Patients can develop malignancies due to various reasons including genetic factors, chemical carcinogens, radiation, and defects in their immune system. The immune system is postulated to carry out routine surveillance for malignancy. Patients who have defective immune responses may be susceptible to malignancies due to complicated underlying mechanisms. These include defective immune response to cancer-causing bacteria, transforming viruses, and concomitant molecular, cellular and immunoregulatory defects. Common variable immune deficiency (CVID) is characterized by hypogammaglobulinemia, impaired antibody responses and an increased susceptibility to infections. A disorderly immune response, or immune dysregulation, may also lead to autoimmune complications and possibly to malignancy. The treatment of CVID involves infusion of replacement doses of immunoglobulin, either intravenously (IGIV) or subcutaneously (SCIG). However, it is unclear whether adequate replacement of immunoglobulins is sufficient to prevent the increased risk of malignancy seen in this disease. We present two cases of unusual solid tumors complicating CVID treated with adequate doses of intravenous immunoglobulins. In this study we review the occurrence of malignancy in patients with CVID and postulate mechanisms that may be involved indigent to this disease. We will also review the role of replacement immunoglobulin and discuss cancer screening in these high risk individuals.

Stationary spiral inserts can effectively enhance heat transfer and temperature blending in the heat convection systems. In this paper, the impact of the segment length on the performance of a stationary insert is studied for flow Re numbers from ~80 to ~7900 through numerical simulation of heat transfer in streams of cold and hot gases flowing across it. The segment length to width ratio is from 1.11 to 2.33. The temperature of the studied gas is from 300 K to 1300 K. It is shown that the insert with variable segment length is more effective in temperature blending for two compressible streams compared with an insert with constant segment length, especially for low-Re-number turbulent flows.

Background: Little is known about the associations of social experiences with mental health service use. Aim: This study aimed to classify social experiences variables in the past year and examine the associations of selected variables in social experiences with mental health service use among US adolescents. Methods: A total of 13,038 adolescents (aged 12 to 17), of which 2208 received mental health services, were from the 2018 National Survey on Drug Use and Health. Multivariate logistic regression (MLR) analysis was conducted. Results: The overall prevalence of mental health service use was 16.1%. 44 variables on social experiences were grouped into 10 disjoint clusters and one variable from each cluster was selected for MLR analysis. Being female, African American, Hispanics, insured and having depression in the past year were associated with increased odds of mental health service use. Negative feelings about going to school, having a serious fight at school/work, active involvement in substance use help programs, knowledge of drug prevention, negative perceptions about the role of religious beliefs on life decisions were positively associated with mental health service use. Conclusion: Mental health service use is associated with feelings about school and peers, perceptions about drug use, and involvement in activities.

Protein aggregation is deleterious to human health and detrimental to therapeutic shelf-life. The physical processes that induce aggregation are the same processes that drive productive folding reactions. As such, protein aggregation is a non-productive form of protein folding. To gain insight into the steps that serve as a partition between the folding and aggregation reactions, the folding mechanisms of several β-rich proteins with links to human disease or medicine were examined. In the ALS-linked protein, SOD1, a subpopulation of the unfolded ensemble is found to be a common source of both nonnative structure and frustrated folding. These behaviors are only observed upon the reduction of the intrinsic disulfide bond, indicating that this covalent interaction wards against aggregation. The nonnative structure presents an attractive target for the development of new therapeutic agents. In VH domains from therapeutic mAbs, the intramolecular disulfide bond protects against aggregation. However, it can also introduce complexity to the folding mechanism. This complexity is linked to the formation of a strained orientation of the disulfide bond. This strained orientation of the disulfide in certain VH domains is energetically unfavorable enough to disrupt the formation of the disulfide in the full length mAbs. The novel relationship observed between disulfide orientation, folding complexity, and incomplete oxidation warrants further examination in other Ig domains. Overall, these results demonstrate that mapping the folding free energy landscape for proteins with roles in human disease or therapeutics can provide valuable insights for developing and improving treatment options.

Background – This study is an attempt to explore the relationship between microcredit and the socio-economic empowerment of women in rural Bangladesh. Microcredit is simply the extension of a small amount of collateral-free institutional loans to jointly liable poor group members to generate employment and income enhancing activities. As it is too difficult for poor members to get loan from the formal credit institutions, Grameen Bank (GB) or other Non-Government Organizations (NGOs) provide small loans to vulnerable groups of the society by which they are expected to empower over his counterparts. Research questions – RQ1: How does micro-credit affect different indicators of women empowerment in the rural areas of Bangladesh? RQ2– Is the impact different from the male counterparts in the sample households? Purpose – This study is an effort to find the impact of microcredit on a number of indicators of women’s empowerment in the rural areas in Bangladesh. Methodology – Quantitative Regression Techniques such as Ordinary Least Square (OLS) and Instrumental Variable (IV) method have been applied to get the relationship between microcredit and women empowerment. Conclusion – Applying nationally representative cross-section survey data, Bangladesh Integrated Household Survey (BIHS) 2015, this thesis is intended to find the causal linkage between microcredit and women empowerment’s with different dimensions of women’s decisions are taken as empowerment indicators: production, resources, income, leadership, savings and time. The analysis has been conducted at the household level. The study assumes that women empowerment is endogenous. After controlling for endogeneity in the estimation by using an instrumental variable (IV) ‘distance to the market’ this study finds a significant relationship between microcredit and different dimensions of women’s empowerment. Participation in the microcredit program is found to be significant in explaining some of the outcome indicators of empowerment for the sampled households.

Nitrogen (N) is a key nutrient input to crops and one of the major pollutants to the environment from agriculture in the United States. Recent developments in site-specific management (SSM) technology have the potential to reduce both N overapplication and underapplication and increase farmers' net returns. In Virginia, due to the high variability of within-field yield-limiting factors such as soil physical properties and fertility, the adoption of SSM is hindered by high gridsampling cost. Many Virginia corn-wheat-soybean farms have practiced generating yield maps using yield monitors for several years even though few variable applications based on yield maps were reported. It is unknown if the information generated by yield monitors under actual production situations can be used to direct N management for increased net returns in this area. The overall objective of the study is to analyze the economic and environmental impact of alternative management strategies for N in corn and wheat production based on site-specific information in eastern Virginia. Specifically, evaluations were made of three levels of site-specific information regarding crop N requirements combined with variable and uniform N application. The three levels of information are information about the yield potential of the predominant soil type within the field, information about yield potentials of all soils within the field (soil zones), information about yield potentials of smaller sub-field units which are aggregated into functional zones. Effects of information on expected net returns and net N (applied N that is not removed by the crop) were evaluated for corn-wheat-soybean fields in eastern Virginia. Ex post and ex ante evaluations of information were carried out. Historical weather data and farm-level yield data were used to generate yield sequences for individual fields. A Markov chain model was used to describe both temporal and spatial yield variation. Soil maps were used to divide a field into several soil management units. Cluster analysis was used to group subfield units into functional zones based on yield monitor data. Yield monitor data were used to evaluate ex post information and variable application values for 1995-1999, and ex ante information and variable application values for 1999. Ex post analysis results show that soil zone information increased N input but decreased net return, while functional zone information decreased N input and increased net returns. Variable application decreased N input compared with uniform application. Variable application based on soil zone information reduced net return due to cost of overapplication or underapplication. Variable application based on functional information increased net return. Ex ante results show that information on spatial variability was not able to increase farmers?net return due to the cost of variable N application and information. Variable rate application decreases N input relative to uniform application. However, imprecision in the spatial predictor makes the variable application unprofitable due to an imbalance between costs of under- and over-application of N. Sensitivity analysis showed that value of information was positive when temporal uncertainty was eliminated. The ex post results of this study suggest there is potential to improve efficiency of N use and farmers?net returns with site specific management techniques. The ex ante results suggest that site specific management improvements should be tested under conditions faced by farmers including imperfect information about temporal and spatial yield variability. / Ph. D.

Este libro es una guía teórico-práctica que permite al estudiante de administración y carreras afines entender los conceptos sobre los que se fundamenta cada tema y aplicarlos a sus análisis administrativos. Para ello, además de una breve explicación teórica, en cada tema se presentan ejemplos resueltos y luego por resolver para fijar el aprendizaje. Finalmente, se cierra cada unidad con una serie de ejercicios aplicados. Esta obra es producto de la experiencia obtenida a lo largo de varios años en la coordinación y dictado de los cursos de la Universidad Peruana de Ciencias Aplicadas como Nivelación de Matemáticas, Lógica Matemática y, principalmente, Matemática Básica para Administradores. Asimismo, está complementado con los aportes y problemas propuestos por la mayoría de los profesores de estos cursos. Se trata entonces de una publicación útil y práctica para administradores, estudiantes y profesores.

En el presente trabajo se presenta el Diseño e Implementación de una Máquina Semi - Automática para Embalar Pallets con un Sistema de Sujeción de Plástico Stretch Film, con un sistema electrónico de control de posición vertical y supervisión general mediante un sistema EXSCADA. El funcionamiento de la máquina consiste en envolver materiales apilados en un pallet o una parrilla con plástico stretch film, de manera eficiente y con gran rendimiento. Con el objetivo de proteger los productos para su transporte y para las prestaciones de calidad que requiere el mercado interno y los clientes finales. El Sistema ExScada, en mención, consiste en concentrar en una PC datos relevantes del funcionamiento de la máquina, así como la interacción gráfica de la misma; además se podrá generar reportes, lo cual contribuirá con la administración y gestión de los productos ha ser distribuidos. El desarrollo del proyecto cubre dos ramas de la ingeniería; la mecánica, la electrónica y la electricidad. En cuanto a la mecánica, se desarrolló toda la estructura teniendo como objetivo un sistema que cuente con una plataforma giratoria para poder envolver la carga, del mismo modo, este sistema debía contar con un equipo que alimente de stretch film durante el proceso de envoltura. Para poder envolver toda la altura de la carga se requería que este equipo alimentador tuviera un desplazamiento vertical, para ello se diseñó una 5 estructura en forma de torre que serviría de carril para el desplazamiento del equipo alimentador. El sistema requiere de dos motorreductores trifásicos: uno para el giro de la plataforma giratoria y el otro para el desplazamiento del equipo alimentador. Las velocidades de giro de estos motorreductores podrán controlarse a través de variadores de velocidad, para ello se utilizó dos variadores de velocidad (Sinamics G-110 Siemens), los cuales son controlados por medio de sus puertos digitales (encendido/ apagado e inversión de giro) y analógicos (variación de frecuencia de trabajo) conectados a un PLC S7-200 de Siemens con un módulo de expansión analógica EM-235. / Tesis

The placebo response can affect inference in analysis of data from clinical trials. It can bias the estimate of the treatment effect, jeopardize the effort of all involved in a clinical trial and ultimately deprive patients of potentially efficacious treatment. The Sequential Parallel Comparison Design (SPCD) is one of the novel approaches addressing placebo response in clinical trials. The analysis of SPCD clinical trial data typically involves classification of subjects as ‘placebo responders’ or ‘placebo non-responders’. This classification is done using a specific criterion and placebo response is treated as a measurable characteristic. However, the use of criterion may lead to subject misclassification due to measurement error or incorrect criterion selection. Subsequently, misclassification can directly affect SPCD treatment effect estimate. We propose to view placebo response as an unknown random characteristic that can be estimated based on information collected during the trial. Two strategies are presented here. First strategy is to model placebo response using criterion classification as a starting point or the observed data, and to include the placebo response estimate into the treatment effect estimation. Second strategy is to jointly model latent placebo response and the observed data, and estimate treatment effect from the joint model. We evaluate both strategies on a wide range of simulated data scenarios in terms of type I error control, mean squared error and power. We then evaluate the strategies in presence of missing data and propose a method for missing data imputation under the non-informative missingness assumption. The data from a recent SPCD clinical trial is used to compare results of the proposed methods with reported results of the trial. / 2018-01-01T00:00:00Z

South Africa has the largest HIV-infected population in the world, with 2015 estimates of 7 million people living with HIV and 180,000 AIDS-related deaths. The South African government began scale-up of a public-sector HIV care and treatment program in 2004, and by the end of 2015, 3.4 million HIV-infected individuals were on antiretroviral therapy (ART). When scale-up began in South Africa, ART was only available to HIV-infected individuals with CD4 counts ≤200 cells/µL or WHO clinical stage 4 disease. In 2010, treatment was extended to patients who were pregnant or who had tuberculosis and a CD4 ≤350 cells/µL, and in 2011, eligibility was extended to all patients with CD4 ≤350 cells/µL. In 2013 patients with WHO clinical stage 3 disease became eligible. In 2015, the eligibility threshold was increased to CD4 ≤500 cells/µL, and in 2016, the South African National Department of Health announced that the country would implement a “test and treat” strategy, offering free ART to all HIV-infected individuals, regardless of CD4 count. This dissertation examines the effectiveness of several expansions and modifications to South Africa’s treatment program. In study 1, we investigated whether the 2011 extension of HIV treatment to patients with CD4 counts ≤350 cells/µL successfully increased the number of newly-eligible patients on treatment (those with CD4 counts between 201–350 cells/µL) without crowding out previously-eligible patients with more severe disease (CD4 counts ≤200 cells/µL), focusing on a network of rural clinics in KwaZulu-Natal. We found encouraging results, with newly-eligible patients (CD4 201–350) initiating treatment at a greater frequency (73.0 additional patients per month; 95% CI: 42.1; 103.9) and 47% faster than before (95% CI: 19%; 82%), while previously eligible patients (CD4 ≤200) experienced no decline in the number of patients initiating treatment or the speed of treatment uptake. In study 2, we evaluated whether the introduction of a single-pill fixed-dose combination (FDC) treatment for ART initiators in South Africa had an impact on attrition from care compared to the previously-recommended multiple-pill regimen. We focused on an urban clinic in Johannesburg, using four different clinic attendance measures to define attrition (generally a combined measure of loss to follow-up and mortality). An intention-to-treat analysis revealed an estimated 11.3 percentage point decrease in attrition (95% CI: -22.0; -0.6) associated with the policy change, while a regression discontinuity analysis estimated an 18.0 percentage point drop in attrition (95% CI: -33.6; -2.4) associated with single-pill FDC treatment relative to multiple pills, controlling for unmeasured confounding. In study 3, we used stratified instrumental variable analysis to examine whether the effect of FDCs on attrition varied across subsets of the patient population in the same Johannesburg clinic we evaluated in study 2. We saw larger effects among women (RD -0.25; 95% CI: -0.42; -0.09), non-anemic patients (RD -0.24; 95% CI: -0.41; -0.08), patients with early-stage (as opposed to advanced) clinical disease (RD -0.20; 95% CI: -0.32; -0.07), and those with high CD4 counts (for CD4 ≥350 cells/µL, RD -0.58; 95% CI: -1.58; 0.42). These results suggest that healthier patients saw the greatest improvement in retention in care following the switch from multiple-pill to single-pill regimens. In an era where the healthiest HIV-infected patients are now being targeted for ART treatment, FDCs can play a large role in preventing attrition from care. These three studies depict an HIV program that has successfully grown to treat increasing numbers of patients using up-to-date strategies of care. Given the immense scale and cost of South Africa’s HIV treatment program, it is important to continue to monitor its effectiveness, especially as it introduces new treatments and strategies and adapts to the changing epidemic.