Human Trafficking: It’s Not Just a Crime

Human trafficking, although commonly conceived of as a crime, is also a matter for the fields of health and public health. Trafficked individuals suffering physical, sexual, and/or psychological abuse can experience acute and chronic health sequelae, bringing them to the attention of health and/or mental health professionals. Communicable infections affect many trafficked individuals and can be transmitted to those not trafficked. The factors that contribute to people being trafficked, like poverty, educational disparities, and systematic oppression based upon identities, are multifaceted and interlinked with other trauma experiences. Incorporation of public health principles into anti-trafficking efforts facilitates a comprehensive and holistic prevention/intervention anti-trafficking strategy. This commentary illustrates how both the health care and public health sectors can contribute to improving the health and well-being of trafficked people, the general public, and to anti-trafficking efforts

New methods for designing and analyzing microarray experiments for the detection of differential expression

This thesis is divided into three sections all pertaining to microarray experimental design and analysis. Microarrays are a tool used in biological research which enables scientists to measure the relative level of expression many genes within an organism at the same time. Microarrays have also opened new research areas in statistics which are currently being investigated concerning different aspects of data normalization, experimental design, and analysis;The first chapter entails a comparison of two commonly used experimental designs in two-dye microarray experiments. Both designs are applicable only to experiments containing treatments with two levels. One design is shown to be more powerful when constrained by the number of arrays. Also, mixed model analysis is often used for both designs. With small sample sizes, mixed model analysis is shown to give inaccurate results under certain conditions. Due to this problem, an alternative method of analysis is proposed for both experimental designs which eliminates this concern;Two-dye microarray experiments require special consideration in design since they have multiple random effect in the model. This is because arrays are usually viewed as a random factor that should always be contained in a model for the data. Research has been done on comparing two-dye microarray experimental designs by requiring calculation of array differences. This is shown to inhibit the power of the analysis by removing inter-block information. There are also experimental designs that are viable options which can not be compared using this method. An alternative method of analysis is proposed which allows for multiple random effects in the model. Under certain conditions, this method is shown to choose designs that either would not be chosen, or cannot be considered, when using methods based on array differences;The third chapter discusses new methods for analyzing microarray experiments by categories. Most commonly, microarray analysis is performed on a gene-by-gene basis with the goal of finding the genes whose expression differ the greatest between varieties of treatments. However, scientists often would like to know what aspect of cell life is affected most by differences in varieties. There could be cases where a group of genes pertaining to the same task are all have a mild change in expression which would not be found using gene-by-gene analysis. Two different resampling based methods are proposed for solving this problem. Both methods are compared and results are visualized on a directed acyclical graph

Directed growth and selective differentiation of neural progenitor cells using a synergistic combination of topographical and soluble cues

The purpose of this study is to develop strategies to facilitate nerve regeneration using a synergistic combination of guidance cues. We are investigating the cellular mechanisms of development using adult rat hippocampal progenitor cells (AHPCs) and have demonstrated that manipulating a combination of physical, chemical and biological cues can lead to oriented astrocyte and neural progenitor cell outgrowth and can influence progenitor cell differentiation. To provide physical guidance, micropatterned polystyrene (PS) substrates were fabricated and chemically modified with laminin. Astrocytes or AHPCs cultured on these substrates align along the grooves of the patterned surface extending highly elongated processes. To further explore AHPC outgrowth and differentiation, physical guidance cues were integrated with the biological influence of astrocytes. AHPCs co-cultured in contact with astrocytes preferentially acquired neuronal morphology, with nearly double the percentage of cells expressing class III beta-tubulin (TuJ1) on the micropatterned half of the substrate, as opposed to the planar half of the substrate, or compared to those growing in the absence of astrocytes. This indicates that substrate three-dimensional topography, in synergy with chemical (laminin) and biological (astrocytes) guidance cues, facilitates neuronal differentiation of AHPCs. This environment provided biological and spatial control over differentiation enhancing neuronal differentiation and promoting neurite alignment on topographically different regions of the same substrate. In a non-contact co-culture system, astrocyte-derived soluble factors enhanced neurite outgrowth and induced neuronal differentiation with significantly more AHPCs TuJ1 immunoreactive than in the contact co-culture. Therefore, soluble cues may have had a stronger influence on neuronal differentiation and neuritic extension compared to contact mediated factors or a combination of soluble and contact mediated factors that were presented by the monolayer of aligned astrocytes. The results also point to the potential role of localized concentration of these factors within the microgrooves as a reason for the differences in differentiation on micropatterned and planar substrates in the contact as opposed to the non-contact co-cultures. This research provides insights into mechanisms of neural stem cell differentiation and a foundation for the development of a promising nerve regeneration strategy incorporating a synergistic combination of cues for guided central nervous system repair following injury

Soluble factors from neocortical astrocytes enhance neuronal differentiation of neural progenitor cells from adult rat hippocampus on micropatterned polymer substrates

Rat adult hippocampal progenitor cells (AHPCs) are self-renewing, multipotent neural progenitors that have the ability to differentiate into neurons and glia. Previously, we demonstrated that coculture of AHPCs with postnatal day two, type 1 cortical astrocytes on laminin-coated micropatterned polymer substrates facilitates selective neuronal differentiation of the AHPCs 1. Under this condition, multi-dimensional cell-cell and/or cell-extracellular matrix interactions, as well as possible soluble factors released from astrocytes provided spatial and temporal control selectively enhancing neuronal differentiation and neurite alignment on topographically different regions of the same substrate. To investigate the potential role of astrocyte-derived soluble factors as cues involved in neuronal differentiation, a non-contact co-culture system was used. Under control conditions, approximately 14% of the AHPCs were immunoreactive (IR) for the neuronal marker, class III β-tubulin (TUJ1-IR). When co-cultured in physical contact with astrocytes, neuronal differentiation increased significantly to about 25%, consistent with our previous results. Moreover, under non-contact co-culture conditions using Transwell insert cultures, neuronal differentiation was dramatically increased to approximately 64%. Furthermore, neurite outgrowth from neuronal cell bodies was considerably greater on the patterned substrate, compared to the non-patterned planar substrate under non-contact co-culture conditions. Taken together, our results demonstrate that astrocyte-derived soluble factors provide cues for specific neuronal differentiation of AHPCs cultured on micropatterned substrates. In addition, a suppressive influence on neuronal differentiation appears to be mediated by contact with co-cultured astrocytes. These results provide important insights into mechanisms for controlling neural progenitor/stem cell differentiation and facilitate development of strategies for CNS repair

STARTING VALUES FOR PROC MIXED WITH REPEATED MEASURES DATA

A major advantage of PROC MIXED for repeated measures data is that one could choose from many different correlated error models. However, MIXED uses default starting values that may cause difficulty obtaining REML estimates of the covariance parameters for several of the models available. This can take the form of excessively long run times or even failure to converge. We have written a program to obtain initial covariance parameter estimates that result in greatly improved performance of the REML algorithm. We will use two covariance models frequently of interest in animal health experiments, the first-order ante-dependence model [ANTE(l)] and the Toeplitz model with heterogeneous variances [TOEPH], to illustrate the use of our procedure

Effects of 24 months of treatment with romosozumab followed by 12 months of denosumab or placebo in postmenopausal women with low bone mineral density : a randomized, double-blind, phase 2, parallel group study

Over 12 months, romosozumab increased bone formation and decreased bone resorption, resulting in increased bone mineral density (BMD) in postmenopausal women with low BMD (NCT00896532). Herein, we report the study extension evaluating 24 months of treatment with romosozumab, discontinuation of romosozumab, alendronate followed by romosozumab, and romosozumab followed by denosumab. Postmenopausal women aged 55 to 85 years with a lumbar spine (LS), total hip (TH), or femoral neck T-score =-3.5 were enrolled and randomly assigned to placebo, one of five romosozumab regimens (70 mg, 140 mg, 210 mg monthly [QM]; 140 mg Q3M; 210 mg Q3M) for 24 months, or open-label alendronate for 12 months followed by romosozumab 140 mg QM for 12 months. Eligible participants were then rerandomized 1:1 within original treatment groups to placebo or denosumab 60 mg Q6M for an additional 12 months. Percentage change from baseline in BMD and bone turnover markers (BTMs) at months 24 and 36 and safety were evaluated. Of 364 participants initially randomized to romosozumab, placebo, or alendronate, 315 completed 24 months of treatment and 248 completed the extension. Romosozumab markedly increased LS and TH BMD through month 24, with largest gains observed with romosozumab 210 mg QM (LS = 15.1%; TH = 5.4%). Women receiving romosozumab who transitioned to denosumab continued to accrue BMD, whereas BMD returned toward pretreatment levels with placebo. With romosozumab 210 mg QM, bone formation marker P1NP initially increased after treatment initiation and gradually decreased to below baseline by month 12, remaining below baseline through month 24; bone resorption marker beta-CTX rapidly decreased after treatment, remaining below baseline through month 24. Transition to denosumab further decreased both BTMs, whereas after transition to placebo, P1NP returned to baseline and beta-CTX increased above baseline. Adverse events were balanced between treatment groups through month 36. These data suggest that treatment effects of romosozumab are reversible upon discontinuation and further augmented by denosumab

Micropatterned polymer films for optic nerve regeneration

In an effort to promote optic nerve regeneration in vivo, directional growth of astrocytes has been achieved on polymer substrates in vitro. The purpose of this project was to investigate the cellular mechanisms of optic nerve repair using astrocyte cultures. Manipulating a combination of physical and chemical cues, astrocyte adhesion and alignment in vitro were examined. To provide physical guidance, micropatterned polymer films of polystyrene (PS) were fabricated. Laminin was selectively adsorbed into the grooves of the patterned surface. Rat type-1 astrocytes were seeded onto micropatterned PS substrates of 10 [mu]m groove width, 10 or 20 [mu]m groove spacing and 3 or 4 [mu]m groove depth. The effects of substrate topography and the adsorption of laminin to the PS substrates on the behavior and morphology of the astrocytes were explored. The astrocytes were found to align parallel to the micropatterned grooves at initial seeding densities of approximately 7500, 13,000, and 20,000 cells per cm2 due to the effects of the physical and chemical guidance mechanisms. Adsorbing laminin in the microgrooves of the micropatterned PS substrates improved cell adhesion and spreading of cytoskeletal filaments significantly. At these initial seeding densities, over 85% alignment in the direction of the grooves was achieved on the micropatterned PS substrates with laminin adsorbed in the grooves. The effects of physical and chemical guidance mechanisms on the behavior and morphology of the astrocytes on the PS substrate were explored to determine their influence on the outgrowth and differentiation of adult neural stem cell cultures in vitro. This combination of guidance cues has the potential to provide a permissive substrate for in vivo regeneration of the diseased or injured optic nerve and other regions of the central nervous system

Characterizing the role of Glycine max NHL gene family members in plant-nematode interactions [abstract]

Abstract only availableSoybean cyst nematode (SCN; Heterodera glycines) is a microscopic parasitic roundworm of soybean that causes nearly $1 billion dollars in annual yield loss in the United States. SCN damages the plant by attaching itself to the soybean root system, where it forms a complex feeding site and drains vital nutrients from the plant. Naturally resistant soybean lines have been used as the primary strategy to manage SCN, because they have evolved a natural mechanism for resisting SCN infection. However, soybean resistance against SCN is derived from a small genetic base and repeated annual plantings of these same resistant lines has selected for populations of SCN that can reproduce on the resistant lines. Therefore, understanding the molecular mechanisms of how some soybean plants have the ability to naturally resist infection by SCN is critical for designing new strategies to improve crop plant resistance to SCN. My project focuses on soybean NDR1/HIN1-like (NHL) genes found to be expressed at higher levels specifically within SCN-induced feeding cells of resistant soybean as compared to susceptible soybean. To gain insight into the potential role of these genes in soybeans ability to resist SCN, full-length gene and cDNA sequences have been isolated using techniques known as genome walking and RACE PCR. RNAi and overexpression constructs have been generated to directly test the function of these genes in SCN resistance. To gain insight into the nematode-responsive regulation of each gene, the endogenous promoter sequences have been isolated and fused to the _-glucuronidase reporter gene for expression studies. This project will give insight into the mechanisms the soybean plant uses to defend itself against SCN infection and hopefully reveal crucial results which aid in the goal of developing SCN resistant soybean.Life Sciences Undergraduate Research Opportunity Progra