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

Estimation of three-dimensional aerodynamic damping using CFD

Aeroelastic phenomena of stall flutter are the result of the negative aerodynamic damping associated with separated flow. From this basis, an investigation has been conducted to estimate the aerodynamic damping from a time-marching aeroelastic computation. An initial investigation is conducted on the NACA 0012 aerofoil section, before transition to 3D propellers and full aeroelastic calculations. Estimates of aerodynamic damping are presented, with a comparison made between URANS and SAS. Use of a suitable turbulence closure to allow for shedding of flow structures during stall is seen as critical in predicting negative damping estimations. From this investigation, it has been found that the SAS method is able to capture this for both the aerofoil and 3D test cases

Search and Seizure: the Relationship and Responsibility of School District Administrators and the Police

School district administrators and police officers need more training regarding their and each others roles in searches and seizures on school property

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

Acceptability of bisphosphonates among patients, clinicians and managers: a systematic review and framework synthesis

Objective: To explore the acceptability of different bisphosphonate regimens for the treatment of osteoporosis among patients, clinicians and managers, payers and academics. Design: A systematic review of primary qualitative studies. Seven databases were searched from inception to July 2019. Screening, data extraction and quality assessment of full-articles selected for inclusion were performed independently by two authors. A framework synthesis was applied to extracted data based on the theoretical framework of acceptability (TFA). The TFA includes seven domains relating to sense-making, emotions, opportunity costs, burden, perceived effectiveness, ethicality and self-efficacy. Confidence in synthesis findings was assessed. Setting: Any developed country healthcare setting. Participants: Patients, healthcare professionals, managers, payers and academics. Intervention: Experiences and views of oral and intravenous bisphosphonates. Results: Twenty-five studies were included, mostly describing perceptions of oral bisphosphonates. We identified, with high confidence, how patients and healthcare professionals make sense (coherence) of bisphosphonates by balancing perceptions of need against concerns, how uncertainty prevails about bisphosphonate perceived effectiveness and a number of individual and service factors that have potential to increase self-efficacy in recommending and adhering to bisphosphonates. We identified, with moderate confidence, that bisphosphonate taking induces concern, but has the potential to engender reassurance, and that both side effects and special instructions for taking oral bisphosphonates can result in treatment burden. Finally, we identified with low confidence that multimorbidity plays a role in people’s perception of bisphosphonate acceptability. Conclusion: By using the lens of acceptability, our findings demonstrate with high confidence that a theoretically informed, whole-system approach is necessary to both understand and improve adherence. Clinicians and patients need supporting to understand the need for bisphosphonates, and clinicians need to clarify to patients what constitutes bisphosphonate treatment success. Further research is needed to explore perspectives of male patients and those with multimorbidity receiving bisphosphonates, and patients receiving intravenous treatment

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