Dopexamine can attenuate the inflammatory response and protect against organ injury in the absence of significant effects on hemodynamics or regional microvascular flow

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Validation of a novel particle isolation procedure using particle doped tissue samples.

A novel particle isolation method for tissue samples was developed and tested using particle-doped peri-articular tissues from ovine cadavers. This enabled sensitivity of the isolation technique to be established by doping tissue samples of 0.25 g with very low particle volumes of 2.5 µm 3 per sample. Image analysis was used to verify that the method caused no changes to particle size or morphologies

Recovery of low volumes of wear debris from rat stifle joint tissues using a novel particle isolation method

Less than optimal particle isolation techniques have impeded analysis of orthopaedic wear debris in vivo. The purpose of this research was to develop and test an improved method for particle isolation from tissue. A volume of 0.018 mm³ of clinically relevant CoCrMo, Ti-6Al-4V or Si₃N₄ particles was injected into rat stifle joints for seven days of in vivo exposure. Following sacrifice, particles were located within tissues using histology. The particles were recovered by enzymatic digestion of periarticular tissue with papain and proteinase K, followed by ultracentrifugation using a sodium polytungstate density gradient. Particles were recovered from all samples, observed using SEM and the particle composition was verified using EDX, which demonstrated that all isolated particles were free from contamination. Particle size, aspect ratio and circularity were measured using image analysis software. There were no significant changes to the measured parameters of CoCrMo or Si₃N₄ particles before and after the recovery process (KS tests, p > 0.05). Titanium particles were too few before and after isolation to analyse statistically, though size and morphologies were similar. Overall the method demonstrated a significant improvement to current particle isolation methods from tissue in terms of sensitivity and efficacy at removal of protein, and has the potential to be used for the isolation of ultra-low wearing total joint replacement materials from periprosthetic tissues

Enteric dysbiosis and fecal calprotectin expression in premature infants.

BackgroundPremature infants often develop enteric dysbiosis with a preponderance of Gammaproteobacteria, which has been related to adverse clinical outcomes. We investigated the relationship between increasing fecal Gammaproteobacteria and mucosal inflammation, measured by fecal calprotectin (FC).MethodsStool samples were collected from very-low-birth weight (VLBW) infants at ≤2, 3, and 4 weeks' postnatal age. Fecal microbiome was surveyed using polymerase chain reaction amplification of the V4 region of 16S ribosomal RNA, and FC was measured by enzyme immunoassay.ResultsWe enrolled 45 VLBW infants (gestation 27.9 ± 2.2 weeks, birth weight 1126 ± 208 g) and obtained stool samples at 9.9 ± 3, 20.7 ± 4.1, and 29.4 ± 4.9 days. FC was positively correlated with the genus Klebsiella (r = 0.207, p = 0.034) and its dominant amplicon sequence variant (r = 0.290, p = 0.003), but not with the relative abundance of total Gammaproteobacteria. Klebsiella colonized the gut in two distinct patterns: some infants started with low Klebsiella abundance and gained these bacteria over time, whereas others began with very high Klebsiella abundance.ConclusionIn premature infants, FC correlated with relative abundance of a specific pathobiont, Klebsiella, and not with that of the class Gammaproteobacteria. These findings indicate a need to define dysbiosis at genera or higher levels of resolution

Eta Carinae and the Luminous Blue Variables

We evaluate the place of Eta Carinae amongst the class of luminous blue variables (LBVs) and show that the LBV phenomenon is not restricted to extremely luminous objects like Eta Car, but extends luminosities as low as log(L/Lsun) = 5.4 - corresponding to initial masses ~25 Msun, and final masses as low as ~10-15 Msun. We present a census of S Doradus variability, and discuss basic LBV properties, their mass-loss behaviour, and whether at maximum light they form pseudo-photospheres. We argue that those objects that exhibit giant Eta Car-type eruptions are most likely related to the more common type of S Doradus variability. Alternative atmospheric models as well as sub-photospheric models for the instability are presented, but the true nature of the LBV phenomenon remains as yet elusive. We end with a discussion on the evolutionary status of LBVs - highlighting recent indications that some LBVs may be in a direct pre-supernova state, in contradiction to the standard paradigm for massive star evolution.Comment: 27 pages, 6 figures, Review Chapter in "Eta Carinae and the supernova imposters" (eds R. Humphreys and K. Davidson) new version submitted to Springe

Elective Open Suprarenal Aneurysm Repair in England from 2000 to 2010 an Observational Study of Hospital Episode Statistics

Background: Open surgery is widely used as a benchmark for the results of fenestrated endovascular repair of complex abdominal aortic aneurysms (AAA). However, the existing evidence stems from single-centre experiences, and may not be reproducible in wider practice. National outcomes provide valuable information regarding the safety of suprarenal aneurysm repair. Methods: Demographic and clinical data were extracted from English Hospital Episodes Statistics for patients undergoing elective suprarenal aneurysm repair from 1 April 2000 to 31 March 2010. Thirty-day mortality and five-year survival were analysed by logistic regression and Cox proportional hazards modeling. Results: 793 patients underwent surgery with 14% overall 30-day mortality, which did not improve over the study period. Independent predictors of 30-day mortality included age, renal disease and previous myocardial infarction. 5-year survival was independently reduced by age, renal disease, liver disease, chronic pulmonary disease, and known metastatic solid tumour. There was significant regional variation in both 30-day mortality and 5-year survival after risk-adjustment. Regional differences in outcome were eliminated in a sensitivity analysis for perioperative outcome, conducted by restricting analysis to survivors of the first 30 days after surgery. Conclusions: Elective suprarenal aneurysm repair was associated with considerable mortality and significant regional variation across England. These data provide a benchmark to assess the efficacy of complex endovascular repair of supra-renal aneurysms, though cautious interpretation is required due to the lack of information regarding aneurysm morphology. More detailed study is required, ideally through the mandatory submission of data to a national registry of suprarenal aneurysm repair

TLR7-mediated skin inflammation remotely triggers chemokine expression and leukocyte accumulation in the brain

Background: The relationship between the brain and the immune system has become increasingly topical as, although it is immune-specialised, the CNS is not free from the influences of the immune system. Recent data indicate that peripheral immune stimulation can significantly affect the CNS. But the mechanisms underpinning this relationship remain unclear. The standard approach to understanding this relationship has relied on systemic immune activation using bacterial components, finding that immune mediators, such as cytokines, can have a significant effect on brain function and behaviour. More rarely have studies used disease models that are representative of human disorders. Methods: Here we use a well-characterised animal model of psoriasis-like skin inflammation—imiquimod—to investigate the effects of tissue-specific peripheral inflammation on the brain. We used full genome array, flow cytometry analysis of immune cell infiltration, doublecortin staining for neural precursor cells and a behavioural read-out exploiting natural burrowing behaviour. Results: We found that a number of genes are upregulated in the brain following treatment, amongst which is a subset of inflammatory chemokines (CCL3, CCL5, CCL9, CXCL10, CXCL13, CXCL16 and CCR5). Strikingly, this model induced the infiltration of a number of immune cell subsets into the brain parenchyma, including T cells, NK cells and myeloid cells, along with a reduction in neurogenesis and a suppression of burrowing activity. Conclusions: These findings demonstrate that cutaneous, peripheral immune stimulation is associated with significant leukocyte infiltration into the brain and suggest that chemokines may be amongst the key mediators driving this response

Electric-field-induced coherent coupling of the exciton states in a single quantum dot

The signature of coherent coupling between two quantum states is an anticrossing in their energies as one is swept through the other. In single semiconductor quantum dots containing an electron-hole pair the eigenstates form a two-level system that can be used to demonstrate quantum effects in the solid state, but in all previous work these states were independent. Here we describe a technique to control the energetic splitting of these states using a vertical electric field, facilitating the observation of coherent coupling between them. Near the minimum splitting the eigenstates rotate in the plane of the sample, being orientated at 45{\deg} when the splitting is smallest. Using this system we show direct control over the exciton states in one quantum dot, leading to the generation of entangled photon pairs

Left ventricular non-compaction: clinical features and cardiovascular magnetic resonance imaging

Background: It is apparent that despite lack of family history, patients with the morphological characteristics of left ventricular non-compaction develop arrhythmias, thrombo-embolism and left ventricular dysfunction. METHODS: Forty two patients, aged 48.7 +/- 2.3 yrs (mean +/- SEM) underwent cardiovascular magnetic resonance (CMR) for the quantification of left ventricular volumes and extent of non-compacted (NC) myocardium. The latter was quantified using planimetry on the two-chamber long axis LV view (NC area). The patients included those referred specifically for CMR to investigate suspected cardiomyopathy, and as such is represents a selected group of patients. RESULTS: At presentation, 50% had dyspnoea, 19% chest pain, 14% palpitations and 5% stroke. Pulmonary embolism had occurred in 7% and brachial artery embolism in 2%. The ECG was abnormal in 81% and atrial fibrillation occurred in 29%. Transthoracic echocardiograms showed features of NC in only 10%. On CMR, patients who presented with dyspnoea had greater left ventricular volumes (both p < 0.0001) and a lower left ventricular ejection fraction (LVEF) (p < 0.0001) than age-matched, healthy controls. In patients without dyspnoea (n = 21), NC area correlated positively with end-diastolic volume (r = 0.52, p = 0.0184) and end-systolic volume (r = 0.56, p = 0.0095), and negatively with EF (r = -0.72, p = 0.0001). CONCLUSION: Left ventricular non-compaction is associated with dysrrhythmias, thromboembolic events, chest pain and LV dysfunction. The inverse correlation between NC area and EF suggests that NC contributes to left ventricular dysfunction

Exploring the equity of GP practice prescribing rates for selected coronary heart disease drugs: a multiple regression analysis with proxies of healthcare need

Background There is a small, but growing body of literature highlighting inequities in GP practice prescribing rates for many drug therapies. The aim of this paper is to further explore the equity of prescribing for five major CHD drug groups and to explain the amount of variation in GP practice prescribing rates that can be explained by a range of healthcare needs indicators (HCNIs). Methods The study involved a cross-sectional secondary analysis in four primary care trusts (PCTs 1–4) in the North West of England, including 132 GP practices. Prescribing rates (average daily quantities per registered patient aged over 35 years) and HCNIs were developed for all GP practices. Analysis was undertaken using multiple linear regression. Results Between 22–25% of the variation in prescribing rates for statins, beta-blockers and bendrofluazide was explained in the multiple regression models. Slightly more variation was explained for ACE inhibitors (31.6%) and considerably more for aspirin (51.2%). Prescribing rates were positively associated with CHD hospital diagnoses and procedures for all drug groups other than ACE inhibitors. The proportion of patients aged 55–74 years was positively related to all prescribing rates other than aspirin, where they were positively related to the proportion of patients aged >75 years. However, prescribing rates for statins and ACE inhibitors were negatively associated with the proportion of patients aged >75 years in addition to the proportion of patients from minority ethnic groups. Prescribing rates for aspirin, bendrofluazide and all CHD drugs combined were negatively associated with deprivation. Conclusion Although around 25–50% of the variation in prescribing rates was explained by HCNIs, this varied markedly between PCTs and drug groups. Prescribing rates were generally characterised by both positive and negative associations with HCNIs, suggesting possible inequities in prescribing rates on the basis of ethnicity, deprivation and the proportion of patients aged over 75 years (for statins and ACE inhibitors, but not for aspirin)