Background.  Sepsis is a syndrome associated with high mortality rates, substantial morbidity and high costs of care. The incidents of sepsis is reported to be high and controversy exists whether gender affect severity or outcome. Little is known about factors determining suscepti­bility for developing the syndrome and severity of the syndrome once developed. Early detection and adequate antibiotic administration are the mainstay of treatment and means to identify patients with particular high risk of adverse outcome are desirable. There are data to suggest that the course of sepsis and outcome from the syndrome may be influenced by inherited differences in the immunological response among humans Aims: Paper I: Assess incidence and outcome for ICU-treated sepsis patients in this region; Paper II: Assess if there are gender differences related to characteristics, aspects of treatment or out­come in sepsis in this region. Paper III: Assess the association of baseline levels of leptin and adiponectin and future sepsis event, and association of these adipokines in the cute phase and sepsis severity and outcome. Paper IV: Assess association of baseline levels of mannose-binding lectin (MBL) and future sepsis event, and MBL levels in the acute phase in relation to sepsis severity and outcome. Results. Paper I:  Overall ICU mortality rate was 25%, while the ICU mortality for patients with septic shock was 58% in this retrospective single university hospital cohort analysis. Cardio­vascular disease and diabetes were the most prevalent comorbidities among patients who died during hospital stay.  Paper II:  No gender-related differences in mortality or length of stay was found in this prospective single center observational study. Differences in aspects of treatment were related to differences in site of infection. Men had more often infections in skin and skin-structures, whereas women more often had abdominal infections. Early organ dysfunction asses­sed as SOFA score at admission was a stronger predictor for hospital mortality for women than for men. The discrepancy was related to the SOFA coagulation-sub score.  Paper III: In this nes­ted case-referent study hyperleptinemia at baseline predicted a first-ever sepsis event, even after adjustment for BMI and other cardiovascular risk factors. Hyperleptinemia in the acute sepsis phase was associated with reduced risk of in-hospital death in men, but associated with increased risk of in-hospital   death in women.  Paper IV: In the same matched cohort as in Paper III high baseline levels of MBL predicted a first ever sepsis event. High MBL levels in the acute phase or an increase from baseline to the acute phase associate with increased in-hospital death in women but not in men. Low MBL levels was not identified as a risk for acute sepsis or in-hospital death. Conclusions. Mortality from severe sepsis is high, equally affecting men and women. There are differences in patient characteristics and inflammatory markers, which associate with in-hospital mortality differentially in men and women. Aspects of gender should be mandatory, and genetic analysis are desired in future sepsis research.

During the early evening of 22 June 2007, a violent tornado impacted the western edge of Elie, Manitoba. This was Canada’s first documented F5 tornado. Three primary research questions were posed: (1) What were the pre-storm environmental conditions on 22 June 2007? (2) How did the storm and associated tornado evolve? (3) How does this event compare to other major tornadic events in Canada and the U.S.? The tornado passed in close proximity to a fixed-location Environment Canada Doppler radar at Woodlands, Manitoba. This allowed for a detailed examination of local mesoscale boundaries that were present prior to and during the event. The Elie tornado was rare in the fact that it looped three times within the main track and it moved approximately 5 km during its 40 minute lifetime causing F5 damage to homes and structures when it was an estimated 50 m wide.

In New Zealand, approximately 10% of births are considered premature, that is less than 37 weeks gestation. With advances in medical technology, young infants are surviving gestation periods as few as 23 weeks. It is expected that many of these severely premature infants will demonstrate some problem in their academic, or cognitive function including language functioning. It is agreed that children who are born severely premature often present with language problems, the nature of the difficulties are not clear. Research examining language abilities that involve cognitive functions such as inference generation have demonstrated that children born prematurely exhibit difficulties with phonologic short-term memory and executive function. Language tasks such as inference understanding require children to integrate real-world knowledge with the linguistic information to generate and produce language that is more complex. The aim of this study was to discover if the language of children born severely premature differs from that of language-age matched peers. This study examined high-level language abilities of school-age children born severely prematurely, specifically, language tasks that involved executive functions including working memory, story inferencing, and recognising absurdities. Six children who were born less than 28 weeks gestation participated in this study. Their results on the above measures were compared to a language-aged matched comparison group, determined by performance on a standardised test. It was hypothesised that the children born severely premature would not differ from their language-age matched peers on measures of general language ability but differences would exist on measures of language processing and inferencing. The findings overall showed little difference between the preterm group and their language-age matched peers on measures except for the measure of chronological age. Although no group difference was found for the measure of working memory, a larger variance on this measure was observed in the preterm group.

To date people with severe and profound intellectual disability have been excluded from participatory research projects. This is often due to complex ethical issues and to concerns about how they would make themselves heard or understood. Razack (1993) suggests that the moral obligation to hear such contributions lies with the listener. This study constitutes an investigation of how such listening occurs with contributors who are labeled as having a severe or profound intellectual disability. Human service practitioners who work closely with, and who constantly find themselves listening to and interpreting for, people with severe and profound intellectual disability were recruited for the study. Five focus groups were conducted with these workers. The study revealed that personal values often underpin the various strategies practitioners employed when listening to people with severe disability. Elements like believing the person has something to say; having the time and perseverance to listen; sharing some common interests/rapport with the person and; being able to minimise the many barriers — physical environment, people, self-attitude — that are instrumental in blocking a listener’s capacity. A model for listening to individuals with severe intellectual disability for the proposes of hearing their story is proposed and implications for further research, policy and practice, and education and training are presented.

Thesis (M.A.)--Baylor University, 2008. / Includes bibliographical references (p. 121-126).

Thesis (M.S. in Meteorology)--Naval Postgraduate School, March 2005. / Thesis Advisor(s): Jeffrey B. Knorr, Carlyle H. Wash. Includes bibliographical references (p. 75-77). Also available online.

Syftet var att studera begreppet akut i avsikt att identifiera dess karaktäristika, förutsättningar och konsekvenser inom ambulanssjukvården. Intresset väcktes då begreppet används i flera olika sammanhang och är individuellt upplevt, vilket kan missuppfattas i kontakten med patient och annan vårdpersonal. Metoden utgjordes av en begreppsanalys och datamaterialet av vetenskapliga artiklar, tidskrifter, läroböcker, uppslagsverk med mera som har med begreppet att göra. I en begreppsanalys förtydligas begreppet genom att man synliggör dess karaktäristika. Genom tydliggöring av begreppets karaktäristika blir det tydligt vad begreppet innebär och vad det inte innebär. Att klargöra ord som ibland används i många sammanhang eller att det är ett vagt begrepp är vanligt inom vårdvetenskapen och kan behöva förtydligas enligt Walker och Avant (2011), för att få fram betydelsen och förhoppningsvis få fram en gemensam innebörd för begreppet. I den lexikala genomgången har lexikon och ordböcker använts. Sammantaget kan man säga att det gemensamma för svenskans och engelskans innebörd av begreppet är främst skarp. Under den litterära analysen har flera utmärkande karaktäristika av begreppet identifierats, detta genom tolkning av de utvalda vetenskapliga artiklarna. I sammanfattningen av begreppet ’akut’ framkommer att det kan beskrivas som en subjektiv upplevelse relaterat till en sjukdom eller tillstånd hos den hjälpsökande personen.

Acute Respiratory Distress Syndrome (ARDS) is an inflammatory disease characterized by pulmonary edema, stiff lungs and hypoxemia. Patients with ARDS are more susceptible to VILI (ventilator induced lung injury). Under mechanical ventilation, lung stress and strain are the main determinants of VILI and in patients with muscle effort patient-ventilator asynchrony may enhance this phenomenon. Ventilation modes PCV and VCV with auto-flow can minimize patient-ventilator asynchrony, but then can liberate the offer of flow and tidal volume, compromising the protective ventilatory strategy in ARDS. This study aimed to evaluate the influence of muscle effort and patient-ventilator asynchrony on pulmonary stress and strain in a mechanic lung model of acute respiratory distress syndrome. An experimental bench study was performed, using a lung simulator, ASL 5000TM, in which was configured a lung model with restrictive respiratory mechanics with complacency of 25ml/cmH2O and resistance of 10 cmH2O/L/sec. Muscle effort was adjusted in three situations: no muscular effort (Pmus = 0), with inspiratory muscle effort (Pmus = -5 cmH2O) and inspiratory and expiratory effort (Pmus = -5/+5 cmH2O), all with breathe rate (b) of 20 bpm. Five ventilators were connected to the simulator through and endotracheal tube No 8.0 mm and adjusted on VCV, VCV with Auto-flowTM (in the ventilator in which it was available) and PCV modes, all with tidal volume (VT): 420 ml, PEEP: 10 cmH2O and breath rate set in two situations: b = 15 bpm (lower than b of the respiratory muscle effort) and b = 25 bpm (higher than b of the respiratory muscle effort). Variables analyzed were: maximum VT, alveolar pressure at the end of inspiration, effective PEEP, driving pressure, transpulmonary pressure at the end of inspiration and expiration, average transpulmonary pressure, inspiratory peak flow and analysis of mechanic curves. In the studied lung model the b of the ventilator adjusted higher of the b of the patient and not the muscle effort was the main determinant for the development of patient-ventilator asynchrony, causing large variations of the VT and pulmonary pressures, intensifying the lung stress and strain. The ventilatory modes had similar behavior, although VCV Auto-flowTM and PCV have presented slightly higher values of VT and pulmonary pressures. Thus it is concluded that the proper adjustment of the programed breath rate in the assisted/controlled modes can minimize patient-ventilator asynchrony, reducing lung stress and strain. / A SÃndrome da AngÃstia RespiratÃria Aguda (SARA) à uma doenÃa inflamatÃria caracterizada por edema pulmonar, pulmÃes rÃgidos e hipoxemia. Pacientes com SARA estÃo mais suscetÃveis à VILI (ventilator induced lung injury). Sob ventilaÃÃo mecÃnica, o stress e o strain pulmonares sÃo os principais determinantes da VILI e nos pacientes com esforÃo muscular a assincronia paciente-ventilador pode potencializar este fenÃmeno. Os modos ventilatÃrios PCV e VCV com AutoFlow podem minimizar a assincronia paciente-ventilador, mas por outro lado podem liberar a oferta de fluxo e volume corrente, comprometendo a estratÃgia ventilatÃria protetora na SARA. Objetivou-se avaliar as influÃncias do esforÃo muscular e da assincronia paciente-ventilador sobre o âstrainâ e o âstressâ pulmonares em modelo pulmonar mecÃnico de sÃndrome da angÃstia respiratÃria aguda. Foi realizado um estudo experimental de bancada, utilizando um simulador de pulmÃo, ASL 5000 no qual foi configurado um modelo pulmonar com mecÃnica respiratÃria restritiva, com complacÃncia de 25ml/cmH2O e resistÃncia de 10 cmH2O/L/sec. O esforÃo muscular foi ajustado em trÃs situaÃÃes: sem esforÃo muscular (Pmus=0), com esforÃo muscular inspiratÃrio (Pmus= -5cmH2O) e esforÃo inspiratÃrio e expiratÃrio (Pmus= -5/+5 cmH2O), todos com frequÃncia respiratÃria (f) de 20rpm. Ao simulador foram conectados cinco ventiladores atravÃs de um tubo orotraqueal n 8,0 mm e ajustados nos modos VCV, VCV com sistema AutoFlow (no ventilador que tinha o sistema disponÃvel) e PCV, todos com volume corrente (VC): 420 ml, PEEP: 10 cmH2O e frequÃncia respiratÃria programada em duas situaÃÃes: f=15rpm (< que a f de esforÃo muscular respiratÃrio) e f=25rpm (> que a f de esforÃo muscular respiratÃrio). As variÃveis analisadas foram: VC mÃximo, a pressÃo alveolar no final da inspiraÃÃo, PEEP efetiva, driving pressure, pressÃo transpulmonar no final da inspiraÃÃo e expiraÃÃo, pressÃo transpulmonar mÃdia, pico de fluxo inspiratÃrio e anÃlise das curvas de mecÃnica. No modelo pulmonar estudado a f do ventilador pulmonar ajustada acima da f do paciente e nÃo o esforÃo muscular o principal determinante para o desenvolvimento de assincronia paciente ventilador, causando grandes variaÃÃes de VC e pressÃes pulmonares, o que intensificou o stress e strain pulmonares. Os modos ventilatÃrios tiveram comportamento semelhante, embora os modos VCV AutoFlow e PCV tenham apresentado valores discretamente maiores de VC e pressÃes pulmonares. Desta forma conclui-se que o ajuste adequado da frequÃncia programada nos modos assistido/controlado podem pode minimizar a assincronia paciente ventilador reduzindo o stress e strain pulmonares. Palavras-

Masters of Science / The Coronaviridae family consists of RNA viruses within the order Nidovirales. The family is classified into two genera, namely the corona- and toroviruses. Coronaviruses are enveloped, single stranded, positive sense RNA viruses with genomes ranging between 27-32kb in size. The 5’ two-thirds of the genome encodes for the 1a/b polyprotein, while the 3’ one-third of the genome encodes for the structural proteins that mediate viral entry into the host cell. These structural proteins include the spike (S), envelope (E), membrane (M) and nucleocapsid (N) proteins. The nucleocapsid protein is expressed at high levels within an infected cell. Studies have shown that this protein plays a key regulatory role in different cellular pathways, including the inhibition of interferon production and the up-regulation of the AP1 signal transduction pathway, amongst others. Also, the N protein is vital in the formation of the ribonucleocapsid core by binding to the viral RNA during virion assembly. The focus of this study is the immune response in whole blood cultures to the presence of human coronavirus (HCoV) NL63 N protein. To characterise the stimulation of the immune activity against HCoV-NL63 N in blood cultures, the HCoV-NL63 N gene was expressed in a bacterial system. In this pilot study, GSTtagged N constructs were then purified and used to treat whole blood cultures from three volunteers. ELISAs were used to measure the cytokine response in these treated whole blood cultures. Results showed that the nucleocapsid protein has an inflammatory response on whole blood cultures. These results have generated vital information in the potential function of the HCoV-NL63 N protein on the immune system. It is suffice to say that the HCoV-NL63 N protein is able to elicit an effective inflammatory response within the host cell. Future studies into the cellular pathways affected by the HCoV-NL63 N protein will clarify its exact role in stimulating the host immune system.

Kyoto University (京都大学) / 0048 / 新制・課程博士 / 博士(工学) / 甲第16502号 / 工博第3495号 / 新制||工||1529(附属図書館) / 29159 / 京都大学大学院工学研究科材料工学専攻 / (主査)教授 辻 伸泰, 教授 白井 泰治, 教授 乾 晴行 / 学位規則第4条第1項該当