Automated inspection of turbine blades: Challenges and opportunities

Current inspection methods for complex shapes and contours exemplified by aircraft engine turbine blades are expensive, time-consuming and labor intensive. The logistics support of new manufacturing paradigms such as integrated product-process development (IPPD) for current and future engine technology development necessitates high speed, automated inspection of forged and cast jet engine blades, combined with a capability of retaining and retrieving metrology data for process improvements upstream (designer-level) and downstream (end-user facilities) at commercial and military installations. The paper presents the opportunities emerging from a feasibility study conducted using 3-D holographic laser radar in blade inspection. Requisite developments in computing technologies for systems integration of blade inspection in production are also discussed

Three allele combinations associated with Multiple Sclerosis

BACKGROUND: Multiple sclerosis (MS) is an immune-mediated disease of polygenic etiology. Dissection of its genetic background is a complex problem, because of the combinatorial possibilities of gene-gene interactions. As genotyping methods improve throughput, approaches that can explore multigene interactions appropriately should lead to improved understanding of MS. METHODS: 286 unrelated patients with definite MS and 362 unrelated healthy controls of Russian descent were genotyped at polymorphic loci (including SNPs, repeat polymorphisms, and an insertion/deletion) of the DRB1, TNF, LT, TGFβ1, CCR5 and CTLA4 genes and TNFa and TNFb microsatellites. Each allele carriership in patients and controls was compared by Fisher's exact test, and disease-associated combinations of alleles in the data set were sought using a Bayesian Markov chain Monte Carlo-based method recently developed by our group. RESULTS: We identified two previously unknown MS-associated tri-allelic combinations: -509TGFβ1*C, DRB1*18(3), CTLA4*G and -238TNF*B1,-308TNF*A2, CTLA4*G, which perfectly separate MS cases from controls, at least in the present sample. The previously described DRB1*15(2) allele, the microsatellite TNFa9 allele and the biallelic combination CCR5Δ32, DRB1*04 were also reidentified as MS-associated. CONCLUSION: These results represent an independent validation of MS association with DRB1*15(2) and TNFa9 in Russians and are the first to find the interplay of three loci in conferring susceptibility to MS. They demonstrate the efficacy of our approach for the identification of complex-disease-associated combinations of alleles

Collaborative International Research in Clinical and Longitudinal Experience Study in NMOSD.

Objective: To develop a resource of systematically collected, longitudinal clinical data and biospecimens for assisting in the investigation into neuromyelitis optica spectrum disorder (NMOSD) epidemiology, pathogenesis, and treatment. Methods: To illustrate its research-enabling purpose, epidemiologic patterns and disease phenotypes were assessed among enrolled subjects, including age at disease onset, annualized relapse rate (ARR), and time between the first and second attacks. Results: As of December 2017, the Collaborative International Research in Clinical and Longitudinal Experience Study (CIRCLES) had enrolled more than 1,000 participants, of whom 77.5% of the NMOSD cases and 71.7% of the controls continue in active follow-up. Consanguineous relatives of patients with NMOSD represented 43.6% of the control cohort. Of the 599 active cases with complete data, 84% were female, and 76% were anti-AQP4 seropositive. The majority were white/Caucasian (52.6%), whereas blacks/African Americans accounted for 23.5%, Hispanics/Latinos 12.4%, and Asians accounted for 9.0%. The median age at disease onset was 38.4 years, with a median ARR of 0.5. Seropositive cases were older at disease onset, more likely to be black/African American or Hispanic/Latino, and more likely to be female. Conclusions: Collectively, the CIRCLES experience to date demonstrates this study to be a useful and readily accessible resource to facilitate accelerating solutions for patients with NMOSD

Influences of Domestication and Island Evolution on Dental Growth in Sheep

Funder: Department of Zoology, University of CambridgeFunder: Leverhulme Trust; doi: http://dx.doi.org/10.13039/501100000275Abstract: Domestication and island evolution can lead to changes of life history along the slow-fast gradient. Shifts of life history patterns, in turn, are potentially related to alterations of patterns and timing of tooth eruption. Schultz’s rule predicts an earlier eruption of molars relative to premolars as fecundity increases during the domestication process. On the other hand, evolution on a predator-free, resource limited island might lead to a generally slow life history and delayed tooth eruption, as in the Plio-Pleistocene Balearic caprine Myotragus. In this study, we investigate tooth eruption and its relation to life history in a unique sheep population that is an example of both domestication and island evolution: the ancient and feral Soay sheep (Ovis aries) of the St. Kilda archipelago, Scotland. Tooth eruption timing and sequence is investigated in a comparative framework featuring new data on other domestic sheep (O. aries), including European mouflon (O. a. musimon), as well as wild sheep (O. vignei, O. cycloceros, O. arkal, O. orientalis, O. ammon). These data indicate that the order of eruption is similar in wild and domestic sheep, despite the fundamental life history changes that came about with domestication. However, in contrast to other domestic sheep breeds, Soay sheep erupt their teeth at an absolute older age and also tend to grow more slowly, which resembles the evolutionary trend in island-adapted Myotragus. Despite these similarities, Soay sheep do not share the slow life history pattern inferred for Myotragus, highlighting the distinctive nature of tooth eruption in Soay sheep

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

Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980-2017: a systematic analysis for the Global Burden of Disease Study 2017.

BACKGROUND: Global development goals increasingly rely on country-specific estimates for benchmarking a nation's progress. To meet this need, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 estimated global, regional, national, and, for selected locations, subnational cause-specific mortality beginning in the year 1980. Here we report an update to that study, making use of newly available data and improved methods. GBD 2017 provides a comprehensive assessment of cause-specific mortality for 282 causes in 195 countries and territories from 1980 to 2017. METHODS: The causes of death database is composed of vital registration (VR), verbal autopsy (VA), registry, survey, police, and surveillance data. GBD 2017 added ten VA studies, 127 country-years of VR data, 502 cancer-registry country-years, and an additional surveillance country-year. Expansions of the GBD cause of death hierarchy resulted in 18 additional causes estimated for GBD 2017. Newly available data led to subnational estimates for five additional countries-Ethiopia, Iran, New Zealand, Norway, and Russia. Deaths assigned International Classification of Diseases (ICD) codes for non-specific, implausible, or intermediate causes of death were reassigned to underlying causes by redistribution algorithms that were incorporated into uncertainty estimation. We used statistical modelling tools developed for GBD, including the Cause of Death Ensemble model (CODEm), to generate cause fractions and cause-specific death rates for each location, year, age, and sex. Instead of using UN estimates as in previous versions, GBD 2017 independently estimated population size and fertility rate for all locations. Years of life lost (YLLs) were then calculated as the sum of each death multiplied by the standard life expectancy at each age. All rates reported here are age-standardised

Mortality in relation to changes in a Healthy Aging Index : the health, aging, and body composition study

Background Baseline scores on a Healthy Aging Index (HAI), including five key physiologic domains, strongly predict health outcomes. This study aimed to characterize 9-year changes in a HAI and explore their relationship to subsequent mortality. Methods Data are from the Health, Aging, and Body Composition study of well-functioning adults aged 70–79 years. A HAI, which ranges from 0 to 10, was constructed at years 1 and 10 of the study including systolic blood pressure, forced expiratory volume, digit symbol substitution test, cystatin C, and fasting glucose. The relationships between the HAI at years 1 and 10 and the change between years and subsequent mortality until year 17 were estimated from Cox proportional hazards models. Results Two thousand two hundred sixty-four participants had complete data on a HAI at year 1, of these 1,122 had complete data at year 10. HAI scores tended to increase (i.e. get worse) over 9-year follow-up, from (mean [SD]) 4.3 (2.1) to 5.7 (2.1); mean within-person change 1.5 (1.6). After multivariable adjustment, HAI score was related to mortality from year 1 (hazard ratio [95% confidence interval] = 1.17 [1.13–1.21] per unit) and year 10 (1.20 [1.14–1.27] per unit). The change between years was also related to mortality (1.08 [1.02–1.15] per unit change). Conclusions HAI scores tended to increase with advancing age and stratified mortality rates among participants remaining at year 10. The HAI may prove useful to understand changes in health with aging

Interstitial Emphysema as a Rare Radiographic Presentation of Bronchial Dehiscence after Lung Transplant

Airway complications after lung transplantation are a major cause of morbidity and mortality. Bronchial dehiscence presents within a month of lung transplantation and is typically diagnosed radiographically as a sentinel gas pocket at the anastomotic site and confirmed with bronchoscopy. A 66-year-old man with idiopathic pulmonary fibrosis who underwent a right lung transplantation 4 weeks prior developed chest pain with palpable crepitus over his right chest wall. A chest X-ray revealed subcutaneous emphysema and a small right-sided pneumothorax. Computed tomography (CT) of the thorax without contrast revealed a gas pocket at the anastomotic site in the mediastinum as well as interstitial emphysema around the proximal bronchi of the right lung that had worsened when compared to CT from 11 days prior. A review of prior CT demonstrated interstitial emphysema without evidence of a sentinel gas pocket. These findings suggest that interstitial emphysema was the initial radiographic manifestation of the bronchial anastomotic site dehiscence. Interstitial emphysema is typically self-limiting, but severe cases can lead to major complications. Interstitial emphysema outside of the immediate postoperative period should be recognized as a possible early radiographic sign of bronchial dehiscence in lung transplant patients with vigilant monitoring of potential complications and strong consideration for early bronchoscopic investigation