Wind tunnel testing of a high aspect ratio wing model

There is much current interest in the development of High Aspect Ratio Wing (HARW) designs for improved aircraft performance. However, there are a lack of relevant data sets available to validate aeroelastic modelling approaches for highly flexible wings. The design and manufacture of a highly flexible 2.4m semi-span wing is described. A series of low speed wind tunnel tests were performed to generate displacement, acceleration, strain gauge, aerodynamic pressure and six component balance measurements for a range of airspeeds and wing root angles of attack. Numerous static and dynamic measurements were made. Preliminary results are shown for the static and dynamic, structural and aerodynamic behaviour over a range of different airspeeds and wing root angles of attack.Peer ReviewedPostprint (published version

Instabilities of interacting matter waves in optical lattices with Floquet driving

We experimentally investigate the stability of a quantum gas with repulsive interactions in an optical one-dimensional lattice subjected to periodic driving. Excitations of the gas in the lowest lattice band are analyzed across the complete stability diagram, from slow to fast driving frequencies and from weak to strong driving strengths. To interpret our results, we expand the established analysis based on parametric instabilities to include modulational instabilities. Extending the concept of modulational instabilities from static to periodically driven systems provides a convenient mapping of the stability in a static system to the cases of slow and fast driving. At intermediate driving frequencies, we observe an interesting competition between modulational and parametric instabilities. We experimentally confirm the existence of both types of instabilities in driven systems and probe their properties. Our results allow us to predict stable and unstable parameter regions for the minimization of heating in future applications of Floquet driving

High-resolution structure of the M14-type cytosolic carboxypeptidase from <em>Burkholderia cenocepacia </em>refined exploiting <em>PDB_REDO </em>strategies

A potential cytosolic metallocarboxypeptidase from Burk­holderia cenocepacia has been crystallized and a synchrotron-radiation microfocus beamline allowed the acquisition of diffraction data to 1.9 Å resolution. The asymmetric unit comprises a tetramer containing over 1500 amino acids, and the high-throughput automated protocols embedded in PDB_REDO were coupled with model–map inspections in refinement. This approach has highlighted the value of such protocols for efficient analyses. The subunit is constructed from two domains. The N-terminal domain has previously only been observed in cytosolic carboxypeptidase (CCP) proteins. The C-terminal domain, which carries the Zn(2+)-containing active site, serves to classify this protein as a member of the M14D subfamily of carboxypeptidases. Although eukaryotic CCPs possess deglutamylase activity and are implicated in processing modified tubulin, the function and substrates of the bacterial family members remain unknown. The B. cenocepacia protein did not display deglutamylase activity towards a furylacryloyl glutamate derivative, a potential substrate. Residues previously shown to coordinate the divalent cation and that contribute to peptide-bond cleavage in related enzymes such as bovine carboxypeptidase are conserved. The location of a conserved basic patch in the active site adjacent to the catalytic Zn(2+), where an acetate ion is identified, suggests recognition of the carboxy-terminus in a similar fashion to other carboxypeptidases. However, there are significant differences that indicate the recognition of substrates with different properties. Of note is the presence of a lysine in the S1′ recognition subsite that suggests specificity towards an acidic substrate

Does a local financial incentive scheme reduce inequalities in the delivery of clinical care in a socially deprived community? A longitudinal data analysis.

BACKGROUND: Socioeconomic deprivation is associated with inequalities in health care and outcomes. Despite concerns that the Quality and Outcomes Framework pay-for-performance scheme in the UK would exacerbate inequalities in primary care delivery, gaps closed over time. Local schemes were promoted as a means of improving clinical engagement by addressing local health priorities. We evaluated equity in achievement of target indicators and practice income for one local scheme. METHODS: We undertook a longitudinal survey over four years of routinely recorded clinical data for all 83 primary care practices. Sixteen indicators were developed that covered five local clinical and public health priorities: weight management; alcohol consumption; learning disabilities; osteoporosis; and chlamydia screening. Clinical indicators were logit transformed from a percentage achievement scale and modelled allowing for clustering of repeated measures within practices. This enabled our study of target achievements over time with respect to deprivation. Practice income was also explored. RESULTS: Higher practice deprivation was associated with poorer performance for five indicators: alcohol use registration (OR 0.97; 95 % confidence interval 0.96,0.99); recorded chlamydia test result (OR 0.97; 0.94,0.99); osteoporosis registration (OR 0.98; 0.97,0.99); registration of repeat prednisolone prescription (OR 0.98; 0.96,0.99); and prednisolone registration with record of dual energy X-ray absorptiometry (DEXA) scan/referral (OR 0.92; 0.86,0.97); practices in deprived areas performed better for one indicator (registration of osteoporotic fragility fracture (OR 1.26; 1.04,1.51). The deprivation-achievement gap widened for one indicator (registered females aged 65-74 with a fracture referred for a DEXA scan; OR 0.97; 0.95,0.99). Two other indicators indicated a similar trend over two years before being withdrawn (registration of fragility fracture and over-75 s with a fragility fracture assessed and treated for osteoporosis risk). For one indicator the deprivation-achievement gap reduced over time (repeat prednisolone prescription (OR 1.01; 1.01,1.01). Larger practices and those serving more affluent areas earned more income per patient than smaller practices and those serving more deprived areas (t = -3.99; p =0.0001). CONCLUSIONS: Any gaps in achievement between practices were modest but mostly sustained or widened over the duration of the scheme. Given that financial rewards may not reflect the amount of work undertaken by practices serving more deprived patients, future pay-for-performance schemes also need to address fairness of rewards in relation to workload

Governance, ownership structure and performance of IPO firms: the impact of different types of private equity investors and institutional environments

This paper examines performance effects of ownership concentration and two types of private equity investors (venture capitalists and business angels) in firms that have recently undergone an initial public offering (IPO) in the United Kingdom and France. We expand and contextualize nascent understanding of multiple agency theory by examining heterogeneity of private equity investors and by suggesting that multiple agency relationships are affected by different institutional contexts. We employ a unique, hand-collected dataset of 224 matched IPOs (112 in each country). Controlling for the endogeneity of private equity investors’ retained share ownership, we find support for the agency theory argument that concentrated ownership improves IPO’s performance. The research also shows that the two types of private equity investors have a differential impact on performance, and the legal institutions in a given country moderate this impact

Inhibition of urokinase plasminogen activator with a novel enzyme inhibitor, wxc-340, ameliorates endotoxin and surgery-accelerated growth of murine metastases

The urokinase plasminogen activator (u-PA) is intimately associated with tumour invasion and metastases. Surgery facilitates accelerated metastatic tumour growth in murine models, a phenomenon related to elevated perioperative bacterial lipopolysaccaride (LPS) and inflammatory cytokine levels. The objectives of the study were to examine the role of u-PA in cytokine-enhanced tumour cell invasion in vitro and surgery-induced accelerated metastatic tumour growth in vivo and to assess the potential benefit of a novel selective u-PA inhibitor WXC-340 in this setting. CT-26 murine colorectal carcinoma cells were stimulated with LPS, tumour necrosis factor α (TNF-α) and interleukin 6 (IL-6). Cell supernatant u-PA expression and activity were determined using a colorimetric assay and Western blot analysis, respectively. Baseline and cytokine-stimulated in vitro invasion were assessed using ECmatrix invasion chambers. Two established murine models of accelerated metastatic tumour growth were used to investigate the consequences of u-PA inhibition on postoperative metastatic tumour burden. The effect of u-PA inhibition in vitro and in vivo was examined using the novel selective u-PA inhibitor, WXC-340. Proinflammatory cytokine stimulation significantly enhanced in vitro u-PA expression, activity and extracellular matrix invasion by approximately 50% compared to controls (P<0.05). This was abrogated by WXC-340. In vivo WXC-340 almost completely ameliorated both LPS- and surgery-induced, metastatic tumour growth compared to controls (P>0.05). In conclusion, u-PA cascade is actively involved in cytokine-mediated enhanced tumour cell invasion and LPS and surgery-induced metastatic tumour growth. Perioperative u-PA inhibition with WXC-340 may represent a novel therapeutic paradigm

Hydrodynamic Regulation of Monocyte Inflammatory Response to an Intracellular Pathogen

Systemic bacterial infections elicit inflammatory response that promotes acute or chronic complications such as sepsis, arthritis or atherosclerosis. Of interest, cells in circulation experience hydrodynamic shear forces, which have been shown to be a potent regulator of cellular function in the vasculature and play an important role in maintaining tissue homeostasis. In this study, we have examined the effect of shear forces due to blood flow in modulating the inflammatory response of cells to infection. Using an in vitro model, we analyzed the effects of physiological levels of shear stress on the inflammatory response of monocytes infected with chlamydia, an intracellular pathogen which causes bronchitis and is implicated in the development of atherosclerosis. We found that chlamydial infection alters the morphology of monocytes and trigger the release of pro-inflammatory cytokines TNF-α, IL-8, IL-1β and IL-6. We also found that the exposure of chlamydia-infected monocytes to short durations of arterial shear stress significantly enhances the secretion of cytokines in a time-dependent manner and the expression of surface adhesion molecule ICAM-1. As a functional consequence, infection and shear stress increased monocyte adhesion to endothelial cells under flow and in the activation and aggregation of platelets. Overall, our study demonstrates that shear stress enhances the inflammatory response of monocytes to infection, suggesting that mechanical forces may contribute to disease pathophysiology. These results provide a novel perspective on our understanding of systemic infection and inflammation

Using the Theoretical Domains Framework (TDF) to understand adherence to multiple evidence-based indicators in primary care : a qualitative study

BACKGROUND: There are recognised gaps between evidence and practice in general practice, a setting posing particular implementation challenges. We earlier screened clinical guideline recommendations to derive a set of 'high-impact' indicators based upon criteria including potential for significant patient benefit, scope for improved practice and amenability to measurement using routinely collected data. Here, we explore health professionals' perceived determinants of adherence to these indicators, examining the degree to which determinants were indicator-specific or potentially generalisable across indicators. METHODS: We interviewed 60 general practitioners, practice nurses and practice managers in West Yorkshire, the UK, about adherence to four indicators: avoidance of risky prescribing; treatment targets in type 2 diabetes; blood pressure targets in treated hypertension; and anticoagulation in atrial fibrillation. Interview questions drew upon the Theoretical Domains Framework (TDF). Data were analysed using framework analysis. RESULTS: Professional role and identity and environmental context and resources featured prominently across all indicators whilst the importance of other domains, for example, beliefs about consequences, social influences and knowledge varied across indicators. We identified five meta-themes representing more general organisational and contextual factors common to all indicators. CONCLUSIONS: The TDF helped elicit a wide range of reported determinants of adherence to 'high-impact' indicators in primary care. It was more difficult to pinpoint which determinants, if targeted by an implementation strategy, would maximise change. The meta-themes broadly underline the need to align the design of interventions targeting general practices with higher level supports and broader contextual considerations. However, our findings suggest that it is feasible to develop interventions to promote the uptake of different evidence-based indicators which share common features whilst also including content-specific adaptations

Baseline natural killer and T cell populations correlation with virologic outcome after regimen simplification to atazanavir/ritonavir alone (ACTG 5201)

Objectives: Simplified maintenance therapy with ritonavir-boosted atazanavir (ATV/r) provides an alternative treatment option for HIV-1 infection that spares nucleoside analogs (NRTI) for future use and decreased toxicity. We hypothesized that the level of immune activation (IA) and recovery of lymphocyte populations could influence virologic outcomes after regimen simplification. Methods: Thirty-four participants with virologic suppression ≥48 weeks on antiretroviral therapy (2 NRTI plus protease inhibitor) were switched to ATV/r alone in the context of the ACTG 5201 clinical trial. Flow cytometric analyses were performed on PBMC isolated from 25 patients with available samples, of which 24 had lymphocyte recovery sufficient for this study. Assessments included enumeration of T-cells (CD4/CD8), natural killer (NK) (CD3+CD56 +CD16+) cells and cell-associated markers (HLA-DR, CD's 38/69/94/95/158/279). Results: Eight of the 24 patients had at least one plasma HIV-1 RNA level (VL) <50 copies/mL during the study. NK cell levels below the group median of 7.1% at study entry were associated with development of VL <50 copies/mL following simplification by regression and survival analyses (p = 0.043 and 0.023), with an odds ratio of 10.3 (95% CI: 1.92-55.3). Simplification was associated with transient increases in naïve and CD25+ CD4+ T-cells, and had no impact on IA levels. Conclusions: Lower NK cell levels prior to regimen simplification were predictive of virologic rebound after discontinuation of nucleoside analogs. Regimen simplification did not have a sustained impact on markers of IA or T lymphocyte populations in 48 weeks of clinical monitoring. Trial Registration: ClinicalTrials.gov NCT00084019