The diploma thesis deals with the attitude of parents and teachers of pupils with chronic diseases in the attenuation of compulsory school attendance at the 1st stage of ordinary primary school. The objective of the work is to identify the problems that parents and teachers of chronically ill students encounter during the educational process. From this basis, the purpose is also to find the basis for the best possible cooperation between parents and teachers. The theoretical idea is represented by individual chronic diseases, namely asthma, cystic fibrosis, pediatric oncological diseases, type 1 diabetes mellitus and epilepsy. In addition, the legislative framework for the education of pupils with these diseases, the methodology of working with pupils with chronic diseases and a search of domestic and foreign research conducted on a similar topic are addressed. The methodological part is devoted to qualitative research, the main goal of which is to find out the attitudes of teachers and parents to the educational process of pupils suffering from the above diseases. Using a questionnaire survey and a semi-structured interview, it is ascertained what are the attitudes of parents and teachers towards the education of pupils with the above-mentioned types of chronic diseases in ordinary primary school....

The purposes of this study are: a) to understand the treatments compliance behavior of the patient with chronic disease at the behavioral level, particularly, the relationship between treatments compliance behavior and normative beliefs; b) develop a behavioral model of patient's treatments compliance behavior that could be used for predicting, combating, treating, tracking and controlling the treatments compliance behavior of the patients with chronic disease. Seventy-two patients from senior daycare centers in the Dallas area, who suffer or had suffered from at least, one chronic disease, participated in the study. Data gathering was conducted using paper-based questionnaire. The most significant finding of this study is the relationship between normative beliefs and the treatments compliance behavior of the patient with chronic disease. Normative beliefs were found to have significant impact on the treatments compliance intent and behavior of the patients with chronic disease. Another important finding showed that side-effects of prescribed treatments have little or no influence on the treatments compliance behavior of the patient with chronic disease. A relationship between the effectiveness of medicine, particularly, predictive medicine, and treatments compliance behavior was established. The design of the study was intended to provide coverages for a set of constructs that may be the interacting units in the environment of any chronic disease treatments decision. It depicts relational, information communications links between the constructs. The Imhonde model of treatments compliance behavior was designed to include cultural norms and other beliefs that are significant for real-time human ailments decisions behaviors. It is recommended that further studies may include the use of a larger population of participants from diverse cultures and localities in multiple states and countries, with the object of finding the differences that culture and local environments may have on the normative leaning for treatments compliance behavioral decisions in chronic disease cases.

Our population is becoming older and with that, the development of chronic diseasesis is also expected to increase. A chronic illness is a long-term illness which lasts throughout a lifetime, or at least for a very long time. A large part of healthcare resources is already devoted to treating chronically ill patients. These patients are often dependent of both care and medication to maintain a meaningful life. To gain a holistic view of these patients health condition by one/two appointments with physicians yearly is not sufficient in order to conclude a certain health-state. The course of disease for these patients changes daily and require follow-up on disease progression continuously to adapt an appropriate treatment plan. Collecting patient-generated health data (PGHD) facilitates in the process of retrieving moreevidence for better assessment of the disease development. While there is obvious importance and benefit of using of PGHD, this data is not commonly used in healthcare.  Further investigation is needed to understand how PGHD can be more useful. This pilot study provides knowledge of the success and failure factors of using PGHD for mainly chronically ill patients, but can be applied to other patient-groups as well. The aim of this thesis work was to collect information about what suppliers, governmental organizations and healthcare professionals require for using PGHD in healthcare setting in a greater extent in the future. Methods used to gather information were participatory interviews in combination with qualitative interview questions. Pattern recognition has been created through a thematic analysis andcluster mapping. The data collection resulted in four areas of improvement; patient behaviour, healthcare organization, digitized health data and equipment. The result shows overall a positive attitude towards the concept of PGHD by all sectors asked in this project. Stakeholders agree on that PGHD can generate positive outcomes for chronically ill patients. The belief of improving workflow in healthcare with PGHD was also positive. The valuable possibilities generated with PGHD are tailored careflows, improved evaluation of disease status and enhanced quality of care and well-being among others. Additionally, several ongoing projects are taking place, which demonstrate great interest in the area. However, before PGHD can be prescribed by healthcare, studies have to be performed including development of national guidelines for reporting PGHD, building a secure infrastructure and introducing new work routines. Future work will be applying AI-analysis of reported PGHD to facilitate the work of caregivers and development of secure storing solutions for instance with block-chain technology. / Vår befolkning blir äldre och med det förväntas utvecklingen av kroniska sjukdomar också att öka. En kronisk sjukdom kallas också för en långvarig sjukdom som varar under hela livet eller åtminstonde under mycket lång tid. En stor del av vårdresurserna ägnas redan åt att behandla kroniskt sjuka patienter. Dessa patienter är ofta beroende av både vård och medicinering för att upprätthålla ett meningsfullt liv. För att få en helhetssyn på dessa patienters hälsotillstånd krävs mer än en eller två möten med sjukvården årligen. Ett fåtal möten per år är inte tillräckligt för att konstatera en rättvis bild av hälsotillståndet. Sjukdomsförloppet för dessa patienter förändras dagligen och kräver fortlöpande uppföljning av sjukdomsutvecklingen för att förstå och anpassa en lämplig behandlingsplan. Insamling av patientgenererad hälsodata (PGHD) underlättar och hjälper till i denna process. Det finns uppenbarliga fördelar med PGHD, men datan används inte vanligtvis i sjukvården. Ytterligare forskning behövs för att förstå hur PGHD kan vara mer användbart. Denna pilotstudie ger kunskap om inflytelserika faktorer för att använda PGHD för huvudsakligen kroniskt sjuka patienter, men kan också tillämpas på andra patientgrupper. Syftet med detta avhandlingsarbete var att samla in information om vad leverantörer, statliga organisationer och vårdpersonal kräver för att använda PGHD i vårdmiljö i framtiden. Metoder som använts för att samla in information var deltagande intervjuer i kombination med kvalitativa intervjufrågor. Resultatet har genomgått en klusterkartläggning och tematisk analys för att skapa mönsterigenkänning. Datainsamlingen resulterade i fyra områden; patientbeteende,vårdorganisation, digitaliserad hälsodata och utrustning. Resultatet visar en positiv inställning till PGHD enligt alla deltagare i studien.Deltagarna är överens om att PGHD kan generera positiva resultat för kroniskt sjuka patienter. Tron att förbättra arbetsflödet inom hälso-och sjukvård med PGHD var också positiv. De värdefulla möjligheterna som genereras med PGHD är bl.a. skräddarsydda vårdflöden, förbättrad utvärdering av sjukdomstatus och förbattradk valitet på vård och välmående bland andra. Dessutom pågår flera pågående projekt som visar stort intresse för området. Innan PGHD kan börja förskrivas av hälsovården måste det utföras fler studier som inkluderar framtagning av nationellariktlinjer för rapportering av PGHD, byggandet av en säker infrastruktur och introduktion av nya arbetsrutiner. Framtida arbete kvarstår dår tillämpning av AI analysmodeller på rapporterad PGHD samt utveckling av säkra lagringslösningar, förslagsvis med blockkedjeteknik, bör vidareutvecklas.

Preliminary investigation at the beginning of this research showed that informatics on point-of-care (POC) devices was limited to basic data generation and processing. This thesis is based on publications of several studies during the course of the research. The aim of the research is to model and analyse information generation and exchange in telehealth systems and to identify and analyse the capabilities of these systems in managing chronic diseases which utilise point-of-care devices. The objectives to meet the aim are as follows: (i) to review the state-of-the-art in informatics and decision support on point-of-care devices. (ii) to assess the current level of servitization of POC devices used within the home environment. (iii) to identify current models of information generation and exchange for POC devices using a telehealth perspective. (iv) to identify the capabilities of telehealth systems. (v) to evaluate key components of telehealth systems (i.e. POC devices and intermediate devices). (vi) to analyse the capabilities of telehealth systems as enablers to a healthcare policy. The literature review showed that data transfer from devices is an important part of generating information. The implication of this is that future designs of devices should have efficient ways of transferring data to minimise the errors that may be introduced through manual data entry/transfer. The full impact of a servitized model for point-of-care devices is possible within a telehealth system, since capabilities of interpreting data for the patient will be offered as a service (c.f. NHS Direct). This research helped to deduce components of telehealth systems which are important in supporting informatics and decision making for actors of the system. These included actors and devices. Telehealth systems also help facilitate the exchange of data to help decision making to be faster for all actors concerned. This research has shown that a large number of capability categories existed for the patients and health professionals. There were no capabilities related to the caregiver that had a direct impact on the patient and health professional. This was not surprising since the numbers of caregivers in current telehealth systems was low. Two types of intermediate devices were identified in telehealth systems: generic and proprietary. Patients and caregivers used both types, while health professionals only used generic devices. However, there was a higher incidence of proprietary devices used by patients. Proprietary devices possess features to support patients better thus promoting their independence in managing their chronic condition. This research developed a six-step methodology for working from government objectives to appropriate telehealth capability categories. This helped to determine objectives for which a telehealth system is suitable.

JUSTIFICATIVA E OBJETIVOS: As doenças cardiovasculares (DCV) constituem uma importante causa de mortalidade em todo mundo, sendo a principal causa de morte e incapacidade no Brasil, determinando um impacto social, econômico e médico de grandes proporções. O desenvolvimento das DCV está correlacionado a vários fatores de risco desde os primeiros anos de vida, com expressão na vida adulta. As sementes da aterosclerose são semeadas muitas décadas antes da manifestação dos pontos finais clínicos. A espessura da média-intimal da carótida (EMIC) é relevante na avaliação da repercussão dos fatores de risco sobre a parede arterial. As condições precursoras dos distúrbios metabólicos e das alterações vasculares relativas à aterosclerose podem ser evitadas ou interrompidas se identificados e tratados a tempo. Com base nessa premissa, o presente trabalho tem como objetivo estudar a relação entre história e condições de vida, fatores de risco cardiovascular e espessura da média-intimal da carótida em crianças escolares de 5 a 9 anos, procedentes de escolas públicas da região central da cidade de Fortaleza - Ceará - Brasil. MÉTODOS: estudo transversal observacional com dados primários colhidos por formulário aplicado a uma amostra da população escolar de instituições públicas em crianças de 5 a 9 anos da região central da cidade de Fortaleza, sorteadas aleatoriamente. Informações relacionadas às características sociodemográficas, dados antropométricos, medidas da pressão arterial, perfil metabólico, e avaliação da espessura da média-intimal da carótida pela ultrassonografia foram realizados. Para análises estatísticas, análises univariadas foram desenvolvidas por meio da comparação de proporções pelo Teste do Qui-quadrado e pela seleção de variáveis independentes, para compor os modelos de regressão logística múltipla. RESULTADOS: Foram investigadas quinhentas crianças de 5-9 anos, sendo do sexo feminino 260 crianças (52%). A medida da EMIC teve média e desvio padrão para EMIC esquerda de 0,42mm (±0,09) e para EMIC direita de 0,39mm (±0,07). Não houve diferenças significativas para os sexos. Houve associação estatisticamente significante e de forma crescente com a idade, sendo 5,02 vezes maior uma criança de 9 anos ter a EMIC aumentada (IC95% = 1,95 - 12,88; p=0,001). A EMIC esteve associada significantemente com o nível de instrução materna baixo (OR = 0,46; IC95% = 0,23 - 0,90), com hipertensão diastólica (OR = 7,61; IC95% = 2,18 - 26,53), com sobrepeso/obesidade (OR = 4,81; IC95% = 2,50 - 9,24), com hipercolesterolemia (OR = 20,8; IC95% = 10,17 - 42,92), com níveis de PCR elevados (OR = 3,03; IC95% = 1,27 - 7,21) e insulina de jejum elevados (OR = 10,4; IC95% = 3,03 - 36,24). CONCLUSÕES: A aterosclerose subclínica já pode ser detectada em crianças pré-púberes de 5 a 9 anos que contenham fatores de risco para doença cardiovascular, indicando doença cardiovascular incipiente. A medida da EMIC pode fornecer um marcador confiável para a saúde vascular, associado a outros critérios de risco, evidenciando que, especialmente no grupo etário pediátrico, a avaliação do risco cardiovascular é benéfica. Considerando a progressão das alterações vasculares ao longo da vida, parece prudente para detectar sinais subclínicos de danos arteriais e aterosclerose muito cedo, e para aliviar a carga aterosclerótica com medidas preventivas / BACKGROUND AND OBJECTIVES: Cardiovascular diseases (CVD) are a major cause of death worldwide. They are main cause of death and disability in Brazil and thus have large social, economic and medical impact. The development of CVD is correlated with several risk factors from the first years of life, with expression in adult life. The seeds of atherosclerosis are sown many decades before the manifestation of clinical symptoms. The carotid intima-media thickness (cIMT) is relevant in assessing the manifestation of risk factors on the arterial wall. The precursor conditions of metabolic disorders and vascular changes related to atherosclerosis can be avoided or disrupted if identified and treated in time. Based on this premise, the objective of this study was to study the relationship between history and life conditions, cardiovascular risk factors, and carotid intima-media thickness in public schoolchildren, aged 5 to 9, in the central region of the city of Fortaleza, Ceará, Brazil. METHODS: an observational cross-sectional study with primary data collected by a form supplied to a sample of the school population of public institutions in the central region of Fortaleza. The children were randomly selected and information related to sociodemographic characteristics, anthropometric data, blood pressure measurements, metabolic profile, and assessment of the carotid-mediated intima-media thickness were collected. For statistical analyzes, univariate analyses were developed by comparing proportions through the Chi-square test and a selection of independent variables to compose the multiple logistic regression models. RESULTS: Five hundred children aged 5-9 years were enrolled, of whom 260 (52%) were female. The cIMT measure had a mean and standard deviation for left cIMT of 0.42mm (± 0.09) and for right cIMT of 0.39mm (± 0.07). There were no significant differences for the sexes. There was a statistically significant and increasing association with age, with a 9-year-old child being 5.02 times more likely to have cIMT (95% CI = 1.95 - 12.88, p = 0.001). The cIMT was significantly associated with low maternal education (OR = 0.46, 95% CI = 0.23-0.90), with diastolic hypertension (OR = 7.61, 95% CI = 2.18-26, 53), overweight/obesity (OR = 4.81, 95% CI = 2.50-9.24), hypercholesterolemia (OR = 20.8, 95% CI = 10.17 - 42.92), high levels of CRP (OR = 3.03, 95% CI = 1.27 - 7.21), and high-fasting insulin (OR = 10.4, 95% CI = 3.03-36.24). CONCLUSIONS: Subclinical atherosclerosis can already be detected in prepubertal children aged 5 to 9 years who have risk factors for cardiovascular disease, indicating incipient cardiovascular disease. The cIMT measure can provide a reliable marker for vascular health, associated with other risk criteria. The measure shows that, especially in the pediatric age group, cardiovascular risk assessment is beneficial. Given the progression of vascular changes throughout life, it seems prudent to detect subclinical signs of arterial damage and atherosclerosis very early and to relieve atherosclerotic burden with preventative measures

JUSTIFICATIVA E OBJETIVOS: As doenças cardiovasculares (DCV) constituem uma importante causa de mortalidade em todo mundo, sendo a principal causa de morte e incapacidade no Brasil, determinando um impacto social, econômico e médico de grandes proporções. O desenvolvimento das DCV está correlacionado a vários fatores de risco desde os primeiros anos de vida, com expressão na vida adulta. As sementes da aterosclerose são semeadas muitas décadas antes da manifestação dos pontos finais clínicos. A espessura da média-intimal da carótida (EMIC) é relevante na avaliação da repercussão dos fatores de risco sobre a parede arterial. As condições precursoras dos distúrbios metabólicos e das alterações vasculares relativas à aterosclerose podem ser evitadas ou interrompidas se identificados e tratados a tempo. Com base nessa premissa, o presente trabalho tem como objetivo estudar a relação entre história e condições de vida, fatores de risco cardiovascular e espessura da média-intimal da carótida em crianças escolares de 5 a 9 anos, procedentes de escolas públicas da região central da cidade de Fortaleza - Ceará - Brasil. MÉTODOS: estudo transversal observacional com dados primários colhidos por formulário aplicado a uma amostra da população escolar de instituições públicas em crianças de 5 a 9 anos da região central da cidade de Fortaleza, sorteadas aleatoriamente. Informações relacionadas às características sociodemográficas, dados antropométricos, medidas da pressão arterial, perfil metabólico, e avaliação da espessura da média-intimal da carótida pela ultrassonografia foram realizados. Para análises estatísticas, análises univariadas foram desenvolvidas por meio da comparação de proporções pelo Teste do Qui-quadrado e pela seleção de variáveis independentes, para compor os modelos de regressão logística múltipla. RESULTADOS: Foram investigadas quinhentas crianças de 5-9 anos, sendo do sexo feminino 260 crianças (52%). A medida da EMIC teve média e desvio padrão para EMIC esquerda de 0,42mm (±0,09) e para EMIC direita de 0,39mm (±0,07). Não houve diferenças significativas para os sexos. Houve associação estatisticamente significante e de forma crescente com a idade, sendo 5,02 vezes maior uma criança de 9 anos ter a EMIC aumentada (IC95% = 1,95 - 12,88; p=0,001). A EMIC esteve associada significantemente com o nível de instrução materna baixo (OR = 0,46; IC95% = 0,23 - 0,90), com hipertensão diastólica (OR = 7,61; IC95% = 2,18 - 26,53), com sobrepeso/obesidade (OR = 4,81; IC95% = 2,50 - 9,24), com hipercolesterolemia (OR = 20,8; IC95% = 10,17 - 42,92), com níveis de PCR elevados (OR = 3,03; IC95% = 1,27 - 7,21) e insulina de jejum elevados (OR = 10,4; IC95% = 3,03 - 36,24). CONCLUSÕES: A aterosclerose subclínica já pode ser detectada em crianças pré-púberes de 5 a 9 anos que contenham fatores de risco para doença cardiovascular, indicando doença cardiovascular incipiente. A medida da EMIC pode fornecer um marcador confiável para a saúde vascular, associado a outros critérios de risco, evidenciando que, especialmente no grupo etário pediátrico, a avaliação do risco cardiovascular é benéfica. Considerando a progressão das alterações vasculares ao longo da vida, parece prudente para detectar sinais subclínicos de danos arteriais e aterosclerose muito cedo, e para aliviar a carga aterosclerótica com medidas preventivas / BACKGROUND AND OBJECTIVES: Cardiovascular diseases (CVD) are a major cause of death worldwide. They are main cause of death and disability in Brazil and thus have large social, economic and medical impact. The development of CVD is correlated with several risk factors from the first years of life, with expression in adult life. The seeds of atherosclerosis are sown many decades before the manifestation of clinical symptoms. The carotid intima-media thickness (cIMT) is relevant in assessing the manifestation of risk factors on the arterial wall. The precursor conditions of metabolic disorders and vascular changes related to atherosclerosis can be avoided or disrupted if identified and treated in time. Based on this premise, the objective of this study was to study the relationship between history and life conditions, cardiovascular risk factors, and carotid intima-media thickness in public schoolchildren, aged 5 to 9, in the central region of the city of Fortaleza, Ceará, Brazil. METHODS: an observational cross-sectional study with primary data collected by a form supplied to a sample of the school population of public institutions in the central region of Fortaleza. The children were randomly selected and information related to sociodemographic characteristics, anthropometric data, blood pressure measurements, metabolic profile, and assessment of the carotid-mediated intima-media thickness were collected. For statistical analyzes, univariate analyses were developed by comparing proportions through the Chi-square test and a selection of independent variables to compose the multiple logistic regression models. RESULTS: Five hundred children aged 5-9 years were enrolled, of whom 260 (52%) were female. The cIMT measure had a mean and standard deviation for left cIMT of 0.42mm (± 0.09) and for right cIMT of 0.39mm (± 0.07). There were no significant differences for the sexes. There was a statistically significant and increasing association with age, with a 9-year-old child being 5.02 times more likely to have cIMT (95% CI = 1.95 - 12.88, p = 0.001). The cIMT was significantly associated with low maternal education (OR = 0.46, 95% CI = 0.23-0.90), with diastolic hypertension (OR = 7.61, 95% CI = 2.18-26, 53), overweight/obesity (OR = 4.81, 95% CI = 2.50-9.24), hypercholesterolemia (OR = 20.8, 95% CI = 10.17 - 42.92), high levels of CRP (OR = 3.03, 95% CI = 1.27 - 7.21), and high-fasting insulin (OR = 10.4, 95% CI = 3.03-36.24). CONCLUSIONS: Subclinical atherosclerosis can already be detected in prepubertal children aged 5 to 9 years who have risk factors for cardiovascular disease, indicating incipient cardiovascular disease. The cIMT measure can provide a reliable marker for vascular health, associated with other risk criteria. The measure shows that, especially in the pediatric age group, cardiovascular risk assessment is beneficial. Given the progression of vascular changes throughout life, it seems prudent to detect subclinical signs of arterial damage and atherosclerosis very early and to relieve atherosclerotic burden with preventative measures

Les maladies chroniques (dont les maladies cardio-vasculaires (MCV)) constituent dans la majorité des pays en Europe voire dans le monde, une des principales causes de mortalité et de morbidité. En Belgique, ces pathologies sont responsables de 37% des décès (33% des décès chez les hommes et 40% chez les femmes) .<p><p>Les études épidémiologiques ont montré que certaines populations sont plus susceptibles que d’autres de développer ou de décéder des maladies cardio-vasculaires (1). Pendant longtemps, l’Europe a été caractérisée par des écarts importants de mortalité cardio-vasculaire entre le Nord, plus à risque, et le Sud. Ces différences entre populations s’expliquent par des facteurs génétiques, environnementaux, sociaux et culturels. <p><p>Parmi les facteurs culturels et environnementaux, des travaux scientifiques montrent, depuis plusieurs dizaines d’années, que l’alimentation et l’état nutritionnel participent de façon essentielle au développement et à l’expression clinique des maladies dans l’ensemble des pays industrialisés. Un équilibre nutritionnel, une consommation alimentaire variée, avec une répartition satisfaisante des quantités ingérées permettent de préserver un bon état de santé. <p><p>Les études épidémiologiques interethniques ont joué un rôle important dans l’avancée de la recherche de ces facteurs. Les études d’observation révèlent que lorsque des sujets d’un groupe ethnique particulier changent d’environnement, leur statut physique change au contact du nouvel environnement et diffère généralement de ceux restés dans le pays d’origine. La comparaison des taux de mortalité et de morbidité des immigrés de longue date aux taux observés dans le pays d’origine permet d’étudier la contribution des facteurs génétiques et environnementaux dans les variations de morbidité et de mortalité.<p><p>Les différences de morbidité et de mortalité entre ethnies ont été largement documentées pour les immigrés hispaniques, africains et sud-asiatiques en Amérique du Nord et en Grande Bretagne. Ces études ont montré que le profil de santé des immigrés est influencé tant par l’environnement du pays de naissance que par celui du pays d’accueil. L’influence de ces deux environnements peut donner lieu à 3 modèles de morbidité et de mortalité :la sous-mortalité (principalement observée parmi les immigrés de première génération issus de pays moins développés), la convergence (mortalité ou morbidité égale. Ce modèle concerne essentiellement les immigrés de seconde génération) et le dépassement (sur-mortalité ou sur-morbidité). <p><p>La santé des immigrés en Belgique est mal connue et peu étudiée. Dans la majorité des statistiques sanitaires comme dans les recherches épidémiologiques, les critères de nationalité et de naissance soit n'apparaissent pas du tout, soit ne font l'objet d'aucune analyse. L'occultation de ces variables a cependant pour conséquence de laisser dans l'ombre des indications précieuses pour la mise en œuvre de politiques de santé publique. <p><p>Bien que d’un intérêt évident en épidémiologie, les études interethniques posent un certain nombre de problèmes méthodologiques. Difficile à traiter, cette question n'en demeure pas moins essentielle à penser. <p> / Doctorat en Sciences de la santé publique / info:eu-repo/semantics/nonPublished

Indiana University-Purdue University Indianapolis (IUPUI) / Juvenile Myelomonocytic Leukemia (JMML) is rare, fatal myeloproliferative disease (MPD) affecting young children, and is characterized by expansion of monocyte lineage cells and hypersensitivity to Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF) stimulation. JMML is frequently associated with gain-of-function mutations in the PTPN11 gene, which encodes the protein tyrosine phosphatase, Shp2. Activating Shp2 mutations are known to promote hyperactivation of the Ras-Erk signaling pathway, but Akt is also observed to have enhanced phosphorylation, suggesting a potential role for Phosphatidylinositol-3-Kinase (PI3K)-Akt signaling in mutant Shp2-induced GM-CSF hypersensitivity and leukemogenesis. Having demonstrated that Class IA PI3K is hyperactivated in the presence of mutant Shp2 and contributes to GM-CSF hypersensitivity, I hypothesized the hematopoietic-specific Class IA PI3K catalytic subunit p110δ is a crucial mediator of mutant Shp2-induced PI3K hyperactivation and GM-CSF hypersensitivity in vitro and MPD development in vivo. I crossed gain-of-function mutant Shp2 D61Y inducible knockin mice, which develop fatal MPD, with mice expressing kinase-dead mutant p110δ D910A to evaluate p110δ’s role in mutant Shp2-induced GM-CSF hypersensitivity in vitro and MPD development in vivo. As a comparison, I also crossed Shp2 D61Y inducible knockin mice with mice bearing inducible knockout of the ubiquitously expressed Class IA PI3K catalytic subunit, p110α. I found that genetic interruption of p110δ, but not p110α, significantly reduced GM-CSF-stimulated hyperactivation of both the Ras-Erk and PI3K-Akt signaling pathways, and as a consequence, resulted in reduced GM-CSF-stimulated hyper-proliferation in vitro. Furthermore, I found that mice bearing genetic disruption of p110δ, but not p110α, in the presence of gain-of-function mutant Shp2 D61Y, had on average, smaller spleen sizes, suggesting that loss of p110δ activity reduced MPD severity in vivo. I also investigated the effects of three PI3K inhibitors with high specificity for p110δ, IC87114, GDC-0941, and GS-9820 (formerly known as CAL-120), on mutant Shp2-induced GM-CSF hypersensitivity. These inhibitors with high specificity for p110δ significantly reduced GM-CSF-stimulated hyperactivation of PI3K-Akt and Ras-Erk signaling and reduced GM-CSF-stimulated hyperproliferation in cells expressing gain-of-function Shp2 mutants. Collectively, these findings show that p110δ-dependent PI3K hyperactivation contributes to mutant Shp2-induced GM-CSF hypersensitivity and MPD development, and that p110δ represents a potential novel therapeutic target for JMML.

Indiana University-Purdue University Indianapolis (IUPUI) / Stroke is the main cause of disability in the United States. Individuals with stroke commonly report sensory impairment affects their recovery. Motor recovery and sensory impairment are related and impact individuals’ ability to perform valued occupations. Despite the prevalence of sensation impairment after stroke, many occupational therapists fail to include sensation assessment and intervention in treatment planning. The exclusion of sensation in occupational therapy interventions during stroke rehabilitation may be due to the lack of literature supporting the association between sensation and occupational performance. The current study aimed to determine the relationship between touch sensation of the affected hand and occupational performance and satisfaction in individuals with chronic stroke. Using a cross-sectional study design, this study associated factors related to hand sensation and function in individuals with chronic stroke. Fifty individuals with chronic stroke participated in a one-time testing session in which assessments related to sensation, movement of the hand and engagement in daily activities were administered. Correlation analyses were utilized to determine relationships between touch sensation of the affected hand with individuals’ abilities to engage in valued daily activities, arm and hand disability, and manual abilities. The main finding of the study was that individuals with intact sensation reported greater ability to perform valued occupations and satisfaction with their performance, as compared with individuals with touch sensation impairment. For individuals with impaired touch sensation of the affected hand, impairment of touch sensation of the hand did not correlate with individuals’ performance or satisfaction with valued occupations, arm or hand movement, or manual abilities. Collectively, the results of this study reflect the complex interaction between touch sensation, occupational performance, motor functioning, and manual abilities of the affected hand for individuals’ who have experienced a stroke. This study informs therapists, rehabilitation scientists, and other healthcare professionals that client-centered, individualized approaches, including a wide array of clinical assessments and intervention, including assessment of occupational performance and sensation, remain important components in stroke rehabilitation.

Indiana University-Purdue University Indianapolis (IUPUI) / Technology dependent children such as those who require a feeding tube, tracheotomy or ventilator are a special group of chronically ill children who require complex care on a daily basis. When these children are hospitalized, the accompanying parent and the nurse caring for the child on the inpatient unit must communicate together about the care of the child. Care for the technology dependent child is optimized when parents and nurses both understand the plan of care for the child. To discover the process of parent-nurse communication that results in mutual understanding of the child’s plan of care, a grounded theory study to explore the perspectives of the parents of previously hospitalized technology dependent children was undertaken. The Theory of Shared Communication emerged from the data and illuminates the parent-nurse communication process. The antecedents of the process are respect for own and others expertise. The communication process consists of six communication behaviors; ask, listen, explain, advocate, verify understanding and negotiate roles. The behaviors are nested within each other and all are not necessarily required for the non-linear process to result in the relational outcome of mutual understanding of the child’s plan of care. An integrative review of the literature regarding the process of communication between parents of hospitalized chronically ill children and their nurses shed light on the components of the process, but no study was found that explicated the entire communication process. A subsequent grounded theory study added the perspectives of the nurses to the original theory. No new components of the process were uncovered, but the nurse’s narratives added significantly to our understanding of the communication process. Additionally, parents of currently hospitalized technology dependent children confirmed the propositions of the Theory of Shared Communication.