Application of stellar photometry to the analysis of microarray images

Improvements in the analysis of microarray images are critical for accurately quantifying gene expression levels. The acquisition of accurate spot intensities directly influences the results and interpretation of statistical analyses. This dissertation discusses the implementation of a novel approach to the analysis of cDNA microarray images. We use a stellar photometric model, the Moffat function, to quantify microarray spots from nylon microarray images. The inherent flexibility of the Moffat shape model makes it ideal for quantifying microarray spots. We apply our novel approach to a Wilms' tumor microarray study and compare our results with a fixed-circle segmentation approach for spot quantification. Our results suggest that different spot feature extraction methods can have an impact on the ability of statistical methods to identify differentially expressed genes. We also used the Moffat function to simulate a series of microarray images under various experimental conditions. These simulations were used to validate the performance of various statistical methods for identifying differentially expressed genes. Our simulation results indicate that tests taking into account the dependency between mean spot intensity and variance estimation, such as the smoothened t-test, can better identify differentially expressed genes, especially when the number of replicates and mean fold change are low. The analysis of the simulations also showed that overall, a rank sum test (Mann-Whitney) performed well at identifying differentially expressed genes. Previous work has suggested the strengths of nonparametric approaches for identifying differentially expressed genes. We also show that multivariate approaches, such as hierarchical and k-means cluster analysis along with principal components analysis, are only effective at classifying samples when replicate numbers and mean fold change are high. Finally, we show how our stellar shape model approach can be extended to the analysis of 2D-gel images by adapting the Moffat function to take into account the elliptical nature of spots in such images. Our results indicate that stellar shape models offer a previously unexplored approach for the quantification of 2D-gel spots. ^

DNA nucleotide excision repair gene single nucleotide polymorphisms and hereditary nonpolyposis colorectal cancer

Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant disease caused by germline mutations in DNA mismatch repair(MMR) genes. The nucleotide excision repair(NER) pathway plays a very important role in cancer development. We systematically studied interactions between NER and MMR genes to identify NER gene single nucleotide polymorphism (SNP) risk factors that modify the effect of MMR mutations on risk for cancer in HNPCC. We analyzed data from polymorphisms in 10 NER genes that had been genotyped in HNPCC patients that carry MSH2 and MLH1 gene mutations. The influence of the NER gene SNPs on time to onset of colorectal cancer (CRC) was assessed using survival analysis and a semiparametric proportional hazard model. We found the median age of onset for CRC among MMR mutation carriers with the ERCC1 mutation was 3.9 years earlier than patients with wildtype ERCC1(median 47.7 vs 51.6, log-rank test p=0.035). The influence of Rad23B A249V SNP on age of onset of HNPCC is age dependent (likelihood ratio test p=0.0056). Interestingly, using the likelihood ratio test, we also found evidence of genetic interactions between the MMR gene mutations and SNPs in ERCC1 gene(C8092A) and XPG/ERCC5 gene(D1104H) with p-values of 0.004 and 0.042, respectively. An assessment using tree structured survival analysis (TSSA) showed distinct gene interactions in MLH1 mutation carriers and MSH2 mutation carriers. ERCC1 SNP genotypes greatly modified the age onset of HNPCC in MSH2 mutation carriers, while no effect was detected in MLH1 mutation carriers. Given the NER genes in this study play different roles in NER pathway, they may have distinct influences on the development of HNPCC. The findings of this study are very important for elucidation of the molecular mechanism of colon cancer development and for understanding why some mutation carriers of the MSH2 and MLH1 gene develop CRC early and others never develop CRC. Overall, the findings also have important implications for the development of early detection strategies and prevention as well as understanding the mechanism of colorectal carcinogenesis in HNPCC. ^

Assessment of the performance of 3m 3500 organic vapor monitors over extended sampling durations

The purpose of this study was to assess the accuracy and precision of airborne volatile organic compound (VOC) concentrations measured using passive air samplers (3M 3500 organic vapor monitors) over extended sampling durations (9 and 15 days). A total of forty-five organic vapor monitor samples were collected at a State of Texas air monitoring site during two different sampling periods (July/August and November 2008). The results of this study indicate that for most of the tested compounds, there was no significant difference between long-term (9 or 15 days) sample concentrations and the means of parallel consecutive short-term (3 days) sample concentrations. Biases of 9 or 15-day measurements vs. consecutive 3-day measurements showed considerable variability. Those compounds that had percent bias values of <10% are suggested as acceptable for long-term sampling (9 and 15 days). Of the twenty-one compounds examined, 10 compounds are classified as acceptable for long-term sampling; these include m,p-xylene, 1,2,4-trimethylbenzene, n-hexane, ethylbenzene, benzene, toluene, o-xylene, d-limonene, dimethylpentane and methyl tertbutyl ether. The ratio of sampling procedure variability relative to variability within days was approximately 1.89 for both sampling periods for the 3-day vs. 9-day comparisons and approximately 2.19 for both sampling periods for the 3-day vs. 15-day comparisons. Considerably higher concentrations of most VOCs were measured during the November sampling period compared to the July/August period. These differences may be a result of varying meteorological conditions during these two time periods, e.g., the differences in wind direction, and wind speed. Further studies are suggested to further evaluate the accuracy and precision of 3M 3500 organic vapor monitors over extended sampling durations. ^

The role of workplace absence as an organizational mechanism in predicting employee alcohol and drug disorders

Background. EAP programs for airline pilots in companies with a well developed recovery management program are known to reduce pilot absenteeism following treatment. Given the costs and safety consequences to society, it is important to identify pilots who may be experiencing an AOD disorder to get them into treatment. ^ Hypotheses. This study investigated the predictive power of workplace absenteeism in identifying alcohol or drug disorders (AOD). The first hypothesis was that higher absenteeism in a 12-month period is associated with higher risk that an employee is experiencing AOD. The second hypothesis was that AOD treatment would reduce subsequent absence rates and the costs of replacing pilots on missed flights. ^ Methods. A case control design using eight years (time period) of monthly archival absence data (53,000 pay records) was conducted with a sample of (N = 76) employees having an AOD diagnosis (cases) matched 1:4 with (N = 304) non-diagnosed employees (controls) of the same profession and company (male commercial airline pilots). Cases and controls were matched on the variables age, rank and date of hire. Absence rate was defined as sick time hours used over the sum of the minimum guarantee pay hours annualized using the months the pilot worked for the year. Conditional logistic regression was used to determine if absence predicts employees experiencing an AOD disorder, starting 3 years prior to the cases receiving the AOD diagnosis. A repeated measures ANOVA, t tests and rate ratios (with 95% confidence intervals) were conducted to determine differences between cases and controls in absence usage for 3 years pre and 5 years post treatment. Mean replacement costs were calculated for sick leave usage 3 years pre and 5 years post treatment to estimate the cost of sick leave from the perspective of the company. ^ Results. Sick leave, as measured by absence rate, predicted the risk of being diagnosed with an AOD disorder (OR 1.10, 95% CI = 1.06, 1.15) during the 12 months prior to receiving the diagnosis. Mean absence rates for diagnosed employees increased over the three years before treatment, particularly in the year before treatment, whereas the controls’ did not (three years, x = 6.80 vs. 5.52; two years, x = 7.81 vs. 6.30, and one year, x = 11.00cases vs. 5.51controls. In the first year post treatment compared to the year prior to treatment, rate ratios indicated a significant (60%) post treatment reduction in absence rates (OR = 0.40, CI = 0.28, 0.57). Absence rates for cases remained lower than controls for the first three years after completion of treatment. Upon discharge from the FAA and company’s three year AOD monitoring program, case’s absence rates increased slightly during the fourth year (controls, x = 0.09, SD = 0.14, cases, x = 0.12, SD = 0.21). However, the following year, their mean absence rates were again below those of the controls (controls, x = 0.08, SD = 0.12, cases, x¯ = 0.06, SD = 0.07). Significant reductions in costs associated with replacing pilots calling in sick, were found to be 60% less, between the year of diagnosis for the cases and the first year after returning to work. A reduction in replacement costs continued over the next two years for the treated employees. ^ Conclusions. This research demonstrates the potential for workplace absences as an active organizational surveillance mechanism to assist managers and supervisors in identifying employees who may be experiencing or at risk of experiencing an alcohol/drug disorder. Currently, many workplaces use only performance problems and ignore the employee’s absence record. A referral to an EAP or alcohol/drug evaluation based on the employee’s absence/sick leave record as incorporated into company policy can provide another useful indicator that may also carry less stigma, thus reducing barriers to seeking help. This research also confirms two conclusions heretofore based only on cross-sectional studies: (1) higher absence rates are associated with employees experiencing an AOD disorder; (2) treatment is associated with lower costs for replacing absent pilots. Due to the uniqueness of the employee population studied (commercial airline pilots) and the organizational documentation of absence, the generalizability of this study to other professions and occupations should be considered limited. ^ Transition to Practice. The odds ratios for the relationship between absence rates and an AOD diagnosis are precise; the OR for year of diagnosis indicates the likelihood of being diagnosed increases 10% for every hour change in sick leave taken. In practice, however, a pilot uses approximately 20 hours of sick leave for one trip, because the replacement will have to be paid the guaranteed minimum of 20 hour. Thus, the rate based on hourly changes is precise but not practical. ^ To provide the organization with practical recommendations the yearly mean absence rates were used. A pilot flies on average, 90 hours a month, 1080 annually. Cases used almost twice the mean rate of sick time the year prior to diagnosis (T-1) compared to controls (cases, x = .11, controls, x = .06). Cases are expected to use on average 119 hours annually (total annual hours*mean annual absence rate), while controls will use 60 hours. The cases’ 60 hours could translate to 3 trips of 20 hours each. Management could use a standard of 80 hours or more of sick time claimed in a year as the threshold for unacceptable absence, a 25% increase over the controls (a cost to the company of approximately of $4000). At the 80-hour mark, the Chief Pilot would be able to call the pilot in for a routine check as to the nature of the pilot’s excessive absence. This management action would be based on a company standard, rather than a behavioral or performance issue. Using absence data in this fashion would make it an active surveillance mechanism. ^

Extension of k-ratio methods to rank-based analyses

An extension of k-ratio multiple comparison methods to rank-based analyses is described. The new method is analogous to the Duncan-Godbold approximate k-ratio procedure for unequal sample sizes or correlated means. The close parallel of the new methods to the Duncan-Godbold approach is shown by demonstrating that they are based upon different parameterizations as starting points.^ A semi-parametric basis for the new methods is shown by starting from the Cox proportional hazards model, using Wald statistics. From there the log-rank and Gehan-Breslow-Wilcoxon methods may be seen as score statistic based methods.^ Simulations and analysis of a published data set are used to show the performance of the new methods. ^

Nurse likelihood to report a pediatric medication error: Examination of the "pre-reporting" period

Each year, hospitalized patients experience 1.5 million preventable injuries from medication errors and hospitals incur an additional $3.5 billion in cost (Aspden, Wolcott, Bootman, & Cronenwatt; (2007). It is believed that error reporting is one way to learn about factors contributing to medication errors. And yet, an estimated 50% of medication errors go unreported. This period of medication error pre-reporting, with few exceptions, is underexplored. The literature focuses on error prevention and management, but lacks a description of the period of introspection and inner struggle over whether to report an error and resulting likelihood to report. Reporting makes a nurse vulnerable to reprimand, legal liability, and even threat to licensure. For some nurses this state may invoke a disparity between a person‘s belief about him or herself as a healer and the undeniable fact of the error.^ This study explored the medication error reporting experience. Its purpose was to inform nurses, educators, organizational leaders, and policy-makers about the medication error pre-reporting period, and to contribute to a framework for further investigation. From a better understanding of factors that contribute to or detract from the likelihood of an individual to report an error, interventions can be identified to help the nurse come to a psychologically healthy resolution and help increase reporting of error in order to learn from error and reduce the possibility of future similar error.^ The research question was: "What factors contribute to a nurse's likelihood to report an error?" The specific aims of the study were to: (1) describe participant nurses' perceptions of medication error reporting; (2) describe participant explanations of the emotional, cognitive, and physical reactions to making a medication error; (3) identify pre-reporting conditions that make it less likely for a nurse to report a medication error; and (4) identify pre-reporting conditions that make it more likely for a nurse to report a medication error.^ A qualitative research study was conducted to explore the medication error experience and in particular the pre-reporting period from the perspective of the nurse. A total of 54 registered nurses from a large private free-standing not-for-profit children's hospital in the southwestern United States participated in group interviews. The results describe the experience of the nurse as well as the physical, emotional, and cognitive responses to the realization of the commission of a medication error. The results also reveal factors that make it more and less likely to report a medication error.^ It is clear from this study that upon realization that he or she has made a medication error, a nurse's foremost concern is for the safety of the patient. Fear was also described by each group of nurses. The nurses described a fear of several things including physician reaction, manager reaction, peer reaction, as well as family reaction and possible lack of trust as a result. Another universal response was the description of a struggle with guilt, shame, imperfection, blaming oneself, and questioning one's competence.^

Effect of patient accrual patterns on power and size of log-rank test for time-to-event outcome in clinical trials

The determination of size as well as power of a test is a vital part of a Clinical Trial Design. This research focuses on the simulation of clinical trial data with time-to-event as the primary outcome. It investigates the impact of different recruitment patterns, and time dependent hazard structures on size and power of the log-rank test. A non-homogeneous Poisson process is used to simulate entry times according to the different accrual patterns. A Weibull distribution is employed to simulate survival times according to the different hazard structures. The current study utilizes simulation methods to evaluate the effect of different recruitment patterns on size and power estimates of the log-rank test. The size of the log-rank test is estimated by simulating survival times with identical hazard rates between the treatment and the control arm of the study resulting in a hazard ratio of one. Powers of the log-rank test at specific values of hazard ratio (≠1) are estimated by simulating survival times with different, but proportional hazard rates for the two arms of the study. Different shapes (constant, decreasing, or increasing) of the hazard function of the Weibull distribution are also considered to assess the effect of hazard structure on the size and power of the log-rank test. ^

The Extended Family: Reviewing an Invaluable Resource

During the last two decades, the extended family has been rediscovered as a viable and meaningful resource for nurturing and protecting children. The purpose of this article is to provide an historical context for involving the extended family in child welfare cases and to identify key factors influencing that involvement.

On-farm Cooperator Trials 2011: Effect of Extended-duration Row Covers on Muskmelon and Winter Squash on Bacterial Wilt and Yield

Susceptible cucurbit crops are difficult to grow in Iowa because of bacterial wilt, caused by Erwinia tracheiphila. Striped and spotted cucumber beetles transmit bacterial wilt. Other insect pests such as squash vine borer and squash bugs may also have an economic impact on yield, particularly in squash.

Relaciones de similitud y valor discriminativo de los indicadores bibliométricos: el caso de los indicadores de Scimago Journal and Country Rank aplicados a las revistas generalistas de paleontología

Los objetivos de este trabajo son: (1) analizar las relaciones de similitud de los indicadores bibliométricos; y (2) estudiar el valor de estos para discriminar/agrupar revistas científicas. Como unidades de estudio se utilizaron los 15 indicadores brindados por SCImago Journal Rank (SCImagoJR), aplicados a las 11 revistas paleontológicas generalistas listadas en dicha fuente durante el lapso 1999-2013. Las relaciones de similitud entre los indicadores se estimaron mediante un fenograma, mientras que el valor de los indicadores para agrupar/discriminar revistas se estimó mediante un análisis de componentes principales. Los resultados permiten concluir que, al menos para las revistas consideradas en este estudio, los 15 indicadores utilizados por SCImagoJR muestran redundancia por grupos, debido a las correlaciones existentes entre indicadores de producción, por una parte, y de citación, por otra. Sin embargo, esto es válido solo a los efectos de agrupar las revistas, ya que al considerar cada indicador por separado se aprecian variaciones entre los mismos, que permiten establecer una caracterización más específica de cada revista e, incluso, colaboran a explicar los resultados del análisis multivariado. Por otra parte, los resultados coinciden con los obtenidos por otros autores al reunir en un mismo grupo al SJR y al número de citas/documento en un período de dos años y en otro al índice h y al indicador número total de citas en un lapso de tres años.

Relaciones de similitud y valor discriminativo de los indicadores bibliométricos: el caso de los indicadores de Scimago Journal and Country Rank aplicados a las revistas generalistas de paleontología

Los objetivos de este trabajo son: (1) analizar las relaciones de similitud de los indicadores bibliométricos; y (2) estudiar el valor de estos para discriminar/agrupar revistas científicas. Como unidades de estudio se utilizaron los 15 indicadores brindados por SCImago Journal Rank (SCImagoJR), aplicados a las 11 revistas paleontológicas generalistas listadas en dicha fuente durante el lapso 1999-2013. Las relaciones de similitud entre los indicadores se estimaron mediante un fenograma, mientras que el valor de los indicadores para agrupar/discriminar revistas se estimó mediante un análisis de componentes principales. Los resultados permiten concluir que, al menos para las revistas consideradas en este estudio, los 15 indicadores utilizados por SCImagoJR muestran redundancia por grupos, debido a las correlaciones existentes entre indicadores de producción, por una parte, y de citación, por otra. Sin embargo, esto es válido solo a los efectos de agrupar las revistas, ya que al considerar cada indicador por separado se aprecian variaciones entre los mismos, que permiten establecer una caracterización más específica de cada revista e, incluso, colaboran a explicar los resultados del análisis multivariado. Por otra parte, los resultados coinciden con los obtenidos por otros autores al reunir en un mismo grupo al SJR y al número de citas/documento en un período de dos años y en otro al índice h y al indicador número total de citas en un lapso de tres años.

Relaciones de similitud y valor discriminativo de los indicadores bibliométricos: el caso de los indicadores de Scimago Journal and Country Rank aplicados a las revistas generalistas de paleontología

Los objetivos de este trabajo son: (1) analizar las relaciones de similitud de los indicadores bibliométricos; y (2) estudiar el valor de estos para discriminar/agrupar revistas científicas. Como unidades de estudio se utilizaron los 15 indicadores brindados por SCImago Journal Rank (SCImagoJR), aplicados a las 11 revistas paleontológicas generalistas listadas en dicha fuente durante el lapso 1999-2013. Las relaciones de similitud entre los indicadores se estimaron mediante un fenograma, mientras que el valor de los indicadores para agrupar/discriminar revistas se estimó mediante un análisis de componentes principales. Los resultados permiten concluir que, al menos para las revistas consideradas en este estudio, los 15 indicadores utilizados por SCImagoJR muestran redundancia por grupos, debido a las correlaciones existentes entre indicadores de producción, por una parte, y de citación, por otra. Sin embargo, esto es válido solo a los efectos de agrupar las revistas, ya que al considerar cada indicador por separado se aprecian variaciones entre los mismos, que permiten establecer una caracterización más específica de cada revista e, incluso, colaboran a explicar los resultados del análisis multivariado. Por otra parte, los resultados coinciden con los obtenidos por otros autores al reunir en un mismo grupo al SJR y al número de citas/documento en un período de dos años y en otro al índice h y al indicador número total de citas en un lapso de tres años.

PaleoTools - extended software package for quantitative paleoenvironmental reconstructions

The Imbrie and Kipp transfer function method (IKM) and the modern analog technique (MAT) are accepted tools for quantitative paleoenvironmental reconstructions. However, no uncomplicated, flexible software has been available to apply these methods on modern computer devices. For this reason the software packages PaleoToolBox, MacTransfer, WinTransfer, MacMAT, and PanPlot have been developed. The PaleoToolBox package provides a flexible tool for the preprocessing of microfossil reference and downcore data as well as hydrographic reference parameters. It includes procedures to randomize the raw databases; to switch specific species in or out of the total species list; to establish individual ranking systems and their application on the reference and downcore databasessemi; and to convert the prepared databases into the file formats of IKM and MAT software for estimation of paleohydrographic parameters.