Wind Tunnel Experiments with Flexible Plates in Transonic Flows

The evolution of adaptive shock control bump (SCB) design has seen the system flexibility increase to a point where the aerodynamic loading can affect the deformation of the plate. By studying the effects of a flexible plate subject to transonic flow the fluid structure interaction can be investigated. In this study an array of thin plates (0.4 and 0.6 mm) with different aspect ratios (1 and 1.33) are exposed to a Mach 1.4 normal shockwave. PIV is used in combination with Schlieren imaging to provide a detailed view of the flow curvature surrounding the plate as well as the global shock structure. A technique that extracts the plate deformation from the PIV images is also presented which provides fluid and structural information for each test. The relationship between plate and flow angle is discussed as well as the effect of plate stiffness and free stream influence of each plate configuration

Uptake of the NICE osteoarthritis guidelines in primary care: a survey of older adults with joint pain

Background Osteoarthritis (OA) is a leading cause of pain and disability. NICE OA guidelines (2008) recommend that patients with OA should be offered core treatments in primary care. Assessments of OA management have identified a need to improve primary care of people with OA, as recorded use of interventions concordant with the NICE guidelines is suboptimal in primary care. The aim of this study was to i) describe the patient-reported uptake of non-pharmacological and pharmacological treatments recommended in the NICE OA guidelines in older adults with a self-reported consultation for joint pain and ii) determine whether patient characteristics or OA diagnosis impact uptake. Methods A cross-sectional survey mailed to adults aged ≥45 years (n = 28,443) from eight general practices in the UK as part of the MOSAICS study. Respondents who reported the presence of joint pain, a consultation in the previous 12 months for joint pain, and gave consent to medical record review formed the sample for this study. Results Four thousand fifty-nine respondents were included in the analysis (mean age 65.6 years (SD 11.2), 2300 (56.7%) females). 502 (12.4%) received an OA diagnosis in the previous 12 months. More participants reported using pharmacological treatments (e.g. paracetamol (31.3%), opioids (40.4%)) than non-pharmacological treatments (e.g. exercise (3.8%)). Those with an OA diagnosis were more likely to use written information (OR 1.57; 95% CI 1.26,1.96), paracetamol (OR 1.30; 95% CI 1.05,1.62) and topical NSAIDs (OR 1.30; 95% CI 1.04,1.62) than those with a joint pain code. People aged ≥75 years were less likely to use written information (OR 0.56; 95% CI 0.40,0.79) and exercise (OR 0.37; 95% CI 0.25,0.55) and more likely to use paracetamol (OR 1.91; 95% CI 1.38,2.65) than those aged < 75 years. Conclusion The cross-sectional population survey was conducted to examine the uptake of the treatments that are recommended in the NICE OA guidelines in older adults with a self-reported consultation for joint pain and to determine whether patient characteristics or OA diagnosis impact uptake. Non-pharmacological treatment was suboptimal compared to pharmacological treatment. Implementation of NICE guidelines needs to examine why non-pharmacological treatments, such as exercise, remain under-used especially among older people

"Well, it's nobody's responsibility but my own." A qualitative study to explore views about the determinants of health and prevention of knee pain in older adults

Dahlgren and Whitehead's 'rainbow' outlines key determinants of health and has been widely adopted within public health policy and research. Public understanding regarding the determinants of health is, however, relatively unknown, particularly in relation to common chronic joint problems like knee pain. We aimed to explore individual attitudes to the prevention of knee pain, and assess how people make sense of their lives by using the rainbow model to explore social determinants of health

Disabling knee pain – another consequence of obesity: Results from a prospective cohort study

BACKGROUND: Obesity is linked to knee osteoarthritis (OA) and knee pain. These are disabling problems that are more prevalent in older adults. No prospective study has estimated the impact of excess weight avoidance on the occurrence of knee pain in the general older population. The aim of this study was to investigate the influence of overweight and obesity on the onset and progression of knee pain and disability in older adults living in the community. METHODS: A prospective cohort study of people aged 50 and over registered with three general practices in North Staffordshire, UK. 5784 people who had responded to a survey in March 2000 were mailed a follow-up questionnaire in March 2003. The main outcome measures were self-reported knee pain and severe knee pain and disability at 3 years measured by the Western Ontario and McMaster Universities Osteoarthritis index. RESULTS: Adjusted response to follow-up was 75%. Among responders with no knee pain at baseline, obesity predicted onset of severe knee pain (relative risk 2.8; 95% CI 1.8, 4.5 compared to normal body mass index (BMI) category). Considering overweight and obese categories together, 19% of new cases of severe knee pain over a 3-year period could potentially be avoided by a one-category shift downwards in BMI; this includes almost half of the new cases that arose in the obese group. CONCLUSION: Obesity accounts for a substantial proportion of severe disabling knee pain. As knee pain is a common disabling condition in older adults living in the community, effective public health interventions about avoidance of excess weight could have a major impact on future lower limb disability in older adults

CAR T cells targeting tumor endothelial marker CLEC14A inhibit tumor growth

Engineering T cells to express chimeric antigen receptors (CARs) specific for antigens on hematological cancers has yielded remarkable clinical responses, but with solid tumors, benefit has been more limited. This may reflect lack of suitable target antigens, immune evasion mechanisms in malignant cells, and/or lack of T cell infiltration into tumors. An alternative approach, to circumvent these problems, is targeting the tumor vasculature rather than the malignant cells directly. CLEC14A is a glycoprotein selectively overexpressed on the vasculature of many solid human cancers and is, therefore, of considerable interest as a target antigen. Here, we generated CARs from 2 CLEC14A-specific antibodies and expressed them in T cells. In vitro studies demonstrated that, when exposed to their target antigen, these engineered T cells proliferate, release IFN-γ, and mediate cytotoxicity. Infusing CAR engineered T cells into healthy mice showed no signs of toxicity, yet these T cells targeted tumor tissue and significantly inhibited tumor growth in 3 mouse models of cancer (Rip-Tag2, mPDAC, and Lewis lung carcinoma). Reduced tumor burden also correlated with significant loss of CLEC14A expression and reduced vascular density within malignant tissues. These data suggest the tumor vasculature can be safely and effectively targeted with CLEC14A-specific CAR T cells, offering a potent and widely applicable therapy for cancer

Cassini multi-instrument assessment of Saturn's polar cap boundary

We present the first systematic investigation of the polar cap boundary in Saturn's high-latitude magnetosphere through a multi-instrument assessment of various Cassini in situ data sets gathered between 2006 and 2009. We identify 48 polar cap crossings where the polar cap boundary can be clearly observed in the step in upper cutoff of auroral hiss emissions from the plasma wave data, a sudden increase in electron density, an anisotropy of energetic electrons along the magnetic field, and an increase in incidence of higher-energy electrons from the low-energy electron spectrometer measurements as we move equatorward from the pole. We determine the average level of coincidence of the polar cap boundary identified in the various in situ data sets to be 0.34° ± 0.05° colatitude. The average location of the boundary in the southern (northern) hemisphere is found to be at 15.6° (13.3°) colatitude. In both hemispheres we identify a consistent equatorward offset between the poleward edge of the auroral upward directed field-aligned current region of ~1.5–1.8° colatitude to the corresponding polar cap boundary. We identify atypical observations in the boundary region, including observations of approximately hourly periodicities in the auroral hiss emissions close to the pole. We suggest that the position of the southern polar cap boundary is somewhat ordered by the southern planetary period oscillation phase but that it cannot account for the boundary's full latitudinal variability. We find no clear evidence of any ordering of the northern polar cap boundary location with the northern planetary period magnetic field oscillation phase

Interplay of Mre11 Nuclease with Dna2 plus Sgs1 in Rad51-Dependent Recombinational Repair

The Mre11/Rad50/Xrs2 complex initiates IR repair by binding to the end of a double-strand break, resulting in 5′ to 3′ exonuclease degradation creating a single-stranded 3′ overhang competent for strand invasion into the unbroken chromosome. The nuclease(s) involved are not well understood. Mre11 encodes a nuclease, but it has 3′ to 5′, rather than 5′ to 3′ activity. Furthermore, mutations that inactivate only the nuclease activity of Mre11 but not its other repair functions, mre11-D56N and mre11-H125N, are resistant to IR. This suggests that another nuclease can catalyze 5′ to 3′ degradation. One candidate nuclease that has not been tested to date because it is encoded by an essential gene is the Dna2 helicase/nuclease. We recently reported the ability to suppress the lethality of a dna2Δ with a pif1Δ. The dna2Δ pif1Δ mutant is IR-resistant. We have determined that dna2Δ pif1Δ mre11-D56N and dna2Δ pif1Δ mre11-H125N strains are equally as sensitive to IR as mre11Δ strains, suggesting that in the absence of Dna2, Mre11 nuclease carries out repair. The dna2Δ pif1Δ mre11-D56N triple mutant is complemented by plasmids expressing Mre11, Dna2 or dna2K1080E, a mutant with defective helicase and functional nuclease, demonstrating that the nuclease of Dna2 compensates for the absence of Mre11 nuclease in IR repair, presumably in 5′ to 3′ degradation at DSB ends. We further show that sgs1Δ mre11-H125N, but not sgs1Δ, is very sensitive to IR, implicating the Sgs1 helicase in the Dna2-mediated pathway

The Knee Clinical Assessment Study – CAS(K). A prospective study of knee pain and knee osteoarthritis in the general population: baseline recruitment and retention at 18 months

BACKGROUND: Selective non-participation at baseline (due to non-response and non-consent) and loss to follow-up are important concerns for longitudinal observational research. We investigated these matters in the context of baseline recruitment and retention at 18 months of participants for a prospective observational cohort study of knee pain and knee osteoarthritis in the general population. METHODS: Participants were recruited to the Knee Clinical Assessment Study – CAS(K) – by a multi-stage process involving response to two postal questionnaires, consent to further contact and medical record review (optional), and attendance at a research clinic. Follow-up at 18-months was by postal questionnaire. The characteristics of responders/consenters were described for each stage in the recruitment process to identify patterns of selective non-participation and loss to follow-up. The external validity of findings from the clinic attenders was tested by comparing the distribution of WOMAC scores and the association between physical function and obesity with the same parameters measured directly in the target population as whole. RESULTS: 3106 adults aged 50 years and over reporting knee pain in the previous 12 months were identified from the first baseline questionnaire. Of these, 819 consented to further contact, responded to the second questionnaire, and attended the research clinics. 776 were successfully followed up at 18 months. There was evidence of selective non-participation during recruitment (aged 80 years and over, lower socioeconomic group, currently in employment, experiencing anxiety or depression, brief episode of knee pain within the previous year). This did not cause significant bias in either the distribution of WOMAC scores or the association between physical function and obesity. CONCLUSION: Despite recruiting a minority of the target population to the research clinics and some evidence of selective non-participation, this appears not to have resulted in significant bias of cross-sectional estimates. The main effect of non-participation in the current cohort is likely to be a loss of precision in stratum-specific estimates e.g. in those aged 80 years and over. The subgroup of individuals who attended the research clinics and who make up the CAS(K) cohort can be used to accurately estimate parameters in the reference population as a whole. The potential for selection bias, however, remains an important consideration in each subsequent analysis

Knee complaints vary with age and gender in the adult population. Population-based reference data for the Knee injury and Osteoarthritis Outcome Score (KOOS)

BACKGROUND: Self-reported knee complaints may vary with age and gender. Reference data from the adult population would help to better interpret the outcome of interventions due to knee complaints. The objectives of the present study were to describe the variation of self-reported knee pain, function and quality of life with age and gender in the adult population and to establish population-based reference data for the Knee injury and Osteoarthritis Outcome Score (KOOS). METHODS: Population-based cohort retrieved from the national population register. The knee-specific Knee injury and Osteoarthritis Outcome Score (KOOS) was mailed to 840 subjects aged 18–84 yrs. RESULTS: 68% response rate. Women in the age group 55–74 reported more knee-related complaints in all the KOOS subscales than age-matched men. The differences were significant for the subscales Pain (p = 0.027), Symptoms (p = 0.003) and ADL function (p = 0.046). In men, worse ADL and Sport and Recreation function was seen in the oldest age group 75–84 years compared to the younger age groups (p < 0.030). In women, worse Pain (p < 0.007), ADL (p < 0.030), Sport and Recreation (p < 0.001) and QOL (p < 0.002) were seen already in the age group 55–74 compared to the younger age groups. CONCLUSION: We found pain and other symptoms, physical function, and knee-related quality of life to vary with age and gender implying the use of age- and gender matched reference values for improved understanding of the outcome after interventions due to knee injury and knee OA