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Introduction Musculoskeletal conditions (MSC) and frailty lead to a significant burden of disease in later life. Living independently remains the aim of older adults but ability to self-care or access care at home may hamper this. Our aim was to consider whether MSC (osteoporosis, sarcopenia, osteoarthritis) and frailty were associated with ability to self-care or influence access to formal/informal care among community-dwelling older adults. Methods Participants were recruited from an established cohort study of community-dwelling adults in the UK. Osteoporosis was assessed using Dual-energy X-ray Absorptiometry. Sarcopenia was assessed using EWSGOP2 criteria. Osteoarthritis of the hand, hip or knee was defined by clinical examination. Frailty was assessed using Fried criteria. Ability to self-care and access to formal/informal care were self-reported. Results 443 men and women (median age 75.5 [IQR 73.5–77.9] years) participated. Osteoporosis affected (n = 74) 21.4% of participants, (n = 115) 26.8% had osteoarthritis, (n = 30) 8.6% had sarcopenia, and (n = 33) 7.6% were identified as frail. Most participants (n = 402 [90.7%]) reported no problems with self-care. Identical proportions of participants received informal (n = 53 [12%]) and formal (n = 53 [12%]) care at home in the previous year. Reporting difficulties with self-care was associated with clinical osteoarthritis (OR 3.48, 95% CI 1.63–7.43, p = 0.001) and frailty (5.29, 2.12–13.2, p Conclusion MSC are associated with informal receipt of care. Presence of two or more MSC convey similar informal care requirements to those living with frailty. Early assessment and management of MSC and frailty in clinical practice may reduce need for care and preserve independence.

Using the Australian Square Kilometre Array Pathfinder to measure 21-cm absorption spectra toward continuum background sources, we study the cool phase of the neutral atomic gas in the far outer disk, and in the inner Galaxy near the end of the Galactic bar at longitude 340 degrees. In the inner Galaxy the cool atomic gas has a smaller scale height than in the solar neighborhood, similar to the molecular gas and the superthin stellar population in the bar. In the outer Galaxy the cool atomic gas is mixed with the warm, neutral medium, with the cool fraction staying roughly constant with Galactic radius. The mean spin temperature, i.e. the ratio of the emission brightness temperature to the absorption, is roughly constant for velocities corresponding to Galactic radius greater than about twice the solar circle radius. The ratio has a value of about 300 K, but this does not correspond to a physical temperature in the gas. If the gas causing the absorption has kinetic temperature of about 100 K, as in the solar neighborhood, then the value 300 K indicates that the fraction of the gas mass in this phase is one-third of the total HI mass., Comment: 29 pages, 12 figures, submitted to Astrophysical Journal

Summary The diversity of the U.S. population is currently not reflected in the genomic workforce and across the greater scientific enterprise. Although diversity and inclusion efforts have focused on increasing the number of individuals from underrepresented groups across scientific fields, structural racism remains. Thus, the cultivation and adoption of diversity as an ethos requires shifting our focus to being intentional about an institution’s character, culture, and climate. One way for this ethos to be sustained is by facilitating an intentional anti-racism approach within the field. Adopting a new perspective on diversity utilizing an anti-racism approach will support genomics researchers as we build supportive, collaborative research environments. We seek to expand critical thought in the framing of diversity in the research enterprise and propose an anti-racism approach that informs deliberate actions required to address structural racism., The cultivation and adoption of diversity in the workforce as an ethos requires shifting our focus to being intentional about an institution’s character, culture, and climate. One way for this ethos to be sustained is by facilitating an intentional anti-racism approach within genomic science.

Purpose/Objective(s) Immune checkpoint inhibitors (ICIs) have led to improved treatment outcomes in a variety of cancers; however, the majority of patients exhibit resistance to ICIs. Overcoming this resistance is a major challenge in immune-oncology. Radiation therapy (RT) has emerged as a promising combination with ICIs since it may act synergistically with ICIs by producing an immunomodulatory effect. NBTXR3, composed of functionalized hafnium oxide nanoparticles, is injected intratumorally and activated by RT. NBTXR3 increases RT energy deposit inside tumor cells and subsequent tumor cell death, without adding toxicity to healthy tissues. Preclinical data demonstrate NBTXR3/RT can trigger a local and systemic anti-tumor immune response and overcome anti-PD-1 resistance. NBTXR3/RT combined with anti-PD-1 may prime the immune system to increase the proportion of ICI responders or convert ICI non-responders to responders. Materials/Methods This multicenter, open-label, phase I trial [NCT03589339] is evaluating NBTXR3/RT/anti-PD-1 in 3 cohorts: (1) Locoregional recurrent or recurrent and metastatic head and neck squamous cell carcinoma (HNSCC) amenable to HN re-irradiation and (2) lung or (3) liver metastases from any primary cancer eligible for anti-PD-1. Stereotactic body RT (SBRT) is delivered at tumor-site selective doses per standard practice. The primary objective is to determine the NBTXR3/RT/anti-PD-1 recommended phase 2 dose in each cohort. Secondary objectives are anti-tumor response (objective response rate), safety, and feasibility of NBTXR3 injection. Results Nine patients have been treated: 3 HNSCC, 4 lung, 2 liver. Overall tumor regression was observed in 8/9 patients of which 7 were anti-PD-1 non-responders. A complete response lasting over 1 year was observed in the injected lymph node in 1 anti-PD-1 naive patient. 2 SAEs related to anti-PD-1 and possibly related to NBTXR3 (G5 pneumonitis, G4 hyperglycemia) were observed in 1 anti-PD-1 naive HNSCC patient and considered DLTs. This patient also experienced 2 other G4 SAEs related to anti-PD-1 (diabetic ketoacidosis, acute kidney injury). SBRT-related safety profile was as expected. Updated safety and efficacy results with additional patients and longer follow-up will be presented. Conclusion Safety data from this first-in-human phase I trial evaluating NBTXR3/RT/anti-PD-1 in patients with advanced cancers, show NBTXR3 intratumoral injection is feasible and well-tolerated in HNSCC, lung, and liver. NBTXR3/RT/anti-PD-1 demonstrated promising signs of efficacy and led to tumor regression in patients having progressed on prior anti-PD-1. These data support further development of NBTXR3 in combination with anti-PD-1 as well as other ICIs.

Purpose/objective(s) Immune checkpoint inhibitors (ICI) can improve outcomes in patients who respond to treatment, however most patients exhibit resistance. Overcoming this resistance is the main challenge in immune-oncology and recent studies suggest radiotherapy (RT) may improve ICI response rates. NBTXR3, composed of functionalized hafnium oxide nanoparticles, is injected intratumorally and activated by RT. NBTXR3 increases RT energy deposit inside tumor cells and subsequent tumor cell death, without adding toxicity to healthy tissues. Here we present evidence that NBTXR3 activated by RT primes the immune system, producing an anti-tumor immune response, including activation of the cGAS-STING pathway, that overcomes anti-PD-1 resistance both in murine models and patients. Materials/methods Abscopal assays were conducted in immunocompetent mice. Anti-PD-1 sensitive or resistant lung tumor cell lines were injected in both flanks. Intratumoral injection of NBTXR3 (or vehicle) followed by RT was performed in right flank (primary) tumors only. Some mice also received anti-PD-1 injections. Tumor growth was monitored, and tumor immune cell infiltrates analyzed by immunohistochemistry (IHC). Separately, in the phase II/III randomized Act.in.Sarc [NCT02379845] trial patients with locally advanced soft tissue sarcoma (STS) received either NBTXR3+RT or RT alone followed by tumor resection. Pre- and post-treatment tumor samples from patients in both groups were analyzed by IHC and Digital Pathology for immune biomarkers. The safety and efficacy of NBTXR3 plus stereotactic body radiotherapy (SBRT) in combination with anti-PD-1 is being evaluated in three cohorts of patients with advanced cancers in the Phase I 1100 [NCT03589339] trial. Results Pre-clinical studies demonstrated that NBTXR3+RT induces an immune response not observed with RT alone and enhances systemic control. IHC showed significant increase of CD8+ T-cell infiltrates in both NBTXR3+RT treated and untreated tumors compared to RT alone. Increased CD8+ T-cell and decreased FOXP3+ Treg density (pre- vs post-treatment) was also observed in tumors from STS patients treated with NBTXR3+RT. Furthermore, NBTXR3+RT in combination with anti-PD-1 improved local and systemic control in mice bearing anti-PD-1 resistant lung tumors, produced long-term memory, and reduced spontaneous lung metastases. Preliminary efficacy data from the 1100 trial showed tumor regression in 8/9 patients. Of note, tumor regression was observed in 6/7 patients who had progressed on prior anti-PD-1. Conclusion The clinical efficacy of NBTXR3+RT has been demonstrated as a single agent in STS. Here we demonstrate that it overcomes resistance to anti-PD-1 treatment mechanisms in mice and led to tumor regression in patients having progressed on anti-PD-1 therapy. These results highlight the potential of NBTXR3+RT to positively impact the immuno-oncology field.

Background Cancer immunotherapies have shown promising clinical outcomes; however, the majority of patients are non-responders or will develop resistance during the course of treatment. One of the current challenges is to increase the response rate to immune checkpoint inhibitors (ICIs). Combining immunotherapy with radiation therapy (RT) is emerging as a valuable strategy to prime the immune response. However, RT dose and ultimate efficacy are limited by toxicity related to exposure of healthy tissues. First-in-class radioenhancer NBTXR3, administered by one-time direct intratumoral injection, is designed at the nanoscale to increase RT dose deposit with subsequent increase in tumor cell killing, without increasing toxicity to normal tissue. Preclinical and early clinical data suggest NBTXR3/RT can prime the immune system and act as an in situ vaccine leading to an anti-tumor immune response, producing both local and systemic (abscopal) effects. We hypothesize NBTXR3/RT in combination with anti-PD-1 (NBTXR3/RT/PD-1), will act synergistically to increase the proportion of ICI responders or convert ICI non-responders to responders. Methods A multicenter, open-label, phase I trial [NCT03589339] evaluating safety and tolerability of NBTXR3/RT/PD-1 in three cohorts: (1; HN lung) lung or (3; liver) liver metastases from any primary cancer eligible for approved anti-PD-1 treatment. NBTXR3 injected volume is based on a percentage of baseline tumor volume. Stereotactic body RT (SBRT) is delivered as per standard practice. The primary objective is to determine NBTXR3/RT/PD-1 recommended phase II dose in each cohort. Secondary objectives are to evaluate anti-tumor response (objective response rate), safety and feasibility of NBTXR3 injection, and NBTXR3 body kinetic profile. Results To date 6 patients have been treated: 3 in H&N (2 anti-PD-1 naive) and 3 in lung (all anti-PD-1 non-responders. No DLT or SAE has been observed. Grade 2 nausea related to NBTXR3 or injection procedure was observed in H&N. 2 H&N patients and 3 lung patients have completed RT and initiated anti-PD-1 treatment. RT-related safety profile was as expected. Tumor shrinkage was observed in 1 anti-PD-1 naive and 2 anti-PD-1 non-responders and additional preliminary efficacy and updated safety results will be presented. Conclusions To date, NBTXR3 administration activated by SBRT in combination with anti-PD-1 treatment has been safe and well tolerated in patients with advanced cancers. Promising early signs of efficacy in anti-PD-1 naive, as well as in patients having progressed on previous anti-PD-1 therapy will be presented. Trial Registration NCT03589339 Ethics Approval This study was approved by local institution’s review board

Background Despite recent advances, resistance to immune checkpoint inhibitors (ICI), observed in over 80% of treated patients, is currently the main challenge immuno-oncology is facing. Intense efforts are being made to identify combination therapies that could improve ICI response rates. Administered intratumorally, NBTXR3 enhances the energy dose deposited by ionizing radiation within tumor cells, increasing the anti-tumor efficacy of radiation therapy (XRT) without adding toxicity to surrounding tissues. Here we present evidence that NBTXR3 activated by XRT primes the immune system, producing an anti-tumor response, including activation of the cGAS-STING pathway, that overcomes anti-PD-1 resistance both in mice models and patients. Methods Abscopal assays were conducted in immunocompetent mice. Tumor cell lines, sensitive or resistant to anti-PD-1, were injected in both flanks of mice. Intratumoral injection of NBTXR3 (or vehicle) followed by XRT was performed in right flank (primary) tumors only. Some mice also received anti-PD-1 injections. Tumor growth was monitored, and tumor immune cell infiltrates were analyzed by immunohistochemistry (IHC). Separately, in the phase II/III randomized trial Act.in.Sarc [NCT02379845] patients with locally advanced soft tissue sarcoma (STS) received either NBTXR3+XRT or XRT alone followed by wide tumor resection. Pre- and post-treatment tumor samples from patients in both groups were analyzed by IHC and Digital Pathology for immune biomarkers. The safety and efficacy (RECIST 1.1/iRECIST) of NBTXR3 plus stereotactic ablative radiotherapy (SABR) in combination with anti-PD-1 is being evaluated in three cohorts of patients with advanced cancers [NCT03589339]. Results Pre-clinical studies demonstrated that NBTXR3+XRT induces an immune response a not observed with XRT alone and enhances systemic control. IHC showed significant increase of CD8+ T-cell infiltrates in both NBTXR3+XRT treated and untreated tumors compared to XRT alone. Similarly, increased CD8+ T-cell density (pre- vs post-treatment) was observed in tumor tissues from STS patients treated with NBTXR3+XRT. Tumor samples from the NBTXR3+XRT group also displayed increased PD-1+ cell density. Furthermore, in combination with anti-PD-1, NBTXR3+XRT improved local and systemic control in mice bearing anti-PD-1 resistant lung tumors, as well as resulted in reduced number of spontaneous lung metastases.Preliminary efficacy data from the first in human trial of NBTXR3+XRT in combination with anti-PD-1 showed tumor response in patients who progressed on prior anti-PD-1. Conclusions The clinical efficacy of NBTXR3+XRT has been demonstrated as a single agent. We now demonstrate that it potentiates anti-PD-1 treatment to overcome resistance mechanisms. These results highlight the potential of NBTXR3+XRT to positively impact the immuno-oncology field. Ethics Approval This study was approved by local institution’s review board

An experimental and computational investigation has been undertaken into the effects of deterioration of the first stage rotor shroud knife-edge seal clearance in a two-stage turbine which has engine representative cavity geometries. Four values of deterioration were investigated which cover the new-condition to old-condition knife-edge seal clearance. Measurements within the first stage rotor shroud cavity show that whilst the leakage mass flow rate increases with deterioration, the angle at which the leakage flow approaches the downstream stator is essentially fixed and independent of the flow coefficient. This is in agreement with a simple over-tip leakage model. Because of the engine representative cavity geometry, the over-shroud leakage flow undergoes little mixing when it re-enters the mainstream and approaches the downstream stator at more than 60° negative incidence. Detailed measurements at the exit of the second stage stator identified two large positive vortices which were not consistent with the horseshoe vortex model for secondary flow. A computational investigation revealed that one vortex originates from the rolling-up within the stator passage of the streamwise vorticity sheet associated with the first stage rotor over-shroud leakage. This roll-up vortex cannot be eliminated. The second vortex is generated within the stator passage by the separation of the over-shroud leakage flow at the leading-edge due to the large negative incidence. It was hypothesised that this separation vortex might be eliminated by locally redesigning the stator. A new stator was designed, manufactured and tested. As predicted, the roll-up vortex was still present but the separation vortex was eliminated. For all the values of deterioration tested the entropy loss coefficient of the new stator and the unchanged second stage rotor were reduced. It is estimated that the new stator would improve the lifetime average efficiency by 0.5% compared to the original.

We investigated the circumstances of ezetimibe discontinuation as its prescribing had been discouraged in some publications. Adults on stable lipid-modifying therapy (LMT) including ezetimibe, who then had >8 weeks cessation in their prescribed ezetimibe regimen (2010–2011) were identified from THIN UK primary care database. Lipid values and parallel changes to other LMT were described overall and in a sub-group with a history of diabetes, cardiovascular disease or familial hypercholesterolaemia (high-risk group). Ezetimibe therapy stopped in 7087 patients after a mean of 38 months; 67.0% were in the high-risk group. No lipid readings were recorded for 16.1% of patients in the year before and 26.2% in the year after ezetimibe stopped; 11.0% and 12.4% in the high-risk group respectively. In the prior year, 60.2% patients with any lipid reading had a total cholesterol (T-cholesterol)

2591 Background: Despite recent advances, resistance to immune checkpoint inhibitors (ICI), observed in over 80% of treated patients, is currently the main challenge in immuno-oncology. Intense efforts are being made to identify combination therapies that could improve ICI response rates. NBTXR3, a novel radioenhancer administered by direct intratumoral injection (ITI), is designed at the nanoscale to increase radiation therapy (XRT) dose deposit within tumor cells and subsequent tumor cell killing, without increasing toxicity to surrounding healthy tissue. Here we present evidence that NBTXR3 activated by XRT primes the immune system, producing an anti-tumor response, including activation of the cGAS-STING pathway, that overcomes anti-PD-1 resistance both in mice models and patients. Methods: Abscopal assays were conducted in immunocompetent mice. Anti-PD-1 sensitive or resistant tumor cell lines, were injected in both flanks of mice. Intratumoral injection of NBTXR3 (or vehicle) followed by XRT was performed in right flank (primary) tumors only. Some mice also received anti-PD-1 injections. Tumor growth was monitored, and tumor immune cell infiltrates analyzed by immunohistochemistry (IHC). Separately, in the phase II/III randomized Act.in.Sarc [NCT02379845] trial patients with locally advanced soft tissue sarcoma (STS) received either NBTXR3+XRT or XRT alone followed by tumor resection. Pre- and post-treatment tumor samples from patients in both groups were analyzed by IHC and Digital Pathology for immune biomarkers. The safety and efficacy (RECIST 1.1/iRECIST) of NBTXR3 plus stereotactic body radiotherapy (SBRT) in combination with anti-PD-1 is being evaluated in three cohorts of patients with advanced cancers [NCT03589339]. Results: Pre-clinical studies demonstrated that NBTXR3+XRT induces an immune response not observed with XRT alone and enhances systemic control. IHC showed significant increase of CD8+ T-cell infiltrates in both NBTXR3+XRT treated and untreated tumors compared to XRT alone. Similarly, increased CD8+ T-cell and decreased FOXP3+ Treg density (pre- vs post-treatment) was observed in tumor tissues from STS patients treated with NBTXR3+XRT. Furthermore, NBTXR3+XRT in combination with anti-PD-1 improved local and systemic control in mice bearing anti-PD-1 resistant lung tumors, as well as reduced the number of spontaneous lung metastases. Preliminary efficacy data from the first in human trial of NBTXR3+XRT in combination with anti-PD-1 showed tumor regression in the majority of patients (8/9). Of note, tumor regression was observed in 6/7 pts who had progressed on prior anti-PD-1. Conclusions: The clinical efficacy of NBTXR3+XRT has been demonstrated as a single agent. We now demonstrate that it potentiates anti-PD-1 treatment to overcome resistance mechanisms. These results highlight the potential of NBTXR3+XRT to positively impact the immuno-oncology field. Clinical trial information: NCT03589339.

2590 Background: Immune checkpoint inhibitors (ICIs) targeting PD-1 are an effective treatment for a variety of cancers. However, the majority of patients (pts) exhibit resistance to ICIs. Overcoming this resistance represents a major challenge in immuno-oncology. Emerging evidence suggests radiation therapy (RT) produces an immunomodulatory effect that may act synergistically with ICIs. However, RT dose and ultimate efficacy are limited by toxicity to surrounding healthy tissues. NBTXR3, a novel radioenhancer administered by direct intratumoral injection (ITI), is designed at the nanoscale to increase RT dose deposit within tumor cells and subsequent tumor cell killing, without increasing toxicity to surrounding healthy tissue. Preclinical data suggest NBTXR3/RT can trigger a local and systemic anti-tumor immune response and overcome anti-PD-1 resistance. NBTXR3/RT combined with anti-PD-1 may prime the immune system to increase the proportion of ICI responders, or convert ICI non-responders to responders. Methods: This is a multicenter, open-label, phase I trial [NCT03589339] to evaluate NBTXR3/RT/anti-PD-1 in 3 cohorts: (1) Locoregional recurrent or recurrent and metastatic head and neck squamous cell carcinoma (HNSCC) amenable to HN re-irradiation, and metastases from any primary cancer eligible for anti-PD-1 (nivolumab or pembrolizumab) treatment specifically localized in the lung (2) or liver (3), respectively. Stereotactic body RT (SBRT) is delivered at tumor-site selective doses per standard practice. The primary objective is NBTXR3/RT/anti-PD-1 recommended phase 2 dose in each cohort. Secondary objectives are anti-tumor response (objective response rate), safety and feasibility of NBTXR3 injection. Results: Nine pts have been treated: 3 HNSCC, 4 lung, 2 liver. 7/9 pts were anti-PD-1 non-responders. Overall tumor regression was observed in 8/9 pts. NBTXR3/RT/anti-PD-1 resulted in tumor regression in 6/7 pts who had progressed on prior anti-PD-1. A complete response in the injected lymph node lasting over 1 year was observed in 1 anti-PD-1 naïve pt. 2 SAEs related to anti-PD-1 and possibly related to NBTXR3 (G5 pneumonitis, G4 hyperglycemia) were observed in 1 anti-PD-1 naïve HNSCC pt and considered DLTs. This pt also experienced 2 other SAEs related to anti-PD-1 (G4 diabetic ketoacidosis, G4 acute kidney injury). SBRT-related safety profile was as expected. Updated results will be presented. Conclusions: Data from this first-in-human phase I trial evaluating NBTXR3/RT/anti-PD-1 in pts with advanced cancers, show NBTXR3 ITI is feasible and well-tolerated. NBTXR3/RT/anti-PD-1 demonstrated promising signs of efficacy. Of particular interest, NBTXR3/RT can overcome ICI resistance in pts having progressed on prior anti-PD-1, supporting further development of NBTXR3 in combination with anti-PD-1 as well as other ICIs. Clinical trial information: NCT03589339.

TPS3173 Background: Despite the past decade of transformative advances in immuno-oncology, the response rate to checkpoint inhibitors (ICIs) remains low (~15%). There is significant interest in developing strategies to overcome resistance to these treatments, thus increasing response rate. Emerging evidence suggests that radiation therapy (RT) could potentially augment the antitumor response to ICIs through synergic effect. However, RT dose and ultimate efficacy are limited by toxicity related to exposure of healthy tissues. NBTXR3 is a first-in-class radioenhancer administered by direct intratumoral injection, designed at the nanoscale to increase RT dose deposition within tumor cells and RT-dependent tumor cell killing, without increasing surrounding normal tissue toxicity. Preclinical and early clinical data suggest NBTXR3 activated by RT can trigger an anti-tumor immune response, producing both local and systemic (abscopal) effects. We hypothesize that NBTXR3 activated by RT, in combination with anti-PD-1 therapy (R3/RT/PD-1), will act synergistically to maximize the local RT effect and produce a systemic response sufficient to increase the proportion of ICI responders or convert ICI non-responders to responders. Methods: This trial [NCT03589339] is a multicenter, open-label, phase I study to evaluate safety and tolerability of R3/RT/PD-1 in three cohorts: (1) Locoregional recurrent or recurrent and metastatic head and neck squamous cell carcinoma (HNSCC) amenable to re-irradiation of the HN field, (2) Lung metastases, or (3) Liver metastases, both from any primary cancer eligible for anti-PD-1 treatment. Approximately two-thirds of patients in each cohort will be anti-PD-1 non-responders. NBTXR3 injected volume is based on a percentage of gross tumor volume (GTV). The primary objective is to determine the R3/RT/PD-1 recommended phase 2 dose in each cohort. Secondary objectives are to evaluate anti-tumor response (objective response rate; ORR), safety and feasibility of NBTXR3 injection, and NBTXR3 body kinetic profile. Exploratory objectives will assess biomarkers of R3/RT/PD-1 response, including PD-L1 status by IHC, as well as mRNA and cytokine immune marker profiling. To date, three patients have been treated, one in cohort 1, two in cohort 2. Clinical trial information: NCT03589339 .

TPS86 Background: Most cancer patients present resistance to immune therapy; only approximately 15% of patients respond to immune checkpoint inhibitors (ICI). Strategies able to increase ICI response are thus of great interest. Radiotherapy (RT), by acting as an immunomodulator is a good candidate to increase the proportion of ICI responders. However, RT dose and ultimate efficacy are limited by potential toxicity to healthy tissues. NBTXR3, a first in class radioenhancer administered by intratumoral injection, has been designed at the nanoscale to increase RT energy dose deposition within the tumor. The result is increased radiation-dependent tumor cell killing, without increasing radiation exposure of healthy tissues. Preclinical and early clinical data suggest NBTXR3 activated by RT can increase the anti-tumor response yielding both local and systemic (abscopal) effects. We hypothesize that NBTXR3 activated by RT, in combination with anti-PD-1 therapy (R3/RT/PD-1), will act synergistically to maximize the local RT effect while also producing a systemic effect sufficient to increase the proportion of ICI responders or convert ICI non-responders to responders. Methods: NANORAY-1100 [NCT03589339] is a multicenter, open-label, phase 1 study to evaluate safety and tolerability of R3/RT/PD-1 in three cohorts: (1) Locoregionally recurrent or recurrent and metastatic head and neck squamous cell carcinoma (HNSCC) amenable to re-irradiation of the HN field, (2) Lung metastases from any primary cancer eligible for anti-PD-1, or (3) Liver metastases from any primary cancer eligible for anti-PD-1. Approximately two-thirds of each cohort will be composed of anti-PD-1 non-responders. NBTXR3 injection volume is based on a percentage of gross tumor volume (GTV) determined by central review. The primary objective is to determine R3/RT/PD-1 RP2D. Secondary objectives are to evaluate anti-tumor response (objective response rate; ORR) of R3/RT/PD-1, safety and feasibility of NBTXR3 injection, and NBTXR3 body kinetic profile. Exploratory objectives will assess biomarkers of R3/RT/PD-1 response, including PD-L1 status by IHC, mRNA and cytokine immune marker profiling. Clinical trial information: NCT03589339.

Background: Inflammatory back pain (IBP) is an early feature of ankylosing spondylitis (AS) and its detection offers the prospect of early diagnosis of AS. However, since back pain is very common but only a very small minority of back pain sufferers have ASpA or AS, screening of back pain sufferers for AS is problematic. In early disease radiographs are often normal so that fulfilment of diagnostic criteria for AS is impossible though a diagnosis of axial SpA can be made if MRI evidence of sacroiliitis is present. This pilot study was designed to indicate whether a cost-effective pick up rate for ASpA/early AS could be achieved by identifying adults with IBP stratified on the basis of age. Methods: Patients aged between 18 and 45 years who were referred to a hospital physiotherapy service with back pain of more than 3 months duration were assessed for IBP. All were asked to complete a questionnaire based on the Berlin IBP criteria. Those who fulfilled IBP criteria were also asked to complete a second short questionnaire enquiring about SpA comorbidities, to have a blood test for HLA-B27 and CRP level and to undergo an MRI scan of the sacroiliac joints. This was a limited scan, using STIR, diffusion-weighted, T1 and T2 sequences of the sacroiliac joints to minimize time in the scanner and cost. The study was funded by a research grant from Abbott Laboratories Ltd. Results: 50 sequential patients agreed to participate in the study and completed the IBP questionnaire. Of these 27 (54%) fulfilled criteria for IBP. Of these, 2 patients reported a history of an SpA comorbidity - 1 psoriasis; 1 ulcerative colitis - and 3 reported a family history of an SpA comorbidity - 2 psoriasis; 1 Crohn's disease. 4 were HLA-B27 positive, though results were not available for 7. Two patients had marginally raised CRP levels (6, 10 -NR ≤ 5). 19 agreed to undergo MRI scanning of the sacroiliac joints and lumbar spine; 4 scans were abnormal, showing evidence of bilateral sacroiliitis on STIR sequences. In all cases the changes met ASAS criteria but were limited. Of these 4 patients 3 were HLA-B27 positive but none gave a personal or family history of an SpA-associated comorbidity and all had normal CRP levels. Conclusions: This was a pilot study yielding only limited conclusions. However, it is clear that: Screening of patients referred for physiotherapy for IBP is straightforward, inexpensive and quick. It appears that IBP is more prevalent in young adults than overall population data suggest so that targeting this population may be efficient. IBP questionnaires could be administered routinely during a physiotherapy assessment. HLA-B27 testing in this group of patients with IBP is a suitable screening tool. The sacroiliac joint changes identified were mild and their prognostic significance is not yet clear so that the value of early screening needs further evaluation. Disclosure statement: C.H. received research funding for this study from Abbott. A.K. received research funding for this study, and speaker and consultancy fees, from Abbott. All other authors have declared no conflicts of interest

British clinical guidelines recommend statins as first-line lipid-modifying treatment (LMT) for patients at high risk of cardiovascular disease (CVD). We undertook an observational study to assess total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels in high-risk patients who were treated with atorvastatin monotherapy by UK general practitioners.This retrospective database study included patients with a prescription for atorvastatin monotherapy between November 30, 2008, and November 30, 2011, with the index date defined as the first atorvastatin prescription during this period. Eligible high-risk patients with evidence of coronary heart disease (CHD), atherosclerotic vascular disease (AVD), diabetes mellitus (DM), or familial hypercholesterolemia (FH) were required to have ≥1 TC and LDL-C measurement between 3 and 12 months after the index date, and continuous enrollment 1 year before and 1 year after the index date. Cholesterol levels were assessed using the National Institute for Health and Care Excellence (NICE) guidelines: TC4.0 mmol/L or LDL-C2.0 mmol/L.Of 2999 high-risk patients (60.2% men; mean [SD] age = 67.9 [10.6] years) meeting selection criteria, 23.9% 28.2%, 36.2%, and 11.6% received prescriptions for atorvastatin 10, 20, 40, and 80 mg, respectively (percentages do not sum to 100 because of rounding). Across all doses, the mean (SD) follow-up TC was 4.08 (0.80) mmol/L and LDL-C 2.08 (0.65) mmol/L. A large proportion of patients (88.8%) had TC 5.0 mmol/L. However, only 45.8% had TC 4.0 mmol/L, and 46.5% had LDL-C 2.0 mmol/L. Although a larger proportion of patients with CHD/AVD + DM reached guideline-recommended lipid levels, only 63.7% of such patients had TC 4.0 or LDL-C 2.0 mmol/L, which are the current targets for this subgroup as recommended by NICE.Less than half of UK high-CVD-risk patients receiving atorvastatin monotherapy achieved guideline-recommended treatment targets for TC, and less than two-thirds of patients with CHD/AVD + DM had values below TC (4.0 mmol/L) or LDL-C (2.0 mmol/L) targets. More effective lipid-lowering strategies may be warranted to optimize cholesterol lowering and target attainment in high-risk patients. Limitations of this study include its retrospective, observational nature.

Background The majority of cancer patients are resistant to immune therapy; only around 15% respond to immune checkpoint inhibitors (ICI). Thus, strategies able to increase ICI response are of great interest. Recent work suggests radiotherapy (RT) can act as an immunomodulator to increase the proportion of ICI responders and improve clinical outcomes. However, RT dose and ultimate efficacy are limited by toxicity related to exposure of healthy tissues. NBTXR3 is a first-in-class radioenhancer administered by intratumoral injection, designed at the nanoscale to increase RT energy dose deposition within the tumor. The result is increased radiation-dependent tumor cell killing, without increasing radiation exposure of healthy tissues. Preclinical and early clinical data suggest NBTXR3 activated by RT can increase the anti-tumor immune response, producing both local and systemic (abscopal) effects. We hypothesize that NBTXR3 activated by RT, in combination with anti-PD-1 therapy (R3/RT/PD-1), will act synergistically to maximize the local RT effect while also producing a systemic response sufficient to increase the proportion of ICI responders or convert ICI non-responders to responders. Trial Design The NANORAY-1100 study is a multicenter, open-label, phase I study that aims to evaluate the safety and tolerability of R3/RT/PD-1 in three cohorts of participants with either: (1) Locoregional recurrent (LRR) or recurrent and metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) amenable to re-irradiation of the head and neck (HN) field, (2) Lung metastases originating from any primary cancer eligible for anti-PD-1 therapy, or (3) Liver metastases originating from any primary cancer eligible for anti-PD-1 therapy. Participants will be enrolled such that approximately two-thirds of each cohort will be anti-PD-1 non-responders. NBTXR3 injection volume is based on percentage of gross tumor volume (GTV), as determined per central review. The primary objective is to determine the RP2D of R3/RT/PD-1. The secondary objectives are to evaluate the anti-tumor response (objective response rate; ORR) of R3/RT/PD-1, the safety and feasibility of NBTXR3 injection, and the body kinetic profile of NBTXR3. Exploratory objectives will assess biomarkers of response to R3/RT/PD-1, including PD-L1 status by IHC, as well as mRNA and cytokine immune marker profiling. Clinical trial identification NCT03589339. Legal entity responsible for the study Nanobiotix, SA. Funding Nanobiotix, SA. Disclosure C. Shen: Honoraria (self): Nanobiotix. K. Jameson: Full / Part-time employment: Nanobiotix. J. Weiss: Honoraria (self): Nanobiotix. T. Hackman: Honoraria (self): Nanobiotix. D. Corum: Full / Part-time employment: Nanobiotix. J.A. Akulian: Honoraria (self): Nanobiotix. R. Dixon: Honoraria (self): Nanobiotix. A. Pearson: Honoraria (self): Nanobiotix. J. Frakes: Honoraria (self): Nanobiotix. P. Said: Full / Part-time employment: Nanobiotix. H. Miraoui: Full / Part-time employment: Nanobiotix. E. Baskin-Bey: Full / Part-time employment: Nanobiotix. T. Seiwert: Honoraria (self): Nanobiotix.

Summary Aims To estimate the prevalence of dyslipidaemias in high-risk patients new to lipid-modifying therapy (LMT), and establish the extent to which these lipid abnormalities are addressed by treatment in UK clinical practice. Methods The PRIMULA study was a retrospective analysis, conducted using the UK General Practice Research Database. Two periods were studied as follows: a pretreatment period, defined as the 12 months before initiation of LMT (the index date), and a follow-up period of at least 12 months. Patients included in the study (n = 25,011) had dyslipidaemia with at least one abnormal lipid measurement [total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) or triglycerides (TG)] in the pretreatment period. All patients were at high risk of cardiovascular events, which was defined as having a history of cardiovascular disease, a 10-year Framingham risk score higher than 20%, diabetes or hypertension, as defined by the Joint British Societies 2 guidelines. Results At the index date, 98% of patients were initiated on statin monotherapy. After 12 months of treatment, 15.2% (sub-group range: 11.0–22.9%) of all high-risk patients had no lipid abnormalities. The proportions of patients with high TC or LDL-C levels decreased from 98.8% to 68.9%, and from 99.2% to 68.7%, respectively, over 12 months. The prevalence of high TG levels decreased from 45.0% to 26.9%, whereas that of low HDL-C levels increased, from 16.6% to 18.0%. Risk factors for cardiovascular events were not consistently associated with the likelihood of attaining optimal lipid levels. Conclusions Despite widespread use of statins, many individuals at high risk of cardiovascular events have persistently abnormal lipid levels, with over two-thirds of patients not achieving target levels of LDL-C or TC. Management of dyslipidaemia is therefore suboptimal in this important high-risk group in UK standard practice.

The cathode coupling voltage in Hall thrusters, which is the voltage difference between the cathode and the thruster beam plasma potential, is considered an indicator of the ease with which electrons flow from cathode to anode.Historically, the coupling voltage has beenminimizedby increasing the amount of propellant injected through the hollow cathode due to early observations that thismaximizes the discharge (or anode) efficiency.However, recent experiments described here show that the total thruster efficiency is independent of the cathode flow over the range from 5 to 10%of the propellant injected into the thruster body through the anode. For this reason, cathode flow rates can be reduced closer to the classic plume mode limit characteristic of the hollow cathode design without impacting the total thruster efficiency. Such reductions in cathode flow rate can significantly extend the cathode life, especially for higher-power Hall thrusters with larger discharge currents, where the normal Hall thruster cathode flow split will significantly exceed the optimum level for cathode operation and life.

OBJECTIVE: The objective of this study is to describe current self-monitoring of blood glucose (SMBG) practice for patients with type 2 diabetes by treatment type and adherence with healthcare professional advice concerning SMBG. In addition, the study aims to investigate the association of SMBG and self-reported episodes of low blood glucose. DESIGN AND SETTING: This cross-sectional survey design study was carried out on patients with type 2 diabetes aged 18 years or over, attending community pharmacies in 97 sites across the United Kingdom. METHODS: Patients picking up a prescription for blood glucose test strips or diabetes medicine from a community pharmacist were asked to complete a questionnaire. The pharmacist was available to assist if requested. Questions included: self-reports of frequency of blood glucose testing; type of diabetes treatment; advice given by healthcare professionals about frequency of blood glucose testing; frequency of episodes of low blood glucose; and last known HbA(1c) level. The final sample size was 554 respondents, who were grouped for analysis as follows: those being treated with insulin, either alone or with any oral medication (n = 167); those being treated with sulfonylureas, either alone or with any oral medication (n = 187); and those being treated with any other medication, or controlled by diet and exercise alone (n = 202). RESULTS: Frequency of SMBG was higher in patients using insulin (median 10 times per week, Q (1), Q (3) = 4.5, 14) than in patients on treatments other than insulin (four times per week, Q (1), Q (3) = 2, 7, p < 0.001). SMBG was carried out at the same frequency in patients not treated with insulin regardless of whether they were prescribed sulfonylureas. Greater frequency of SMBG was associated with self-reports of one or more episodes of low blood glucose in the previous six months. CONCLUSIONS: Among patients with type 2 diabetes, those treated with insulin used SMBG at a greater frequency than those not treated with insulin. Increased frequency of testing was associated with increased frequency of self-reported episodes of low blood glucose, even among patients not taking insulin or sulfonylureas. This raises the possibility that episodes of hypoglycaemia may not be accurately identified, leading to unnecessary fear, or conversely that treatment is not being adjusted to avoid such morbidity. Although further work is needed to explore this association in a representative, prospective cohort of patients, possible explanations for reports of low-blood glucose should be discussed with patients using SMBG more frequently to ensure they are able to accurately identify episodes of hypoglycaemia.

The wear of the keeper electrode in discharge hollow cathodes is a major impediment to the implementation of ion propulsion onboard long-duration space science missions. The development of a predictive theoretical model for hollow cathode keeper life has long been sought, but its realization has been hindered by the complexities associated with the physics of the partially ionized gas and the associated erosion mechanisms in these devices. Thus, although several wear mechanisms have been hypothesized, a quantitative explanation of life test erosion profiles has remained incomplete. A two-dimensional model of the partially ionized gas in a discharge cathode has been developed and applied to understand the mechanisms that drove the erosion of the keeper in two long-duration life tests of a 30-cm ion thruster. An extensive set of comparisons between predictions by the numerical simulations and measurements of the plasma properties and of the erosion patterns is presented. It is found that the near-plume plasma oscillations, predicted by theory and observed by experiment, effectively enhance the resistivity of the plasma as well as the energy of ions striking the keeper.

Objective: Sitagliptin is a novel oral incretin enhancer that acts by inhibiting the dipeptidyl peptidase 4 enzyme and is indicated in Europe as a treatment adjunct to metformin (MF), sulphonylurea (SU), MF plus SU and diet and exercise, in the management of type 2 diabetes mellitus. The objective of the current analysis was to evaluate the cost-effectiveness of adding sitagliptin to the regimens of patients with haemoglobin A1c (HbA1C) above the International Diabetes Federation goal (6.5%) while on MF in six European countries: Austria, Finland, Portugal, Scotland (United Kingdom), Spain and Sweden. Methods: A discrete event simulation model, which employed the United Kingdom Prospective Diabetes Study (UKPDS) Outcomes Model risk equations for predicting risks of diabetes-related complication, was used. Lifetime costs and benefits were projected for alternative treatment strategies of adding sitagliptin, compared with adding rosiglitazone or a SU to MF in patients not at HbA1C goal on MF monotherapy. Changes in HbA1C as well as side effects associated with these different treatment strategies were based on clinical trial data. Mean baseline values from local epidemiologic studies involving patients with type 2 diabetes not at HbA1C goal on MF monotherapy were included in the current analysis. Costs of medications, side effects and direct costs of diabetes-related complications were based on country-specific data. UKPDS-based disutility weights associated with diabetes complications were incorporated. Disutilities associated with medication side effects were based on published data. All future costs and benefits were discounted according to local guidelines on cost-effectiveness analysis. One-way sensitivity analyses were conducted by varying key input parameters. Findings: The discounted incremental cost-effectiveness ratios (ICER) associated with the addition of sitagliptin to MF, compared with adding rosiglitazone, in the different countries analysed ranged from treatment with sitagliptin being dominant (cost saving with improved health outcome) to its being cost-effective [€4,766 per quality-adjusted life year (QALY)]. Treatment with sitagliptin added to MF was cost-effective compared with adding a SU, with discounted ICER values ranging from €5949/QALY to €20 350/QALY across countries. Sensitivity analyses showed that these results were robust to changes in input parameters, including clinical efficacy, costs and utility weights for both diabetes-related complications and hypoglycaemia. Conclusions: Compared with adding rosiglitazone or a SU to MF, adding sitagliptin to MF is projected to be either cost saving or cost-effective for patients with type 2 diabetes who are not at HbA1C goal on MF.

Deep space missions and satellite station-keeping applications continue to demand higher power ion thrusters and Hall thrusters capable of providing high thrust and longer life. Depending on the thruster size, the hollow cathodes may be required to produce discharge currents in the 10-100 A range with lifetimes in excess of 10 years. A lanthanum hexaboride (LaB 6 ) hollow cathode has been developed for space applications to increase the current capability from the cathode and ease the handling and gas purity requirements. This cathode uses a LaB 6 insert in an all-graphite hollow cathode structure with an integral graphite keeper. Three different sizes of the LaB 6 cathode have been successfully operated at discharge currents of up to 100 A to date. Although the LaB 6 cathode insert operates at a higher temperature than the conventional BaO dispenser cathode, LaB 6 offers the capability of long life and orders of magnitude less sensitivity to propellant impurities and air exposure than conventional dispenser cathodes.

Aims: To assess adherence to the United Kingdom’s (UK) National Institute for Health and Care Excellence (NICE) guidelines for initiating and continuing glucagon-like peptide-1 (GLP-1) receptor agonists in patients with type 2 diabetes (T2DM).Research Design & Methods: A retrospective cohort study of 7,133 primary care patients ≥40 years with a first prescription for GLP-1 receptor agonist following publication of NICE guideline/guidance. Patient characteristics and levels of clinical monitoring were assessed using descriptive analyses.Main outcome measures: Main outcomes were the proportion of patients initiating GLP-1 receptor agonist as part of NICE recommended dual- or triple-therapy regimens; the proportions meeting NICE triple therapy initiation criteria (glycosylated haemoglobin [HbA1c] ≥7.5% and body mass index [BMI] ≥35kg/m2) and the proportions continuing GLP-1 receptor agonist at 6 months according to NICE recommendations.Results: Mean age at initiating GLP-1 receptor agonist was 58.2 years (SD 9.4), BMI 38.4 kg/m2 (SD 6.8) and HbA1c 9.2% (SD 3.2%). Overall, only 25% of patients initiated GLP-1 receptor agonist as part of a NICE-recommended regimen. Of patients initiated on a recommended triple-therapy regimen, 50% (646/1284) fulfilled both NICE HbA1c and BMI initiation criteria. Approximately 18% (32/174) of patients continuing NICE-recommended dual-therapy at 6 months achieved a 1% reduction in HbA1c and 6.4% (33/515) continuing with NICE recommended triple-therapy achieved both NICE’s target reductions for HbA1c and body weight. About 8% of patients continuing exenatide as triple therapy (N=243) achieved both targets.Conclusions: Adherence to NICE guidance for initiating and continuing GLP-1 receptor agonists is low. However, lack of data on ethnicity (for assessing NICE’s BMI criteria) and on contraindications and/or hypersensitivity to other diabetes medication in the treatment pathway have limited our ability to fully assess adherence to GLP-1 prescribing.Further research is warranted to better understand general practitioners prescribing decisions given the cost of prescribing GLP-receptor agonists.

SummaryBackground This study aimed to estimate the prevalence of chronic kidney disease (CKD) in the UK in 2010 and to assess prevalence, comorbidities and comedications associated with the disease over time, following inclusion of CKD in the Quality and Outcomes Framework (QOF). Methods This was a retrospective, longitudinal study assessing individuals with prevalent or incident CKD (identified using estimated glomerular filtration rate readings and/or Read codes) in the General Practice Research Database (GPRD) in 2010. Individuals were assessed at two time points: in 2010 and at the date of their first classification of CKD in the GPRD. Results The prevalence of stage 3–5 CKD in 2010 was 5.9%. In patients with stage 3–5 CKD at first classification, their disease remained stable, progressed or improved by 2010 in approximately 50%, 10–15% and 25–30% of patients, respectively. Diagnoses of cardiovascular-related comorbidities (hypertension, hypercholesterolaemia, diabetes and cardiovascular disease), and treatment with antihypertensives and lipid-modifying therapy (LMT), increased with worsening disease severity. When patients were stratified by diagnosis date, the proportion of patients with stage 3–5 CKD and cardiovascular-related comorbidities decreased with time, and the relative use of LMT and antihypertensives among patients with hypercholesterolaemia and hypertension increased with time. Conclusions Chronic kidney disease is generally stable or progressive, although more patients improve disease stage than previously assumed. Data suggest that the introduction of CKD into the QOF has increased awareness of CKD among physicians in the UK, allowing for earlier intervention and better control of CKD progression.

Background Although low-density lipoprotein cholesterol (LDL-C) is the primary lipid target for cardiovascular disease (CVD) risk reduction, high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) have also emerged as risk factors. This study evaluated attainment of goal/normal lipid levels in current clinical practice among high-risk patients following lipid-modifying therapy (LMT). Methods Data for patients aged ≥ 35 years and on LMT for ≥ 12 months were identified from electronic medical records (United Kingdom and Sweden) and extracted from medical charts (Canada and Spain). High CVD risk was defined according to the Adult Treatment Panel III guidelines. An index period was defined, from January 1995–July 2008, during which patients received an initial LMT prescription. Prevalence of lipid abnormalities was assessed 12 months before and after the index date. Multivariate logistic regressions evaluated predictors of attaining goal/normal lipid levels. Results Among 12,768 high-risk patients, 75% had elevated LDL-C, 37% low HDL-C, and 30% elevated TG before LMT. Despite therapy (97% statins only), 23% had elevated LDL-C, 36% low HDL-C, 16% elevated TG, and 17% had ≥ 2 abnormal lipid levels. Framingham risk score > 20% (Odds Ratio, 95% confidence interval: 0.37,0.31–0.43), diabetes (0.75,0.64–0.88), hypertension (1.26,1.09–1.46), current smoker (0.82,0.70–0.95) and increased body mass index (0.95,0.94–0.96) were associated with the likelihood of attaining ≥ 2 normal lipid levels (vs. LDL-C goal only). Conclusion Current approaches to lipid management improve LDL-C goal attainment; however, control of multiple lipid risk factors remains poor. Patients may benefit from more comprehensive approaches to lipid management, which treat multiple lipid abnormalities, as suggested in clinical guidelines.

A collaboration between California Polytechnic Corporation with Georgia Tech Research Institute (GTRI) and DHC Engineering worked on a NASA NRA to develop predictive capabilities for the design and performance of Cruise Efficient, Short Take-Off and Landing (CESTOL) subsonic aircraft. The work presented in this paper gives details of a large scale wind tunnel effort to validate predictive capabilities for this NRA for aerodynamic and acoustic performance during takeoff and landing. The model, Advanced Model for Extreme Lift and Improved Aeroacoustics (AMELIA), was designed as a 100 passenger, N+2 generation, regional, cruise efficient short takeoff and land (CESTOL) airliner with hybrid blended wing-body with circulation control. AMELIA is a 1/11 scale with a corresponding 10 ft wing span. The National Full-Scale Aerodynamic Complex (NFAC) 40 ft by 80 ft wind tunnel was chosen to perform the large-scale wind tunnel test. The NFAC was chosen because both aerodynamic and acoustic measurements will be obtained simultaneously, the tunnel is large enough that the

Skin friction accounts for nearly half of commercial airliner cruise drag. As drag reduction correlates to lower fuel burn, it becomes a critical design parameter. Computational Fluid Dynamics (CFD) simulates fluid flow around aircraft, allowing designs to be numerically tested and optimized. However, CFD struggles to correctly predict drag, slowing aircraft design. Therefore, NASA is funding research announcements to improve validation databases for high risk technologies. One such NRA is AMELIA, the Advanced Model for Extreme Lift and Improved Aeroacoustics, which is a cruise efficient, short takeoff and landing aircraft. AMELIA was tested in the National Full-Scale Aerodynamics Complex (NFAC) 40by 80-foot wind tunnel in the winter of 2011-2012. Extensive acoustic and aerodynamic measurements were completed. The Fringe-Imaging Skin Friction (FISF) technique was implemented, making global skin friction measurements for ten critical test points. The method proved difficult to implement in a large scale tunnel, resulting in a decrease in photogrammetry quality and test productivity. Despite this, the average skin friction uncertainty magnitude was 5.7% of cf with directional variation of ±1.7°. Results are as expected, with streamlines generally parallel to the freestream without slot blowing and normal to the slot with circulation control. Skin friction increased by an order of magnitude with blowing employed. As expected, skin friction was a maximum at the leading edge and rapidly decreased moving aft in a streamwise direction for the baseline case. With blowing, skin friction was shown to rise before the trailing edge slot.

This paper details the extensive effort required to achieve uniform flow from the AMELIA wind tunnel model’s circulation control wings. Performed in September of 2011 in the Fluid Mechanics Lab at NASA Ames Research Center, the calibration required a 500hp instrument-quality air compressor capable of delivering 250 CFM at pressures greater than 70 psi. It was found that the geometery within AMELIA’s circulation control supply plenums produced highly vortical flow, resulting in poor circulation control performance as measured by traversing external and stationary internal total pressure probes, as well as surface oil flow. Adjustments were made within AMELIA to the supply conditions of each plenum including internal butterfly valve position, model inlet pressure, and total volume flow rate delivered to the model. Each plenum was further modified with a treatment of metal foam and various other materials including perforated plates, metal barriers, and Rigimesh material. The combination of metal foam and densly woven Rigimesh resulted in uniform spanwise flow at acceptable plenum pressures.