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Shelley: Welcome, everybody. We are delighted to spend a little bit of time with you discussing Henry the Eighth. We’re delighted that that was the common show that people selected as part of the conference, and hopefully you enjoyed that on Monday evening. We have additional actors who will be joining us. They are on their way over. But in the meantime, by way of introduction, my name is Stuart. I’m the education director at the Festival. I’ve been with the Festival full time now for three seasons, with a brief stint in 2016 doing summer camps and classes. We have Alaysia Duncan with us, we have Geoffrey Kent, and we will hopefully have Topher Embrey and Christopher Centinaro joining us shortly. We’ll get started, and I’m going to just give the welcoming question. If you’ll tell us a little bit about yourself, the roles that you play this season, Henry the Eighth and other plays, and where you’re from. We’ll get started there, and then we’ll move forward.

Spatial filtering has been utilized in acoustic, radar, and communications fields for many years. Developments in dynamic measurement hardware have made it economically feasible to employ sensor arrays for experimental structural dynamic analysis. This has made spatial filtering a viable method of processing structural response data. Spatial filters, or \"modal filters\", may be used to estimate the modal coordinate states of a structure. Since temporal information is not used, the estimates of the modal coordinates are obtained with no time delay. The research presented in this dissertation investigates means of calculating discrete modal filters using only the experimentally measured frequency response function (FRF) matrix, and estimates of the poles associated with the modal coordinate states which are to be estimated. An analytical model of the system is not needed. This allows modal filters to be calculated for any arbitrary, distributed parameter system. The term \"discrete modal filter\" is used to distinguish a modal filter calculated using system properties known only at discrete points in space, from one which is calculated using continuous representations of system properties. The existence, uniqueness, and robustness characteristics of all possible, spatial based, modal filters, which are implemented with discrete sensors, are discussed. A modal filter calculation algorithm, the Modified Reciprocal Modal Vector (MRMV) method, is developed, and is verified utilizing an FRF matrix measured on a 4.5 meter space truss. The effect of number and location of sensors, on the accuracy and robustness of the discrete modal filter are explored. A minimum norm solution is demonstrated to be the desirable solution for robustness considerations. Discrete modal filters are implemented off-line on measured FRFs, and also on time domain data, in real time. The application of discrete modal filtering to modal control is discussed. The MRMV method reduces the system modeling requirement for modal control. Other applications and further developments of the method are suggested.

A new method to estimate a structure's inertia properties using a prototype load cell designed to measure all loads and moments applied to a structure is presented. This prototype six-axis transducer approach employs 32 piezoelectric sensing elements which are arranged to form the load cell. These redundant measurements are used to determine the principal forces and moments from an overdetermined set of equations. Calibration of this multi-crystal load cell is performed with a fixture that utilizes a calibration mass and quasi-freefree boundary conditions. The resulting calibration matrix is a 6x32 transformation from the coupled measurements to a decoupled set of pseudo measurements consisting of the forces acting on a structure. With this transducer and its calibration matrix, a system's inertia properties can be estimated. A thorough discussion of both the calibration and inertia estimation procedure with a experimental test case is presented.

Years of using, misusing, and overusing antibiotics and other antimicrobial drugs has led to the emergence of multidrug-resistant 'superbugs.' The IOM's Forum on Microbial Threats held a public workshop April 6-7 to discuss the nature and sources of drug-resistant pathogens, the implications for global health, and the strategies to lessen the current and future impact of these superbugs.

Active surveillance trials for low-risk ductal carcinoma in situ (DCIS) are in progress in the United States and Europe. In some of these trials, the presence of comedo necrosis in the DCIS has been an exclusion criterion for trial entry. However, the minimum amount of necrosis required by pathologists for a diagnosis of comedo necrosis is not well-defined. We surveyed 35 experienced breast pathologists to assess their diagnostic threshold for comedo necrosis. Pink circles representing necrosis ranging in extent from 10 to 80% of the duct diameter were superimposed on eight replicate histologic images of a single duct involved by low nuclear grade, solid pattern DCIS. These images were circulated by e-mail to the participating pathologists who were asked to select the image that represents the minimum amount of necrosis that they require for a diagnosis of comedo necrosis. Among the 35 participants, the minimum extent of the duct diameter required for a diagnosis of comedo necrosis was 10% for 4 pathologists, 20% for 5, 30% for 11, 40% for 7, 50% for 6, 60% for 1 and 70% for 1. There was no single threshold about which more than one-third of the pathologists agreed met the minimal criteria for comedo necrosis. We conclude that even among experienced breast pathologists, the threshold for comedo necrosis is highly variable. Our findings highlight the need for a standardized definition of comedo necrosis as a trial criterion, and more generally where it may be used as a marker of increased risk of recurrence for therapeutic decision making.

Significance In 2014, Ebola virus became a household term. The ongoing outbreak in West Africa is the largest Ebola virus outbreak ever recorded, with over 20,000 cases and over 8,000 deaths to date. Very little is known about the human cellular immune response to Ebola virus infection, and this lack of knowledge has hindered development of effective therapies and vaccines. In this study, we characterize the human immune response to Ebola virus infection in four patients. We define the kinetics of T- and B-cell activation, and determine which viral proteins are targets of the Ebola virus-specific T-cell response in humans. Four Ebola patients received care at Emory University Hospital, presenting a unique opportunity to examine the cellular immune responses during acute Ebola virus infection. We found striking activation of both B and T cells in all four patients. Plasmablast frequencies were 10–50% of B cells, compared with less than 1% in healthy individuals. Many of these proliferating plasmablasts were IgG-positive, and this finding coincided with the presence of Ebola virus-specific IgG in the serum. Activated CD4 T cells ranged from 5 to 30%, compared with 1–2% in healthy controls. The most pronounced responses were seen in CD8 T cells, with over 50% of the CD8 T cells expressing markers of activation and proliferation. Taken together, these results suggest that all four patients developed robust immune responses during the acute phase of Ebola virus infection, a finding that would not have been predicted based on our current assumptions about the highly immunosuppressive nature of Ebola virus. Also, quite surprisingly, we found sustained immune activation after the virus was cleared from the plasma, observed most strikingly in the persistence of activated CD8 T cells, even 1 mo after the patients’ discharge from the hospital. These results suggest continued antigen stimulation after resolution of the disease. From these convalescent time points, we identified CD4 and CD8 T-cell responses to several Ebola virus proteins, most notably the viral nucleoprotein. Knowledge of the viral proteins targeted by T cells during natural infection should be useful in designing vaccines against Ebola virus.

Rift Valley fever (RVF) is a zoonotic disease caused by Rift Valley fever virus (RVFV) found in Africa and the Middle East. Outbreaks can cause extensive morbidity and mortality in humans and livestock. Following the diagnosis of two acute human RVF cases in Kabale district, Uganda, we conducted a serosurvey to estimate RVFV seroprevalence in humans and livestock and to identify associated risk factors. Humans and animals at abattoirs and villages in Kabale district were sampled. Persons were interviewed about RVFV exposure risk factors. Human blood was tested for anti-RVFV IgM and IgG, and animal blood for anti-RVFV IgG. 655 human and 1051 animal blood samples were collected. Anti-RVFV IgG was detected in 78 (12%) human samples; 3 human samples (0.5%) had detectable IgM only, and 7 (1%) had both IgM and IgG. Of the 10 IgM-positive persons, 2 samples were positive for RVFV by PCR, confirming recent infection. Odds of RVFV seropositivity were greater in participants who were butchers (odds ratio [OR] 5.1; 95% confidence interval [95% CI]: 1.7-15.1) and those who reported handling raw meat (OR 3.4; 95% CI 1.2-9.8). No persons under age 20 were RVFV seropositive. The overall animal seropositivity was 13%, with 27% of cattle, 7% of goats, and 4% of sheep seropositive. In a multivariate logistic regression, cattle species (OR 9.1; 95% CI 4.1-20.5), adult age (OR 3.0; 95% CI 1.6-5.6), and female sex (OR 2.1; 95%CI 1.0-4.3) were significantly associated with animal seropositivity. Individual human seropositivity was significantly associated with animal seropositivity by subcounty after adjusting for sex, age, and occupation (p < 0.05). Although no RVF cases had been detected in Uganda from 1968 to March 2016, our study suggests that RVFV has been circulating undetected in both humans and animals living in and around Kabale district. RVFV seropositivity in humans was associated with occupation, suggesting that the primary mode of RVFV transmission to humans in Kabale district could be through contact with animal blood or body fluids.

Background Breast cancer treatment is multimodal, but not all patients benefit from each treatment, and many experience morbidities significantly impacting quality of life. There is increasing interest in tailoring breast cancer treatments to optimize oncological outcomes and reduce treatment burden, but it is vital that future trials focus on treatments that most impact patients. This study was designed to explore patient experiences of treatment to inform future research. Methods An online survey was co-developed with patient advocates to explore respondents’ experiences of breast cancer treatment. Questions included simple demographics, treatments received, and views regarding omitting treatments if that is deemed safe. The survey was circulated via social media and patient advocacy groups. Responses were summarized by using simple statistics; free text was analyzed thematically. Results Of the 235 participants completing the survey, 194 (82.6%) would choose to omit a specific treatment if safe to do so. The most commonly selected treatments were chemotherapy ( n = 69, 35.6%) and endocrine therapy ( n = 61, 31.4%) mainly due to side effects. Fewer respondents would choose to omit surgery ( n = 40, 20.6%) or radiotherapy ( n = 20, 10.3%). Several women commented that survival was their “absolute priority” and that high-quality evidence to support the safety of reducing treatment would be essential. Conclusions Patients with breast cancer are individuals who may wish to optimize different components of their treatment. A portfolio of studies co-designed with patients is needed to establish an evidence base for greater treatment personalization with studies focused on reducing avoidable chemotherapy and endocrine therapy a priority.