and methodsPathogenic HIT-like antibodies (KKO) and control antibodies (RTO) were added to samples of whole blood containing Unfractionated Heparin and Platelet Factor 4. The formed clot microstructure was investigated by rheological measurements (fractal dimension; df) and scanning electron microscopy (SEM), and platelet activation was measured by flow cytometry.Results and conclusionsOur results revealed striking effects of KKO on clot microstructure. A significant difference in df was found between samples containing KKO (df = 1.80) versus RTO (df = 1.74; p < 0.0001). This increase in df was often associated with an increase in activated platelets. SEM images of the clots formed with KKO showed a network consisting of a highly branched and compact arrangement of thin fibrin fibres, typically found in thrombotic disease. This is the first study to identify significant changes in clot microstructure formed in blood containing HIT-like antibodies. These observed alterations in clot microstructure can be potentially exploited as a much-needed biomarker for the detection, management and monitoring of HIT-associated thrombosis.

Background: One of the main challenges for extrusion 3D bioprinting is the identification of non-synthetic bioinks with suitable rheological properties and biocompatibility. Our aim was to optimize and compare the printability of crystal, fibril and blend formulations of novel pulp derived nanocellulose bioinks and assess biocompatibility with human nasoseptal chondrocytes. Methods: The printability of crystalline, fibrillated and blend formulations of nanocellulose was determined by assessing resolution (grid-line assay), post-printing shape fidelity and rheology (elasticity, viscosity and shear thinning characteristics) and compared these to pure alginate bioinks. The optimized nanocellulose-alginate bioink was bioprinted with human nasoseptal chondrocytes to determine cytotoxicity, metabolic activity and bioprinted construct topography. Results: All nanocellulose-alginate bioink combinations demonstrated a high degree of shear thinning with reversible stress softening behavior which contributed to post-printing shape fidelity. The unique blend of crystal and fibril nanocellulose bioink exhibited nano- as well as micro-roughness for cellular survival and differentiation, as well as maintaining the most stable construct volume in culture. Human nasoseptal chondrocytes demonstrated high metabolic activity post printing and adopted a rounded chondrogenic phenotype after prolonged culture. Conclusions: This study highlights the favorable rheological, swelling and biocompatibility properties of nanocellulose-alginate bioinks for extrusion-based bioprinting.

Medical devices, such as ventricular assist devices (VADs), introduce both foreign materials and artificial shear stress to the circulatory system. The effects these have on leukocytes and the immune response are not well understood. Understanding how these two elements combine to affect leukocytes may reveal why some patients are susceptible to recurrent device-related infections and provide insight into the development of pump thrombosis. Biomaterials-DLC: diamond-like carbon-coated stainless steel; Sap: single-crystal sapphire; and Ti: titanium alloy (Ti6 Al4 V) were attached to the parallel plates of a rheometer. Whole human blood was left between the two discs for 5 minutes at +37°C with or without the application of shear stress (0 s-1 or 1000 s-1 ). Blood was removed and used for complete blood cell counts, flow cytometry (leukocyte activation, cell death, microparticle generation, phagocytic ability, and reactive oxygen species [ROS] production), and the production of pro-inflammatory cytokines. L-selectin expression on monocytes was decreased when blood was exposed to the biomaterials both with and without shear. Applying shear stress to blood on a Sap and Ti surface led to activation of neutrophils shown as decreased L-selectin expression. Sap and Ti blunted the LPS-stimulated macrophage migration inhibitory factor (MIF) production, most notably when sheared on Ti. The biomaterials used here have been shown to activate leukocytes in a static environment. The introduction of shear appears to exacerbate this activation. Interestingly, a widely accepted biocompatible material (Ti) utilized in many different types of devices has the capacity for immune cell activation and inhibition of MIF secretion when combined with shear stress. These findings contribute to our understanding of the contribution of biomaterials and shear stress to recurrent infections and vulnerability to sepsis in some VAD patients as well as pump thrombosis.

For the first time, we report on the superior performance of the dual-drain gallium nitride (GaN) magnetic field-effect transistor (MagFET) at elevated temperatures. The IV characteristics of the devices reported here were collected under dc conditions and tested at elevated temperatures, 300, 323, 373, and 448 K using a custom-made heating stage, with a thermal feedback loop to accurately control the temperature. Light exposure experiments were conducted during raised temperature levels using an LED light source of wavelength 470 nm. The relative sensitivity of the GaN dual-drain MagFET was calculated and demonstrated a degradation from 9.78% T-1 at 300 K to 8.36% T-1 at 323 K, 6.10% T-1 at 373 K, and 3.79% T-1 at 448 K. This is equal to a small sensitivity decrease of 0.04% T-1/K. It is proposed that the observed reduction in sensitivity reported herein is due to increased phonon scattering in the 2-D electron gas channel. Despite this reduced sensitivity at elevated temperatures, the lowest sensitivity measured at 448 K surpasses those reported for silicon competitors.

The three-dimensional simulations, calibration, measured currents and calculated relative sensitivities of the first-ever fabricated double-drain gallium nitride (GaN) magnetic field effect transistor (MagFET) are given in this work. The MagFETs are GaN high electron mobility transistors (HEMTs) capable of operating under harsh environments. Geometrical and operational analysis are carried out on MagFETs using commercial simulation software Silvaco. The analysis shows promising relative sensitivities of 6.84%T-1 and 5.04%T-1 at ambient temperatures of 400 K and 500 K, respectively. In addition, the relative sensitivity of fabricated device is improved from 12%T-1 to 24%T-1 at 300 K by optimising device geometrical parameters.

The suitability of controlled stress large amplitude oscillatory shear (LAOStress) for the characterisation of the nonlinear viscoelastic properties of fully formed fibrin clots is investigated. Capturing the rich nonlinear viscoelastic behaviour of the fibrin network is important for understanding the structural behaviour of clots formed in blood vessels which are exposed to a wide range of shear stresses. We report, for the first time, that artefacts due to ringing exist in both the sample stress and strain waveforms of a LAOStress measurement which will lead to errors in the calculation of nonlinear viscoelastic properties. The process of smoothing the waveforms eliminates these artefacts whilst retaining essential rheological information. Furthermore, we demonstrate the potential of LAOStress for characterising the nonlinear viscoelastic properties of fibrin clots in response to incremental increases of applied stress up to the point of fracture. Alternating LAOStress and small amplitude oscillatory shear measurements provide detailed information of reversible and irreversible structural changes of the fibrin clot as a consequence of elevated levels of stress. We relate these findings to previous studies involving large scale deformations of fibrin clots. The LAOStress technique may provide useful information to help understand why some blood clots formed in vessels are stable (such as in deep vein thrombosis) and others break off (leading to a life threatening pulmonary embolism).

Hospital at Home (HAH) care, where acutely unwell patients are treated at home is widely accepted across the world as a cost effective alternative to inpatient care for specific adult groups. HAH is utilised for the paediatric population in many countries although it is not a service routinely offered in the UK. This review investigates whether HAH care could be an acceptable and cost effective option for acutely unwell paediatric patients in the UK.

A unique atlas giving a comprehensive picture of the effect of the recession on Britain. Essential reading for a broad audience with a national snap-shot of Britain during this time.

Background Suicide rates changed considerably in men aged <45 years in England and Wales between 1980 and 2005. The impact of these changes on the geographic distribution of suicide is unknown.Methods Mapping of geo-coded standardised mortality ratios for suicide in 1113 census tracts (mean population 46 000) in England and Wales, smoothed using Bayesian hierarchical models, for 15-44 year old men during 1981-1985, 1991-1995 and 2001-2005.Results Young male suicide rates rose by 50% between the early 1980s and the 1990s but declined to pre-1980 levels by 2005. The spatial distribution of suicide changed markedly over these years. The 'bull'seye' pattern of increases in suicide rates from the suburbs to the centre of London was abolished, although they persisted in other major cities. Suicide rates among young men in Wales changed from being relatively lower than other regions to being considerably higher. Similarly, by 2001-2005 suicide rates in northern and south western regions were relatively higher than elsewhere with the predominant feature being a north-west/ south-east divide in suicide. These changes in the spatial epidemiology of suicide were not explained by changes in area levels of single person households, unemployment or the unmarried population.Conclusion There has been a marked change in the spatial epidemiology of suicide in young men in the last 25 years, particularly in central London where the RR of suicide has declined and Wales where risks have risen. These changes do not appear to be explained by recognised suicide risk factors and require investigation to inform prevention strategies.

Objective To report on the extent of inequality in premature mortality as measured between geographical areas in Britain.Design Observational study of routinely collected mortality data and public records. Population subdivided by age, sex, and geographical area (parliamentary constituencies from 1991 to 2007, pre-1974 local authorities over a longer time span).Setting Great Britain.Participants Entire population aged under 75 from 1990 to 2007, and entire population aged under 65 in the periods 1921-39, 1950-3, 1959-63, 1969-73, and 1981-2007.Main outcome measure Relative index of inequality (RII) and ratios of inequality in age-sex standardised mortality ratios under ages 75 and 65. The relative index of inequality is the relative rate of mortality for the hypothetically worst-off compared with the hypothetically best-off person in the population, assuming a linear association between socioeconomic position and risk of mortality. The ratio of inequality is the ratio of the standardised mortality ratio of the most deprived 10% to the least deprived 10%.Results When measured by the relative index of inequality, geographical inequalities in age-sex standardised rates of mortality below age 75 have increased every two years from 1990-1 to 2006-7 without exception. Over this period the relative index of inequality increased from 1.61 (95% confidence interval 1.52 to 1.69) in 1990-1 to 2.14 (2.02 to 2.27) in 2006-7. Simple ratios indicated a brief period around 2001 when a small reduction in inequality was recorded, but this was quickly reversed and inequalities up to the age of 75 have now reached the highest levels reported since at least 1990. Similarly, inequalities in mortality ratios under the age of 65 improved slightly in the early years of this century but the latest figures surpass the most extreme previously reported. Comparison of crudely age-sex standardised rates for those below age 65 from historical records showed that geographical inequalities in mortality are higher in the most recent decade than in any similar time period for which records are available since at least 1921.Conclusions Inequalities in premature mortality between areas of Britain continued to rise steadily during the first decade of the 21st century. The last time in the long economic record that inequalities were almost as high was in the lead up to the economic crash of 1929 and the economic depression of the 1930s. The economic crash of 2008 might precede even greater inequalities in mortality between areas in Britain.

This article gives a little background about young people living in Britain. Most of the material is drawn from the chapter on young adults in Identity in Britain (Thomas and Dorling, 2007), an atl...

An atlas of mortality in Britain based on data from 1981 to 2004, this new study explores causes of death across the UK, including a description of the cause of death, a map and cartogram showing the spatial distribution of that cause, a commentary on the pattern observed and the reason for it.

OBJECTIVES:It is known that African American men have a greater risk of prostate cancer than white men. We investigated whether this was true for first-generation black Caribbean and black African men in the United Kingdom. METHODS:A clinical cohort study design recruiting all cases of prostate cancer diagnosed over a 5-yr period and residing in defined areas of London and Bristol. We calculated the age-standardised incidence rates and relative risk for all black men, and black Caribbean and black African men versus white men. RESULTS:Black men had higher age-adjusted rates of prostate cancer (166 per 100,000, 95% confidence interval [95%CI], 151-180 per 100,000) than white men (56.4 per 100,000, 95%CI, 53.3-59.5 per 100,000). The relative risks for all black, black Caribbean, and black African men were 3.09 (95%CI, 2.79-3.43; p<0.0001), 3.19 (95%CI, 2.85-3.56; p<0.0001) and 2.87 (95%CI, 2.34-3.53; p<0.0001), respectively. There was no strong evidence that the rates for black Caribbean differed from black African men. The higher risk in black men compared with white men was more apparent in younger age groups (p value for interaction<0.001). CONCLUSIONS:Black men in the United Kingdom have substantially greater risk of developing prostate cancer compared with white men, although this risk is lower than that of black men in the United States. The similar rates in black Caribbean and black African men suggest a common genetic aetiology, although migration may be associated with an increased risk attributable to a gene-environment interaction.