De novo head and neck cancer after liver transplant with antibody-based immunosuppression induction

Background Powerful antibody-based immunosuppression induction is now used routinely during organ transplantation, and may place patients at even higher risk of post-transplant cancer. Materials and Methods Incidence of de-novo head and neck cancer was extracted from the records of 1685 consecutive adult, deceased donor liver transplant recipients with a minimum 1-year follow-up from 2001 to 2015. There were 121 patients positively identified as having developed de-novo head and neck cancer post-liver transplant. Records of these patients were analyzed to determine demographics, history of cancer pre-liver transplant, de-novo cancer type and location, treatment modalities, and alcohol and tobacco exposure. Results Of the 121 patients who developed cancer of the head and neck (7%), there were 103 cutaneous (6%) and 25 non-cutaneous (1%). For non-cutaneous cancers, factors associated with increased risk of cancer included alcohol abuse (p<0.001), any smoking history (p=0.05), and increasing exposure to tobacco (p<0.01). Ten-year Cox regression patient survival demonstrates a survival disadvantage for patients who develop non-cutaneous cancer (p=0.06), but a survival advantage for patients who develop cutaneous cancer (p<0.01). Conclusions The incidence and pattern of head and neck cancer in this population of liver transplant patients was similar to those published previously, suggesting that induction immunosuppression does not increase risk of these types of cancers. Long term survival was worse for patients with non-cutaneous cancers, but better for those with cutaneous cancers, though the reason is unclear

"A study of some electroactive, thin organic films prepared by plasma and electrochemical techniques"

Electron Spectroscopy for Chemical Applications (ESCA) and Cyclic Voltaimnetry (CV) have been used to study the surface and electro chemistries of electroactive, thin organic films. A method is developed for the preparation of such films by the synthesis of a molecule containing both an electroactive centre (ferrocene or iron (II) or ruthenium (II) trisbipyridyl) bonded to an electro-polymerizable unit (pyrrole). The surface chemistries of polypyrrole, polyaniline and electrodes potentiostatted in ferrocene solutions were also investigated and results corpared to previous studies where possible. The poly-Ru(II)- and particularly the poly-Fe(II)- films are stable to electrochemical cycling between the +2 and +3 oxidation states. The poly-Fe(II)-, and probably the poly-Ru(II)-, trisbipyridyl films have charge transfer diffusion coefficients similar to those previously reported for other films containing similar redox centres. Redox conductivity has been demonstrated for an aged sample of the poly-Fe(II)- film. Electroactive films, prepared by two different methods of plasma polymerization of substituted ferrocene moncsners are described. In each case the ferrocene/ferricenium electroactivity is degraded, by repeated potential cycling. The incorporation of ferrocene into a plasma polymer does not necessarily produce an electroactive film. A preliminary investigation of the surface and electrochemistry of electrode deposits, prepared by cathodic reduction of perfluorocyclo-pentene, is described. The deposits appear similar in some respects to cathodically reduced PTFE

In search of understanding : examining the life role management approach of fathers who are coaches

textThe role of the father is changing in United States society (Bianchi, Robinson, & Milkie, 2006). Trend analysis indicates that men are beginning to be more involved in the family role, especially in regards to housework, cooking, cleaning, and childcare duties (Galinsky, Aumann, & Bond, 2011; Harrington, Van Deusen, & Humberd, 2011). Further research suggests that the basic definition of what makes a good father are also expanding (Bianchi et al., 2006). A good father is now defined as a co- financial provider, a disciplinarian, as well as a co-caretaker of the home and children (Rohner & Veneziano, 2001). In conjunction with these cultural changes, the research outside the realm of sport indicates that men are experiencing higher levels of work- family conflict than they did even ten years ago (Galinsky et al., 2011; Harrington et al., 2011; Parker & Wang, 2013). However, in the sport industry, orthodox masculine pressures celebrating competition, aggression, sacrifice, and commitment largely remain prominent (Dixon & Bruening, 2005; Wilson, 2002). Therefore, individuals working in sport are faced with shifting societal pressures and inflexible industry cultural norms (Graham & Dixon, 2014). Research on mothers in the sport industry suggests that work-family conflict is a significant source of tension for women working in sport (Bruening & Dixon, 2007; Dixon & Bruening, 2007). Furthermore, there is some evidence that men are experiencing levels of work-family conflict that is parallel with their female counterparts (Schenewark & Dixon, 2012). However, less is understood about the experiences of fathers who are coaches from an in-depth standpoint. Fundamental questions about how men experience, interpret, and cope with the competing pressures to be a good father and a good employee have largely gone unexplored (Graham & Dixon, 2014). As a result, the purpose of this study was to gain a deeper understanding of the experiences of fathers in sport. To that end, 24 fathers who were also high school head coaches from Texas volunteered for a study investigating their work-life balance experiences. The findings indicate that indeed fathers in sport are faced with tension and strain stemming from both the coaching role and the family role. The findings also suggest that men cope with these tensions by carefully managing the resources of time, energy, and attention. In addition, the fathers reported depending heavily on their wives for support in the coaching role. Furthermore, the data indicate that organizational support mechanisms were simply an unused and distrusted source of support that only became an option in extreme cases or health crises. These findings have important implications for theory as well as management. More specifically, the findings of this study had direct implications in regards to theories on role conflict, role engulfment, coping strategies, and masculinity. From a practical stance, this study also has important implications for sport managers in the areas of motivation, citizenship behavior, voicing behavior, and insights on how to support men in athletics.Kinesiology and Health Educatio

Scaling Robot Motion Planning to Multi-core Processors and the Cloud

Imagine a world in which robots safely interoperate with humans, gracefully and efficiently accomplishing everyday tasks. The robot's motions for these tasks, constrained by the design of the robot and task at hand, must avoid collisions with obstacles. Unfortunately, planning a constrained obstacle-free motion for a robot is computationally complex---often resulting in slow computation of inefficient motions. The methods in this dissertation speed up this motion plan computation with new algorithms and data structures that leverage readily available parallel processing, whether that processing power is on the robot or in the cloud, enabling robots to operate safer, more gracefully, and with improved efficiency. The contributions of this dissertation that enable faster motion planning are novel parallel lock-free algorithms, fast and concurrent nearest neighbor searching data structures, cache-aware operation, and split robot-cloud computation. Parallel lock-free algorithms avoid contention over shared data structures, resulting in empirical speedup proportional to the number of CPU cores working on the problem. Fast nearest neighbor data structures speed up searching in SO(3) and SE(3) metric spaces, which are needed for rigid body motion planning. Concurrent nearest neighbor data structures improve searching performance on metric spaces common to robot motion planning problems, while providing asymptotic wait-free concurrent operation. Cache-aware operation avoids long memory access times, allowing the algorithm to exhibit superlinear speedup. Split robot-cloud computation enables robots with low-power CPUs to react to changing environments by having the robot compute reactive paths in real-time from a set of motion plan options generated in a computationally intensive cloud-based algorithm. We demonstrate the scalability and effectiveness of our contributions in solving motion planning problems both in simulation and on physical robots of varying design and complexity. Problems include finding a solution to a complex motion planning problem, pre-computing motion plans that converge towards the optimal, and reactive interaction with dynamic environments. Robots include 2D holonomic robots, 3D rigid-body robots, a self-driving 1/10 scale car, articulated robot arms with and without mobile bases, and a small humanoid robot.Doctor of Philosoph

Differentiating the medial patterns of operatic adaptations: Macbeth

The processes that underlie the creation of operatic adaptations are similar to those of film adaptations, yet the language and discourse that is used in the two fields is considerably different. In opera, the adaptation is viewed as being the notated music score which contains the libretto. In film, however, discourse related to film adaptation tends to focus on the qualities of the production of the screenplay, not on the screenplay itself, viewing the film as being based on the source text instead of it being based on the screenplay. While these differences may be due to contractual issues – screenplays involving only one film production, operas involving as many stage productions as requested – and similar cultural values as those ascribed to composers also being ascribed to directors instead of the screenplay writers, it nevertheless provides a reason to consider the implications that the operatic adaptations have for the understanding of other media, including but not limited to screen-based media. This dissertation therefore argues for a reassessment of product creation processes as viewed by Adaptation Studies and Intermedial Studies through the differentiation of medial patterns of operas in intermedial and intramedial contexts. A four-phase model divided into conception, adaptation/composition, production, and reception is proposed that could realign adaptation research away from a predominantly qualitative approach that combines reception based on the aesthetics of a production, to combine quantitative and qualitative methods that also examine the text-types created by adapters. In doing so, research and education in English Studies would benefit from clearer theoretical foundations that do not mostly link a source text with the aesthetic qualities of the production, but with the textual links to the structural conventions of the medial form involved. It is proposed here that the concept of fidelity to a source text, if it must be used in research or in education, should be discussed in various forms: fidelity to the text of the source text (textual fidelity), fidelity to the structural conventions of the text-type/medium (medial fidelity), and the subjective fidelity of the aesthetics of a production (aesthetic fidelity). The splitting of the fidelity concept proposed in this research could advantage English Studies – and many other academic fields – by providing a deeper understanding related to the interpretations of a source text: do the interpretations of the source text occur in the written form in the text-type formed in the adaptation/composition phase or in the visual and/or auditory mediation of the text-type into a directed adaptation during the production phase? Has an interpretation of the text occurred through mediation of text by the adapter (e.g. screenwriter) or the director? The quantitative analysis in this research involved 75 adaptations of Macbeth in two groups of adaptations, directed and printed, and eleven categories of media, including eight operas. The analysis provided data regarding the percentage of text in each medial category and the number and type of alterations made to the text that form the patterns of each medium. Following the intermedial findings, intramedial analysis of all 14 available operatic adaptations of Macbeth was also undertaken, including three individual case studies and two comparative case studies on some lesser known Macbeth operas. The theoretical basis of the dissertation revolves around concepts by Linda Hutcheon in Adaptation Studies and Lars Elleström in Intermedial Studies. Evidence and observations from the intermedial and intramedial analyses and the case studies provide support for the extension of some of Hutcheon’s concepts (e.g. adaptation as process, and knowing and unknowing audiences) and raise issues that highlight some problematic areas of others, such as modes of engagement

Evaluation of a novel mRNA-pertussis vaccine against emerging clinical isolates of Bordetella pertussis

Bordetella pertussis is a Gram-negative obligate aerobe that causes a respiratory disease known as pertussis or whooping cough. Pertussis is most severe in younger children, especially infants but the bacteria has been known to colonize adult populations. Before the introduction of the whole-cell pertussis (wP; wP-DTP) vaccine reported numbers of pertussis cases within the US routinely topped 100,000 cases per year. However, with the widespread usage of the wP vaccine case numbers began dropping and reached a low of less than 5,000 cases per year in the late 1970’s and early 80’s. It appeared that B. pertussis was heading towards eradication, but the wP vaccine proved to be highly reactogenic due to remnant endotoxin from the manufacturing process. This reactogenicity caused fear in wP vaccination both abroad and within the US which led to an increase in cases during the late 1980s in the US. Thankfully, work was already being done on the development of an acellular pertussis (aP) vaccine to replace the reactogenic wP. In 1996, the first aP vaccine, combined with diphtheria and tetanus toxoid (DTaP), was licensed for use within the US. These vaccines proved to be less reactogenic as measured by adverse effects but with that came a different immune response to aP vaccination versus wP vaccination. Coinciding with the introduction of DTaP vaccination was a steady increase in pertussis case numbers within the US peaking at over 50,000 in 2012. The theories on this increase include genomic differences in emerging clinical isolates (ECIs) of B. pertussis, rapid waning immunity of DTaP induced immunity, and the humoral Th2 skewed immune response by DTaP vaccination. Each theory has its own merits and we hypothesized that the increase observed in pertussis cases is a combination of all three theories and we propose a potential solution to this increase by using a novel mRNA-DTP vaccine. We first wanted to evaluate if genomic differences between ECIs and historic isolates were causing different levels of pathogenesis and innate immune response in a naïve mouse model. To begin, we cultured 15 different isolates of B. pertussis in a liquid medium and extracted RNA from end log-phase growth of the bacteria. RNAseq was performed and we observed many differences in the transcriptomic profile of ECIs compared to historic isolates in virulence factors including ptxA (pertussis toxin; PT), fhaB (filamentous hemagglutinin; FHA), prn (pertactin; PRN), sphB1 (serine protease homolog of Bordetella 1; SphB1) and brkA (Bordetella resistant to killing genetic locus A; BrkA). However, when the experiment was repeated and end log-phased growth had its proteomic profiles analyzed we observed a major reduction in these differences especially for BrkA, SphB1, and FHA. Next, we intranasally (IN) challenged mice with 15 different isolates of B. pertussis (13 ECIs and 2 historic isolates) to assay markers of disease burden including leukocytosis and bacterial burden. All test isolates had similar levels of bacterial burden, as quantified by CFU, in the lung, trachea, and nasal lavage 3 days post-challenge. We did observe a slight increase in white blood cell and neutrophil counts in the blood of mice challenged with ECIs compared to historic isolates. To complete the study, we chose four representative isolates including one historical (UT25Sm1; UT25) and three ECIs (D420, H762, and I762) to observe differences in host immune response in the lungs of challenged mice. Briefly, mice were IN challenged as before and lungs were harvested 3 days post-challenge. RNA was extracted from the lungs and RNAseq was performed which revealed no major differences in host gene activation and repression in challenged mice. Even though there were large differences in the transcriptomic profiles of ECIs, there was no difference in the host genomic response or bacterial burden upon challenge in mice between ECIs and historic isolates. There was a slight increase in leukocytosis in ECI challenged mice. These data suggest that genomic differences in ECIs are not a major contributor to increased pathogenesis leading to an increase in reported pertussis cases. We then continued the previous study by introducing a vaccination component to evaluate if ECIs were better at evading vaccine-mediated immunity. Mice were primed and boosted with 1/80th human dose of either DTaP or wP vaccine and IN challenged with one of the four representative isolates used previously. We observed that B. pertussis specific IgG antibodies induced by both DTaP and wP vaccinations bound to all tested isolates similarly. Vaccinated mice were then IN challenged with either UT25Sm1 (historic) or an ECI (D420, H762, or I762) and we observed that both vaccines controlled the induction of proinflammatory cytokines regardless of which challenge isolate was used. We next investigated if PT produced by ECIs was able to evade neutralizing antibodies and induce leukocytosis. Again, DTaP was able to reduce leukocytosis regardless of the challenge isolate. ECIs did not induce more white blood cells or neutrophils on days 3 and 7 post-challenge compared to the historic isolate. Lastly, we investigated if ECIs challenge would lead to increased bacterial burden post-challenge. Bacterial clearance of ECIs was comparable to the historic isolate control in the lung, trachea, and nasal lavage 3 days post-challenge. Interestingly, while the burden was not increased more than the historic isolate, it appeared that ECIs were able to persist longer in the lungs in mice. All these data taken together suggest ECIs are not able to evade aP vaccine-mediated immunity in mice. After evaluating the role ECIs may have in the rise in pertussis cases, we wanted to develop a standardized aerosol challenge protocol due to the inconsistencies in this challenge method in the field. The protocol was developed using commercially available nebulizers, dosing chamber, and dose controller to remove any difference in laboratory designed challenge systems. We observed that this aerosol protocol was reproducible and deposited near identical numbers of bacteria from challenge to challenge. Along the same line, we developed a streptomycin resistant ECI (D420Sm1) from the baboon challenge model challenge isolate (D420). This lab adapted isolate has a single nucleotide polymorphism which confers streptomycin resistance. D420Sm1 has near identical growth characteristics and pathogenesis to the parent D420 isolate. Lastly, we aimed to evaluate a potential solution to the rise in pertussis cases with a novel mRNA-DTP vaccine. To begin, we sought to optimize the PtxA-mRNA antigen for future inclusion in the mRNA-DTP vaccine. Mice were vaccinated with either a control vaccine (DTaP, wP, gPT), an experimental recombinant PT protein (Protein) vaccine, or one of two mRNA vaccines (mRNA-C210 or mRNA-C180). Post-boost, no vaccine induced IgG antibody titers specific to any B oligomer of PT. Both the mRNA-C210 and mRNA-C180 induced IgG antibodies to PT and PtxA. Mice were then challenged with purified PT and leukocytosis was evaluated 3 days later. Again, both mRNA vaccines reduced leukocytosis and neutrophilia compared to the mock vaccinated group and similar to DTaP. The mRNA-C180 antigen was selected due to the higher IgG antibody titers specific to PT holotoxin and this antigen was included in the study formulation of mRNA-DTP. Also, we utilized the coughing rat model of pertussis to add a coughing parameter to the study. Briefly, Sprague-Dawley rats were vaccinated with 1/10th human dose of DTaP or wP, or 10 μg of mRNA-DTP. Serological analysis via ELISA revealed that mRNA-DTP was immunogenic in rats and induced comparable titers of PRN-specific, FHA-specific, and B. pertussis-specific IgG antibodies to DTaP and wP vaccination. mRNA-DTP did induce PT-specific IgG antibodies however they were lower than DTaP vaccinated rats. Interestingly, in previous experiments in mice the mRNA-DTP vaccine was able to skew towards Th1 subclass of IgG antibodies however in rats the subclass was skewed towards Th2 IgG1 subclass. Even so, bacterial burden in respiratory tissues were reduced for all vaccine groups and an even further reduction was observed in mRNA-DTP compared to DTaP vaccination. Moreover, mRNA-DTP vaccination reduced bacterial burden to the lower limit of detection in the nasal lavage by day 9 post-challenge. Next, we aimed to evaluate if mRNA-DTP vaccination would reduce coughing in rats comparable to the DTaP group because DTaP vaccination is known to reduce disease manifestations. We observed that coughing began on day 4 post-challenge and for MVC remained for the duration of the experiment. All vaccine groups were able to limit coughing compared to MVC however mRNA-DTP was able to completely abrogate the coughing phenotype and only a single cough was recorded during the study. This was comparable to the non-challenged group which had only three recorded coughs unrelated to B. pertussis challenge. These data suggest that mRNA-DTP was able to protect rats from bacterial burden and pertussis manifestations comparable to currently licensed DTaP and wP vaccines. The work presented in this thesis suggests that genomic differences in ECIs compared to historic isolates is not a major factor in the recent increase in pertussis cases. Further, it provides a standardized protocol for aerosol challenge and the adaptation of an ECI to be used in laboratory studies. The main finding in this thesis is that a novel mRNA-DTP vaccine was shown to be a potential solution to the increase in pertussis cases

Hydrothermal Crystal Growth of Lithium Tetraborate and Lithium -Metaborate

Growth of lithium tetraborate by the hydrothermal method was attempted in 10-6 M LiOH, both by spontaneous nucleation and transport growth. Tetraborate grew out of the first spontaneous nucleation reaction, while the seed dissolved and lithium gamma-metaborate formed during the transport growth reactions. A species thermodynamic stability study showed gamma-metaborate formed exclusively from 350°C to 550°C, and Li3B5O8(OH)2 was observed at 250°C; tetraborate was not observed. A solubility study on lithium tetraborate did not achieve equilibrium conditions, but did demonstrate that gamma-metaborate is significantly more thermodynamically stable than tetraborate under the tested conditions. Formation of lithium tetraborate hydrothermally was shown to result from kinetic growth

Robot Tracking of Human Subjects in Field Environments

Future planetary exploration will involve both humans and robots. Understanding and improving their interaction is a main focus of research in the Intelligent Systems Branch at NASA's Johnson Space Center. By teaming intelligent robots with astronauts on surface extra-vehicular activities (EVAs), safety and productivity can be improved. The EVA Robotic Assistant (ERA) project was established to study the issues of human-robot teams, to develop a testbed robot to assist space-suited humans in exploration tasks, and to experimentally determine the effectiveness of an EVA assistant robot. A companion paper discusses the ERA project in general, its history starting with ASRO (Astronaut-Rover project), and the results of recent field tests in Arizona. This paper focuses on one aspect of the research, robot tracking, in greater detail: the software architecture and algorithms. The ERA robot is capable of moving towards and/or continuously following mobile or stationary targets or sequences of targets. The contributions made by this research include how the low-level pose data is assembled, normalized and communicated, how the tracking algorithm was generalized and implemented, and qualitative performance reports from recent field tests