Sensory integration techniques are a common treatment procedure among occupational therapists. The goal is to "apply" input that competes with input from problem behavior. Although this is a commonly recommended intervention, there is limited empirical evaluation with adults with intellectual disabilities. Therefore, we evaluated the effectiveness of occupational therapist-suggested sensory stimuli on the automatically maintained problem behavior of adults. Specifically, we compared the effects of non-contingent access to sensory stimuli and non-contingent access to highly preferred stimuli on the rate of problem behavior. Results suggested that, relative to highly preferred stimuli, sensory stimuli had either a limited effect on problem behavior, or in some cases, were correlated with increases in problem behavior. This suggests that sensory stimuli may not produce the same automatic stimulation as problem behavior. We will discuss implications for treatment, including methods for better identifying stimuli for use in the treatment of automatically maintained problem behavior.

The World Health Organization (WHO) estimates 488 million people worldwide suffer from a visual impairment and of these about 327 million have severe visual impairments. Some individuals with severe visual impairments can navigate and orient independently in well-known surroundings, but even for these people independent navigation and orientation are likely to be a challenge in unfamiliar places. To overcome these challenges, assistive technologies have been developed to support independent wayfinding tasks; however, those with severe visual impairments often experience frustration when they try to use assistive technologies since these technologies lack address the environmental factors that influence their independent wayfinding. This research developed and evaluated the efficacy of a framework called an environmental user interface (EUI). In particular, this research explored whether or not the proposed EUI framework was effective when used with user-centered design (UCD) to design a wayfinding system to capture environmental requirements, thus aiding those with severe visual impairments. Two studies, the first of which consisted of a requirements elicitation and the second usability testing, were conducted. The studies revealed that the EUI framework was indeed more effective than the conventional UCD design method alone in identifying environmental factors, and participants with severe visual impairments preferred to use the prototype designed using UCD and the EUI framework. The proposed EUI framework was found to be an effective way to enhance the design process as it played an important role in eliciting a greater number of environmental factors, and hence produced a device that was preferred by the users with visual impairments. Both prototypes influenced how well the wayfinding tasks were performed by the five participants with severe visual impairments, but the prototype implemented based on the requirements elicited by UCD and the EUI framework was much preferred by the participants. / Ph. D.

This is a work in the epistemology of functional neuroimaging (fNI) and it applies the error-statistical (ES) philosophy to inferential problems in fNI to formulate and address these problems. This gives us a clear, accurate, and more complete understanding of what we can learn from fNI and how we can learn it. I review the works in the epistemology of fNI which I group into two categories; the first category consists of discussions of the theoretical significance of fNI findings and the second category discusses methodological difficulties of fNI. Both types of works have shortcomings; the first category has been too theory-centered in its approach and the second category has implicitly or explicitly adopted the assumption that methodological difficulties of fNI cannot be satisfactorily addressed. In this dissertation, I address these shortcomings and show how and what kind of experimental knowledge fNI can reliably produce which would be theoretically significant. I take fMRI as a representative fNI procedure and discuss the history of its development. Two independent trajectories of research in physics and physiology eventually converge to give rise to fMRI. Thus, fMRI findings are laden in the theories of physics and physiology and I propose how this creates a kind of useful theory-ladenness which allows for the representation of and intervention in the constructs of cognitive neuroscience. Duhemian challenges and problems of underdetermination are often raised to argue that fNI is of little, if any, epistemic value for psychology. I show how the ES notions of severe tests and error probabilities can be applied in epistemological analyses of fMRI. The result is that hemodynamic hypotheses can be severely tested in fMRI experiments and I demonstrate how these hypotheses are theoretically significant and fuel the growth of experimental knowledge in cognitive neuroscience. Throughout this dissertation, I put the emphasis on the experimental knowledge we obtain from fNI and argue that this is the fruitful approach that enables us to see how fNI can contribute to psychology. In doing so, I offer an error-statistical epistemology of fNI, which hopefully will be a significant contribution to the philosophy of psychology. / Ph. D.

Serious issues including solidification porosity, columnar grains, and large grain sizes are common during fusion-based metal additive manufacturing due to the inherent melting and solidification that occurs during printing. In recent years, a high-temperature, rapid plastic deformation technique called additive friction stir deposition (AFSD) has shown great promise in overcoming these issues. Because the deposited material stays in the solid state during printing, there are no melting and solidification events and the process can result in as-printed material that is fully-dense with equiaxed, fine grains. As AFSD is an emerging process, developing an understanding of the synergy between material deformation and the resultant microstructure evolution, especially the strain magnitude, its influence on dynamic microstructure evolution, and material flow details, is imperative for the full implementation of AFSD. Therefore, the purpose of this work is to investigate the severe plastic deformation in AFSD through complementary studies on the concurrent evolution of shape and microstructure during the deposition of dissimilar aluminum alloys. In this work, we systematically study (1) the entire deposition via dissimilar cladding along with (2) specific volumes within the deposited layer via embedded tracers printed at varied processing parameters. X-ray computed tomography and electron backscatter diffraction are employed to visualize the complex shape of the deposits and understand the microstructure progression. Investigation of dissimilar cladding of homogeneous AA2024 feed-rods onto an AA6061 substrate establishes a working understanding of the mechanisms related to material flow and microstructure evolution across the whole deposit (macroscopic shape evolution) as well as at the interface between the deposit and the substrate. Variations in tooling and rotation rate affect the interfacial features, average grain size, and depth of microstructural influence. The non-planar and asymmetric nature of AFSD on the macro-scale is revealed and a maximum boundary of deposited material is established which gives a frame of reference for the next material flow study within the deposition zone. An understanding of the mesoscopic morphological evolution and concurrent dynamic microstructure evolution of representative volumes within the deposition zone is determined by comparing depositions of hybrid feed-rods (AA6061 matrix containing an embedded tracer of AA2024). Samples were printed with and without an in-plane velocity to compare initial material feeding to steady-state deposition. Variations in initial tracer location and tool rotation rate/in-plane velocity pairs affect the final morphology, intensity of mixing, and microstructure of the deposited tracer material. The tracer material undergoes drastic mesoscopic shape evolution from millimeter-scale cylinders to long, curved micro-ribbons. There is simultaneous grain refinement in AA2024 via geometric dynamic recrystallization during initial material feeding, after which the grain size remains relatively constant at a steady-state size. The lower bound of strain is estimated based on extrusion, torsion, and shear-thinning factors. The step-by-step mesoscopic deformation and microstructure evolution is further elucidated by characterizing depositions of hybrid feed-rods with a series of embedded tracers. The AFSD tooling is stopped quickly at the end of the deposition with a quench applied to "freeze" the sample. X-ray computed tomography reveals multiple intermediate morphologies including the progression from a cylinder to a tight spiral, to a flattened spiral shape, and to a thin disc. EBSD mapping shows that a refined microstructure is formed soon after the material leaves to tool head with areas off the centerline reaching a fully recrystallized state more quickly. The findings from this work summarize the current understanding of the link between material deformation and microstructure evolution in AFSD. Hopefully these first fundamental studies on the co-evolution of material flow and grain structure during AFSD can inspire future work, especially in the area of heterogeneous multi-material printing. / Doctor of Philosophy / Additive friction stir deposition (AFSD) is a new metal 3D printing process that uses friction to heat up and deposit materials rather than using a laser to melt the material into place. This is beneficial since it avoids problems that come from melting and solidification (e.g., porosity, hot cracking, residual stresses, columnar grains). Since AFSD is such a new technology, an understanding of some of the fundamental processing science is needed in order to predict and control the performance of the resultant parts. This is because the processing of a material affects its structure (at multiple scales, for example macro-, micro-, atomic) which then affects the properties a material will exhibit which, finally, dictates the performance of the overall part. Therefore, the purpose of this work is to explore how the feed material is transformed and deposited into the final layer after printing and to link the original processing conditions to the resultant structure. To investigate the interface between the deposited layer and the substrate, we use a simple feed-rod of one aluminum alloy (AA2024) and deposit it onto a substrate of another aluminum alloy (AA6061). To look at just one small volume within the deposited layer, we use a hybrid feed-rod that is mostly AA6061 except for small cylinders of AA2024 that are placed either in the center or on the edge of the feed-rod so that we can track the AA2024. Printing these feed-rods under different processing conditions will help us understand the connection between processing and structure. Using a characterization technique called X-ray computed tomography we can visualize a 3D representation of the final position for the AA2024 material. In order to evaluate the structure on the micro-scale, a characterization technique called electron backscatter diffraction is used to show the individual grains of our metal. The main contributions of this work are as follows: 1) a lower bound of strain is estimated for AFSD, 2) various intermediate deformation steps are captured for the tracer cylinders including a progression from cylinder to multiple spiral shapes to a thin disc to long ribbons, 3) these deformation steps are linked to different microstructures, and 4) changing the tool geometry and other processing parameters significantly alters the range of shapes and microstructures developed in the deposited material. These findings bring us closer to a fully controllable system as well as sparking some interesting areas for future research because of the complex shapes we observed. These results could lead to the customization and optimization of 3D spirals, ribbons, etc. designed for a certain application.

Human noroviruses (HuNoVs) are the leading cause of viral epidemic acute gastroenteritis and responsible for the deaths of over 200,000 children each year worldwide. HuNoV research has been hampered by the long absence of a readily reproducible cell culture system and a suitable small animal model, while gnotobiotic (Gn) pigs have been a unique animal model for understanding HuNoV pathogenesis and immunity, as well as evaluating vaccine and therapeutics. Recent reports of HuNoVs infection and replication in B cells supplemented with commensal bacteria Enterobacter cloacae and in Blab/c mice deficient in RAG/IL2RG have gained extensive attention, and my studies utilized the well-established Gn pig model to investigate the effects of these two interventions on HuNoV infection. Surprisingly, the colonization of E. cloacae inhibited HuNoV infectivity in Gn pigs, evidenced by the significantly reduced HuNoV shedding in feces and HuNoV titers in intestinal tissues and blood compared to control pigs. Moreover, HuNoV infection of enterocytes but not B cells was observed with or without E. cloacae colonization, indicating B cells were not a target cell type for HuNoV in Gn pigs. On the other hand, using RAG2/IL2RG deficient pigs generated by CRISPR/Cas9 system, with confirmed severe combined immunodeficiency, I evaluated the effects of host immune responses on HuNoV infection. Compared to wild-type Gn pigs, longer HuNoV shedding was observed in RAG2/IL2RG deficient pigs (16 versus 27 days), and higher HuNoV titers were detected in intestinal tissues and contents and in blood, indicating increased and prolonged HuNoV infection in RAG2/IL2RG deficient pigs. In addition, I evaluated dietary interventions including probiotics and rice bran using Gn pig model of HuNoV infection and diarrhea. While the colonization of probiotic bacteria Lactobacillus rhamnosus GG (LGG) and Escherichia coli Nissle 1917 (EcN) in Gn pigs completely inhibited HuNoV fecal shedding, the two cocktail regimens, in which rice bran feeding started either 7 days prior to or 1 day after viral inoculation in the LGG+EcN colonized Gn pigs, exhibited dramatic anti-HuNoV effects, including reduced incidence and shorter duration of diarrhea, as well as shorter duration of virus fecal shedding. The anti-HuNoV effects of the cocktail regimens were associated with the enhanced IFN-𝛾⁺ T cell responses, increased production of intestinal IgA and IgG, and longer villus length. Taken together, my dissertation work improves our understanding of HuNoV infection and immunity, and further supports for Gn pigs as a valuable model for future studies of human enteric virus infection, host immunity, and interventions. / Ph. D. / Human noroviruses (HuNoVs) are the leading cause of viral epidemic acute gastroenteritis. Using the gnotobiotic pig model of HuNoV infection and diarrhea, we found that (1) the colonization of a commensal bacterium E. cloacae inhibited HuNoV infectivity, and B cells were not a target cell type for HuNoV in gnotobiotic pigs. (2) Increased and prolonged HuNoV infection in RAG2/IL2RG deficient pigs, which had severe combined immunodeficiency. (3) The dietary supplementation of rice bran and colonization of two probiotic bacteria significantly reduced HuNoV infectivity and diarrhea, and the beneficial effects were associated with enhanced intestinal immunity and health. Taken together, the dissertation work improves our understanding of HuNoV infection and immunity, and further supports for gnotobiotic pigs as a valuable model for future studies of human enteric virus infection, host immunity, and interventions.

Our research primarily focuses on the risk assessment and vulnerabilities of commercial broiler farms/houses due to severe weather events. The area of focus is counties within a 60-mile radius of broiler processing plants, as most broiler farms/houses are centrally located around these plants. Using data from the National Oceanic and Atmospheric Administration (NOAA), we calculate a risk index to evaluate the vulnerability of these counties. This study incorporates historical weather event data to identify patterns and predict future risks, providing valuable insights for disaster preparedness and mitigation strategies. Through a detailed analysis of various severe weather events, including tornadoes, hurricanes, floods, and lightning, we aim to highlight the specific vulnerabilities of broiler farms/houses and propose targeted strategies to enhance their resilience against these climatic threats. By focusing on high-risk areas, we ensure that our findings are both relevant and actionable, enabling stakeholders to implement effective risk management practices. This research fills an important gap in the existing literature. and also contributes significantly to the development of robust predictive models and comprehensive risk assessments for the poultry industry. Key Words: broiler production plants, severe weather events, risk assessment, NOAA data, vulnerability analysis, predictive modeling, climatic threats, resilience enhancement, machine learning models, Bayesian risk, geospatial analysis, hypothesis testing, nowcasting.

Yes / There is global interest in the reconfiguration of community mental health services, including primary care, to improve clinical and cost effectiveness. This study seeks to describe patterns of service use, continuity of care, health risks, physical healthcare monitoring and the balance between primary and secondary mental healthcare for people with severe mental illness in receipt of secondary mental healthcare in the UK. We conducted an epidemiological medical records review in three UK sites. We identified 297 cases randomly selected from the three participating mental health services. Data were manually extracted from electronic patient medical records from both secondary and primary care, for a 2-year period (2012-2014). Continuous data were summarised by mean and s.d. or median and interquartile range (IQR). Categorical data were summarised as percentages. The majority of care was from secondary care practitioners: of the 18 210 direct contacts recorded, 76% were from secondary care (median, 36.5; IQR, 14-68) and 24% were from primary care (median, 10; IQR, 5-20). There was evidence of poor longitudinal continuity: in primary care, 31% of people had poor longitudinal continuity (Modified Modified Continuity Index ≤0.5), and 43% had a single named care coordinator in secondary care services over the 2 years. The study indicates scope for improvement in supporting mental health service delivery in primary care. Greater knowledge of how care is organised presents an opportunity to ensure some rebalancing of the care that all people with severe mental illness receive, when they need it. A future publication will examine differences between the three sites that participated in this study. / This paper presents independent research funded by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research programme (grant reference no. RP-PG-0611-20004). Professors Siobhan Reilly, Richard Byng and Max Birchwood are partially supported by the NIHR Applied Research Collaboration (ARC) for North West Coast, Care South West Peninsula and West Midlands, respectively.

Yes / Quality of residential care for people with severe dementia is in urgent need of improvement. One reason for this may be the assumption that people with severe dementia are unaware of what is happening to them. However, there is converging evidence to suggest that global assumptions of unawareness are inappropriate. This trial platform study aims to assist care staff in perceiving and responding to subtle signs of awareness and thus enhance their practice. Methods/Design: In Stage One, a measure of awareness in severe dementia will be developed. Two focus groups and an expert panel will contribute to item and scale development. In Stage Two observational data will be used to further develop the measure. Working in four care homes, we will recruit 40 individuals with severe dementia who have no, or very limited, verbal communication. Data on inter-rater reliability and frequency of all items and exploratory factor analysis will be used to identify items to be retained. Test-retest and inter-rater reliability for the new measure will be calculated. Correlations with scores for well-being and behaviour and with proxy ratings of quality of life will provide an indication of concurrent validity. In Stage Three the new measure will be used in a single blind cluster randomised trial. Eight care homes will participate, with 10 residents recruited in each giving a total sample of 80 people with severe dementia. Homes will be randomised to intervention or usual care conditions. In the intervention condition, staff will receive training in using the new measure and will undertake observations of designated residents. For residents with dementia, outcomes will be assessed in terms of change from baseline in scores for behaviour, well-being and quality of life. For care staff, outcomes will be assessed in terms of change from baseline in scores for attitudes, care practice, and well-being. Discussion: The results will inform the design of a larger-scale trial intended to provide definitive evidence about the benefits of increasing the sensitivity of care staff to signs of awareness in residents with severe dementia. Trial Registration: ISRCTN59507580 http://www.controlled-trials.com.

Introduction: The pathogenesis and treatment of allergic bronchopulmonary aspergillosis (ABPA), severe asthma-non fungal sensitised (SANFS) and severe asthma with fungal sensitization (SAFS) is poorly understood. IL-17A, IgE and microbiome may be associated with pathogenesis of asthma, but their role in fungal-associated asthma is uncertain. Further, the efficacy of voriconazole, posaconazole and nebulised amphotericin B (NAB) in ABPA and SAFS has not been fully studied. Aims and objectives: The aim of this PhD thesis was to evaluate the role of IL-17A, IgE and lung microbiome in patients with SANFS, SAFS and ABPA. We also studied the efficacy and safety of NAB, voriconazole and posaconazole. Methods: Airway lymphocytes and peripheral blood mononuclear cells (PBMC) from patients with ABPA (n=16), SAFS (n=15), SANFS (n=11), mild asthma (MA) (n=6) and NH (n=11) were characterized by flow cytometric analysis (FACS) to determine the % of CD (+) IL-17A expressing cells. We also evaluated microbiome population using culture and PCR plus sequencing from BAL of these patients. In chapter 3, we analysed total and specific IgE in blood from adult cohorts of SAFS (n=34) and ABPA (n=48) using ImmunoCAP 100. In chapter 5 we studied the efficacy of voriconazole and posaconazole and in chapter 6; we studied the efficacy of NAB.Results: %CD4+IL-17A expressing cells were significantly higher in patients with severe asthma and correlated positively with serum neutrophil and presence of fungi in the airways. ABPA, SAFS and SANFS were similar but all were significantly higher than MA and NH. There were no differences in IL-17A expression between blood and the lung. Fungi were more frequently associated with severe asthma and low FEV1. Steroid treatment significantly increased airway fungal load. IgE against staphylococcal aureus (SE-IgE) correlated positively with FEV1 and OCS dose. Voriconazole and posaconazole improved asthma severity and radiological abnormalities. NAB was associated bronchospasm, but was extrely effective in the few patients (n=3) that took treatment for >12 months. These responders had unique characteristics. Conclusions: IL-17A, SE-IgE, and lung microbiome are associated with asthma severity. Steroid use in these patients may increase airway fungal load. Whereas voriconazole and posaconazole are efficacious, the use of NAB is associated with significant bronchospasm. SE-IgE -high asthma patients may be a distinct asthma phenotype. Larger studies are needed.

La prise en charge des patients souffrant d’un trouble mental justifie une meilleure compréhension des mécanismes influençant les comportements des patients et des cliniciens vis-à-vis des stratégies thérapeutiques. Le principal objectif de cette thèse est d’étudier et d’identifier le rôle des attitudes des patients et des cliniciens vis-à-vis du comportement d’usage d’une thérapeutique. Pour cela, nous avons réalisé plusieurs études permettant d’appréhender cette problématique dans différentes pathologies et envers différentes thérapeutiques.Concernant les attitudes des patients envers leur traitement, nous avons détaillé un travail visant à évaluer les croyances de patients souffrant de schizophrénie envers leur antipsychotique et une étude qualitative sur les attitudes des patients bipolaires envers leur prise en charge en phase d’euthymie. Nous avons montré l’impact des attitudes négatives sur le niveau d’observance ou d’adhésion des patients à leur prise en charge et l’intérêt de cibler des stratégies de prise en charge individualisées visant à améliorer ces attitudes. Concernant les psychiatres, nous avons présenté une étude évaluant les attitudes des cliniciens vis-à-vis des recommandations professionnelles ainsi qu’un travail concernant leurs attitudes envers les antipsychotiques d’action prolongée. Certaines attitudes des psychiatres apparaissaient associées à une plus faible utilisation des recommandations ou des formulations d’action prolongée. Nos résultats montrent ainsi que l’observance ou l’adhésion des patients à une prise en charge ou le choix thérapeutique des cliniciens sont sous-tendus par leurs attitudes. L’étude des attitudes dans le domaine de la santé mentale apparaît comme une étape indispensable dans la compréhension de certains comportements d’usage des thérapeutiques. Les données issues des travaux présentés mais aussi d’études récentes permettent d’envisager un changement de paradigme dans l’appréhension des comportements d’observance des patients et de décision médicale des cliniciens dans le choix d’une thérapeutique centré sur leurs attitudes. / The management of patients with severe mental illnesses needs a better understanding of thefactors affecting the behaviours of clinicians and patients toward therapeutic strategies.The main objective of this thesis was to assess and identify the role of the clinician’s attitudes and patients’ attitudes toward the medication use behaviour. We conducted several studies to address this point in different mental disorders and for different type of treatment. Concerning the patients ‘attitudes toward treatment, we reported data from a study assessing the beliefs toward antipsychotics of schizophrenic patients and from a qualitative study assessing the patient’s attitudes toward the management of bipolar disorder in euthymic periods. We showed that the negative attitudes had a marked impact on the level of adherence of patients and could determine individual targets of interventions to improve them. Concerning the psychiatrists, we reported two studies assessing the clinician’s attitudes toward guidelines and long-acting injectable antipsychotics. Some specific attitudes were associated with a lower use of guidelines or long-acting formulations. These findings showed that the adherence of patient to treatment and the medical decisions of clinicians were related to their attitudes. The assessment of attitudes or beliefs in the field of mental health appears to be an essential step to promote a better comprehension of some treatment use behaviours. Our results and from other recent studies support a new paradigm for the patient adherence to treatment and the medical decision of clinicians focused on their attitudes as predicting variables.