Sensitivity Analysis for the Assessment of Causal Vaccine Effects on Viral Load in HIV Vaccine Trials

Vaccines with limited ability to prevent HIV infection may positively impact the HIV/AIDS pandemic by preventing secondary transmission and disease in vaccine recipients who become infected. To evaluate the impact of vaccination on secondary transmission and disease, efficacy trials assess vaccine effects on HIV viral load and other surrogate endpoints measured after infection. A standard test that compares the distribution of viral load between the infected subgroups of vaccine and placebo recipients does not assess a causal effect of vaccine, because the comparison groups are selected after randomization. To address this problem, we formulate clinically relevant causal estimands using the principal stratification framework developed by Frangakis and Rubin (2002), and propose a class of logistic selection bias models whose members identify the estimands. Given a selection model in the class, procedures are developed for testing and estimation of the causal effect of vaccination on viral load in the principal stratum of subjects who would be infected regardless of randomization assignment. We show how the procedures can be used for a sensitivity analysis that quantifies how the causal effect of vaccination varies with the presumed magnitude of selection bias.

Importance of canopy porosity into vineyard and the relationship with the grape maturity. Digital estimation method

In warm and dry climates, the use of porous systems should be required in order to allow a better leaf distribution inside the plant, causing more space in the clusters area and enhancing determined physiological processes so in the leaf (photosynthesis, v entilation, transpiration) as in berry (growth and maturation). Plant geometry indexes, yield and must composition have been studied in three different systems: sprawl with 12 shoots/m (S1); sprawl system with 18 shoots/m (S2) and vertical positioned syste m or VSP with 12 shoots/m (VSP1). Total leaf area increases as the crop load does, whoever surface area depends on to two factors: crop load and the training system (VSP vs. sprawl), which can provide differences in leaf exposure efficiencies. The main objective of this study was to validate digital photography measurements used to compare porosity differences among treatments and, as they affect plant microclimate and, therefore, yield and berry quality. Also, all previous studied indexes (LAI, SA, SFEr) tended to overestimate the relationship between exposed leaf surface and porosity of each treatment, but the use of digital method proved to be an effective tool in order to assess canopy porosity. Results showed that not positioned and free systems (sprawl) scored between 25- 50% more porosity in the clusters area than the fixed vertical system (VSP), which resulted in a better plant microclimate for test conditions, mainly by improving the exposure of internal clusters and internal canopy ventilation. On the other hand, higher crop load treatment (S2) showed a real increase in yield (16%) without any relevant change into must composition, even improving total anthocyanin content into berry during ripening

Importance of canopy porosity into vineyard and the relationship with the grape maturity. Digital estimation method

In warm and dry climates, the use of porous systems should be required in order to allow a better leaf distribution inside the plant, causing more space in the clusters area and enhancing determined physiological processes so in the leaf (photosynthesis, ventilation, transpiration) as in berry (growth and maturation). Plant geometry indexes, yield and must composition have been studied in three different systems: sprawl with 12 shoots/m (S1); sprawl system with 18 shoots/m (S2) and vertical positioned system or VSP with 12 shoots/m (VSP1). Total leaf area increases as the crop load does, whoever surface area depends on to two factors: crop load and the training system (VSP vs . sprawl), which can provide differences in leaf exposure efficiencies. The main objective of this study was to validate digital photography measurements used to compare porosity differences among treatments and, as they affect plant microclimate and, therefore, yield and berry quality. Also, all previous studied indexes (LAI, SA, SFEr) tended to overestimate the relationship between exposed leaf surface and porosity of each treatment, but the use of digital method proved to be an effective tool in order to assess canopy porosity. Results showed that not positioned and free systems (sprawl) scored between 25 - 50% more porosity in the clusters area than the fixed vertical system (VSP), which resulted in a better plant microclimate for test conditions, mainly by improving the exposure of internal clusters and internal canopy ventilation. On the other hand, higher crop load treatment (S2) showed a real increase in yield (16%) without any relevant change into must composition, even improving total anthocyanin content into berry during ripening

Disentangling the impact of seroconversion age and set-point viral load on ART-free HIV survival

Thesis (Master's)--University of Washington, 2016-06

Estimation of productivity in Korean electric power plants:a semiparametric smooth coefficient model

This paper analyzes the impact of load factor, facility and generator types on the productivity of Korean electric power plants. In order to capture important differences in the effect of load policy on power output, we use a semiparametric smooth coefficient (SPSC) model that allows us to model heterogeneous performances across power plants and over time by allowing underlying technologies to be heterogeneous. The SPSC model accommodates both continuous and discrete covariates. Various specification tests are conducted to compare performance of the SPSC model. Using a unique generator level panel dataset spanning the period 1995-2006, we find that the impact of load factor, generator and facility types on power generation varies substantially in terms of magnitude and significance across different plant characteristics. The results have strong implication for generation policy in Korea as outlined in this study.

Estimation of productivity in Korean electric power plants:a semiparametric smooth coefficient model

This paper analyzes the impact of load factor, facility and generator types on the productivity of Korean electric power plants. In order to capture important differences in the effect of load policy on power output, we use a semiparametric smooth coefficient (SPSC) model that allows us to model heterogeneous performances across power plants and over time by allowing underlying technologies to be heterogeneous. The SPSC model accommodates both continuous and discrete covariates. Various specification tests are conducted to assess the performance of the SPSC model. Using a unique generator level panel dataset spanning the period 1995-2006, we find that the impact of load factor, generator and facility types on power generation varies substantially in terms of magnitude and significance across different plant characteristics. The results have strong implications for generation policy in Korea as outlined in this study.

A Luenberger state observer for stator resistance estimation in sensorless induction motor drives

The primary objective of this paper is to elimination of the problem of sensitivity to parameter variation of induction motor drive. The proposed sensorless strategy is based on an algorithm permitting a better simultaneous estimation of the rotor speed and the stator resistance including an adaptive mechanism based on the lyaponov theory. To study the reliability and the robustness of the sensorless technique to abnormal operations, some simulation tests have been performed under several cases. The proposed sensorless vector control scheme showed a good performance behavior in the transient and steady states, with an excellent disturbance rejection of the load torque. © 2013 Praise Worthy Prize S.r.l. - All rights reserved.

Scaphoid Fracture Nonunion: Correlation Of Radiographic Imaging, Proximal Fragment Histologic Viability Evaluation, And Estimation Of Viability At Surgery: Diagnosis Of Scaphoid Pseudarthrosis.

The purpose of this study was to correlate the pre-operative imaging, vascularity of the proximal pole, and histology of the proximal pole bone of established scaphoid fracture non-union. This was a prospective non-controlled experimental study. Patients were evaluated pre-operatively for necrosis of the proximal scaphoid fragment by radiography, computed tomography (CT) and magnetic resonance imaging (MRI). Vascular status of the proximal scaphoid was determined intra-operatively, demonstrating the presence or absence of puncate bone bleeding. Samples were harvested from the proximal scaphoid fragment and sent for pathological examination. We determined the association between the imaging and intra-operative examination and histological findings. We evaluated 19 male patients diagnosed with scaphoid nonunion. CT evaluation showed no correlation to scaphoid proximal fragment necrosis. MRI showed marked low signal intensity on T1-weighted images that confirmed the histological diagnosis of necrosis in the proximal scaphoid fragment in all patients. Intra-operative assessment showed that 90% of bones had absence of intra-operative puncate bone bleeding, which was confirmed necrosis by microscopic examination. In scaphoid nonunion MRI images with marked low signal intensity on T1-weighted images and the absence of intra-operative puncate bone bleeding are strong indicatives of osteonecrosis of the proximal fragment.

Percepção de esforço em exercício sob fadiga em normóxia e hipóxia

Universidade Estadual de Campinas . Faculdade de Educação Física

Effect of cyclic load on vertical misfit of prefabricated and cast implant single abutment

OBJECTIVES: The purpose of this in vitro study was to evaluate misfit alterations at the implant/abutment interface of external and internal connection implant systems when subjected to cyclic loading. MATERIAL AND METHODS: Standard metal crowns were fabricated for 5 groups (n=10) of implant/abutment assemblies: Group 1, external hexagon implant and UCLA cast-on premachined abutment; Group 2, internal hexagon implant and premachined abutment; Group 3, internal octagon implant and prefabricated abutment; Group 4, external hexagon implant and UCLA cast-on premachined abutment; and Group 5, external hexagon implant and Ceraone abutment. For groups 1, 2, 3 and 5, the crowns were cemented on the abutments and in group 4 crowns were screwed directly on the implant. The specimens were subjected to 500,000 cycles at 19.1 Hz of frequency and non-axial load of 133 N in a MTS 810 machine. The vertical misfit (μm) at the implant/abutment interface was evaluated before (B) and after (A) application of the cyclic loading. Data were analyzed statistically by using two-away ANOVA and Tukey's post-hoc test (p<0.05). RESULTS: Before loading values showed no difference among groups 2 (4.33±3.13), 3 (4.79±3.43) and 5 (3.86±4.60); between groups 1 (12.88±6.43) and 4 (9.67±3.08), and among groups 2, 3 and 4. However, groups 1 and 4 were significantly different from groups 2, 3 and 5. After loading values of groups 1 (17.28±8.77) and 4 (17.78±10.99) were significantly different from those of groups 2 (4.83±4.50), 3 (8.07±4.31) and 5 (3.81±4.84). There was a significant increase in misfit values of groups 1, 3 and 4 after cyclic loading, but not for groups 2 and 5. CONCLUSIONS: The cyclic loading and type of implant/abutment connection may develop a role on the vertical misfit at the implant/abutment interface.

PENCALC: a program for penetrance estimation in autosomal dominant diseases

We present a computer program developed for estimating penetrance rates in autosomal dominant diseases by means of family kinship and phenotype information contained within the pedigrees. The program also determines the exact 95% credibility interval for the penetrance estimate. Both executable (PenCalc for Windows) and web versions (PenCalcWeb) of the software are available. The web version enables further calculations, such as heterozygosity probabilities and assessment of offspring risks for all individuals in the pedigrees. Both programs can be accessed and down-loaded freely at the home-page address http://www.ib.usp.br/~otto/software.htm.

Marcador in vitro da resposta glicêmica dos alimentos como ferramenta de auxílio à prescrição e avaliação de dietas

As dietas de baixo índice glicêmico e baixa carga glicêmica têm sido associadas à redução do risco de doenças crônicas. Por esse motivo há um interesse crescente na sua aplicação para avaliação e orientação nutricional. No entanto, existem limitações quanto ao uso de dados publicados de índice glicêmico e carga glicêmica, pela variedade e formas de processamento dos alimentos vegetais existentes. Devido à dificuldade de realização de ensaios in vivo, uma vez que são custosos, trabalhosos, invasivos e necessitam de período considerável de experimentação, foram desenvolvidas metodologias in vitro que, a partir da velocidade de digestão dos carboidratos, permitem estimar o índice glicêmico dos alimentos de forma prática, simples e econômica. O presente trabalho apresenta o uso de um marcador in vitro, o índice de hidrólise, na estimativa do índice glicêmico e da carga glicêmica, o método mais empregado por pesquisadores brasileiros, visando à sua aplicação por profissionais da área de Nutrição. Os cálculos e as interpretações para estimativa do Índice glicêmico e da carga glicêmica são apresentados por meio de um exemplo prático com alguns alimentos brasileiros e com o grão de amaranto submetido a diferentes processamentos. Na ausência de dados referentes à resposta glicêmica do alimento de interesse, os valores do marcador in vitro podem ser utilizados para estimar o índice glicêmico e a carga glicêmica dos alimentos. Porém, este marcador não deve ser utilizado indiscriminadamente, uma vez que leva em consideração apenas os fatores intrínsecos aos alimentos que influenciam o aproveitamento dos carboidratos disponíveis.

Estimation and prediction of parameters and breeding values in soybean using REML/BLUP and Least Squares

The aim of this study was to compare REML/BLUP and Least Square procedures in the prediction and estimation of genetic parameters and breeding values in soybean progenies. F(2:3) and F(4:5) progenies were evaluated in the 2005/06 growing season and the F(2:4) and F(4:6) generations derived thereof were evaluated in 2006/07. These progenies were originated from two semi-early, experimental lines that differ in grain yield. The experiments were conducted in a lattice design and plots consisted of a 2 m row, spaced 0.5 m apart. The trait grain yield per plot was evaluated. It was observed that early selection is more efficient for the discrimination of the best lines from the F(4) generation onwards. No practical differences were observed between the least square and REML/BLUP procedures in the case of the models and simplifications for REML/BLUP used here.

The frequency of CD127(low) expressing CD4(+)CD25(high) T regulatory cells is inversely correlated with human T lymphotrophic virus type-1 (HTLV-1) proviral load in HTLV-1-infection and HTLV-1-associated myelopathy/tropical spastic paraparesis

Background: CD4(+)CD25(high) regulatory T (T(Reg)) cells modulate antigen-specific T cell responses, and can suppress anti-viral immunity. In HTLV-1 infection, a selective decrease in the function of T(Reg) cell mediated HTLV-1-tax inhibition of FOXP3 expression has been described. The purpose of this study was to assess the frequency and phenotype of T(Reg) cells in HTLV-1 asymptomatic carriers and in HTLV-1-associated neurological disease (HAM/TSP) patients, and to correlate with measures of T cell activation. Results: We were able to confirm that HTLV-1 drives activation, spontaneous IFN gamma production, and proliferation of CD4+ T cells. We also observed a significantly lower proportion of CTLA-4(+) T(Reg) cells (CD4(+)CD25(high) T cells) in subjects with HAM/TSP patients compared to healthy controls. Ki-67 expression was negatively correlated to the frequency of CTLA-4(+) T(Reg) cells in HAM/TSP only, although Ki-67 expression was inversely correlated with the percentage of CD127(low) T(Reg) cells in healthy control subjects. Finally, the proportion of CD127(low) T(Reg) cells correlated inversely with HTLV-1 proviral load. Conclusion: Taken together, the results suggest that T(Reg) cells may be subverted in HAM/TSP patients, which could explain the marked cellular activation, spontaneous cytokine production, and proliferation of CD4(+) T cells, in particular those expressing the CD25(high)CD127(low) phenotype. T(Reg) cells represent a potential target for therapeutic intervention for patients with HTLV-1-related neurological diseases.

Real-Time PCR in HIV/Trypanosoma cruzi Coinfection with and without Chagas Disease Reactivation: Association with HIV Viral Load and CD4(+) Level

Background: Reactivation of chronic Chagas disease, which occurs in approximately 20% of patients coinfected with HIV/Trypanosoma cruzi (T. cruzi), is commonly characterized by severe meningoencephalitis and myocarditis. The use of quantitative molecular tests to monitor Chagas disease reactivation was analyzed. Methodology: Polymerase chain reaction (PCR) of kDNA sequences, competitive (C-) PCR and real-time quantitative (q) PCR were compared with blood cultures and xenodiagnosis in samples from 91 patients (57 patients with chronic Chagas disease and 34 with HIV/T. cruzi coinfection), of whom 5 had reactivation of Chagas disease and 29 did not. Principal Findings: qRT-PCR showed significant differences between groups; the highest parasitemia was observed in patients infected with HIV/T. cruzi with Chagas disease reactivation (median 1428.90 T. cruzi/mL), followed by patients with HIV/T. cruzi infection without reactivation (median 1.57 T. cruzi/mL) and patients with Chagas disease without HIV (median 0.00 T. cruzi/mL). Spearman's correlation coefficient showed that xenodiagnosis was correlated with blood culture, C-PCR and qRT-PCR. A stronger Spearman correlation index was found between C-PCR and qRT-PCR, the number of parasites and the HIV viral load, expressed as the number of CD4(+) cells or the CD4(+)/CD8(+) ratio. Conclusions: qRT-PCR distinguished the groups of HIV/T. cruzi coinfected patients with and without reactivation. Therefore, this new method of qRT-PCR is proposed as a tool for prospective studies to analyze the importance of parasitemia (persistent and/or increased) as a criterion for recommending pre-emptive therapy in patients with chronic Chagas disease with HIV infection or immunosuppression. As seen in this study, an increase in HIV viral load and decreases in the number of CD4(+) cells/mm(3) and the CD4(+)/CD8(+) ratio were identified as cofactors for increased parasitemia that can be used to target the introduction of early, pre-emptive therapy.