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Machine learning algorithms provide detailed description of the anaerobic digestion process, but the impact of data preparation procedures and hyperparameter optimization has rarely been investigated. A genetic algorithm was developed for optimizing data preparation and model hyperparameters to simulate dynamic methane production from steady-state anaerobic digestion of agricultural residues at full-scale. A long short-term memory neural network was used as prediction model. Results indicate that batch size, learning rate and number of neurons are the most important model parameters for accurate description of methane production rates, whereas combination of hyperparameter and data preparation optimization shows best model efficiencies, with a root mean square scaled error of 76.5 %. Mass of solid feed, time and mass of volatile solids are the most relevant input features. This study provides fundamental steps for optimal prediction of dynamic biomethane production, as a reliable basis for improving bioconversion efficiency during anaerobic digestion of agricultural residues., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Flexible biogas production can enable demand-oriented energy supply without the need for expensive gas storage expansions, but poses challenges to the stability of the anaerobic digestion (AD) process. In this work, biogas production of laboratory-scale AD of maize silage and sugar beets was optimized to cover the residual load of an electricity self-sufficient community using a simple process model based on first-order kinetics. Experiments show a good agreement between biogas demand, predicted, and measured biogas production. By optimizing biogas conversion schedules based on the measured gas production, a gas storage capacity of 7-8 h was identified for maximum flexibility, which corresponds to typical gas storage sizes at industrial biogas plants in Germany. Various stability indicators were continuously monitored and proved resilient process conditions. These results demonstrate that demand-oriented biogas production using model predictive control is a promising approach to enable existing biogas plants to provide balancing energy., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Due to a limited number of available measurements on agricultural biogas plants, established process models, such as the Anaerobic Digestion Model No. 1 (ADM1), are rarely applied in practise. To provide a reliable basis for model-based monitoring and control, different model simplifications of the ADM1 were implemented for process simulation of semi-continuous anaerobic digestion experiments using agricultural substrates (maize silage, sugar beet silage, rye grain and cattle manure) and industrial residues (grain stillage). Individual model structures enable a close depiction of biogas production rates and characteristic intermediates (ammonium nitrogen, propionic and acetic acid) with equal accuracy as the original ADM1. The impact of different objective functions and standard parameter values on parameter estimates of first-order hydrolysis constants and microbial growth rates were evaluated. Due to the small number of required model parameters and suitable system characteristics, simplified model structures show clear advantages for practical application on agricultural biogas plants., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Rigorous process models provide a reliable basis for model-based monitoring and control of anaerobic digestion plants. Due to the complex model structure and non-linear system characteristics, the established Anaerobic Digestion Model No. 1 (ADM1) is rarely applied in industrial plant operation. The present investigation proposes a systematic procedure for successive model simplification and presents the description of five model variants of a mass-based ADM1. Individual model structures greatly differ in their number of implemented process phases, characteristic components and required parameters. Simplified model variants combine nutrient degradation and biogas formation based on first-order sum reactions, whereas complex model structures describe individual degradation pathways and intermediates during acido- and acetogenesis. Characteristic features of the derived model structures as well as the stoichiometric methane potentials and microbial biomass yields of the underlying degradation pathways of individual model variations are evaluated and discussed in detail., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Methane emissions from livestock manure are primary contributors to GHG emissions from agriculture and options for their mitigation must be found. This paper presents the results of a study on methane emissions from stored liquid dairy cow manure during summer and winter storage periods. Manure from the summer and winter season was stored under controlled conditions in barrels at ambient temperature to simulate manure storage conditions. Methane emissions from the manure samples from the winter season were measured in two time periods: 0 to 69 and 0 to 139 days. For the summer storage period, the experiments covered four time periods: from 0 to 70, 0 to 138, 0 to 209, and 0 to 279 continuous days, with probing every 10 weeks. Additionally, at the end of all storage experiments, samples were placed into eudiometer batch digesters, and their methane emissions were measured at 20 °C for another 60 days to investigate the potential effect of the aging of the liquid manure on its methane emissions. The experiment showed that the methane emissions from manure stored in summer were considerably higher than those from manure stored in winter. CH 4 production started after approximately one month, reaching values of 0.061 kg CH 4 kg -1 Volatile Solid (VS) and achieving high total emissions of 0.148 kg CH 4 kg -1 VS (40 weeks). In winter, the highest emissions level was 0.0011 kg CH 4 kg -1 VS (20 weeks). The outcomes of these experimental measurements can be used to suggest strategies for mitigating methane emissions from manure storage., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Inter-laboratory reproducibility of biomethane potential (BMP) is dismal, with differences in BMP values for the same sample exceeding a factor of two in some cases. A large group of BMP researchers directly addressed this problem during a workshop held in Leysin, Switzerland, in June 2015. The workshop resulted in a new set of guidelines for BMP tests published in 2016, which is the subject of the present commentary. The work has continued with two international inter-laboratory studies and one additional workshop held in Freising, Germany, in 2018. The dataset generated by the two inter-laboratory studies were used to refine the validation criteria for BMP tests. Based on these new results an update to the original guidelines is proposed here.

Cattle manure is an agricultural residue, which could be used as source to produce methane in order to substitute fossil fuels. Nevertheless, in practice the handling of this slowly degradable substrate during anaerobic digestion is challenging. In this study, the influence of the pre-treatment of cattle manure with pressure-swing conditioning (PSC) on the methane production was investigated. Six variants of PSC (combinations of duration 5 min, 30 min, 60 min and temperature 160 °C, 190 °C) were examined with regards to methane yield in batch tests. PSC of cattle manure showed a significant increase up to 109% in the methane yield compared to the untreated sample. Kinetic calculations proved also an enhancement of the degradation speed. One PSC-variant (190 °C/30 min) and untreated cattle manure were chosen for comparative fermentation tests in continuously stirred tank reactors (CSTR) in lab-scale with duplicates. In the continuous test a biogas production of 428 mL/g volatile solids (VS) (54.2% methane) for untreated manure was observed and of 456 mL/g VS (53.7% methane) for PSC-cattle-manure (190 °C/30 min). Significant tests were conducted for methane yields of all fermentation tests. Furthermore, other parameters such as furfural were investigated and discussed.

The process of anaerobic digestion in which waste biomass is transformed to methane by complex microbial communities has been modeled for more than 16 years by parametric gray box approaches that simplify process biology and do not resolve intracellular microbial activity. Information on such activity, however, has become available in unprecedented detail by recent experimental advances in metatranscriptomics and metaproteomics. The inclusion of such data could lead to more powerful process models of anaerobic digestion that more faithfully represent the activity of microbial communities. We augmented the Anaerobic Digestion Model No. 1 (ADM1) as the standard kinetic model of anaerobic digestion by coupling it to Flux-Balance-Analysis (FBA) models of methanogenic species. Steady-state results of coupled models are comparable to standard ADM1 simulations if the energy demand for non-growth associated maintenance (NGAM) is chosen adequately. When changing a constant feed of maize silage from continuous to pulsed feeding, the final average methane production remains very similar for both standard and coupled models, while both the initial response of the methanogenic population at the onset of pulsed feeding as well as its dynamics between pulses deviates considerably. In contrast to ADM1, the coupled models deliver predictions of up to 1,000s of intracellular metabolic fluxes per species, describing intracellular metabolic pathway activity in much higher detail. Furthermore, yield coefficients which need to be specified in ADM1 are no longer required as they are implicitly encoded in the topology of the species' metabolic network. We show the feasibility of augmenting ADM1, an ordinary differential equation-based model for simulating biogas production, by FBA models implementing individual steps of anaerobic digestion. While cellular maintenance is introduced as a new parameter, the total number of parameters is reduced as yield coefficients no longer need to be specified. The coupled models provide detailed predictions on intracellular activity of microbial species which are compatible with experimental data on enzyme synthesis activity or abundance as obtained by metatranscriptomics or metaproteomics. By providing predictions of intracellular fluxes of individual community members, the presented approach advances the simulation of microbial community driven processes and provides a direct link to validation by state-of-the-art experimental techniques.

Ensiling of sugarcane trash (SCT) and sugarcane stalks (SCS) was studied to assess the effects of molasses (MOL) and lactic acid bacteria (LAB) inoculant on methane potential. The experiment was run for 70 days and monitoring parameters were analyzed at days 0, 5, 15 and 70. Biochemical methane potential (BMP) tests performed with fresh and ensiled material at day 70 showed an increase in methane potential by 24.0%, 23.4%, 1.7% and 71.1% for SCS ctr , SCT ctr , SCT mol and SCT mol + lab , respectively. Such improved performance is explained by the formation of organic acids (mostly acetate and lactate) which were able to decrease the pH of the silages from 5.7-5.9 to 3.8-4.2 for all SCT treatments and from 5.9 up to 3.4 for SCS treatment. Thus, the ensiling process provided similar effects to a pre-treatment at low acid concentrations, which in turn improved the digestibility of the cellulosic biomass for methane production., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

For biogas-producing continuous stirred tank reactors, an increase in dilution rate increases the methane production rate as long as substrate input can be converted fully. However, higher dilution rates necessitate higher specific microbial growth rates, which are assumed to have a strong impact on the apparent microbial biomass yield due to cellular maintenance. To test this, we operated two reactors at 37°C in parallel at dilution rates of 0.18 and 0.07 days -1 (hydraulic retention times of 5.5 and 14 days, doubling times of 3.9 and 9.9 days in steady state) with identical inoculum and a mixture of volatile fatty acids as sole carbon sources. We evaluated the performance of the Anaerobic Digestion Model No. 1 (ADM1), a thermodynamic black box approach (TBA), and dynamic flux balance analysis (dFBA), to describe the experimental observations. All models overestimated the impact of dilution rate on the apparent microbial biomass yield when using default parameter values. Based on our analysis, a maintenance coefficient value below 0.2 kJ per carbon mole of microbial biomass per hour should be used for the TBA, corresponding to 0.12 mmol ATP per gram dry weight per hour for dFBA, which strongly deviates from the value of 9.8 kJ Cmol h -1 that has been suggested to apply to all anaerobic microorganisms at 37°C. We hypothesized that a decrease in dilution rate might select taxa with minimized maintenance expenditure. However, no major differences in the dominating taxa between the reactors were observed based on amplicon sequencing of 16S rRNA genes and terminal restriction fragment length polymorphism analysis of mcrA genes. Surprisingly, Methanosaeta dominated over Methanosarcina even at a dilution rate of 0.18 days -1 , which contradicts previous model expectations. Furthermore, only 23-49% of the bacterial reads could be assigned to known syntrophic fatty acid oxidizers, indicating that unknown members of this functional group remain to be discovered. In conclusion, microbial maintenance was found to be much lower for acetogenesis and methanogenesis than previously assumed, likely due to the exceptionally low growth rates in anaerobic digestion. This finding might also be relevant for other microbial systems operating at similarly low growth rates.

Ammonia inhibition is an important reason for reactor failures and economic losses in anaerobic digestion. Its impact on acetic acid degradation is well-studied, while its effect on propionic and butyric acid degradation has received little attention and is consequently not considered in the Anaerobic Digestion Model No. 1 (ADM1). To compare ammonia inhibition of the degradation of these three volatile fatty acids (VFAs), we fed a mixture of them as sole carbon source to three continuous stirred tank reactors (CSTRs) and increased ammonium bicarbonate concentrations in the influent from 52 to 277 mM. The use of this synthetic substrate allowed for the determination of degradation efficiencies for the individual acids. While butyric acid degradation was hardly affected by the increase of ammonia concentration, propionic acid degradation turned out to be even more inhibited than acetic acid degradation with degradation efficiencies dropping to 31 and 65% for propionic and acetic acid, respectively. The inhibited reactors acclimatized and approximated pre-disturbance degradation efficiencies toward the end of the experiment, which was accompanied by strong microbial community shifts, as observed by amplicon sequencing of 16S rRNA genes and terminal restriction fragment length polymorphism (T-RFLP) of mcrA genes. The acetoclastic methanogen Methanosaeta was completely replaced by Methanosarcina . The propionic acid degrading genus Syntrophobacter was replaced by yet unknown propionic acid degraders. The butyric acid degrading genus Syntrophomonas and hydrogenotrophic Methanomicrobiaceae were hardly affected. We hypothesized that the ammonia sensitivity of the initially dominating taxa Methanosaeta and Syntrophobacter led to a stronger inhibition of the acetic and propionic acid degradation compared to butyric acid degradation and hydrogenotrophic methanogenesis, which were facilitated by the ammonia tolerant taxa Syntrophomonas and Methanomicrobiaceae . We implemented this hypothesis into a multi-taxa extension of ADM1, which was able to simulate the dynamics of both microbial community composition and VFA concentration in the experiment. It is thus plausible that the effect of ammonia on VFA degradation strongly depends on the ammonia sensitivity of the dominating taxa, for syntrophic propionate degraders as much as for acetoclastic methanogens.

Background: Demand-driven biogas production could play an important role for future sustainable energy supply. However, feeding a biogas reactor according to energy demand may lead to organic overloading and, thus, to process failures. To minimize this risk, digesters need to be actively steered towards containing more robust microbial communities. This study focuses on acetogenesis and methanogenesis as crucial process steps for avoiding acidification. We fed lab-scale anaerobic digesters with volatile fatty acids under various feeding regimes and disturbances. The resulting microbial communities were analyzed on DNA and RNA level by terminal restriction fragment length polymorphism of the mcrA gene, 16S rRNA gene amplicon sequencing, and a [2- 13 C]-acetate assay. A modified Anaerobic Digestion Model 1 (ADM1) that distinguishes between the acetoclastic methanogens Methanosaeta and Methanosarcina was developed and fitted using experimental abiotic and biotic process parameters., Results: Discontinuous feeding led to more functional resilience than continuous feeding, without loss in process efficiency. This was attributed to a different microbial community composition. Methanosaeta dominated the continuously fed reactors, while its competitor Methanosarcina was washed out. With discontinuous feeding, however, the fluctuating acetic acid concentrations provided niches to grow and co-exist for both organisms as shown by transcription analysis of the mcrA gene. Our model confirmed the higher functional resilience due to the higher abundance of Methanosarcina based on its higher substrate uptake rate and higher resistance to low pH values. Finally, we applied our model to maize silage as a more complex and practically relevant substrate and showed that our model is likely transferable to the complete AD process., Conclusions: The composition of the microbial community determined the AD functional resilience against organic overloading in our experiments. In particular, communities with higher share of Methanosarcina showed higher process stability. The share of these microorganisms can be purposefully increased by discontinuous feeding. A model was developed that enables derivation of the necessary feeding regime for a more robust community with higher share of Methanosarcina .

Anaerobic digestion of sugarcane straw co-digested with sugarcane filter cake was investigated with a special focus on macronutrients supplementation for an optimized conversion process. Experimental data from batch tests and a semi-continuous experiment operated in different supplementation phases were used for modeling the conversion kinetics based on continuous stirred-tank reactors. The semi-continuous experiment showed an overall decrease in the performance along the inoculum washout from the reactors. By supplementing nitrogen alone or in combination to phosphorus and sulfur the specific methane production significantly increased (P<0.05) by 17% and 44%, respectively. Although the two-pool one-step model has fitted well to the batch experimental data (R 2 >0.99), the use of the depicted kinetics did not provide a good estimation for process simulation of the semi-continuous process (in any supplementation phase), possibly due to the different feeding modes and inoculum source, activity and adaptation., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

For future energy supply systems with high proportions from renewable energy sources, biogas plants are a promising option to supply demand-driven electricity to compensate the divergence between energy demand and energy supply by uncontrolled sources like wind and solar. Apart expanding gas storage capacity a demand-oriented feeding with the aim of flexible gas production can be an effective alternative. The presented study demonstrated a high degree of intraday flexibility (up to 50% compared to the average) and a potential for an electricity shutdown of up to 3 days (decreasing gas production by more than 60%) by flexible feeding in full-scale. Furthermore, the long-term process stability was not affected negatively due to the flexible feeding. The flexible feeding resulted in a variable rate of gas production and a dynamic progression of individual acids and the respective pH-value. In consequence, a demand-driven biogas production may enable significant savings in terms of the required gas storage volume (up to 65%) and permit far greater plant flexibility compared to constant gas production., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Almost 1 out of every 3 homeless women (32%) in the United States, United Kingdom, and Australia has experienced childhood sexual trauma. We assessed lifetime sexual trauma histories among 29 homeless women from three Southern California community sites: one residential safe house and two safe parking areas. More than half of the women (54%) reported a history of sexual trauma. That rate was higher (86%) among women living at the safe home than among women staying at the safe parking sites (only 42%). All four of the women who had served in the military reported having experienced military sexual trauma. The high percentages of sexual trauma found in homeless women highlight the need for effective interventions for sexual trauma.

Different methods for optimization the anaerobic digestion (AD) of sugarcane filter cake (FC) with a special focus on volatile fatty acids (VFA) production were studied. Sodium hydroxide (NaOH) pretreatment at different concentrations was investigated in batch experiments and the cumulative methane yields fitted to a dual-pool two-step model to provide an initial assessment on AD. The effects of nitrogen supplementation in form of urea and NaOH pretreatment for improved VFA production were evaluated in a semi-continuously operated reactor as well. The results indicated that higher NaOH concentrations during pretreatment accelerated the AD process and increased methane production in batch experiments. Nitrogen supplementation resulted in a VFA loss due to methane formation by buffering the pH value at nearly neutral conditions (∼ 6.7). However, the alkaline pretreatment with 6g NaOH/100g FCFM improved both the COD solubilization and the VFA yield by 37%, mainly consisted by n-butyric and acetic acids., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The current pre-/posttest pilot study recruited homeless women from "safe" car parks and transitional housing to evaluate the use of mantram in regard to insomnia. At baseline, study participants completed measures of cognitive function, depression, and the Insomnia Severity Index (ISI). In 40 minutes, women were taught three skills of the Mantram Repetition Program (MRP) in the natural environment: (a) silently repeating a mantram several times, several times per day; (b) repeating the mantram slowly every night before sleep; and (c) focusing full attention on the mantram during repetitions. One week later, participants completed a second ISI. Of the 29 women recruited, 83% completed 1-week follow up. After 1 week, 88% were using their mantram daily and one half were using it prior to sleep. Insomnia severity significantly decreased (p = 0.03), with a mean difference of 2.36 (SD = 4.75). The practice of MRP, an intervention that is portable and easy to teach, shows significant promise in decreasing insomnia in this unique population., (Copyright 2015, SLACK Incorporated.)

Different model structures were compared to simulate the characteristic process variables of the anaerobic digestion of maize, sugar beet and grain silage. Depending on the type and number of the required components, it can be shown that in comparison to the complex Anaerobic Digestion Model No. 1 (ADM1) different simplified model structures can describe the gas production rate, ammonia nitrogen and acetate concentration or pH value equally well. Since the reduction of the predominantly fast kinetics of the methanogenesis, acetogenesis or acidogenesis will only have little effect on the simulation of the specific gas production, it can be proven that the hydrolysis is the rate-limiting step during the uninhibited anaerobic digestion of complex particulate substrates. However, the stoichiometric comparison reveals that the model protein gelatine is not suitable for a representative characterization of agricultural energy crops., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Today in the digital age, with our advances in modern technology and communication, there are additional stressors for our military personnel and Veterans. Constant dangers exist both on and off the battlefield, unlike prior wars that had clearly-defined war zones. In addition, medical advances have assisted in saving the lives of many more gravely injured troops than ever previously possible. As the wars in Iraq and Afghanistan come to an end, large numbers of service men and women are returning home with multiple injuries. This group of Veterans has significantly higher rates of posttraumatic stress disorder (PTSD) and traumatic brain injury than ever before reported. Although existing PTSD therapies have been found to be highly effective for many Veterans, there is a substantial minority unsatisfactorily treated. Mantram repetition, an innovative, complementary, evidence-based treatment, is proving to be successful for these new Veterans. When used regularly it helps with "road rage, impatience, anger, frustration, and being out of control." A mantram is a brief, sacred word or phrase that embodies divine power or the greatest positive energy one can imagine (Easwaran, 2008a). Mantram repetition is a simple, quick, personal, portable, and private complementary practice that may be used as an adjunct to current treatments for PTSD. Growing research evidence supports mantram repetition's value for dissemination and adoption in the 21st century. This chapter summarizes Mantram Program research conducted from 2003 to 2014. It describes the health-related benefits of the Mantram Program in various populations. The current research focuses on benefits for managing psychological distress and promoting quality of life in Veterans. Future areas for research are suggested.

The recognition that colorectal cancer (CRC) is a heterogeneous disease in terms of clinical behaviour and response to therapy translates into an urgent need for robust molecular disease subclassifiers that can explain this heterogeneity beyond current parameters (MSI, KRAS, BRAF). Attempts to fill this gap are emerging. The Cancer Genome Atlas (TGCA) reported two main CRC groups, based on the incidence and spectrum of mutated genes, and another paper reported an EMT expression signature defined subgroup. We performed a prior free analysis of CRC heterogeneity on 1113 CRC gene expression profiles and confronted our findings to established molecular determinants and clinical, histopathological and survival data. Unsupervised clustering based on gene modules allowed us to distinguish at least five different gene expression CRC subtypes, which we call surface crypt-like, lower crypt-like, CIMP-H-like, mesenchymal and mixed. A gene set enrichment analysis combined with literature search of gene module members identified distinct biological motifs in different subtypes. The subtypes, which were not derived based on outcome, nonetheless showed differences in prognosis. Known gene copy number variations and mutations in key cancer-associated genes differed between subtypes, but the subtypes provided molecular information beyond that contained in these variables. Morphological features significantly differed between subtypes. The objective existence of the subtypes and their clinical and molecular characteristics were validated in an independent set of 720 CRC expression profiles. Our subtypes provide a novel perspective on the heterogeneity of CRC. The proposed subtypes should be further explored retrospectively on existing clinical trial datasets and, when sufficiently robust, be prospectively assessed for clinical relevance in terms of prognosis and treatment response predictive capacity. Original microarray data were uploaded to the ArrayExpress database (http://www.ebi.ac.uk/arrayexpress/) under Accession Nos E-MTAB-990 and E-MTAB-1026., (© 2013 Swiss Institute of Bioinformatics. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.)

The oncogenicity of the L858R mutant form of the epidermal growth factor receptor (EGFR) in non-small-cell lung cancer is thought to be due to the constitutive activation of its kinase domain. The selectivity of the marketed drugs gefitinib and erlotinib for L858R mutant is attributed to their specific recognition of the active kinase and to weaker ATP binding by L858R EGFR. We present crystal structures showing that neither L858R nor the drug-resistant L858R+T790M EGFR kinase domain is in the constitutively active conformation. Additional co-crystal structures show that gefitinib and dacomitinib, an irreversible anilinoquinazoline derivative currently in clinical development, may not be conformation specific for the active state of the enzyme. Structural data further reveal the potential mode of recognition of one of the autophosphorylation sites in the C-terminal tail, Tyr-1016, by the kinase domain. Biochemical and biophysical evidence suggest that the oncogenic mutations impact the conformational dynamics of the enzyme., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Decision support interventions have been developed to help men clarify their values and make informed decisions about prostate cancer testing, but they seldom target high-risk black and immigrant men., Purpose: This study evaluated the efficacy of a decision support intervention focused on prostate cancer testing in a sample of predominantly immigrant black men., Methods: Black men (N = 490) were randomized to tailored telephone education about prostate cancer testing or a control condition., Results: Post-intervention, the intervention group had significantly greater knowledge, lower decision conflict, and greater likelihood of talking with their physician about prostate cancer testing than the control group. There were no significant intervention effects on prostate specific antigen testing, congruence between testing intention and behavior, or anxiety., Conclusions: A tailored telephone decision support intervention can promote informed decision making about prostate cancer testing in black and predominantly immigrant men without increasing testing or anxiety.

Purpose: Our purpose was development and assessment of a BRAF-mutant gene expression signature for colon cancer (CC) and the study of its prognostic implications., Materials and Methods: A set of 668 stage II and III CC samples from the PETACC-3 (Pan-European Trails in Alimentary Tract Cancers) clinical trial were used to assess differential gene expression between c.1799T>A (p.V600E) BRAF mutant and non-BRAF, non-KRAS mutant cancers (double wild type) and to construct a gene expression-based classifier for detecting BRAF mutant samples with high sensitivity. The classifier was validated in independent data sets, and survival rates were compared between classifier positive and negative tumors., Results: A 64 gene-based classifier was developed with 96% sensitivity and 86% specificity for detecting BRAF mutant tumors in PETACC-3 and independent samples. A subpopulation of BRAF wild-type patients (30% of KRAS mutants, 13% of double wild type) showed a gene expression pattern and had poor overall survival and survival after relapse, similar to those observed in BRAF-mutant patients. Thus they form a distinct prognostic subgroup within their mutation class., Conclusion: A characteristic pattern of gene expression is associated with and accurately predicts BRAF mutation status and, in addition, identifies a population of BRAF mutated-like KRAS mutants and double wild-type patients with similarly poor prognosis. This suggests a common biology between these tumors and provides a novel classification tool for cancers, adding prognostic and biologic information that is not captured by the mutation status alone. These results may guide therapeutic strategies for this patient segment and may help in population stratification for clinical trials.

Introduction: The RNASEL and HPC2/ELAC2 genes have been implicated in hereditary prostate cancer. Further assessment of the role of these genes in sporadic prostate cancer in African American men (AAM) is warranted., Methods: Genotyping of HPC2/ELAC2 variants (S217L, A541T), along with RNASEL variants (R462Q and E541D) was completed in 155 African American sporadic and 88 familial prostate cancer cases, and 296 healthy male controls. Logistic regression analysis was performed and odds ratios (OR) were calculated, while correcting for both age and population stratification using admixture informative markers., Results: The HPC2/ELAC2 217L allele was significantly associated with risk of prostate cancer when taking all cases into account (OR = 1.6; 1.0-2.6; P = 0.03). The RNASEL 541D allele was associated with a decrease in risk of prostate cancer in sporadic cases (OR = 0.4; 0.2-0.8; P = 0.01). We did not detect an association between prostate cancer risk and the RNASEL R462Q variant. Results from haplotype analyses of the two RNASEL variants revealed highly significant differences in haplotype allele frequencies between cases and controls suggesting a synergistic effect at the RNASEL locus. One haplotype in particular (462R-541D) is far more frequent in our control population and shows a strong protective effect against prostate cancer (OR = 0.47, P = 8.1 x 10(-9))., Conclusions: These results suggest that HPC2/ELAC2 and RNASEL may play a role, however minor, in prostate cancer risk among AAM.

Objective: The objective of this study was to characterize the rat monosodium iodoacetate (MIA)-induced model for osteoarthritis (OA) and determine the translatability of this model to human disease. This was accomplished through pathway, network and system level comparisons of transcriptional profiles generated from animal and human disease cartilage., Methods: An OA phenotype was induced in rat femorotibial joints following a single injection of 200mug MIA per knee joint for a period of 2 or 4 weeks. Lesion formation in the rat joints was confirmed by histology. Gene expression changes were measured using the Agilent rat whole genome microarrays. Cartilage was harvested from human knees and gene expression changes were measured using the Agilent human arrays., Results: One thousand nine hundred and forty-three oligos were differentially expressed in the MIA model, of these, approximately two-thirds were up-regulated. In contrast, of the 2130 differentially expressed oligos in human disease tissue, approximately two-thirds were down-regulated. This dramatic difference was observed throughout each level of the comparison. The total overlap of genes modulated in the same direction between rat and human was less than 4%. Matrix degradation and inflammatory genes were differentially regulated to a much greater extent in MIA than human disease tissue., Conclusion: This study demonstrated, through multiple levels of analysis, that little transcriptional similarity exists between rat MIA and human OA derived cartilage. As disease modulatory activities for potential therapeutic agents often do not translate from animal models to human disease, this and like studies may provide a basis for understanding the discrepancies.

Purpose/objectives: To measure knowledge of hereditary prostate cancer in a group of high-risk African American men., Design: Cross-sectional, correlational pilot study., Setting: Four geographic sites: Detroit, MI; Houston, TX; Chicago, IL; and Columbia, SC., Sample: 79 men enrolled in the African American Hereditary Prostate Cancer Study., Methods: Telephone interviews., Main Research Variables: Knowledge of hereditary prostate cancer., Findings: Knowledge of hereditary prostate cancer was low., Conclusions: The high percentage of incorrect responses on questions that measure genetic testing, prevention, and risk based on a positive family history highlights educational needs., Implications for Nursing: A critical need exists for nurses to educate high-risk African American men about hereditary prostate cancer.

Background: The African American Hereditary Prostate Cancer (AAHPC) Study was designed to recruit families with early-onset disease fulfilling criteria of >or=4 affected., Methods: We present a approximately 10 cM genome-wide linkage (GWL) analysis on 77 families including 254 affected and 274 unaffected genotyped., Results: Linkage analysis revealed three chromosomal regions with GENEHUNTER multipoint HLOD scores >or=1.3 for all 77 families at 11q22, 17p11, and Xq21. One family yielded genome-wide significant evidence of linkage (LOD = 3.5) to the 17p11 region with seven other families >or=2.3 in this region. Twenty-nine families with no-male-to-male (MM) transmission gave a peak HLOD of 1.62 (alpha = 0.33) at the Xq21 locus. Two novel peaks >or=0.91 for the 16 families with '>6 affected' occurred at 2p21 and 22q12., Conclusions: These chromosomal regions in the genome warrant further follow-up based on the hypothesis of multiple susceptibility genes with modest effects, or several major genes segregating in small subsets of families., ((c) 2006 Wiley-Liss, Inc.)

Background: The EphB2 gene was recently implicated as a prostate cancer (PC) tumour suppressor gene, with somatic inactivating mutations occurring in approximately 10% of sporadic tumours. We evaluated the contribution of EphB2 to inherited PC susceptibility in African Americans (AA) by screening the gene for germline polymorphisms., Methods: Direct sequencing of the coding region of EphB2 was performed on 72 probands from the African American Hereditary Prostate Cancer Study (AAHPC). A case-control association analysis was then carried out using the AAHPC probands and an additional 183 cases of sporadic PC compared with 329 healthy AA male controls. In addition, we performed an ancestry adjusted association study where we adjusted for individual ancestry among all subjects, in order to rule out a spurious association due to population stratification., Results: Ten coding sequence variants were identified, including the K1019X (3055A-->T) nonsense mutation which was present in 15.3% of the AAHPC probands but only 1.7% of 231 European American (EA) control samples. We observed that the 3055A-->T mutation significantly increased risk for prostate cancer over twofold (Fisher's two sided test, p = 0.003). The T allele was significantly more common among AAHPC probands (15.3%) than among healthy AA male controls (5.2%) (odds ratio 3.31; 95% confidence interval 1.5 to 7.4; p = 0.008). The ancestry adjusted analyses confirmed the association., Conclusions: Our data show that the K1019X mutation in the EphB2 gene differs in frequency between AA and EA, is associated with increased risk for PC in AA men with a positive family history, and may be an important genetic risk factor for prostate cancer in AA.

Hospital readmission is an important indicator of patient care outcomes and is widely used in evaluating the quality of health care provided. However, few definitions of the term "readmission" are listed in the literature, and exact measurement parameters regarding readmission are seldom stated. The term readmission is indiscriminately used and defined, making accurate comparisons of results difficult across studies if not impossible. This article analyzes the concept readmission, creates a criteria-based definition for the term, and proposes a measurement instrument on the basis of these criteria to consistently quantify readmission in quality management programs and research studies. Multiple databases were searched using various key terms to locate literature covering adult and pediatric populations and all clinical conditions or diagnoses. Articles were selected on the basis of the specified inclusion/exclusion criteria.

Background: Treatments for clinically localized prostate carcinoma are accompanied by sexual, urinary, and bowel dysfunction and other sequelae that can result in significant distress and reduced well being. Methods capable of improving quality of life are needed that can be integrated into clinical practice. To address this need, a nurse-driven, cancer care intervention was developed and tested., Methods: Within 6 weeks after completing treatment, 99 patients, along with their partners, were enrolled into a prospective, controlled trial and were randomized to receive the cancer care intervention or to receive standard care. Participants in the intervention arm met once each month for 6 months with an oncology nurse intervenor, who helped patients identify their quality-of-life needs using an interactive computer program. The intervener then provided education and support tailored to participants' needs. Primary outcome variables included 1) disease-specific quality of life, including sexual, urinary, and bowel outcomes and cancer worry; 2) depression; 3) dyadic adjustment; and 4) general quality of life. Outcomes data were collected prior to randomization and again at 4 months, 7 months, and 12 months posttreatment., Results: Patients in the intervention arm experienced long-term improvements in quality-of-life outcomes related to sexual functioning and cancer worry compared with patients who received standard care. Baseline depression moderated the impact of the intervention on several other quality-of-life outcomes., Conclusions: The findings of the current study indicated that a computer-assisted, nurse-driven intervention was capable of providing durable improvements in the quality of life of men who underwent treatment for clinically localized prostate carcinoma.

The metathesis reaction of potassium (tris(tert-butyl)silyl)phosphanide with GaCl(3) in a molar ratio of 1:1 leads to the formation of [Cl(2)GaP(H)Si(t)Bu(3)](2) (1) as a mixture of cis and trans isomers with very large (1)J(P,H) and (2)J(P,P) coupling constants. The molecular structure of 1 shows a Ga(2)P(2) cycle with nearly planar coordinated phosphorus atoms under neglection of the hydrogen atoms and Ga-P distances of 239 pm. The reaction of GaCl(3) with 3 equiv of potassium (tris(tert-butyl)silyl)phosphanide as well as the reaction of 1 with 2 equiv of KP(H)Si(t)Bu(3) yields [(t)Bu(3)SiP(H)Ga(mu-PSi(t)Bu(3))](2) (2). The central moiety comprises a four-membered Ga(2)P(2) cycle with one planar P atom and extremely short Ga-P bonds of approximately 226 pm, the other being in a pyramidal environment with an angle sum of 298.4 degrees. The structure of 2 can be described as a GaPGa heteroallyl system which is bonded to a phosphanidyl substituent. This idea and its dependency on the steric demand of the trialkylsilyl groups are investigated by DFT calculations on different isomers of 2.

Cyclooxygenase-2 (COX-2) is a key rate-limiting enzyme that converts arachidonic acid into pro-inflammatory prostaglandins. COX-2 expression is strongly correlated with increased tumor microvasculature density and plays an important role in inhibiting apoptosis, stimulating angiogenesis and promoting tumor cell metastasis and invasion. However, little is known about the role that sequence variation of the COX-2 gene contributes to prostate cancer. Thus, we searched for polymorphisms in the promoter region of the COX-2 gene using denaturing high-performance liquid chromatography. Four single nucleotide polymorphisms (SNPs), -1285A/G, -1265G/A, -899G/C and -297C/G, were detected and confirmed by direct sequencing. Three of the SNPs in the promoter region of COX-2 gene create at least three putative transcription factor binding sites and eliminate CCAAT/enhancer binding protein alpha (C/EBP alpha) and NF-kappa B binding sites. A case-control study of the four SNPs in African American (n = 288), Bini Nigerian (n = 264) and European American (n = 184) prostate cancer cases and age-matched controls revealed that SNP -297G was associated with a decreased risk for prostate cancer [odds ratio (OR) = 0.49; CI = 0.2-0.9; P = 0.01]. The effect on risk was observed in both African Americans (OR = 0.51; CI = 0.2-0.9; P = 0.01) and European Americans (OR = 0.33; CI = 0.1-0.9; P = 0.02). In addition, SNPs -1265A and -899C were associated with increased prostate cancer risk in African Americans (OR = 2.72; CI = 1.3-5.8; P = 0.007 and OR = 3.67; CI = 1.4-9.9; P = 0.007, respectively). Haplotype analyses revealed modest effects on susceptibility to prostate cancer across populations. Haplotype GGCC conferred increased risk in the African American and Nigerian populations. Conversely, haplotype AGGG exhibited a negative association with prostate cancer risk in African Americans (OR = 0.4; CI = 0.1-0.9; P = 0.02) and European Americans (OR = 0.2; CI = 0.1-0.9; P = 0.03). These data suggest that variation of the COX-2 promoter may influence the risk and development of prostate cancer.

Introduction: The African-American Hereditary Prostate Cancer (AAHPC) Study was designed to recruit African-American families fulfilling very stringent criteria of four or more members diagnosed with prostate cancer at a combined age at diagnosis of 65 years or less. This report describes the clinical characteristics of a sample of affected AAHPC family members., Methods: In all, 92 African-American families were recruited into the study between 1998 and 2002. Complete clinical data including age and PSA at diagnosis, number of affected per family, stage, grade, and primary treatment were available on 154 affected males. Nonparametric Wilcoxon two-sample tests and Fisher's exact test (two-tailed), were performed to compare families with 4-6 and >6 affected males with respect to clinical characteristics., Results: The mean number of affected men per family was 5.5, with a mean age at diagnosis of 61.0 (+/-8.4) years. Age at diagnosis, PSA and Gleason score did not show significant differences between the two groups of families. Based on the Gleason score, 77.2% of affected males had favorable histology. Significantly, there were marked differences between the two groups in the frequency of node-positive disease (P=0.01) and distant metastases (P=0.0001). Radical prostatectomy was the preferred primary therapy for 66.2% of all affected men followed by 20.8% who chose radiation therapy., Conclusions: Our findings suggest that affected males who carry the highest load of genetic factors are at the highest risk for early dissemination of disease, thus efforts at early diagnosis and aggressive therapeutic approaches may be warranted in these families. Since the primary therapy choices in our study favored definitive treatment (87.0%) when compared to the 1983 and 1995 SEER data in which 28 and 64% received definitive treatment, respectively, it appears that affected African-American men in multiplex families may be demonstrating the reported psycho-social impact of family history on screening practices and treatment decisions for prostate cancer.

Twelve fertile stallions were divided into two groups, either receiving gonadotropin-releasing hormone (GnRH) (n = 6) or Placebo (n = 6). Based on the history of frozen/thawed semen characteristics three stallions within each group were assigned as being "good freezers" [GnRH (+); Placebo (+)] and three stallions were assigned as being "poor freezers" [GnRH (-); Placebo (-)]. The study was performed as a "blinded" investigation and stallions were treated twice daily by an intramuscular injection of 1 ml GnRH (Buserelin), 50 microg) or Placebo. The experiment was divided into three time periods. Period A (pre-treatment) was performed between 16 November and 20 December; Period B (treatment) was performed during 6 weeks between 21 December and 31 January; and Period C (post-treatment) was performed between 1 February and 12 February. Semen was collected every Monday, Wednesday, Friday, and analysed for motion characteristics by the use of a computerized semen analyser, and sperm morphology immediately after collection. The spermatozoa were cryopreserved, stored in liquid nitrogen, and evaluated for motility (computer assisted semen analysis), membrane integrity (carboxyfluoresceine diacetate (CFDA) combined with propidium-iodide (PI), CFDA/PI), viability and sperm morphology (Eosine-Nigrosine, EN), and osmotic reactivity (hypo-osmotic swelling test, HOS) following thawing in a water bath. The viability of spermatozoa was expressed as the difference between pre-freeze and post-thaw values. A libido score of 1-4, the number of mounts on the phantom before ejaculation, and ejaculation latency were used to evaluate the stallions sexual behavior. Effect of treatment was analysed by comparing time intervals within groups as well as comparing groups within time intervals using SAS statistics software. GnRH treatment decreased the number of mounts before ejaculation (GnRH (total): 2.5 +/- 1.14 versus 1.8 +/- 1.06, P < 0.05), and shortened ejaculation latency. Cessation of treatment increased ejaculation latency in the GnRH group (4.7 +/- 4.98 min versus 7.2+/-7.88min, P<0.05). With the exception of libido score all parameters of sexual behavior were superior in the GnRH (+) group compared to the Placebo (-) group during the treatment period (P < 0.05). GnRH administration increased progressive motility (GnRH (+): 30.7 +/- 10.74% versus 38.4 +/- 15.1%, P < 0.05; GnRH (total): 24.9 +/- 11.80% versus 31.9 +/- 14.68%, P < 0.05), membrane intact spermatozoa CFDA/PI (GnRH (-): 16.8 +/- 7.17% versus 26.2 +/- 7.02%, P < 0.05; GnRH (total): 23.1 +/- 12.33% versus 29.5 +/- 10.77%, P < 0.05) and HOS positive spermatozoa (GnRH (+): 33.2 +/- 11.29% versus 42.2 +/- 10.36%, P < 0.05; GnRH (total): 32.9 +/- 10.23% versus 40.1 +/- 10.30%, P < 0.05) of frozen/thawed spermatozoa. Following cessation of treatment, the viability of frozen/thawed spermatozoa decreased. GnRH treated stallions had lower losses of live stained spermatozoa (EN) compared to the Placebo group (GnRH (total): 17.6 +/- 4.77 versus Placebo (total): 27.2 +/- 5.44, P < 0.05). This was particularly observed in the "poor freezer" group (GnRH (-): 16.6 +/- 4.35 versus Placebo (-): 31.3 +/- 5.87; P < 0.05). In conclusion, exogenous GnRH was shown to improve sexual behavior and increase the quality of frozen/thawed spermatozoa in fertile stallions during the non-breeding season. Nevertheless, it seems that, although significance was achieved relative to improvement to post-thaw sperm quality, that the "real" change in sperm quality seems negligible in fertile stallions. The mechanism of GnRH effect was not determined but this study may support the possibility of a direct gonadal or epididymal effect of exogenous GnRH in the stallion.

The lithiation of potassium triisopropylsilylphosphanide yields the corresponding phosphanediide. The subsequent metathesis reaction with SrI(2) and BaI(2) in the presence of hexamethyldisiloxane gives hexalithium hexapotassium strontium hexakis(triisopropylsilylphosphanediide)bis(trimethylsilanolate) (1) and the corresponding barium derivative (2), respectively. The alkaline earth metal atoms are surrounded octahedrally by the phosphanediide ligands. Six P(3) faces of the octahedron are capped by the K atoms, and the P-P edges of two opposite P(3) faces are bridged by the lithium atoms. The Li cations are also bonded to the Me(3)SiO substituents giving a coordination number of three for the alkali metals.

This research tested the effects of a long-term psychosocial nursing intervention designed to decrease mental distress in adolescents following a catastrophic event. Advanced Practice Psychiatric Nurses conducted the Catastrophic Stress Intervention (CSI) in two South Carolina high schools for three years following Hurricane Hugo. The CSI consisted of nine protocols designed to decrease adolescents' mental distress by increasing their understanding of stress and by enhancing their self-efficacy and social support. Adolescents (N = 1030) were randomized to intervention or control groups and completed one baseline and five postintervention measures of mental distress, self-efficacy, and social support. The hypothesis was that intervention adolescents would have less mental distress than control adolescents. The research also addressed the particular time points at which differences between intervention and control adolescents might be shown. Repeated measures multivariate analysis of variance, with exposure to the hurricane, self-efficacy, and social support as control variables, showed that intervention adolescents reported less mental distress than control adolescents at 12, 18, and 24 months but that this difference dissipated by 30 and 36 months. Implications for the CSI and timing of interventions with adolescents after a catastrophic event are discussed.

Six regions for prostate cancer genes have been identified, and it is anticipated that prostate cancer susceptibility testing will be available in the future. This correlational study identified predictors for interest in prostate cancer susceptibility testing among African American men. Participants were 320 African American men from the African American Hereditary Prostate Cancer Study and the South Carolina Prostate Cancer Education and Screening Study participated. Two questions measured interest in genetic prostate cancer susceptibility testing and family history of prostate cancer. Chi-square analyses by family history as well as demographics (age, education, marital status) were performed. Most of the men (277 [87%]) indicated an interest in genetic prostate cancer susceptibility testing. Interest in undergoing testing did not vary by family history, age, or education. Marital status was the only significant demographic predictor. Men who were married were significantly more likely to respond with a "yes" to interest in prostate cancer susceptibility testing than were men who were not married. The high "yes" response rate and the men's confusion between the genetic prostate cancer susceptibility testing and prostate cancer screening highlight the need for public education once prostate cancer genes are identified and available for public testing.

The purpose of this correlational study was to measure structural obstacles to a free prostate cancer screening. The sample consisted of 549 men, 69% who were African-American. The men attended a prostate cancer educational program and were offered free prostate cancer screening at their physician of choice. Structural obstacles that were predictors in screening participation were "making an appointment" (p = 0.02), "planning for an appointment" (p = 0.05), and "reminders of prostate cancer screening" (p = 0.02). The demographic variables of race and marital status were also predictors of screening participation. Implications for health education are given.

A genome-wide scan of high-risk prostate cancer families in North America has demonstrated linkage of a particular marker to Chromosome Iq (HPC11. An even greater proportion of African-American families have shown linkage to HPC 1. Therefore, investigators at the National Human Genome Research Institute [NHGRI] in collaboration with Howard University and a predominantly African-American group of urologists established the African-American Hereditary Prostate Cancer (AAHPC) Study Network to confirm the suggested linkage of HPC in African Americans with a gene on Chromosome 1. Blood samples from recruited families were sent to Howard University for extraction of DNA. The DNA was sent to NHGRI at NIH where the genotyping and genetic sequence analysis was conducted. Genotype data are merged with pedigree information so that statistical analysis can be performed to establish potential linkage. From March 1, 1998, to June 1, 1999, a total of 40 African-American families have been recruited who met the study criteria. Preliminary results suggest that racial/ethnicity grouping may affect the incidence and extent of linkage of prostate cancer to specific loci. The importance of these findings lays in the future treatment of genetic-based diseases.

Background: Problem behaviours that occur during Alzheimer's disease (AD) can have major impact on caregivers. How caregivers react to these behaviours may determine the total impact experienced from caregiving., Purpose: This study examined the relationships between problematic behaviours and caregiving impact in 30 primary caregivers of persons with AD. The first question explored the relationship between frequency of problem behaviour and impact; the second explored the relationship between caregiver reactions to problem behaviours and impact from caregiving., Methods: The frequency of problem behaviour and the caregiver reaction was measured using The Revised Memory and Behaviour Problem Checklist (Teri et al. 1992). The impact from caregiving was operationalized using the Cost of Care Index developed by Kosberg and Cairl (1986)., Results: Significant associations were found for 11 of the 20 subscales that measured the association between the frequency of problem behaviour in the client and the impact from caregiving experienced by the caregiver. In comparison, the association between caregiver's reaction to problem behaviours and impact from caregiving was even more significant in value with 15 subscales of 20 being significant. Female caregivers experienced a greater reaction to disruptive and depressive behaviour when compared with male caregivers even though both genders reported similar frequencies of problem behaviours. In regard to findings about the impact from caregiving, four of the six indicators were higher for women than for men., Conclusions: Caregiver reaction to problem behaviours was more highly associated with impact from caregiving than the actual frequency of the behaviours. These findings have great implications for intervention programs. Caregivers, especially females, need to receive individualized, specific education/training on how to understand and manage disruptive and depressive behaviour in persons with AD.

There is limited data on the relationship between perceived health status and the demographic variables of education and income in African American men. A sample of 2,001 men (72% African Americans and 28% Caucasians) who were participating in prostate cancer screening was studied to identify predictors of men's health status. Data on the concepts of self-rated health status, age, race, education, income, living arrangements, and marital status were collected. Findings indicated that men who were more likely to report excellent health status were older Caucasians, had more than a high school education, an annual income over 25,021 dollars, were living with others, and were married. Men more likely to report fair health status were older African Americans, unmarried, had less than a high school education, had an annual income less than 9,600 dollars, were living alone, and were unmarried. Implications for targeting at-risk men are presented.

While studies have implicated alleles at the CAG and GGC trinucleotide repeats of the androgen receptor gene with high-grade, aggressive prostate cancer disease, little is known about the normal range of variation for these two loci, which are separated by about 1.1 kb. More importantly, few data exist on the extent of linkage disequilibrium (LD) between the two loci in different human populations. Here we present data on CAG and GGC allelic variation and LD in six diverse populations. Alleles at the CAG and GGC repeat loci of the androgen receptor were typed in over 1000 chromosomes from Africa, Asia, and North America. Levels of linkage disequilibrium between the two loci were compared between populations. Haplotype variation and diversity were estimated for each population. Our results reveal that populations of African descent possess significantly shorter alleles for the two loci than non-African populations (P<0.0001). Allelic diversity for both markers was higher among African Americans than any other population, including indigenous Africans from Sierra Leone and Nigeria. Analysis of molecular variance revealed that approx. 20% of CAG and GGC repeat variance could be attributed to differences between the populations. All non-African populations possessed the same common haplotype while the three populations of African descent possessed three divergent common haplotypes. Significant LD was observed in our sample of healthy African Americans. The LD observed in the African American population may be due to several reasons; recent migration of African Americans from diverse rural communities following urbanization, recurrent gene flow from diverse West African populations, and admixture with European Americans. This study represents the largest genotyping effort to be performed on the two androgen receptor trinucleotide repeat loci in diverse human populations.

African-American men are more likely to develop and die from prostate cancer than are European-American men; yet, factors responsible for the racial disparity in incidence and mortality have not been elucidated. Socioeconomic disadvantage is more prevalent among African-American than among European-American men. Socioeconomic disadvantage can lead to psychosocial stress and may be linked to negative lifestyle behaviors. Regardless of socioeconomic position, African-American men routinely experience racism-induced stress. We propose a theoretical framework for an association between psychosocial stress and prostate cancer. Within the context of history and culture, we further propose that psychosocial stress may partially explain the variable incidence of prostate cancer between these diverse groups. Psychosocial stress may negatively impact the immune system leaving the individual susceptible to malignancies. Behavioral responses to psychosocial stress are amenable to change. If psychosocial stress is found to negatively impact prostate cancer risk, interventions may be designed to modify reactions to environmental demands.

Objectives: Special challenges and unique opportunities for nurses in the 21st century related to prostate cancer screening are reviewed., Data Sources: Current health care literature pertaining to prostate cancer screening issues., Conclusions: Decisions that weigh the immediate risks of incontinence and erectile dysfunction against the long-term potential risk of death from advanced cancer must be made with conflicting values and incomplete data., Implications for Nursing Practice: With their expertise in patient education nurses are in a unique position to communicate the risks and benefits of prostate cancer screening in a manner in which patients can understand. A sample nursing care plan is presented for shared decision making.

A genome-wide scan of high-risk prostate cancer families in North America has demonstrated linkage of a particular marker to Chromosome 1q (HPC1). An even greater proportion of African-American families have shown linkage to HPC1. Therefore, investigators at the National Human Genome Research Institute (NHGRI) in collaboration with Howard University and a predominantly African-American group of urologists established the African-American Hereditary Prostate Cancer (AAHPC) Study Network to confirm the suggested linkage of HPC in African Americans with a gene on Chromosome 1. Blood samples from recruited families were sent to Howard University for extraction of DNA. The DNA was sent to NHGRI at NIH where the genotyping and genetic sequence analysis was conducted. Genotype data are merged with pedigree information so that statistical analysis can be performed to establish potential linkage. From March 1, 1998, to June 1, 1999, a total of 40 African-American families have been recruited who met the study criteria. Preliminary results suggest that racial/ethnicity grouping may affect the incidence and extent of linkage of prostate cancer to specific loci. The importance of these findings lays in the future treatment of genetic-based diseases.

Telomerase has been detected by telomerase repeat amplification protocol (TRAP) assay in cervical dysplasia and squamous cell carcinoma but not in most normal cervical tissues. In the present study, the cellular localization of the protein catalytic subunit of telomerase (hTERT) and the RNA component (hTR) were investigated by a sensitive immunohistochemical technique and by in situ hybridization, respectively. hTERT protein was detected in all diagnostic categories of cervical specimens. hTERT was localized predominantly to the lower suprabasal levels of normal squamous mucosa but was detected throughout virtually all levels of the lesional epithelium in low-grade squamous intraepithelial lesions (LSILs), high-grade squamous intraepithelial lesions (HSILs), and squamous cell carcinoma (SCC). Telomerase expression correlated with hTERT detection in SCC and HSIL but was not detected by TRAP assay in most samples of normal mucosa or LSIL. The distribution of hTR correlated with the localization of hTERT in HSIL and SCC but was restricted to the basal and suprabasal cell layers in normal mucosa and LSIL.

The African American Hereditary Prostate Cancer (AAHPC) Study is an ongoing multicenter genetic linkage study organized by Howard University and the National Human Genome Research Institute (NHGRI), with support from the Office for Research on Minority Health and the National Cancer Institute. The goals of the study are to: (i) look for evidence of involvement of chromosome 1q24-25 (HPC1) in African American men with hereditary prostate cancer (HPC) and (ii) conduct a genome-wide search for other loci associated with HPC in African American men. To accomplish these goals, a network has been established including Howard University, the NHGRI, and six Collaborative Recruitment Centers (CRCs). The CRCs are responsible for the identification and enrollment of 100 African American families. To date, 43 families have been enrolled. Recruitment strategies have included mass media campaigns, physician referrals, community health-fairs/prostate cancer screenings, support groups, tumor registries, as well as visits to churches, barber shops, and universities. By far, the most productive recruitment mechanisms have been physician referrals and tumor registries, yielding a total of 35 (81%) families. Approximately 41% (n = 3400) of probands initially contacted by phone or mail expressed interest in participating; the families of 2% of these met the eligibility criteria, and 75% of those families have been enrolled in the study, indicating a 0.5% recruitment yield (ratio of participants to contacts). As the first large-scale genetic linkage study of African Americans, on a common disease, the challenges and successes of the recruitment process for the AAHPC Study should serve to inform future efforts to involve this population in similar studies.

This cross-sectional survey measured relationships among blood pressure and measures of psychologic distress, family structure, and economic status in a sample of adolescents exposed to Hurricane Hugo. Spielberger's Anger Scale and Derogatis' Brief Symptom Inventory were used. Data analysis revealed 5% of the 1079 adolescents were hypertensive. Multiple regression analyses revealed the following predictors of higher diastolic blood pressure: African-American race, recipient of subsidized lunch, exposure to Hurricane Hugo, and higher anger-in scores in males. The effects of a catastrophic event such as a hurricane on blood pressure and the effects of introjected anger have implications for both health care consumers and providers.

Vulvar intraepithelial neoplasias (VINs) are potentially premalignant lesions of the squamous mucosa. The immunohistochemical distribution of the catalytic protein subunit of telomerase (hTERT) and the patterns of X chromosome inactivation were investigated as markers of neoplasia in samples from a patient with multifocal and diffuse VIN. hTERT nuclear staining in VIN correlated with squamous maturation and the degree of nuclear atypia. Normal mucosa revealed faint nuclear staining of parabasal cells and lower intermediate layer squamous cells. Monoclonal composition was demonstrated in 0 of 3 samples of VIN1, 2 of 3 samples of VIN2, and 13 of 13 samples of VIN3. The patterns of X chromosome inactivation indicated intramucosal extension and multifocal origin of individual lesions. Five samples of histologically normal vulvar squamous epithelium revealed a random pattern of X chromosome inactivation, consistent with polyclonal composition. All 19 samples from 9 lesions contained human papillomavirus (HPV)-16 sequences. Neither mutations in the p53 tumor suppressor gene or K-ras oncogenes nor loss of heterozygosity at 7 chromosomal loci were detected in any of the 19 samples of VIN. These results demonstrate that HPV-associated VIN may result from multifocal and diffuse 2-dimensional intraepithelial expansion of an immortalized monoclonal cell population.