Exhaust Plume Effects on Sonic Boom for a Delta Wing and a Swept Wing-Body Model

Supersonic travel is not allowed over populated areas due to the disturbance caused by the sonic boom. Research has been performed on sonic boom reduction and has included the contribution of the exhaust nozzle plume. Plume effect on sonic boom has progressed from the study of isolated nozzles to a study with four exhaust plumes integrated with a wing-body vehicle. This report provides a baseline analysis of the generic wing-body vehicle to demonstrate the effect of the nozzle exhaust on the near-field pressure profile. Reductions occurred in the peak-to-peak magnitude of the pressure profile for a swept wing-body vehicle. The exhaust plumes also had a favorable effect as the nozzles were moved outward along the wing-span

Integrated Systems Design of a Cargo Aircraft with Environmentally Responsible Goals

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97068/1/AIAA2012-1759.pd

Response to BMP4 signalling during ES cell differentiation defines intermediates of the ectoderm lineage

The formation and differentiation of multipotent precursors underlies the generation of cell diversity during mammalian development. Recognition and analysis of these transient cell populations has been hampered by technical difficulties in accessing them in vivo. In vitro model systems, based on the differentiation of embryonic stem (ES) cells, provide an alternative means of identifying and characterizing these populations. Using a previously established mouse ES-cell-based system that recapitulates the development of the ectoderm lineage we have identified a transient population that is consistent with definitive ectoderm. This previously unidentified progenitor occurs as a temporally discrete population during ES cell differentiation, and differs from the preceding and succeeding populations in gene expression and differentiation potential, with the unique ability to form surface ectoderm in response to BMP4 signalling.Nathan T. Harvey, James N. Hughes, Ana Lonic, Charlotte Yap, Catherine Long, Peter D. Rathjen and Joy Rathje

Evaluation of the antibody response to the EBV proteome in EBV-associated classic Hodgkin lymphoma

The humoral immune response to Epstein–Barr virus (EBV) in classical Hodgkin lymphoma (cHL) stratified by EBV tumor status is unclear. We examined IgG and IgA antibody responses against 202 protein sequences representing 86 EBV proteins using a microarray and sera from 139 EBV‐positive cHL cases, 70 EBV‐negative cHL cases and 141 population‐based controls frequency matched to EBV‐positive cHL cases on sex and age by area (UK, Denmark and Sweden). We leveraged existing data on the proportion of circulating B‐cells infected by EBV and levels of serum CCL17, a chemokine secreted by cHL tumor cells, from a subset of the cHL cases in the UK. Total IgG but not IgA response level was significantly different between EBV‐positive cHL cases and controls. The distinct serological response included significant elevations in 16 IgG antibodies and 2 IgA antibodies, with odds ratioshighest vs. lowest tertile > 3 observed for the following EBV proteins: LMP1 (oncogene), BcLF1 (VCAp160, two variants) and BBLF1 (two variants). Our cHL IgG signature correlated with the proportion of circulating EBV‐infected B‐cells, but not serum CCL17 levels. We observed no differences in the anti‐EBV antibody profile between EBV‐negative cHL cases and controls. BdRF1(VCAp40)‐IgG and BZLF1(Zta)‐IgG were identified as the serological markers best able to distinguish EBV‐positive from EBV‐negative cHL tumors. Our results support the hypothesis that differences in the EBV antibody profile are specific to patients with EBV‐positive cHL and are not universally observed as part of a systematically dysregulated immune response present in all cHL cases

Obesity at age 20 and the risk of miscarriages, irregular periods and reported problems of becoming pregnant: the Adventist Health Study-2

In a group of 46,000 North-American Adventist women aged 40 and above, we investigated the relationships between body mass index (BMI, kg/m(2)) at age 20 and the proportion of women who reported at least one miscarriage, periods with irregular menstruation or failing to become pregnant even if trying for more than one straight year. Approximately 31, 14 and 17 %, respectively, reported the three different problems related to reproduction. Positive age- and marital status adjusted relationships were found between BMI at age 20 and periods with irregular menstruation or failing to become pregnant even if trying for more than 1 year, but not with the risk of miscarriages. Women with BMI ≥ 32.5 kg/m(2) when aged 20 had approximately 2.0 (95 % CI: 1.6, 2.4) and 1.5 (95 % CI: 1.3, 1.9) higher odds for irregular periods or failing to get pregnant, respectively, than women with BMI in the 20–24.9 kg/m(2) bracket. These relationships were consistently found in a number of strata of the population, including the large proportion of the women who never had smoked or never used alcohol. Underweight (BMI < 18.5 kg/m(2)) when aged 20 marginally (approximately 15 %) increased the risk of failing to get pregnant within a year. Thus, obesity at age 20 increases the risk of reporting some specific reproductive problems, but not the risk of miscarriages. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10654-012-9749-8) contains supplementary material, which is available to authorized users

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Current Australasian practice for diagnosis and management of idiopathic pulmonary fibrosis: where are we now?

Background and objective: Recent international consensus statements have refined evidence-based guidelines for the diagnosis and management of idiopathic pulmonary fibrosis (IPF). This study sought to investigate how closely these guidelines are adhered to and to compare current practices with those of a similar cohort 15 years ago. Methods: A questionnaire on IPF diagnosis and management was distributed to respiratory physicians practising in Australia and New Zealand, in 2012–2013, and results were compared with a similar survey conducted in 1999. Results: A total of 172 and 144 questionnaires were completed in 1999 and 2012–2013, respectively. The most important investigations in both survey populations were high-resolution computed tomography scans, spirometry, diffusing capacity for carbon monoxide, chest X-ray, static lung volumes and autoimmune serology. In 1999, physicians were more likely to perform arterial blood gases, bronchoalveolar lavage and transbronchial lung biopsy. In the 2012–2013 cohort, 6-min walk tests and pulse oximetry were more widely utilized. Treatment choices differed considerably between the two survey populations. In 1999, the majority would offer a steroid-based regimen, whereas most would not use any specific treatment or would refer for trial participation in 2012–2013. Conclusions: Approach to IPF diagnosis and management is not uniform and has changed over 15 years. Surveyed respiratory physicians were generally practising in accordance with clinical guidelines, although significant variation in practice was identified in both cohorts. This study identifies the need to standardize care of IPF patients across Australia and New Zealand.Lauren K. Troy, Sally A. Chapman, Fiona Lake, Margaret L. Wilsher, Liarna B. Honeysett, Sacha Macansh, and Tamera J. Cort

Predicting the spatiotemporal expression of local and referred acute muscle pain in individual subjects

While current data suggest that all referred pain derives from common mechanisms of central sensitisation, there is a paucity of data directly comparing referral in different limbs. Does a common mechanism result in similar precepts of referral from similar stimuli in different limbs? We tested the hypothesis that, in a given subject, the incidence, intensity and spatiotemporal expression of referred pain are similar during the muscle pain induced by bolus intramuscular injection of hypertonic saline into flexor carpi radialis (FCR) and tibialis anterior (TA). We also tested the hypothesis that an increase in stimulus intensity causes a parallel increase in the incidence and intensity of local and referred pain, by comparing the responses to 5 and 10 % hypertonic saline in two groups of subjects. 29 subjects mapped areas of local and referred pain, rating intensities on a visual analogue scale every 30 s until the cessation of pain. Following an injection of 5 % hypertonic saline into TA, 86 % of subjects who had previously reported referred pain (or its absence) in the hand during FCR pain reported referred pain (or its absence) in the foot. Following an injection of the 10 % solution, 67 % of subjects reported a pattern in the lower limb that was the same as that seen in the upper limb. We conclude that the expression of referred pain is largely consistent in widely separated limb segments in individual subjects and is largely dependent on inter-subject differences. This may have implications for the development of chronic pain following an acute episode of pain