Hierarchical Bayesian Modeling of Spatio-temporal Patterns of Lung Cancer Incidence Risk in Georgia, USA: 2000–2007

Lung cancer is the second most commonly diagnosed cancer in both men and women in Georgia, USA. However, the spatio-temporal patterns of lung cancer risk in Georgia have not been fully studied. Hierarchical Bayesian models are used here to explore the spatio-temporal patterns of lung cancer incidence risk by race and gender in Georgia for the period of 2000–2007. With the census tract level as the spatial scale and the 2-year period aggregation as the temporal scale, we compare a total of seven Bayesian spatio-temporal models including two under a separate modeling framework and five under a joint modeling framework. One joint model outperforms others based on the deviance information criterion. Results show that the northwest region of Georgia has consistently high lung cancer incidence risk for all population groups during the study period. In addition, there are inverse relationships between the socioeconomic status and the lung cancer incidence risk among all Georgian population groups, and the relationships in males are stronger than those in females. By mapping more reliable variations in lung cancer incidence risk at a relatively fine spatio-temporal scale for different Georgian population groups, our study aims to better support healthcare performance assessment, etiological hypothesis generation, and health policy making

Enhanced removal of Cryptosporidium parvum oocysts and Cryptosporidium-sized microspheres from recreational water through filtration

Cryptosporidium species are the cause of cryptosporidiosis, which has symptoms such as watery diarrhea, dehydration, fever, nausea, body fatigue, and abdominal cramps. Infants, the elderly, and people with severely compromised immune systems are more susceptible and could die from cryptosporidiosis. Numerous waterborne outbreaks of cryptosporidiosis have been linked to swimming pools in United Kingdom, United States, Australia, and Canada. The concerns of public health and increasing demands for recreational opportunities have pushed the need for enhanced removals of Cryptosporidium from swimming pools to emergent. Unfortunately, relatively little information is available on Cryptosporidium removal from pilot-scale or full-scale swimming pools or spas. Water quality was evaluated for thirty five national swimming pools at first to evaluate the chemical constituents of the swimming pools. Based on these data, three representative swimming pool waters were developed using cluster analysis, which were applied in subsequent experiments. Based on this survey, an average pool would have a pH of 7.5 with 1.5 mg/L of free chlorine, and the alkalinity and hardness would be 94 mg/L and 238 mg/L as CaCO3, respectively. The average turbidity would be 0.33 NTU, and the DOC concentration would be 5 mg/L. Zeta potentials of Cryptosporidium oocyst-sized microspheres in three pool waters were titrated with six coagulants to determine dose-response relationships. Overdosing of organic polymer coagulants (i.e., coagulants A, B, and F) was shown to be possible. No significant differences were observed for any of the coagulants' performance in the three water formulations test. High-rate sand filtration (which refers to a filtration rate up to 37 m/h with coagulant addition before sand filtration) was evaluated in this study. A series of experiments were conducted to develop a novel operational procedure for high-rate sand filtration and provide field-relevant results. Results indicated that the highest removals occurred when coagulant was fed continuously by a coagulant pump. Extended/excessive dosing coagulant A (the only coagulant used in this part of the study) led to coagulant A build up in the system and reduced microsphere removal efficiency. Three alternative treatment techniques were evaluated for ability to enhance Cryptosporidium-sized microsphere removals from a 5,500 L pilot-scale pool, including feeding coagulants prior to sand filter, adding a layer of perlite on top of the sand filter's media without coagulation, and diatomaceous earth (DE) filtration. High-rate sand filtration without coagulation (control experiment) removed 20% - 63% of microspheres. Up to 99% Cryptosporidium-sized microsphere removal was achieved through high-rate sand filtration with coagulants A, B, D, and F at 37 m/h. Coagulant C was a chitosan-based product that removed less than 80% of microspheres under the studied conditions. Coagulant E (polyaluminum chloride) removed more than 90% of microspheres at 30 m/h. Adding perlite on the top of a sand filter increased the Cryptosporidium oocysts-sized microsphere removals to 79%, 99%, 99.7%, and 99.8% with 0.24 kg·perlite/m2, 0.37 kg·perlite/m2, 0.49 kg·perlite/m2 and 0.61 kg·perlite/m2, respectively. At least 0.7 kg·bull;DE/m 2 was required to achieve approximately 99% of Cryptosporidium-sized microspheres by DE filtration. Cryptosporidium parvum and Cryptosporidium -sized microsphere removals from full-scale swimming pools were evaluated. Coagulants B, D, E, and F were individually fed into swimming pools both with remediation dose and maintenance dose. Approximately 90% of Cryptosporidium parvum and microspheres were removed by filtration with coagulant B (1.56 mg/L), coagulant D (305g/m2), and coagulant F (1.56 mg/L) under remediation conditions. Eighty two percent of Cryptosporidium and 97% of microspheres were removed with coagulant E (0.1 mg·Al/L) under remediation conditions. Under maintenance dosing conditions: up to 93% of Cryptosporidium and 77% of microsphere were removed by coagulant B; as high as 99% of Cryptosporidium and 98% of microsphere were removed with coagulant D; 98% of Cryptosporidium and 93% of microsphere were removed with coagulant E; up to 85% of Cryptosporidium and 82% of microsphere were removed with coagulant F. Organic polymer coagulants accumulated in the swimming pool water (as measured for coagulant A concentration under the study conditions) and led to poor filter performance over time. Additionally, Cryptosporidium parvum removals by perlite/sand filter was 88%, and microspheres removal was 99.8% (0.5 kg·perlite/m2). DE filtration provided above 99.8% removals both for Cryptosporidium parvum and microspheres. Cartridge filters only achieved 22% removal of microspheres from a full-scale spa. To summarize, Cryptosporidium and microspheres could be effectively removed on a continuing basis by DE filtration, perlite/sand filtration, and high-rate sand filtration with continuously feeding of coagulant D or E. Performance of coagulant D and E tended to decrease with increased filter pressure, which could warrant additional research. Coagulant A, B, and F achieved up to 99% removal at the recommended dosage, but Cryptosporidium and microsphere removals decreased to less than 90% (typically within 48 hours) as the polymer coagulants accumulated in the pool

Modular Capacitated Maximal Covering Location Problem for the Optimal Siting of Emergency Vehicles

To improve the application of the maximal covering location problem (MCLP), several capacitated MCLP models were proposed to consider the capacity limits of facilities. However, most of these models assume only one fixed capacity level for the facility at each potential site. This assumption may limit the application of the capacitated MCLP. In this article, a modular capacitated maximal covering location problem (MCMCLP) is proposed and formulated to allow several possible capacity levels for the facility at each potential site. To optimally site emergency vehicles, this new model also considers allocations of the demands beyond the service covering standard. Two situations of the model are discussed: the MCMCLP-facility-constraint (FC), which fixes the total number of facilities to be located, and the MCMCLP-non-facility-constraint (NFC), which does not. In addition to the model formulations, one important aspect of location modeling—spatial demand representation—is included in the analysis and discussion. As an example, the MCMCLP is applied with Geographic Information System (GIS) and optimization software packages to optimally site ambulances for the Emergency Medical Services (EMS) Region 10 in the State of Georgia. The limitations of the model are also discussed

A new assessment model for tumor heterogeneity analysis with [18]F-FDG PET images

It has been shown that the intratumor heterogeneity can be characterized with quantitative analysis of the [18]F-FDG PET image data. The existing models employ multiple parameters for feature extraction which makes it difficult to implement in clinical settings for the quantitative characterization. This article reports an easy-to-use and differential SUV based model for quantitative assessment of the intratumor heterogeneity from 3D [18]F-FDG PET image data. An H index is defined to assess tumor heterogeneity by summing voxel-wise distribution of differential SUV from the [18]F-FDG PET image data. The summation is weighted by the distance of SUV difference among neighboring voxels from the center of the tumor and can thus yield increased values for tumors with peripheral sub-regions of high SUV that often serves as an indicator of augmented malignancy. Furthermore, the sign of H index is used to differentiate the rate of change for volume averaged SUV from its center to periphery. The new model with the H index has been compared with a widely-used model of gray level co-occurrence matrix (GLCM) for image texture characterization with phantoms of different configurations and the [18]F-FDG PET image data of 6 lung cancer patients to evaluate its effectiveness and feasibility for clinical uses. The comparison of the H index and GLCM parameters with the phantoms demonstrate that the H index can characterize the SUV heterogeneity in all of 6 2D phantoms while only 1 GLCM parameter can do for 1 and fail to differentiate for other 2D phantoms. For the 8 3D phantoms, the H index can clearly differentiate all of them while the 4 GLCM parameters provide complicated patterns in the characterization. Feasibility study with the PET image data from 6 lung cancer patients show that the H index provides an effective single-parameter metric to characterize tumor heterogeneity in terms of the local SUV variation, and it has higher correlation with tumor volume change after radiotherapy (R2 = 0.83) than the 4 GLCM parameters (R2 = 0.63, 0.73, 0.59 and 0.75 for Energy, Contrast, Local Homogeneity and Entropy respectively). The new model of the H index has the capacity to characterize the intratumor heterogeneity feature from 3D [18]F-FDG PET image data. As a single parameter with an intuitive definition, the H index offers potential for clinical applications

Deep sequencing identifies novel and conserved microRNAs in peanuts (Arachis hypogaea L.)

<p>Abstract</p> <p>Background</p> <p>MicroRNAs (miRNAs) are a new class of small, endogenous RNAs that play a regulatory role in the cell by negatively affecting gene expression at the post-transcriptional level. miRNAs have been shown to control numerous genes involved in various biological and metabolic processes. There have been extensive studies on discovering miRNAs and analyzing their functions in model species, such as <it>Arabidopsis </it>and rice. Increasing investigations have been performed on important agricultural crops including soybean, conifers, and <it>Phaselous vulgaris </it>but no studies have been reported on discovering peanut miRNAs using a cloning strategy.</p> <p>Results</p> <p>In this study, we employed the next generation high through-put Solexa sequencing technology to clone and identify both conserved and species-specific miRNAs in peanuts. Next generation high through-put Solexa sequencing showed that peanuts have a complex small RNA population and the length of small RNAs varied, 24-nt being the predominant length for a majority of the small RNAs. Combining the deep sequencing and bioinformatics, we discovered 14 novel miRNA families as well as 75 conserved miRNAs in peanuts. All 14 novel peanut miRNAs are considered to be species-specific because no homologs have been found in other plant species except ahy-miRn1, which has a homolog in soybean. qRT-PCR analysis demonstrated that both conserved and peanut-specific miRNAs are expressed in peanuts.</p> <p>Conclusions</p> <p>This study led to the discovery of 14 novel and 22 conserved miRNA families from peanut. These results show that regulatory miRNAs exist in agronomically important peanuts and may play an important role in peanut growth, development, and response to environmental stress.</p

The Beck Cognitive Insight Scale (BCIS): translation and validation of the Taiwanese version

<p>Abstract</p> <p>Background</p> <p>Over the last few decades, research concerning the insight of patients with schizophrenia and its relationships with other clinical variables has been given much attention in the clinical setting. Since that time, a series of instruments assessing insight have been developed. The purpose of this study was to examine the reliability and validity of the Taiwanese version of the Beck Cognitive Insight Scale (BCIS). The BCIS is a self-administered instrument designed to evaluate cognitive processes that involves reevaluating patients' anomalous experiences and specific misinterpretations.</p> <p>Methods</p> <p>The English language version of the BCIS was translated into Taiwanese for use in this study. A total of 180 subjects with and without psychosis completed the Taiwanese version of the BCIS and additional evaluations to assess researcher-rated insight scales and psychopathology. Psychometric properties (factor structures and various types of reliability and validity) were assessed for this translated questionnaire.</p> <p>Results</p> <p>Overall, the Taiwanese version of the BCIS showed good reliability and stability over time. This translated scale comprised a two-factor solution corresponding to reflective attitude and certain attitude subscales. Following the validation of the internal structure of the scale, we obtained an R-C (reflective attitude minus certain attitude) index of the translated BCIS, representing the measurement of cognitive insight by subtracting the score of the certain attitude subscale from that of the reflective attitude subscale. As predicted, the differences in mean reflective attitude, certain attitude and R-C index between subjects with and without psychosis were significant. Our data also demonstrated that psychotic patients were significantly less reflective, more confident in their beliefs, and had less cognitive insight compared with nonpsychotic control groups.</p> <p>Conclusions</p> <p>In light of these findings, we believe that the Taiwanese version of BCIS is a valid and reliable instrument for the assessment of cognitive insight in psychotic patients.</p

A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci.

We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10⁻¹²) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10⁻¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻¹¹) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻¹¹), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis

CAG Repeat Variants in the POLG1 Gene Encoding mtDNA Polymerase-Gamma and Risk of Breast Cancer in African-American Women

The DNA polymerase-gamma (POLG) gene, which encodes the catalytic subunit of enzyme responsible for directing mitochondrial DNA replication in humans, contains a polyglutamine tract encoded by CAG repeats of varying length. The length of the CAG repeat has been associated with the risk of testicular cancer, and other genomic variants that impact mitochondrial function have been linked to breast cancer risk in African-American (AA) women. We evaluated the potential role of germline POLG-CAG repeat variants in breast cancer risk in a sample of AA women (100 cases and 100 age-matched controls) who participated in the Women's Circle of Health Study, an ongoing multi-institutional, case-control study of breast cancer. Genotyping was done by fragment analysis in a blinded manner. Results from this small study suggest the possibility of an increased risk of breast cancer in women with minor CAG repeat variants of POLG, but no statistically significant differences in CAG repeat length were observed between cases and controls (multivariate-adjusted odds ratio 1.74; 95% CI, 0.49–6.21). Our study suggests that POLG-CAG repeat length is a potential risk factor for breast cancer that needs to be explored in larger population-based studies

Discovery of a Distinct Superfamily of Kunitz-Type Toxin (KTT) from Tarantulas

BACKGROUND: Kuntiz-type toxins (KTTs) have been found in the venom of animals such as snake, cone snail and sea anemone. The main ancestral function of Kunitz-type proteins was the inhibition of a diverse array of serine proteases, while toxic activities (such as ion-channel blocking) were developed under a variety of Darwinian selection pressures. How new functions were grafted onto an old protein scaffold and what effect Darwinian selection pressures had on KTT evolution remains a puzzle. PRINCIPAL FINDINGS: Here we report the presence of a new superfamily of ktts in spiders (TARANTULAS: Ornithoctonus huwena and Ornithoctonus hainana), which share low sequence similarity to known KTTs and is clustered in a distinct clade in the phylogenetic tree of KTT evolution. The representative molecule of spider KTTs, HWTX-XI, purified from the venom of O. huwena, is a bi-functional protein which is a very potent trypsin inhibitor (about 30-fold more strong than BPTI) as well as a weak Kv1.1 potassium channel blocker. Structural analysis of HWTX-XI in 3-D by NMR together with comparative function analysis of 18 expressed mutants of this toxin revealed two separate sites, corresponding to these two activities, located on the two ends of the cone-shape molecule of HWTX-XI. Comparison of non-synonymous/synonymous mutation ratios (omega) for each site in spider and snake KTTs, as well as PBTI like body Kunitz proteins revealed high Darwinian selection pressure on the binding sites for Kv channels and serine proteases in snake, while only on the proteases in spider and none detected in body proteins, suggesting different rates and patterns of evolution among them. The results also revealed a series of key events in the history of spider KTT evolution, including the formation of a novel KTT family (named sub-Kuntiz-type toxins) derived from the ancestral native KTTs with the loss of the second disulfide bridge accompanied by several dramatic sequence modifications. CONCLUSIONS/SIGNIFICANCE: These finding illustrate that the two activity sites of Kunitz-type toxins are functionally and evolutionally independent and provide new insights into effects of Darwinian selection pressures on KTT evolution, and mechanisms by which new functions can be grafted onto old protein scaffolds

Assessing cognitive insight in nonpsychiatric individuals and outpatients with schizophrenia in Taiwan: an investigation using the Beck Cognitive Insight Scale

<p>Abstract</p> <p>Background</p> <p>The Beck Cognitive Insight Scale (BCIS) was designed for the assessment of the cognitive processes involved in self-reflection and the ability to modify erroneous beliefs and misinterpretations. Studies investigating the factor structure of the BCIS have indicated a two-factor model in the psychotic population. The factor structure of the BCIS, however, has not received much consideration in the nonpsychiatric population. The present study examined the factor structure and validity of the BCIS and compared its scores between nonpsychiatric individuals and outpatients with psychosis.</p> <p>Method</p> <p>The Taiwanese version of the BCIS was administered to 507 nonpsychiatric individuals and 118 outpatients with schizophrenia. The psychometric properties of the BCIS were examined through the following analyses: exploratory and confirmatory factor analyses, reliability, correlation analyses, and discriminative validity.</p> <p>Results</p> <p>The BCIS showed adequate internal consistency and stability over time. Exploratory and confirmatory factor analyses on the 15-item measure indicated a two-factor solution that supported the two dimensions of the Taiwanese BCIS, which was also observed with the original BCIS. Following the construct validation, we obtained a composite index (self-reflectiveness minus self-certainty) of the Taiwanese BCIS that reflected cognitive insight. Consistent with previous studies, our results indicated that psychosis is associated with low self-reflectiveness and high self-certainty, which possibly reflect lower cognitive insight. Our results also showed that better cognitive insight is related to worse depression in patients with schizophrenia spectrum disorders, but not in nonpsychiatric individuals. The receiver operating characteristic (ROC) analyses revealed that the area under the curve (AUC) was 0.731. A composite index of 3 was a good limit, with a sensitivity of 87% and a specificity of 51%.</p> <p>Conclusion</p> <p>The BCIS proved to be useful for measuring cognitive insight in Taiwanese nonpsychiatric and psychotic populations.</p