Self-reported fatigue and associated factors six years after stroke

Several studies have found that fatigue is one of the most commonly reported symptoms after stroke and the most difficult to cope with. The present study aimed to investigate the presence and severity of self-reported fatigue six years after stroke onset and associated factors. The cohort "Life After Stroke Phase I" (n = 349 persons) was invited at six years to report fatigue (Fatigue Severity Scale 7-item version), perceived impact of stroke and global recovery after stroke (Stroke Impact Scale), anxiety and depression (Hospital Anxiety and Depression Scale), life satisfaction (Life Satisfaction Checklist) and participation in everyday social activities (Frenchay Activities Index). At six years 37% of the 102 participants in this cross-sectional study reported fatigue. The results showed that in nearly all SIS domains the odds for post-stroke fatigue were higher in persons with a higher perceived impact. Furthermore, the odds for post-stroke fatigue were higher in those who had experienced a moderate/severe stroke and had signs of depression and anxiety. Fatigue is still present in one-third of persons as long as six years after stroke onset and is perceived to hinder many aspects of functioning in everyday life. There is an urgent need to develop and evaluate interventions to reduce fatigue.

Size-selective mortality and environmental factors affecting early marine growth during early marine life stages of sub-yearling Chinook salmon in Puget Sound, Washington

Thesis (Master's)--University of Washington, 2016-08

Ecological drivers of a vector borne pathogen: distribution and abundance of Borrelia burgdorferi sensu lato and its vector Ixodes ricinus in Scotland

Vector-borne disease emergence in recent decades has been associated with different environmental drivers including changes in habitat, hosts and climate. Lyme borreliosis is among the most important vector-borne diseases in the Northern hemisphere and is an emerging disease in Scotland. Transmitted by Ixodid tick vectors between large numbers of wild vertebrate host species, Lyme borreliosis is caused by bacteria from the Borrelia burgdorferi sensu lato species group. Ecological studies can inform how environmental factors such as host abundance and community composition, habitat and landscape heterogeneity contribute to spatial and temporal variation in risk from B. burgdorferi s.l. In this thesis a range of approaches were used to investigate the effects of vertebrate host communities and individual host species as drivers of B. burgdorferi s.l. dynamics and its tick vector Ixodes ricinus. Host species differ in reservoir competence for B. burgdorferi s.l. and as hosts for ticks. Deer are incompetent transmission hosts for B. burgdorferi s.l. but are significant hosts of all life-stages of I. ricinus. Rodents and birds are important transmission hosts of B. burgdorferi s.l. and common hosts of immature life-stages of I. ricinus. In this thesis, surveys of woodland sites revealed variable effects of deer density on B. burgdorferi prevalence, from no effect (Chapter 2) to a possible ‘dilution’ effect resulting in lower prevalence at higher deer densities (Chapter 3). An invasive species in Scotland, the grey squirrel (Sciurus carolinensis), was found to host diverse genotypes of B. burgdorferi s.l. and may act as a spill-over host for strains maintained by native host species (Chapter 4). Habitat fragmentation may alter the dynamics of B. burgdorferi s.l. via effects on the host community and host movements. In this thesis, there was lack of persistence of the rodent associated genospecies of B. burgdorferi s.l. within a naturally fragmented landscape (Chapter 3). Rodent host biology, particularly population cycles and dispersal ability are likely to affect pathogen persistence and recolonization in fragmented habitats. Heterogeneity in disease dynamics can occur spatially and temporally due to differences in the host community, habitat and climatic factors. Higher numbers of I. ricinus nymphs, and a higher probability of detecting a nymph infected with B. burgdorferi s.l., were found in areas with warmer climates estimated by growing degree days (Chapter 2). The ground vegetation type associated with the highest number of I. ricinus nymphs varied between studies in this thesis (Chapter 2 & 3) and does not appear to be a reliable predictor across large areas. B. burgdorferi s.l. prevalence and genospecies composition was highly variable for the same sites sampled in subsequent years (Chapter 2). This suggests that dynamic variables such as reservoir host densities and deer should be measured as well as more static habitat and climatic factors to understand the drivers of B. burgdorferi s.l. infection in ticks. Heterogeneity in parasite loads amongst hosts is a common finding which has implications for disease ecology and management. Using a 17-year data set for tick infestations in a wild bird community in Scotland, different effects of age and sex on tick burdens were found among four species of passerine bird (Chapter 5). There were also different rates of decline in tick burdens among bird species in response to a long term decrease in questing tick pressure over the study. Species specific patterns may be driven by differences in behaviour and immunity and highlight the importance of comparative approaches. Combining whole genome sequencing (WGS) and population genetics approaches offers a novel approach to identify ecological drivers of pathogen populations. An initial analysis of WGS from B. burgdorferi s.s. isolates sampled 16 years apart suggests that there is a signal of measurable evolution (Chapter 6). This suggests demographic analyses may be applied to understand ecological and evolutionary processes of these bacteria. This work shows how host communities, habitat and climatic factors can affect the local transmission dynamics of B. burgdorferi s.l. and the potential risk of infection to humans. Spatial and temporal heterogeneity in pathogen dynamics poses challenges for the prediction of risk. New tools such as WGS of the pathogen (Chapter 6) and blood meal analysis techniques will add power to future studies on the ecology and evolution of B. burgdorferi s.l.

Protein quality and distribution determines anabolic signaling, cellular energetics, and body composition

Building and maintaining muscle is critical to the quality of life for adults and elderly. Physical activity and nutrition are important factors for long-term muscle health. In particular, dietary protein – including protein distribution and quality – are under-appreciated determinants of muscle health for adults. The most unequivocal evidence for the benefit of optimal dietary protein at individual meals is derived from studies of weight management. During the catabolic condition of weight loss, higher protein diets attenuate loss of lean tissue and partition weight loss to body fat when compared with commonly recommended high carbohydrate, low protein diets. Muscle protein turnover is a continuous process in which proteins are degraded, and replaced by newly synthesized proteins. Muscle growth occurs when protein synthesis exceeds protein degradation. Regulation of protein synthesis is complex, with multiple signals influencing this process. The mammalian target of rapamycin (mTORC1) pathway has been identified as a particularly important regulator of protein synthesis, via stimulation of translation initiation. Key regulatory points of translation initiation effected by mTORC1 include assembly of the eukaryotic initiation factor 4F (eIF4F) complex and phosphorylation of the 70 kilodalton ribosomal protein S6 kinase (S6K1). Assembly of the eIF4F initiation complex involves phosphorylation of the inhibitory eIF4E binding protein-1 (4E-BP1), which releases the initiation factor eIF4E and allows it to bind with eIF4G. Binding of eIF4E with eIF4G promotes preparation of the mRNA for binding to the 43S pre-initiation complex. Consumption of the amino acid leucine (Leu) is a key factor determining the anabolic response of muscle protein synthesis (MPS) and mTORC1 signaling to a meal. Research from this dissertation demonstrates that the peak activation of MPS following a complete meal is proportional to the Leu content of a meal and its ability to elevate plasma Leu. Leu has also been implicated as an inhibitor of muscle protein degradation (MPD). In particular, there is evidence suggesting that in muscle wasting conditions Leu supplementation attenuates expression of the ubiquitin-proteosome pathway, which is the primary mode of intracellular protein degradation. However, this is untested in healthy, physiological feeding models. Therefore, an experiment was performed to see if feeding isonitrogenous protein sources with different Leu contents to healthy adult rats would differentially impact ubiquitin-proteosome (protein degradation) outcomes; and if these outcomes are related to the meal responses of plasma Leu. Results showed that higher Leu diets were able to attenuate total proteasome content but had no effect on ubiquitin proteins. This research shows that dietary Leu determines postprandial muscle anabolism. In a parallel line of research, the effects of dietary Leu on changes in muscle mass overtime were investigated. Animals consuming higher Leu diets had larger gastrocnemius muscle weights; furthermore, gastrocnemius muscle weights were correlated with postprandial changes in MPS (r=0.471, P<0.01) and plasma Leu (r=0.400, P=0.01). These results show that the effect of Leu on ubiquitin-proteosome pathways is minimal for healthy adult rats consuming adequate diets. Thus, long-term changes in muscle mass observed in adult rats are likely due to the differences in MPS, rather than MPD. Factors determining the duration of Leu-stimulated MPS were further investigated. Despite continued elevations in plasma Leu and associated translation initiation factors (e.g., S6K1 and 4E-BP1), MPS returned to basal levels ~3 hours after a meal. However, administration of additional nutrients in the form of carbohydrate, Leu, or both ~2 hours after a meal was able to extend the elevation of MPS, in a time and dose dependent manner. This effect led to a novel discovery that decreases in translation elongation activity was associated with increases in activity of AMP kinase, a key cellular energy sensor. This research shows that the Leu density of dietary protein determines anabolic signaling, thereby affecting cellular energetics and body composition.

Quality of life after first-ever stroke: An interviewbased study from Blantyre, Malawi

Background In post-stroke patients, impairment of quality of life (QOL) has been associated with functional impairment, age, anxiety, depression, and fatigue. Good social support, higher education, and better socioeconomic status are associated with better QOL among stroke survivors. In Africa, studies from Nigeria and Tanzania have reported on post-stroke QOL. Aim The aim of this study was to describe QOL more than six months after first-ever stroke in Malawi. Methods This was an interview-based study about a stroke-surviving cohort. Adult patients were interviewed six or twelve months after their first ever stroke. HIV status, modified stroke severity scale (mNIHSS) score, and brain scan results were recorded during the acute phase of stroke. At the time of the interviews, the modified Rankin scale (mRS) was used to assess functional outcome. The interviews applied the Newcastle Stroke-specific Quality of Life Measure (NEWSQOL). All the data were analysed using Statview™: the X2 test compared proportions, Student’s t-test compared means for normally distributed data, and the Kruskal-Wallis test was used for nonparametric data. Results Eighty-one patients were followed up at least six months after the acute stroke. Twenty-five stroke patients (ten women) were interviewed with the NEWSQOL questionnaire. Good functional outcome (lower mRS score) was positively associated with better QOL in the domains of activities of daily living (ADL)/self-care (p = 0.0024) and communication (p = 0.031). Women scored worse in the fatigue (p = 0.0081) and cognition (p = 0.048) domains. Older age was associated with worse QOL in the ADL (p = 0.0122) domain. Seven patients were HIV-seroreactive. HIV infection did not affect post-stroke QOL. Conclusion In Malawi, within specific domains, QOL after stroke appeared to be related to patients’ age, sex, and functional recovery in this small sample of patients.

Longitudinal distribution and lateral pattern of megalopal settlement and juvenile recruitment of Carcinus maenas (L.) (Brachyura, Portunidae) in the Mira River Estuary, Portugal

Settlement is a critical process in the life history of crabs, and thus affecting the abundance, distribution and structure of estuarine communities. The spatial pattern of settlement of megalopae of the shore crab Carcinus maenas along a longitudinal estuarine gradient (Mira River Estuary, Portugal) was examined, as well as its effects on the juvenile population. To measure megalopal settlement, four replicate collectors were deployed in six equally spaced stations along the estuarine axis. Juveniles were collected on the same locations with a quadrat randomly deployed on the substrate. To assess fine-scale megalopal settlement within a curved region of the estuary, replicate collectors were deployed on both margins along Moinho da Asneira curve. Megalopae settled differently along the six longitudinal points, with a tendency to attenuate their settlement upstream. Within the curved region, megalopae preferentially settled on the left margin collectors, probably due to the weaker velocity speeds felt on this margin. Concerning the overall juvenile density, there were significant differences among the stations distributed along the estuary, but they did no reflect a longitudinal dispersion attenuation pattern. Size-frequency distribution of the juvenile population showed that the average size is higher on the left margin. Recruits (carapace length between 1.0 mm and 3.4 mm) were more abundant on the upstream stations. Density of early juveniles (3.4 mm-6.5 mm) and juveniles (6.5 mm-10 mm) was more stable throughout the estuary axis than that of recruits. This distribution pattern may result from tidal excursion processes or mechanisms to avoid biotic interactions, such as predation and competition. (c) 2006 Elsevier Ltd. All rights reserved.

Fitting phase type distribution to service process with sequential phases

The work of this thesis is concerned with fitting Hypo-exponential and Erlang phase type distributions for modeling real life processes with non-exponential service time. There exist situations where exponential distributions cannot explain the distribution of service time properly. This thesis presents the application of two traditional statistical estimation techniques to approximate the service distributions of processes with coefficient of variation less than one. It also presents an algorithm to fit Hypo-exponential distribution for complex situations which can’t be handled properly with traditional estimation techniques. The result shows the effect of variation of sample size and other parameters on the efficiency of the estimation techniques by comparing their respective outputs. Furthermore it checks how accurately the proposed algorithm approximates a given distribution.

Spatial distribution patterns and movements of Holothuria arguinensis in the Ria Formosa (Portugal)

Holothurian populations are under pressure worldwide because of increasing demand for beche-de-mer, mainly for Asian consumption. Importations to this area from new temperate fishing grounds provide economic opportunities but also raise concerns regarding future over-exploitation. Studies on the habitat preferences and movements of sea cucumbers are important for the management of sea cucumber stocks and sizing of no-take zones, but information on the ecology and behavior of temperate sea cucumbers is scarce. This study describes the small-scale distribution and movement patterns of Holothuria arguinensis in the intertidal zone of the Ria Formosa national park (Portugal).Mark/recapture studieswere performed to record theirmovements over time on different habitats (sand and seagrass). H. arguinensis preferred seagrass habitats and did not show a size or life stage-related spatial segregation. Its density was 563 ind. ha−1 and mean movement speed was 10 m per day. Movement speed did not differ between habitats and the direction of movement was offshore during the day and shoreward during the night. Median home range size was 35 m2 and overlap among home ranges was 84%. H. arguinensis' high abundance, close association with seagrass and easy catchability in the intertidal zone, indicate the importance of including intertidal lagoons in future studies on temperate sea cucumber ecology since those systems might require different management strategies than fully submerged habitats.

Exposure to Stressful Life Events and Lung Cancer Risk

Objectif: Examiner l’association entre l'exposition aux évènements stressants de la vie et le cancer du poumon. Méthodes: Les données proviennent d’une étude cas-témoins, menée chez les hommes et les femmes vivant dans la région métropolitaine de Montréal entre 1996 et 2001. Le cancer du poumon d’un cas éligible devait être confirmé histologiquement à l’un des 18 hôpitaux de cette région. Les témoins ont été sélectionnés aléatoirement de la liste électorale du Québec et ont été appariés au cas par fréquence de groupes d'âge et par sexe. Un questionnaire a été administré en entrevue pour recueillir les données, dont l’évaluation de huit évènements stressants de la vie par le participant. Si le participant avait vécu un évènement stressant ciblé durant les six dernières années, il devait aussi coter cet évènement sur une échelle de trois points. La régression logistique non conditionnelle a été utilisée pour estimer les rapports de cotes ainsi que leurs intervalles de confiance à 95%. Des analyses par sexe, niveau de tabagisme et par type histologique ont été réalisées. Nous avons aussi analysé l’association entre le cancer du poumon et le nombre total d'évènements, les évènements de perte et les évènements socioéconomiques, ainsi que chaque évènement individuellement. Les analyses des scores d'impact autoévalués et avec un score externe de perception, ont également été menées. Résultats: La population de ce projet comprend 1061 cas et 1422 témoins, âgés de 35 à 70 ans. Les participants inclus avaient répondu aux sections du questionnaire portant sur les facteurs de style de vie et sur l'historique de tabagisme. Dans l'ensemble, nous n’avons pas observé d’association entre le cancer du poumon et l'exposition aux évènements stressants de la vie. Nous avons observé une diminution du risque pour les évènements socioéconomiques autoévalués comme peu stressants (RC=0,50; IC 95%= 0,31 - 0,81). Conclusion: Nos résultats suggèrent que les évènements socioéconomiques sont associées à un risque réduit si ces évènements sont considérés comme peu stressant.

Multifunctional Nanoparticles in Cancer: in vitro Characterization, in vivo Distribution

A novel biocompatible and biodegradable polymer, termed poly(Glycerol malate co-dodecanedioate) (PGMD), was prepared by thermal condensation method and used for fabrication of nanoparticles (NPs). PGMD NPs were prepared using the single oil emulsion technique and loaded with an imaging/hyperthermia agent (IR820) and a chemotherapeutic agent (doxorubicin, DOX). The size of the void PGMD NPs, IR820-PGMD NPs and DOX-IR820-PGMD NPs were approximately 90 nm, 110 nm, and 125 nm respectively. An acidic environment (pH=5.0) induced higher DOX and IR820 release compared to pH=7.4. DOX release was also enhanced by exposure to laser, which increased the temperature to 42°C. Cytotoxicity of DOX-IR820-PGMD NPs was comparable in MES-SA but was higher in Dx5 cells compared to free DOX plus IR820 (pIn vivomouse studies showed that NP formulation significantly improved the plasma half-life of IR820 after tail vein injection. Significant lower IR820 content was observed in kidney in DOX-IR820-PGMD NP treatment as compared to free IR820 treatment in our biodistribution studies (p

Exposure to Stressful Life Events and Lung Cancer Risk

Objectif: Examiner l’association entre l'exposition aux évènements stressants de la vie et le cancer du poumon. Méthodes: Les données proviennent d’une étude cas-témoins, menée chez les hommes et les femmes vivant dans la région métropolitaine de Montréal entre 1996 et 2001. Le cancer du poumon d’un cas éligible devait être confirmé histologiquement à l’un des 18 hôpitaux de cette région. Les témoins ont été sélectionnés aléatoirement de la liste électorale du Québec et ont été appariés au cas par fréquence de groupes d'âge et par sexe. Un questionnaire a été administré en entrevue pour recueillir les données, dont l’évaluation de huit évènements stressants de la vie par le participant. Si le participant avait vécu un évènement stressant ciblé durant les six dernières années, il devait aussi coter cet évènement sur une échelle de trois points. La régression logistique non conditionnelle a été utilisée pour estimer les rapports de cotes ainsi que leurs intervalles de confiance à 95%. Des analyses par sexe, niveau de tabagisme et par type histologique ont été réalisées. Nous avons aussi analysé l’association entre le cancer du poumon et le nombre total d'évènements, les évènements de perte et les évènements socioéconomiques, ainsi que chaque évènement individuellement. Les analyses des scores d'impact autoévalués et avec un score externe de perception, ont également été menées. Résultats: La population de ce projet comprend 1061 cas et 1422 témoins, âgés de 35 à 70 ans. Les participants inclus avaient répondu aux sections du questionnaire portant sur les facteurs de style de vie et sur l'historique de tabagisme. Dans l'ensemble, nous n’avons pas observé d’association entre le cancer du poumon et l'exposition aux évènements stressants de la vie. Nous avons observé une diminution du risque pour les évènements socioéconomiques autoévalués comme peu stressants (RC=0,50; IC 95%= 0,31 - 0,81). Conclusion: Nos résultats suggèrent que les évènements socioéconomiques sont associées à un risque réduit si ces évènements sont considérés comme peu stressant.

Optical sensing of the fatigue damage state of CFRP under realistic aeronautical load sequences

Abstract: We present an optical sensing methodology to estimate the fatigue damage stateof structures made of carbon fiber reinforced polymer (CFRP), by measuring variations on the surface roughness. Variable amplitude loads (VAL), which represent realistic loads during aeronautical missions of fighter aircraft (FALSTAFF) have been applied to coupons until failure. Stiffness degradation and surface roughness variations have been measured during the life of the coupons obtaining a Pearson correlation of 0.75 between both variables. The data were compared with a previous study for Constant Amplitude Load (CAL) obtaining similar results. Conclusions suggest that the surface roughness measured in strategic zones is a useful technique for structural health monitoring of CFRP structures, and that it is independent of the type of load applied. Surface roughness can be measured in the field by optical techniques such as speckle, confocal perfilometers and interferometry, among others.

Impact of exercise on innate immunity in multiple sclerosis progression and symptomatology

Multiple Sclerosis (MS), an idiopathic progressive immune-mediated neurological disorder of the central nervous system (CNS), is characterized by recurrent episodes of inflammatory demyelination and consequent axonal deterioration. It accounts for functional deterioration and lasting disability among young adults. A body of literature demonstrates that physical activity counteracts fatigue and depression and may improve overall quality of life in MS patients. Furthermore, much data indicates that exercise ameliorates chronic neuroinflammation and its related pathologies by tipping cytokine profiles toward an anti-inflammatory signature. Recent data has focused on the direct impact of exercise training on the innate immune system by targeting toll-like receptors (TLRs), signaling pattern recognition receptors that govern the innate immune response, shedding light on the physiological role of TLRs in health and disease. Indeed, TLRs continue to emerge as players in the neuroinflammatory processes underpinning MS. This review will highlight evidence that physical activity and exercise are potential immunomodulatory therapies, targeting innate signaling mechanism(s) to modulate MS symptom development and progression.