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Biophysical characterisation of two mutations causing long QT syndrome and Brugada syndromeHuang, Hai 11 April 2018 (has links)
Le syndrome du QT long (LQTs) et le syndrome de Brugada (BS) sont deux maladies cardiaques héréditaires, pouvant causer la mort subite en relation avec des torsades de pointe dues à une fibrillation ventriculaire. SCN5A est le gène codant pour la sous-unité a du canal Na4 dépendant du voltage, exprimé dans le cœur humain. Objectif : Dans la présente étude, deux mutations (R1193Q et F1344S) dans le gène SCN5A ont été identifiées. La mutation R1193Q a été trouvée chez deux patients après le test de provocation à la procainamide par voie intraveineuse. Un des patients est atteint de BS et l'autre est atteint à la fois de BS et de LQTs. La mutation F1344S a été trouvée chez un autre patient atteint uniquement de BS. Méthode : Les canaux mutants ont été exprimés dans un système d'expression de mammifère (lignée cellulaire tsA 201) et les propriétés biophysiques ont été étudiées avec la technique de patch clamp en configuration cellule entière. Résultats : L'analyse des séquences montre un changement de G à A à la position 3587 sur l'exon 20. La mutation RI 193Q montre un déplacement négatif de 5mV de l'inactivation et un courant Na+ persistant. Le déplacement vers des potentiels négatifs de l'inactivation est responsable d'une perte de fonction causant l'élévation du segment ST chez le patient atteint de BS. La présence du courant persistant est responsable du gain de fonction causant l'augmentation de l'intervalle QT chez le patient avec LQTs. La mutation F1344S montre une manifestation typique de BS sur l'électrocardiogramme pendant une période de fièvre. Le séquençage a révélé un changement de T à C à la position 4031 sur l'exon 23. L'analyse biophysique montre une perte de fonction due au déplacement de la courbe d'activation vers des potentiels positifs à 23°C et ce déplacement est exacerbé à 40.5°C avec une pente plus lente. Conclusion : Les différentes manifestations cliniques de ces deux mutations sont la conséquence des anormalités électrophysiologiques distinctes du canal Na+ cardiaque mutant décrites dans cette étude. Pour les patients porteurs de R1193Q, la prescription de quelques drogues pouvant provoquer le LQTs et le BS doit être limitée. Pour éviter les épisodes de fibrillation ventriculaire, l'hyperthermie doit être contrôlée chez les patients porteurs de la mutation F1344S. / Long QT syndrome (LQTs) and Brugada syndrome (BS) are two distinct hereditary cardiac diseases, causing sudden cardiac death related to torsade de pointes and ventricular tachycardia (VT) / ventricular fibrillation (VF). SCN5A is the gene encoding the principal voltage-gated Na+ channel a-subunit, which is only expressed in the human heart. Objective: In present study, two mutations (R1193Q and F1344S) in SCN5A have been identified. RI 193Q mutation was found in two patients, one with BS and another with an overlap of BS and LQTs after the intravenous procainamide test. F1344S mutation was found in another patient with BS. Method: The mutant channels were expressed in a mammalian expression System (tsA 201 cell Une) and the biophysical properties were studied by the patch clamp technique with whole cell configuration. Results: The sequence analysis showed a G to A base change at position 3587 in exon 20. The R1193Q mutation produced a negative shift for 5 mV of inactivation and a persistent Na+ current. The negative shift of inactivation is responsible for loss of the function, leading to ST segment elevation in BS. The persistent Na+ current is responsible for gain of function, causing QT interval prolongation in LQTs. The F1344S mutation presented a typical BS manifestation on ECG during fever period. The sequencing analysis revealed a T to C base change at position 4031 in exon 23. The biophysical analysis showed loss of function due to significantly positive shift of activation at both 23°C and 40.5°C, but the shift was more important at 40.5°C with a slower slope factor. Conclusion: The different clinical manifestations of these two mutations probably derive from the distinct electrophysiological abnormalities of the mutant cardiac Na+ channels reported in this study. For patients with RI 193Q mutation, some drugs that likely precipitate LQTs and BS should be limited to prescribe. To prevent from VT/VF events, hyperthermia should be effectively controlled in the patients with F1344S mutation.
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PREHISTORIC AGRICULTURAL ADAPTATION AND SETTLEMENT IN LONG HOUSE VALLEY, NORTHEASTERN ARIZONA.HARRILL, BRUCE GILBERT. January 1982 (has links)
A recently completed intensive archaeological survey of Long House Valley in northeastern Arizona has provided a detailed body of data on prehistoric settlement distribution and environmental variation. Long House Valley was occupied between A.D. 1 and 1300 by prehistoric agriculturalists referred to as the Kayenta Anasazi. This study examines the changing relationship between settlement locations and agricultural adaptations from A.D. 500 to 1300 in Long House Valley. As part of this analysis, the archaeological, ethnographic, and environmental background of the Kayenta region is reviewed as a basis for understanding the nature of agricultural adaptation in this region. Agricultural practices of the Hopi Indians of northern Arizona provide the basis for a model of probable agricultural field locations. This combined with an examination of the physiographic, hydrographic, and edaphic features in the valley allow identification of potential field areas. Changes in the potential of identified field areas are postulated on the basis of variation in available moisture as determined from a regional dendroclimatic reconstruction. Prehistoric habitation site locations and their changing distribution through time are examined against these proposed changes in field potential. This study demonstrates that there is a distinct positive correlation between settlement location and potential field location as determined by available moisture. Beginning about A.D. 1150 deteriorating environmental conditions in the form of decreased moisture, arroyo cutting, and lowered water table are considered the primary determinants of changes in site locations. These changes are viewed as an adaptive response by the Kayenta Anasazi to conditions of decreased moisture. Continuing deterioration of the environment made the practice of agriculture impossible and resulted in the total abandonment of Long House Valley and the entire Kayenta region by A.D. 1300.
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Daughterhood to motherhood: The impacts of childhood exposure to family violence on subsequent mothering.Mendis, Kathy, kamen3@bigpond.com.au January 2006 (has links)
Research indicates children's exposure to family violence results in long-term negative consequences, hindering social skill development and impacting on the ability to function as healthy, productive adults. Also, there exists a widely accepted theory, called the 'cycle of violence', which hypothesises that children who have experienced violence at the hands of their parents tend to grow up to become violent parents themselves. Some evidence for this theory has been found following research with groups of abusive parents and people who have committed crimes, This study explores the specific impacts of childhood exposure to family violence on the subsequent mothering of a group of women drawn from the general population. A qualitative approach using a methodology that combined feminist and narrative approaches was used. Nine women who have been exposed to family violence in childhood including physical, emotional/psychological, sexual abuse and witness to violence between parents participated in interviews which explored their experiences of mothering
Each woman was interviewed twice to collect stories of childhood and of mothering experiences. These were analysed revealing that the women's mothering was affected by their childhood exposure to family violence in several ways, ranging from direct emotional impacts to indirect impacts of conceptualisations formed in the light of childhood experiences. This study adds to the existing knowledge of the long-term impacts of childhood exposure to family violence by focussing specifically on subsequent mothering. The findings encourage social work and health care personnel to appreciate that women exposed to family violence in childhood have specific issues with their mothering and there is a need to address these issues. It also challenges the weight given to the cycle of violence theory in intervention and prevention strategies in child abuse and family violence sectors
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Financial impact of the Medicare prospective payment system on long term acute care hospitals.Saqr, Hatem A. Mikhail, Osama. Bressler, Jan. January 2007 (has links)
Thesis (M.P.H.)--University of Texas Health Science Center at Houston, School of Public Health, 2007. / Source: Masters Abstracts International, Volume: 46-01, page: 0311. Adviser: Osama Mikhail. Includes bibliographical references.
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Effect of the Garmin Forerunner on threshold pace for intercollegiate distance runners /Smith, Jacob W. January 2009 (has links)
Master's thesis - - State University of New York College at Cortland, 2009 - - Department of Kinesiology. / Includes bibliographical references (p. 25-7).
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Exploring the uses of mental skills by competitive road running athletesNgobese, Khayelihle Mbongeleni Emmanuel January 2015 (has links)
Research on athletes has shown that mental skills are an important component of being a successful athlete. The importance of these mental skills is seen in the number of athletes who have formally started training using mental skills training programmes (MST) according to the literature. The study of mental skills in South Africa lags behind other countries like USA, UK and Sweden. This particular study explored the use of mental skills by road running athletes. The study was conducted with six competitive marathon athletes. Semi-structured interviews were conducted as part of an elaborate qualitative methodology design. The data collected from these semi-structured interviews was analysed using thematic analysis. The results show that road running athletes use mental skills that include; mental rehearsal, planning, goal setting and self-talk. The athletes in this research showed the importance of mental skills and it is recommended that formal training in these mental skills will be highly beneficial not only to road running athletes but for all South African sports people in general
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Organizational Structural and Cultural Variables as Predictors of Quality in Federally Approved Nursing Homes.Desormeaux, Lorraine V 14 December 2002 (has links) (PDF)
The purpose of this study was to determine the extent to which nursing home organizational structure and cultural variables were related to the outcomes reported by the Health Care Finance Administration public use data set (HCFA-NHCD). A second purpose was to examine the effects of a new style of nursing home management called the Eden Alternative™ concept. A related purpose was to test the usefulness of the HCFA-NHCD in predicting the quality of care for residents in federally approved nursing homes. Secondary data analysis was conducted on the HCFA-NHCD, as published in December 2001. Descriptive statistics and measures of association were used to assess the degree of relationship between the organizational structure and culture variables and the eight clinical health indicators of the HCFA-NHCD. Multiple regression analyses were conducted to measure the impact of the organizational structure and culture variables on the quality of care for residents in federally approved nursing homes.
When compared with previously collected statistics, these findings suggest that there is a nationwide trend towards smaller nursing homes; smaller Eden homes were associated with a higher level of individualized attention. Smaller Eden homes with council representation had better scores on a majority of the eight clinical health indicators when compared to their counterparts with no council representation. Council representation was inversely related to a nursing homes' reliance on RN and LPLVN services. However, a regression model assessing the impact of organizational structure and cultural variables on the quality of care for residents in federally approved nursing homes had very limited predictive power (R2=2.2%). The findings of this study suggest that quality improvements in the HCFA-NHCD are needed in order to better serve families.
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Time-dependent behaviour of fibre reinforced polymer (FRP) bars and FRP reinforced concrete beams under sustained load / Le comportement à long terme des barres en polymères renforcés de fibres (PRF) et des poutres en béton armées avec des barres en PRF sous charge permanenteYoussef, Tarik A January 2010 (has links)
An extensive experimental/research program has taken place at the University of Sherbrooke FRP Durability Facility. The program, consisting of four phases, studies the creep performance of FRP bars as well as the overall long-term behaviour of FRP reinforced concrete beams. Phase 1 deals with the creep performance of two types of GFRP bars subjected to different levels of sustained axial load; causing creep rupture at higher levels. In Phase 2, six different types of GFRP bars are tested under two levels of allowable service load, according to the currently available North American standards. The test duration, for the two phases, exceeded 10000 hours (417 days) wherein regular monitoring' of creep strain evolution took place and. the creep coefficient of GFRP bars was calculated. Residual tensile tests and microstructural analysis followed the long-term testing period. It was found that 45 % of the GFRP bars' tensile strength, fu,ave , is a safe limit for GFRP exhibiting sustained load, in standard laboratory conditions. Microstructural analysis shows that the increase in creep strain, after the 10000 hour period, is negligible for GFRP bars under allowable service load. Phase 3 consists of twenty reinforced concrete beams (ten pairs) comprising GFRP, CFRP, and steel reinforcing bars. The dimensions of which are 100 mm x 150 mm x 1800 mm, installed under third-point sustained load, for a period exceeding one year. Exhibiting a maximum applied moment of 25 % of their nominal moment capacity, Mn , all beams were regularly monitored in terms of (i) time-dependent deflection, (ii) strain increase in concrete and reinforcement and (iii) crack widths. Theoretical predictions for immediate deflection were calculated, using three methods (ACI 440.1R-06, CAN/CSA S806-02 and the ISIS Canda Design Manual (2007)), and compared to the obtained experimental results. Results showed that the calculations, regarding immediate deflection, under estimate by 67 %; underestimate by 10 %; overestimate by 11 %, for the aforementioned methods, respectively. The long-term to immediate deflection ratio, .l, was calculated for all beams and compared to ACI 440.1R-06 and CAN/CSA S806-02 predictions. Results showed that the North American standards are conservative as regards long-term deflection prediction. Immediate crack width results were compared to the prediction equations adopted by ACI 440.1R-06 and CAN/CSA S6-06, on the one hand, and by the ISIS Canada Design Manual (2007) on the other hand. Satisfactory results were found when the k b bond-coefficient factor is taken as 1.2 and 1.0, respectively. From the obtained data, the time-dependent kt multiplier, accounting for crack width increase after one year, was deduced as 1.7 and 1.5 for both models, respectively. Phase 4 deals with four full-scale GFRP reinforced concrete beams, of dimensions (215 mm x 400 mm x 4282 mm), subjected to uniform distributed load for a period of six months. Sizeable concrete blocks (of dimensions 610 mm x 762 mm x 1219 mm and weight = 13334 kN) were arranged on top of the beams to simulate sustained uniform distributed load. The main study parameters, of this phase, are (i) bottom reinforcement ratio and (ii) type of upper/compression reinforcement (GFRP and/or steel). The applied moment ranges from 15 to 21 % of the nominal moment capacity for the beams. Numerical modelling took place using a computer program (Fortran-2003) based on the age-adjusted effective modulus method, to predict the long-term deflection of the beams. The creep and shrinkage coefficients were calculated based on the ACI Committee 209 recommendations (1992) and CEB-FIP Model Code (1990). The theoretical curves were in very good agreement with the measured values. Furthermore, the empirical models available in ACI 440.1R-06 and CAN/CSA S806-02 were used for long-term deflection prediction. These predictions showed that both models can serve as upper bound and lower bound limits for the measured long-term deflection curves, respectively. As regards crack width prediction, the equations adopted by ACI 440.1R-06 (same as that of CAN/CSA S6-06) and by the ISIS Canada Design Manual (2007) yield satisfactory results when the kb bond-coefficient factor is 1.2 and 1.0 respectively (similar to phase 3). For both equations the time-dependent kt multiplier is deduced as 1.4, after six months.--Résumé abrégé par UMI.
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Adapting cognitive behavioural therapy interventions for anxiety or depression to meet the needs of people with long-term physical health conditions : a mixed-methods studyHadert, Aimee January 2013 (has links)
Objective(s). An increasing demand exists for psychological interventions to increase recovery from depression and anxiety in people with long-term physical health conditions (LTCs). Guided self-help (GSH) may meet this need, however, there is limited evidence of GSH’s appropriateness for people with LTCs. Design. A mixed-methods study using qualitative interviews with people with stroke and Chronic Obstructive Pulmonary Disease (COPD), and a quantitative survey of professionals who support guided self-help, explored opinions about whether self-help is appropriate, and whether suggested adaptations varied across LTCs. Results. Opinions varied about the appropriateness of standard self-help and adaptations required. Illness beliefs may help explain differences between the two LTCs and individual interviewees. The majority of professionals surveyed felt competent supporting people with LTCs, and reported having access to appropriate self-help material. Conclusions. Recommendations for improving the appropriateness of contents of guided self-help for people with LTCs are provided. Supporting professionals need relevant knowledge and skills to integrate information about the LTC into the intervention, and offer flexible, personalised delivery to support participation.
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Nephropathic cystinosis associated with cardiomyopathy: A 27-year clinical follow-upDixit, Mehul, Greifer, Ira January 2002 (has links)
BACKGROUND:Nephropathic cystinosis is an autosomal recessive disease resulting from intracellular accumulation of cystine leading to multiple organ failure.CASE REPORT:We describe the clinical course of a patient managed from the age of six until his death at the age of 33 years. He underwent multiple surgery, including two renal transplants, developed transplant renal artery stenosis that was managed medically, and progressive heart failure at the age of 33 years. His death from a ruptured pseudoaneurysm associated with a restrictive cardiomyopathy is noteworthy. A limited cardiac autopsy revealed the presence of cystine crystals in interstitial cardiac histiocytes and one myocardial cell, along with 1000-fold higher tissue cystine content of the left ventricular myocardium compared to patients without cystinosis, suggesting the possibility of direct cystine mediated metabolic injury.
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