Relationship between Jump Performance and Asymmetry

The purpose of this dissertation is to investigate the relationship between jump performance and asymmetry. This investigation was divided into three separate studies. The first aim investigated which asymmetry variables for eccentric and concentric phases best predicted jump height (JH) during different jump types. The aim of the second study was to determine if asymmetry variables differed between jump type and genders. Fourteen participants performed countermovement jumps (CMJ) and drop vertical jumps (DVJ). The DVJ were administered from a 30.5 cm platform leading with dominant leg striking separate force platforms with each foot. Vertical ground reaction forces were used to determine eccentric and concentric phases. Variables identified for each leg during both phases were: average force, rate of force development, velocity, power and impulse. Asymmetry for each variable was calculated using the formula: (DL – NDL) / (DL + NDL)*100. Flight time was derived from ground contact during landing phase subtracted from takeoff during propulsion phase. The third study investigated if asymmetry variable differed between CMJ with and overhead goal (OG) or no overhead goal (NOG). Sixteen participants performed maximal effort CMJ with OG and NOG. Data processing and identifying of variables followed same methods as first two studies. The first aim used a linear stepwise regression and determined only impulse asymmetry during the concentric phase for CMJ (F(1,12) = 44.564, p.001, R2 = 0.788), and for DVJ only eccentric peak force and concentric RFD were selected as predictors of JH (F(2,11) = 23.962, p\u3c 0.001, R2 = 0.813). The second aim used a 2 (jump type) x 2 (gender) mixed factor ANOVA and determined only peak concentric GRF asymmetry (F(1,12) = 6.442, p\u3e0.026) and average iv concentric GRF asymmetry (F(1,12) = 5.145, p\u3e0.043) had an interaction between gender and jump type ( \u3e0.05). The third aim used a dependent t-test and determined that JH (t(15) = -2.565,

Ozone and Tracer Transport Variations in the Summer Northern Hemisphere Stratosphere

Constituent observations from the Upper Atmosphere Research Satellite (UARS) in combination with estimates of the residual circulation are used to examine the transport and chemical budgets of HF, CH4 and O3 in the summer Northern Hemisphere. Budget calculations of HF, CH4 and O3 show that the transport tendency due to the residual circulation increases in magnitude and is largely opposed by eddy motions through the summer months. Ozone budget analyses show that between 100 and 31 hPa, the magnitudes of the mean circulation and eddy transport terms increase through the summer months, producing tendencies that are factors of 2 to 3 times larger than the observed ozone change in the stratosphere. Chemical loss dominates the observed ozone decrease only at the highest latitudes, poleward of about 70°N. A comparison of observations from the Total Ozone Mapping Spectrometer with UARS-calculated total ozone suggests that poleward of 50°N, between 35% and 55% of the seasonal ozone decline during the summer occurs at altitudes below 100 hPa. The overall uncertainties, associated primarily with calculations of the residual circulation and eddy transport, are relatively large, and thus prevent accurate and useful constraints on the ozone chemical rate in the lower stratosphere

Antioxidant and lipid supplementation improve the development of photoreceptor outer segments in pluripotent stem cell-derived retinal organoids

The generation of retinal organoids from human pluripotent stem cells (hPSC) is now a well-established process that in part recapitulates retinal development. However, hPSC-derived photoreceptors that exhibit well-organized outer segment structures have yet to be observed. To facilitate improved inherited retinal disease modeling, we determined conditions that would support outer segment development in maturing hPSC-derived photoreceptors. We established that the use of antioxidants and BSA-bound fatty acids promotes the formation of membranous outer segment-like structures. Using new protocols for hPSC-derived retinal organoid culture, we demonstrated improved outer segment formation for both rod and cone photoreceptors, including organized stacked discs. Using these enhanced conditions to generate iPSC-derived retinal organoids from patients with X-linked retinitis pigmentosa, we established robust cellular phenotypes that could be ameliorated following adeno-associated viral vector-mediated gene augmentation. These findings should aid both disease modeling and the development of therapeutic approaches for the treatment of photoreceptor disorders

Assessment of AAV vector tropisms for mouse and human pluripotent stem cell-derived RPE and photoreceptor cells

Adeno-associated viral vectors are showing great promise as gene therapy vectors for a wide range of retinal disorders. To date, evaluation of therapeutic approaches has depended almost exclusively on the use of animal models. With recent advances in human stem cell technology, stem-cell derived retina now offers the possibility to assess efficacy in human organoids in vitro. Here we test 6 AAV serotypes (AAV2/2, AAV2/9, AAV2/8, AAV2/8T(Y733F), AAV2/5 and ShH10) to determine their efficiency in transducing mouse and human pluripotent stem cell (PSC)-derived RPE and photoreceptor cells in vitro. All the serotypes tested were capable of transducing RPE and photoreceptor cells in vitro. AAV ShH10 and AAV2/5 are the most efficient vectors at transducing both mouse and human RPE, while AAV2/8 and ShH10 achieved similarly robust transduction of human ESC-derived cone photoreceptors. Furthermore, we show that hESC-derived photoreceptors can be used to establish promoter specificity in human cells in vitro. The results of this study will aid capsid selection and vector design for pre-clinical evaluation of gene therapy approaches, such as gene editing, that require the use of human cells and tissues

Determination of glucose exchange rates and permeability of erythrocyte membrane in preeclampsia and subsequent oxidative stress-related protein damage using dynamic-19F-NMR

The cause of the pregnancy condition preeclampsia (PE) is thought to be endothelial dysfunction caused by oxidative stress. As abnormal glucose tolerance has also been associated with PE, we use a fluorinated-mimic of this metabolite to establish whether any oxidative damage to lipids and proteins in the erythrocyte membrane has increased cell membrane permeability. Data were acquired using 19F Dynamic-NMR (DNMR) to measure exchange of 3-fluoro-3-deoxyglucose (3-FDG) across the membrane of erythrocytes from 10 pregnant women (5 healthy control women, and 5 from women suffering from PE). Magnetisation transfer was measured using the 1D selective inversion and 2D EXSY pulse sequences, over a range of time delays. Integrated intensities from these experiments were used in matrix diagonalisation to estimate the values of the rate constants of exchange and membrane permeability. No significant differences were observed for the rate of exchange of 3-FDG and membrane permeability between healthy pregnant women and those suffering from PE, leading us to conclude that no oxidative damage had occurred at this carrier-protein site in the membrane

Role of the Amygdala in Antidepressant Effects on Hippocampal Cell Proliferation and Survival and on Depression-like Behavior in the Rat

The stimulation of adult hippocampal neurogenesis by antidepressants has been associated with multiple molecular pathways, but the potential influence exerted by other brain areas has received much less attention. The basolateral complex of the amygdala (BLA), a region involved in anxiety and a site of action of antidepressants, has been implicated in both basal and stress-induced changes in neural plasticity in the dentate gyrus. We investigated here whether the BLA modulates the effects of the SSRI antidepressant fluoxetine on hippocampal cell proliferation and survival in relation to a behavioral index of depression-like behavior (forced swim test). We used a lesion approach targeting the BLA along with a chronic treatment with fluoxetine, and monitored basal anxiety levels given the important role of this behavioral trait in the progress of depression. Chronic fluoxetine treatment had a positive effect on hippocampal cell survival only when the BLA was lesioned. Anxiety was related to hippocampal cell survival in opposite ways in sham- and BLA-lesioned animals (i.e., negatively in sham- and positively in BLA-lesioned animals). Both BLA lesions and low anxiety were critical factors to enable a negative relationship between cell proliferation and depression-like behavior. Therefore, our study highlights a role for the amygdala on fluoxetine-stimulated cell survival and on the establishment of a link between cell proliferation and depression-like behavior. It also reveals an important modulatory role for anxiety on cell proliferation involving both BLA-dependent and –independent mechanisms. Our findings underscore the amygdala as a potential target to modulate antidepressants' action in hippocampal neurogenesis and in their link to depression-like behaviors

La Ingeniería Automotriz clave para el desarrollo sostenible de Ecuador

El presente texto es una contribución al desarrollo de la sostenibilidad ecuatoriana y mantiene el debate sobre temas del estudio de la Ingeniería Automotriz. El mérito del libro radica en una triple condición: alimenta la investigación académica ecuatoriana, contribuye a llenar el vacío de producción científica automotriz direccionada a las necesidades del Ecuador y reconoce el esfuerzo de los investigadores que se dedican a la producción académica técnica. La Universidad Politécnica Salesiana —en su sede Guayaquil— realizó en 2018, las Segundas Jornadas Científicas de Ingeniería Automotriz; este texto es el producto final de ese evento académico, cuyas memorias técnicas son constituidas por ocho resultados de investigaciones en Ingeniería Automotriz que aportarán desarrollo sostenible al Ecuador en áreas como: el diseño, el control de contaminación, la eficiencia energética y la movilidad. Este recorrido por varias ramas de la Ingeniería Automotriz muestra al lector múltiples aplicaciones y cambios de paradigmas en la industria; no somos solamente consumidores de tecnología, somos también productores de la misma. Este texto da cuenta del desarrollo de la industria automotriz ecuatoriana. Ing. Renato Fierro J. MSc

The clinical effectiveness and cost-effectiveness of abatacept, adalimumab, etanercept and tocilizumab for treating juvenile idiopathic arthritis: a systematic review and economic evaluation

Background: Juvenile idiopathic arthritis (JIA) is characterised by joint pain, swelling and limitation of movement caused by inflammation. Subsequent joint damage can lead to disability and growth restriction. Treatment commonly includes disease modifying anti-rheumatic drugs (DMARD) such as methotrexate. Clinical practice now favours newer drugs termed biologic DMARDs where indicated.Objective: To assess the clinical and cost-effectiveness of four biologic DMARDs (etanercept, abatacept, adalimumab and tocilizumab - with or without methotrexate where indicated) for the treatment of JIA (systemic or oligoarticular JIA excluded).Data sources: Electronic bibliographic databases including MEDLINE, EMBASE, The Cochrane Library and DARE were searched for published studies from inception to May 2015 for English language articles. Bibliographies of related papers, systematic reviews and company submissions were screened and experts were contacted to identify additional evidence.Review methods: Systematic reviews of clinical-effectiveness, health-related quality of life and cost-effectiveness were undertaken according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. A cost-utility decision analytic model was developed to compare estimated cost-effectiveness of biologic DMARDs versus methotrexate. The base case time horizon was 30 years and the model took a National Health Service (NHS) perspective, with costs and benefits discounted at 3.5%.Results: Four placebo-controlled RCTs met the inclusion criteria for the clinical-effectiveness review (one RCT evaluating each biologic DMARD). Only one RCT included UK participants. Participants had to achieve an American College of Rheumatology Pediatric (ACR Pedi) 30 response to open-label lead-in treatment in order to be randomised. An exploratory adjusted indirect comparison suggests that the four biologic DMARDs are similar with fewer disease flares and greater proportions with ACR Pedi 50 and 70 responses among participants randomised to continued biologic DMARD. However, confidence intervals were wide, the number of trials was low and there was clinical heterogeneity between trials. Open-label extensions of the trials showed that generally ACR responses remained constant or even increased after the double-blind phase. The proportions of adverse events and serious adverse events were generally similar between treatment and placebo groups. Four economic evaluations of biologic DMARDs for patients with JIA were identified but all had limitations. Two quality of life studies were included, one of which informed the cost-utility model. The incremental cost-effectiveness ratio (ICER) for adalimumab, etanercept and tocilizumab versus methotrexate was £38,127, £32,526 and £38,656 per QALY, respectively. The ICER for abatacept versus methotrexate as a second line biologic was £39,536 per QALY.Limitations: The model does not incorporate the natural history of JIA in terms of long-term disease progression, as the current evidence is limited. There are no head-to-head trials of biologic DMARDs and clinical evidence for specific JIA subtypes is limited.Conclusions: Biologic DMARDs are superior to placebo (with methotrexate where permitted) in children with (predominantly) polyarticular course JIA, and an insufficient response to previous treatment. Randomised comparisons of biologic DMARDs with long-term efficacy and safety follow- are needed to establish comparative effectiveness. RCTs for JIA subtypes where evidence is lacking are also required.Funding: The National Institute for Health Research Health Technology Assessment programme. <br/