Assessing the improved discriminatory power of a new biomarker in prognostic models

Although the area under the receiver operating characteristic (AUC) is the most popular measure of the performance of prediction models, it has limitations, especially when it is used to evaluate the added discrimination of a new biomarker in the model. Pencina et al. (2008) proposed two indices, the net reclassification improvement (NRI) and integrated discrimination improvement (IDI), to supplement the improvement in the AUC (IAUC). Their NRI and IDI are based on binary outcomes in case-control settings, which do not involve time-to-event outcome. However, many disease outcomes are time-dependent and the onset time can be censored. Measuring discrimination potential of a prognostic marker without considering time to event can lead to biased estimates. In this dissertation, we have extended the NRI and IDI to survival analysis settings and derived the corresponding sample estimators and asymptotic tests. Simulation studies were conducted to compare the performance of the time-dependent NRI and IDI with Pencina’s NRI and IDI. For illustration, we have applied the proposed method to a breast cancer study.^ Key words: Prognostic model, Discrimination, Time-dependent NRI and IDI ^

Development of a Bayesian Joint Logistic Model to Better Study the Association between Haplotypes and Disease

In 2011, there will be an estimated 1,596,670 new cancer cases and 571,950 cancer-related deaths in the US. With the ever-increasing applications of cancer genetics in epidemiology, there is great potential to identify genetic risk factors that would help identify individuals with increased genetic susceptibility to cancer, which could be used to develop interventions or targeted therapies that could hopefully reduce cancer risk and mortality. In this dissertation, I propose to develop a new statistical method to evaluate the role of haplotypes in cancer susceptibility and development. This model will be flexible enough to handle not only haplotypes of any size, but also a variety of covariates. I will then apply this method to three cancer-related data sets (Hodgkin Disease, Glioma, and Lung Cancer). I hypothesize that there is substantial improvement in the estimation of association between haplotypes and disease, with the use of a Bayesian mathematical method to infer haplotypes that uses prior information from known genetics sources. Analysis based on haplotypes using information from publically available genetic sources generally show increased odds ratios and smaller p-values in both the Hodgkin, Glioma, and Lung data sets. For instance, the Bayesian Joint Logistic Model (BJLM) inferred haplotype TC had a substantially higher estimated effect size (OR=12.16, 95% CI = 2.47-90.1 vs. 9.24, 95% CI = 1.81-47.2) and more significant p-value (0.00044 vs. 0.008) for Hodgkin Disease compared to a traditional logistic regression approach. Also, the effect sizes of haplotypes modeled with recessive genetic effects were higher (and had more significant p-values) when analyzed with the BJLM. Full genetic models with haplotype information developed with the BJLM resulted in significantly higher discriminatory power and a significantly higher Net Reclassification Index compared to those developed with haplo.stats for lung cancer. Future analysis for this work could be to incorporate the 1000 Genomes project, which offers a larger selection of SNPs can be incorporated into the information from known genetic sources as well. Other future analysis include testing non-binary outcomes, like the levels of biomarkers that are present in lung cancer (NNK), and extending this analysis to full GWAS studies.

Texas Health & Safety Code, Section 165.002 - Right to Breastfeed in Texas

The language used in Section 165.002 of the Texas Health and Safety Code renders breastfeeding women vulnerable and susceptible to harassment, discrimination, and persecution via the Texas Penal Code, Sec. 30.05 (Criminal Trespassing), Sec. 21.08 (Indecent Exposure), and Sec. 21.22 (Indecency with a Child). ^ The overall goal of this paper is to develop a solution to this problem via a proposed law or legislative action that offers protection and support for breastfeeding women who choose to nurse in public. Data to inform these recommendations were collected through a literature review and structured interviews with several breastfeeding stakeholders. A literature review of state and federal breastfeeding legislation was conducted to compare and contrast differences between existing legislation in the United States. Interviews were conducted with breastfeeding legislation stakeholders, which included state legislators who have been active in breastfeeding legislation, breastfeeding mothers, and representatives from the Central Texas Healthy Mothers Healthy Babies Coalition (Centex HMHB Coalition), Texas Breastfeeding Coalition (TXBF coalition), La Leche League International, and the Texas Business Association. Data from the literature and legislation reviews and interviews were transcribed and examined for common themes using qualitative data techniques. ^ Overall, most of the stakeholders came to a general consensus on three points, (1) breastfeeding women are supported by stakeholders within the community, (2) other legislation or penal codes should not override the right to breastfeed, and (3) the current breastfeeding legislation needs to be improved to adequately support breastfeeding women. The interviews with breastfeeding legislation stakeholders yielded two major recommendations for the improvement of Section 165.002 of the Texas Health and Safety Code: advocacy efforts to change the wording of the legislation and education to inform people about the legislation. ^ The right to breastfeed is an important public health issue in that it provides a host of health benefits for mothers and children, and is more economical and environmentally superior to alternative feeding methods. While breastfeeding in public is not illegal nor ever has been, adequate legislation is important to affirm this right for women so that they can confidently feed their children without embarrassment or harassment.^

Occupational health and safety among commercial sex workers in Ghana

The topic of occupational health and safety (OHS) has been investigated for many years and continues to be a concept often researched today. Generally speaking OHS research has been centered around food safety, construction safety, transportation safety, fire safety, drug and alcohol testing, health and medical management, and industrial hygiene to name a few. However, the concept of OHS concerning female commercial sex workers (FCSWs) has rarely been investigated, often neglected, seldom discussed and is lacking in sound research. Although regarded as the "oldest profession", commercial sex work (CSW) has consistently been ignored, disregarded and under-researched due to the illegality and stigmatization of prostitution. This paper reviews occupational safety and health issues faced by FCSWs in Tema and Accra, Ghana, through in-depth interviews, visits to women's homes, field work, informal conversations and participant observations with FCSWs over a period of two months. Facets of OHS that emerged among FCSWs included sexually transmissible infections, risks associated with harassment and violence from police and clients, alcohol and drug use, irregular hospital visits and/or lack of hospital visits, immigration issues, legal and policing risks. We argue that CSW be viewed as an occupation in great need of interventions to reduce workplace risks and improve the health and safety of FCSWs^