Polybrominated diphenyl ether (PBDE) exposure in North Americans: Cause for concern?

Polybrominated diphenyl ethers (PBDEs) are brominated flame retardants (BFRs) that have been widely produced and used as flame retardants since the 1970’s in many consumer products such as carpet and drape linings, plastics used in electronics, computer and television casings and polyurethane foam used in chairs, sofas and mattresses. PBDEs are persistent organic pollutants (POPs), which, by definition, are toxic in nature, persistent in the environment and accumulative in living organisms. Animal studies have found PBDEs to cause health defects such as fetal malformations, delayed onset of puberty, decreased sperm count, behavioral changes, permanent learning and memory impairment, endocrine disruption, as well as cancer at high doses. Recent research involving humans reported that elevated breast milk PBDEs levels in their mothers are associated with cryptorchidism (absence of one or both testes from the scrotum) in newborn boys and adverse birth outcomes as well as elevated serum PBDE levels in mothers are associated with low sperm count in young men. There are three commonly manufactured PBDE commercial mixtures: Penta-, Octa-, and Deca-BDEs. Two of them (Octa- and Penta-BDEs) have been banned by the European Union and are being voluntarily phased out in the United States. However, Deca continues to be manufactured, used, and imported in the United States. This MPH thesis consists of a literature review of peer reviewed scientific articles concerned with PBDEs in the environment and in humans, as well as a discussion concerning different routes of exposure to PBDEs and their blood, milk and tissue levels as surrogates for body burdens in North Americans and in people from other countries. Results of this literature review shows PBDE levels in human blood, milk and tissues are higher in North Americans than people from other countries worldwide. To date, the highest level of PBDEs was found in a toddler’s blood in a California study. Despite the fact that PBDEs are associated with adverse health effects, and highest levels of PBDEs in North Americans, Deca-BDE is still manufactured, used and imported in the United States. There is an urgent need of new federal regulatory policy to ban completely the production, importation and use of all commercial mixtures of PBDEs.^

Air Force Web Preventive Health Assessment (AF WEBPHA) mental health screening effectiveness

The U.S. Air Force assesses Active Duty Air Force (ADAF) health annually using the Air Force Web-based Preventative Health Assessment (AF WebPHA). The assessment is based on a self-administered survey used to determine the overall Air Force health and readiness, as well as, the individual health of each airman. Individual survey responses as well as groups of responses generate further computer generated assessment and result in a classification of 'Critical', 'Priority', or 'Routine', depending on the need and urgency for further evaluation by a health care provider. The importance of the 'Priority' and 'Critical' classifications is to provide timely intervention to prevent or limit unfavorable outcomes that may threaten an airman. Though the USAF has been transitioning from a paper form to the online WebPHA survey for the last three years it was not made mandatory for all airmen until 2009. The survey covers many health aspects including family history, tobacco use, exercise, alcohol use, and mental health. ^ Military stressors such as deployment, change of station, and the trauma of war can aggravate and intensify the common baseline worries experienced by the general population and place airmen at additional risks for mental health concerns and illness. This study assesses the effectiveness of the AF WebPHA mental health screening questions in predicting a mental health disorder diagnosis according to International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes generated by physicians or their surrogates. In order to assess the sensitivity, specificity, and positive predictive value of the AF WebPHA as a screening tool for mental health, survey results were compared to ascertain if they generated any mental health disorder related diagnosis for the period from January 1, 2009 to March 31, 2010. ^ Statistical analysis of the AF WebPHA mental health responses when compared with matching ICD-9-CM codes found that the sensitivity for 'Critical' or 'Priority' responses was only 3.4% and that it would correctly predict those who had the selected mental health diagnosis 9% of the time.^

Risk factors for diabetic retinopathy in Mexican Americans in Starr County, Texas

The prevalence of diabetes in Mexican Americans is disproportionately higher than in non-Hispanic whites. The rate of diabetic retinopathy resulting from prolonged diabetes is also greater in Mexican Americans than in non-Hispanic whites. A longitudinal study was carried out on data collected from Mexican Americans in Starr County, Texas to assess the association between socioeconomic and acculturation factors with diabetic retinopathy prevalence, incidence, and progression in those free of diabetic retinopathy or who had only early non-proliferative diabetic retinopathy. A multivariable analysis was done. ^ The incidence rate was 12.78 cases per year and the progression rate was 8.55 cases per year. The baseline characteristics of the population revealed that more people with occupations synonymous with lower income jobs like trade workers and machine operators had early non-proliferative diabetic retinopathy. A multivariable analysis revealed that those with early non-proliferative diabetic retinopathy were more likely to have been born in Mexico as compared to those free of diabetic retinopathy. Surprisingly, a multivariable analysis also showed that those that progressed in diabetic retinopathy disease status were more likely to have been employed as compared to those that did not. ^ This analysis reveals that Mexican Americans are heterogeneous in socioeconomic and acculturation factors that may be used to deter the incidence and progression of diabetic retinopathy severity. These findings could be targeted to create culturally sensitive intervention programs that will improve the detection and treatment of diabetic retinopathy in the work arena in addition to programs that will impact those that do not work. Workplace preventative health screenings and dissemination of language-specific informational brochures is warranted to curb the rates of progression in those employed. ^ A limitation of this study is the narrow surrogates used for assessing socioeconomic and acculturation status. To fully evaluate these variables, a study using a questionnaire with a multitude of surrogates for socioeconomic and acculturation factors should be employed.^

Factors associated with HPV16 status and survival among patients with squamous cell carcinoma of the oropharynx

Background: Squamous cell carcinoma of the oropharynx (SCCOP) is characterized by local tumor aggressiveness, high recurrence rates, a high incidence of second primary tumors, and medical comorbidities. Significant trends in demographic and clinical characteristics as well as survival among SCCOP patients have been observed over time, likely owing to the changing etiology of the disease. Human papillomavirus type 16 (HPV16) infection is associated with a significant proportion of these cancers. Biomarkers that may aid in identifying patients that are at higher risk of recurrence and death are important so that these patients may be followed more closely to improve their quality of life. ^ Study population and methods: The retrospective review (Specific Aim 2) included 3891 newly diagnosed, previously untreated patients presenting to our institution between 1955 and 2004. A total of 2299 patients treated at our institution were included in survival and recursive partitioning analysis. The prospective cohort study (Specific Aim 3) included 266 patients presenting to our institution between January 2006 and September 2009. ^ Results: The results from the retrospective review showed that over time, patients presented at younger ages and were more likely to have base of tongue/tonsil tumors and to be never/former smokers and moreover survival improved significantly over time. In survival and recursive partitioning analyses, the TNM staging system was efficient in prognosticating patients prior to 1995. However, in the recent decade, the TNM staging system was completely inadequate. The factors having the greatest positive effect on overall survival since 1995 were those common to HPV-associated SCCOP. The results from the prospective cohort study indicate that patients with high nodal stage and those with late stage disease have increased levels of pretreatment serum HPV DNA. ^ Conclusions: We saw a distinct improvement in survival among SCCOP patients over the past 50 years at our institution. The main factors contributing to this were changes in clinical characteristics, in particular surrogates for HPV status. The current TNM staging system for SCCOP is inadequate and incorporation of HPV status (and perhaps smoking status) is encouraged. Furthermore, although pretreatment circulating levels of HPV DNA was associated with higher N category and overall disease stage, it has limited utility as a marker for recurrence among SCCOP patients.^

Indeterminate QunatiFERON-TB Gold In-Tube assay results in association with procedural specimen collection in children

BACKGROUND. The development of interferon-gamma release assays (IGRA) has introduced powerful tools in diagnosing latent tuberculosis infection (LTBI) and may play a critical role in the future of tuberculosis diagnosis. However, there have been reports of high indeterminate results in young patient populations (0-18 years). This study investigated results of the QunatiFERON-TB Gold In-Tube (QFT-GIT) IGRA in a population of children (0-18 years) at Texas Children's Hospital in association with specimen collection procedures using surrogate variables. ^ METHODS. A retrospective case-control study design was used for this investigation. Cases were defined as having QFT-GIT indeterminate results. Controls were defined as having either positive or negative results (determinates). Patients' admission status, staff performing specimen collection, and specific nurse performing specimen collection were used as surrogates to measure specimen collection procedures. ^ To minimize potential confounding, abstraction of patients' electronic medical records was performed. Abstracted data included patients' medications and evaluation at the time of QFT-GIT specimen collection in addition to their medical history. QFT-GIT related data was also abstracted. Cases and controls were characterized using chi-squared tests or Fisher's exact tests across categorical variables. Continuous variables were analyzed using one-way ANOVA and t-tests for continuous variables. A multivariate model was constructed by backward stepwise removal of statistically significant variables from univariate analysis. ^ RESULTS. Patient data was abstracted from 182 individuals aged 0-18 years from July 2010 to August 2011 at Texas Children's Hospital. 56 cases (indeterminates) and 126 controls (determinates) were enrolled. Cancer was found to be an effect modifier with subsequent stratification resulting in a cancer patient population too small to analyze (n=13). Subsequent analyses excluded these patients. ^ The exclusion of cancer patients resulted in a population of 169 patients with 49 indeterminates (28.99%) and 120 determinates (71.01%), with mean ages of 9.73 (95% CI: 8.03, 11.43) years and 11.66 (95% CI: 10.75, 12.56) years (p = 0.033), respectively. Median age of patients who were indeterminates and determinates were 12.37 and 12.87 years, respectively. Lack of data for our specific nurse surrogate (QFTNurse) resulted in its exclusion from analysis. The final model included only our remaining surrogate variables (QFTStaff and QFTInpatientOutpatient). The staff collecting surrogate (QFTStaff) was found to be modestly associated with indeterminates when nurses collected the specimen (OR = 1.54, 95% CI: 0.51, 4.64, p = 0.439) in the final model. Inpatients were found to have a strong and statistically significant association with indeterminates (OR = 11.65, 95% CI: 3.89, 34.9, p < 0.001) in the final model. ^ CONCLUSION. Inpatient status was used as a surrogate for indication of nurse drawn blood specimens. Nurses have had little to no training regarding shaking of tubes versus phlebotomists regarding QFT-GIT testing procedures. This was also measured by two other surrogates; specifically a medical note stating whether a nurse or phlebotomist collected the specimen (QFTStaff) and the name and title of the specific nurse if collection was performed by a nurse (QFTNurse). Results indicated that inpatient status was a strong and statistically significant factor for indeterminates, however, nurse collected specimens and indeterminate results had no statistically significant association in non-cancer patients. The lack of data denoting the specific nurse performing specimen collection excluded the QFTNurse surrogate in our analysis. ^ Findings suggests training of staff personnel in specimen procedures may have little effect on the number of indeterminates while inpatient status and thus possibly illness severity may be the most important factor for indeterminate results in this population. The lack of congruence between our surrogate measures may imply that our inpatient surrogate gauged illness severity rather than collection procedures as intended. ^ Despite the lack of clear findings, our analysis indicated that more than half of indeterminates were found in specimens drawn by nurses and as such staff training may be explored. Future studies may explore methods in measuring modifiable variables during pre-analytical QFT-GIT procedures that can be discerned and controlled. Identification of such measures may provide insight into ways to lowering indeterminate QFT-GIT rates in children.^

End -of -life planning and decision -making: Implications for adults with mental retardation

This research focused on the topic of end-of-life planning and decision-making for adults affected by mental retardation. Adults with mental retardation have unique challenges in this regard, including difficulty communicating their wishes without assistance and diminished decision-making skills. The primary research objective was to identify factors that can affect opportunities for adults with mental retardation in community-based services settings (and their advocates) to be involved in planning and deciding about their own end-of-life experience. ^ A descriptive qualitative inquiry was designed to explore issues related to death and dying, and the notion of end-of-life planning, from the perspective of adults with mental retardation who receive publicly-funded community services ("clients") and family members of individuals who receive such services. Study participants were recruited from a single mental retardation service provider in a large urban setting (the "Agency"). Sixteen clients and 14 families of Agency clients took part. Client data collection was accomplished through face-to-face interviews, focus group meetings, and record reviews; family members were involved in a face-to-face interview only. ^ An initial coding scheme was developed based upon literature and policy reviews, and themes related to the research questions. Analysis involved extracting data from transcripts and records and placing it into appropriate thematic categories, building support for each theme with the accumulated data. Coding themes were modified to accommodate new data when it challenged existing themes. ^ Findings suggest that adults with mental retardation do have the requisite knowledge, interest, and ability to participate in decisions about their end-of-life experience and handling of affairs. Siblings are overwhelmingly the chosen future surrogates and they (or their children) will likely be the end-of-life advocates for their brothers and sisters affected by mental retardation. Findings further point to a need for increased awareness, accurate information, and improved communication about end-of-life issues, both in general and particular to adults affected by mental retardation. Also suggested by the findings is a need to focus on creating accommodations and adaptations that can best uncover a person's authentic views on life and death and related end-of-life preferences. Practical implications and suggestions for further research are also discussed. ^

EPANET Input Files of New York tunnels and Pacific City used in a metamodel-based optimization study

Metamodels have proven be very useful when it comes to reducing the computational requirements of Evolutionary Algorithm-based optimization by acting as quick-solving surrogates for slow-solving fitness functions. The relationship between metamodel scope and objective function varies between applications, that is, in some cases the metamodel acts as a surrogate for the whole fitness function, whereas in other cases it replaces only a component of the fitness function. This paper presents a formalized qualitative process to evaluate a fitness function to determine the most suitable metamodel scope so as to increase the likelihood of calibrating a high-fidelity metamodel and hence obtain good optimization results in a reasonable amount of time. The process is applied to the risk-based optimization of water distribution systems; a very computationally-intensive problem for real-world systems. The process is validated with a simple case study (modified New York Tunnels) and the power of metamodelling is demonstrated on a real-world case study (Pacific City) with a computational speed-up of several orders of magnitude.

Fine spatial pattern of an epiphytic lichen species is affected by habitat conditions in two forest types in the Iberian Mediterranean region

Persistence and abundance of species is determined by habitat availability and the ability to disperse and colonize habitats at contrasting spatial scales. Favourable habitat fragments are also heterogeneous in quality, providing differing opportunities for establishment and affecting the population dynamics of a species. Based on these principles, we suggest that the presence and abundance of epiphytes may reflect their dispersal ability, which is primarily determined by the spatial structure of host trees, but also by host quality. To our knowledge there has been no explicit test of the importance of host tree spatial pattern for epiphytes in Mediterranean forests. We hypothesized that performance and host occupancy in a favourable habitat depend on the spatial pattern of host trees, because this pattern affects the dispersal ability of each epiphyte and it also determines the availability of suitable sites for establishment. We tested this hypothesis using new point pattern analysis tools and generalized linear mixed models to investigate the spatial distribution and performance of the epiphytic lichen Lobaria pulmonaria, which inhabits two types of host trees (beeches and Iberian oaks). We tested the effects on L. pulmonaria distribution of tree size, spatial configuration, and host tree identity. We built a model including tree size, stand structure, and several neighbourhood predictors to understand the effect of host tree on L. pulmonaria. We also investigated the relative importance of spatial patterning on the presence and abundance of the species, independently of the host tree configuration. L. pulmonaria distribution was highly dependent on habitat quality for successful establishment, i.e., tree species identity, tree diameter, and several forest stand structure surrogates. For beech trees, tree diameter was the main factor influencing presence and cover of the lichen, although larger lichen-colonized trees were located close to focal trees, i.e., young trees. However, oak diameter was not an important factor, suggesting that bark roughness at all diameters favoured lichen establishment. Our results indicate that L. pulmonaria dispersal is not spatially restricted, but it is dependent on habitat quality. Furthermore, new spatial analysis tools suggested that L. pulmonaria cover exhibits a distinct pattern, although the spatial pattern of tree position and size was random.

Fine spatial pattern of an epiphytic lichen species is affected by habitat conditions in two forest types in the Iberian Mediterranean region

Persistence and abundance of species is determined by habitat availability and the ability to disperse and colonize habitats at contrasting spatial scales. Favourable habitat fragments are also heterogeneous in quality, providing differing opportunities for establishment and affecting the population dynamics of a species. Based on these principles, we suggest that the presence and abundance of epiphytes may reflect their dispersal ability, which is primarily determined by the spatial structure of host trees, but also by host quality. To our knowledge there has been no explicit test of the importance of host tree spatial pattern for epiphytes in Mediterranean forests. We hypothesized that performance and host occupancy in a favourable habitat depend on the spatial pattern of host trees, because this pattern affects the dispersal ability of each epiphyte and it also determines the availability of suitable sites for establishment. We tested this hypothesis using new point pattern analysis tools and generalized linear mixed models to investigate the spatial distribution and performance of the epiphytic lichen Lobaria pulmonaria, which inhabits two types of host trees (beeches and Iberian oaks). We tested the effects on L. pulmonaria distribution of tree size, spatial configuration, and host tree identity. We built a model including tree size, stand structure, and several neighbourhood predictors to understand the effect of host tree on L. pulmonaria. We also investigated the relative importance of spatial patterning on the presence and abundance of the species, independently of the host tree configuration. L. pulmonaria distribution was highly dependent on habitat quality for successful establishment, i.e., tree species identity, tree diameter, and several forest stand structure surrogates. For beech trees, tree diameter was the main factor influencing presence and cover of the lichen, although larger lichen-colonized trees were located close to focal trees, i.e., young trees. However, oak diameter was not an important factor, suggesting that bark roughness at all diameters favoured lichen establishment. Our results indicate that L. pulmonaria dispersal is not spatially restricted, but it is dependent on habitat quality. Furthermore, new spatial analysis tools suggested that L. pulmonaria cover exhibits a distinct pattern, although the spatial pattern of tree position and size was random.

An optimization method for conceptual design in engineering systems based on high order singular value decomposition

Se presenta un nuevo método de diseño conceptual en Ingeniería Aeronáutica basado el uso de modelos reducidos, también llamados modelos sustitutos (‘surrogates’). Los ingredientes de la función objetivo se calculan para cada indiviudo mediante la utilización de modelos sustitutos asociados a las distintas disciplinas técnicas que se construyen mediante definiciones de descomposición en valores singulares de alto orden (HOSVD) e interpolaciones unidimensionales. Estos modelos sustitutos se obtienen a partir de un número limitado de cálculos CFD. Los modelos sustitutos pueden combinarse, bien con un método de optimización global de tipo algoritmo genético, o con un método local de tipo gradiente. El método resultate es flexible a la par que mucho más eficiente, computacionalmente hablando, que los modelos convencionales basados en el cálculo directo de la función objetivo, especialmente si aparecen un gran número de parámetros de diseño y/o de modelado. El método se ilustra considerando una versión simplificada del diseño conceptual de un avión. Abstract An optimization method for conceptual design in Aeronautics is presented that is based on the use of surrogate models. The various ingredients in the target function are calculated for each individual using surrogates of the associated technical disciplines that are constructed via high order singular value decomposition and one dimensional interpolation. These surrogates result from a limited number of CFD calculated snapshots. The surrogates are combined with an optimization method, which can be either a global optimization method such as a genetic algorithm or a local optimization method, such as a gradient-like method. The resulting method is both flexible and much more computationally efficient than the conventional method based on direct calculation of the target function, especially if a large number of free design parameters and/or tunablemodeling parameters are present. The method is illustrated considering a simplified version of the conceptual design of an aircraft empennage.

A stochastic model updating method for parameter variability quantification based on response surface models and Monte Carlo simulation

Stochastic model updating must be considered for quantifying uncertainties inherently existing in real-world engineering structures. By this means the statistical properties,instead of deterministic values, of structural parameters can be sought indicating the parameter variability. However, the implementation of stochastic model updating is much more complicated than that of deterministic methods particularly in the aspects of theoretical complexity and low computational efficiency. This study attempts to propose a simple and cost-efficient method by decomposing a stochastic updating process into a series of deterministic ones with the aid of response surface models and Monte Carlo simulation. The response surface models are used as surrogates for original FE models in the interest of programming simplification, fast response computation and easy inverse optimization. Monte Carlo simulation is adopted for generating samples from the assumed or measured probability distributions of responses. Each sample corresponds to an individual deterministic inverse process predicting the deterministic values of parameters. Then the parameter means and variances can be statistically estimated based on all the parameter predictions by running all the samples. Meanwhile, the analysis of variance approach is employed for the evaluation of parameter variability significance. The proposed method has been demonstrated firstly on a numerical beam and then a set of nominally identical steel plates tested in the laboratory. It is found that compared with the existing stochastic model updating methods, the proposed method presents similar accuracy while its primary merits consist in its simple implementation and cost efficiency in response computation and inverse optimization.

Rapid plant diversification: Planning for an evolutionary future

Systematic conservation planning is a branch of conservation biology that seeks to identify spatially explicit options for the preservation of biodiversity. Alternative systems of conservation areas are predictions about effective ways of promoting the persistence of biodiversity; therefore, they should consider not only biodiversity pattern but also the ecological and evolutionary processes that maintain and generate species. Most research and application, however, has focused on pattern representation only. This paper outlines the development of a conservation system designed to preserve biodiversity pattern and process in the context of a rapidly changing environment. The study area is the Cape Floristic Region (CFR), a biodiversity hotspot of global significance, located in southwestern Africa. This region has experienced rapid (post-Pliocene) ecological diversification of many plant lineages; there are numerous genera with large clusters of closely related species (flocks) that have subdivided habitats at a very fine scale. The challenge is to design conservation systems that will preserve both the pattern of large numbers of species and various natural processes, including the potential for lineage turnover. We outline an approach for designing a system of conservation areas to incorporate the spatial components of the evolutionary processes that maintain and generate biodiversity in the CFR. We discuss the difficulty of assessing the requirements for pattern versus process representation in the face of ongoing threats to biodiversity, the difficulty of testing the predictions of alternative conservation systems, and the widespread need in conservation planning to incorporate and set targets for the spatial components (or surrogates) of processes.

Methylomic and Transcriptomic Insights Linking Air Pollution and Atherosclerosis

Thesis (Ph.D.)--University of Washington, 2016-06

Designing supramolecular structures from models of cyclic peptide scaffolds with heterocyclic constraints

Cyclic peptides containing oxazole and thiazole heterocycles have been examined for their capacity to be used as scaffolds in larger, more complex, protein-like structures. Both the macrocyclic scaffolds and the supramolecular structures derived therefrom have been visualised by molecular modelling techniques. These molecules are too symmetrical to examine structurally by NMR spectroscopy. The cyclic hexapeptide ([Aaa-Thz](3), [Aaa-Oxz](3)) and cyclic octapeptide ([Aaa-Thz](4), [Aaa-Oxz](4)) analogues are composed of dipeptide surrogates (Aaa: amino acid, Thz: thiazole, Oxz: oxazole) derived from intramolecular condensation of cysteine or serine/threonine side chains in dipeptides like Aaa-Cys, Aaa-Ser and Aaa-Thr. The five-membered heterocyclic rings, like thiazole, oxazole and reduced analogues like thiazoline, thiazolidine and oxazoline have profound influences on the structures and bioactivities of cyclic peptides derived therefrom. This work suggests that such constrained cyclic peptides can be used as scaffolds to create a range of novel protein-like supramolecular structures (e.g. cylinders, troughs, cones, multi-loop structures, helix bundles) that are comparable in size, shape and composition to bioactive surfaces of proteins. They may therefore represent interesting starting points for the design of novel artificial proteins and artificial enzymes. (C) 2002 Elsevier Science Inc. All rights reserved.

Of sheep and rain: large-scale population dynamics of the red kangaroo

1. We analysed time-series data from populations of red kangaroos (Macropus rufus, Desmarest) inhabiting four areas in the pastoral zone of South Australia. We formulated a set of a priori models to disentangle the relative effects of the covariates: rainfall, harvesting, intraspecific competition, and domestic herbivores, on kangaroo population-growth rate. 2. The statistical framework allowed for spatial variation in the growth-rate parameters, response to covariates, and environmental variability, as well as spatially correlated error terms due to shared environment. 3. The most parsimonious model included all covariates but no area-specific parameter values, suggesting that kangaroo densities respond in the same way to the covariates across the areas. 4. The temporal dynamics were spatially correlated, even after taking into account the potentially synchronizing effect of rainfall, harvesting and domestic herbivores. 5. Counter-intuitively, we found a positive rather than negative effect of domestic herbivore density on the population-growth rate of kangaroos. We hypothesize that this effect is caused by sheep and cattle acting as a surrogate for resource availability beyond rainfall. 6. Even though our system is well studied, we must conclude that approximating resources by surrogates such as rainfall is more difficult than previously thought. This is an important message for studies of consumer-resource systems and highlights the need to be explicit about population processes when analysing population patterns.