bluuebunny/crossref_metadata_2025 huggingface dataset:
Soil carbon cycling and sequestration in a seasonally saturated wetland receiving agricultural runoff
Authors: Maynard J. J. , Dahlgren R. A. , O'Geen A. T.
Published: November 2011

Abstract. The fate of organic carbon (C) lost by erosion is not well understood in agricultural settings. Recent models suggest that wetlands and other small water bodies may serve as important long-term sinks of eroded C, receiving ~30 % of all eroded material in the US. To better understand the role of seasonally-saturated wetlands in sequestering eroded C, we examined the spatial and temporal dynamics of C and sediment accumulation in a 13-year-old constructed wetland used to treat agricultural runoff. The fate of C sequestered within deposited sediment was modeled using point-sampling, remote sensing, and geostatistics. Using a spatially-explicit sampling design, annual net rates of sedimentation and above-ground biomass were measured during two contrasting years (vegetated (2004) vs. non-vegetated (2005)), followed by collection of sediment cores to the antecedent soil layer, representing 13 years of sediment and C accumulation. We documented high annual variation in the relative contribution of endogenous and exogenous C sources, as well as absolute rates of sediment and C deposition. This annual variation, however, was muted in the long-term (13 yr) sediment record, which showed consistent vertical patterns of uniform C distribution (~14 g kg–1) and δ13C signatures in high depositional environments. This was in contrast to low depositional environments which had high levels of surface C enrichment (20–35 g kg–1) underlain by C depleted (5–10 g kg–1) sediments and an increasing δ13C signature with depth indicating increased decomposition. These results highlight the importance of sedimentation in physically protecting soil organic carbon and its role in controlling the long-term C concentration of seasonally-saturated wetland soils. While significant enrichment of surface sediments with endogenous C occurred in newly deposited sediment (i.e., 125 kg m2 in 2004), fluctuating cycles of flooding and drying maintained the long-term C concentration at the same level as inflowing sediment (i.e., 14 g kg–1), indicating no additional long-term storage of endogenous C. These results demonstrate that constructed flow-through wetlands can serve as important sinks for eroded C and sediment in agricultural landscapes, however, additional C sequestration via enrichment from endogenous sources may be limited in seasonally-saturated wetlands due to rapid decomposition during drying cycles.
Influence of parallel computational uncertainty on simulations of the Coupled General Climate Model
Authors: Song Z. , Qiao F. , Lei X. , Wang C.
Published: November 2011

Abstract. This paper investigates the impact of the parallel computational uncertainty on climate simulations using the Community Climate System Model Version 3 (CCSM3). A series of sensitivity experiments have been conducted and the analyses are focused on the Global and Nino3.4 sea surface temperatures. It is shown that the amplitude of the deviation induced by the parallel computational uncertainty is the same order as that of the climate system change. However, the ensemble mean method can reduce the influence and the ensemble member number of 15 is enough to ignore simulated errors. For climatology, the influence can be ignored when the climatological mean is calculated by using more than 30-yr simulations. It is also found that the parallel computational uncertainty has no effect on the simulated periods of climate variability such as ENSO. Finally, it is suggested that the influence of the parallel computational uncertainty on Coupled General Climate Models (CGCMs) can be a quality standard or a metric for developing CGCMs.
Cow milk consumption, insulin‐like growth factor‐I, and human biology: A life history approach
Authors: Wiley Andrea S.
Published: November 2011

Objective:

To assess the life history consequences of cow milk consumption at different stages in early life (prenatal to adolescence), especially with regard to linear growth and age at menarche and the role of insulin‐like growth factor I (IGF‐I) in mediating a relationship among milk, growth and development, and long‐term biological outcomes.

Methods:

United States National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2004 and review of existing literature.

Results:

The literature tends to support milk's role in enhancing growth early in life (prior to age 5 years), but there is less support for this relationship during middle childhood. Milk has been associated with early menarche and with acceleration of linear growth in adolescence. NHANES data show a positive relationship between milk intake and linear growth in early childhood and adolescence, but not middle childhood, a period of relatively slow growth. IGF‐I is a candidate bioactive molecule linking milk consumption to more rapid growth and development, although the mechanism by which it may exert such effects is unknown.

Conclusions:

Routine milk consumption is an evolutionarily novel dietary behavior that has the potential to alter human life history parameters, especially vis‐à‐vis linear growth, which in turn may have negative long‐term biological consequences. Am. J. Hum. Biol. 2012. © 2011 Wiley Periodicals, Inc.
Associations between transition‐specific stress experience, nocturnal decline in ambulatory blood pressure, and C‐reactive protein levels among transgender men
Authors: Dubois L. Zachary
Published: November 2011

Objectives:

To characterize challenges experienced during stages of female‐to‐male sex transition and investigate associations between transition‐specific measures of psychosocial stress, nocturnal decline in ambulatory blood pressure (amBP), and changes in C‐reactive protein (CRP) levels.

Methods:

For this biocultural study, 65 healthy transmen who were using testosterone (T) therapy participated in interviews to assess transition‐specific stress experience. They provided perceived stress scores, self‐esteem scores, 24‐h amBP measures, salivary samples for T levels, and a blood spot for CRP levels. Psychosocial stress was examined in relation to amBP and CRP using linear regression while adjusting for age, body mass index, and smoking.

Results:

There were no differences in mean levels of amBP in association with stage of transition. Men reporting stress associated with being “out” as transgender had significantly diminished nocturnal decline in systolic and diastolic amBP compared to men who did not report such stress. The associations remained significant when examined among men in stages 1 and 2 (≤3 years on T), but not among men in stage 3 (>3 years on T) of transition. Men reporting stress related to “passing” as someone born male had higher CRP levels than those who did not report such stress. The association remained significant when examined among men in stages 2 and 3 (>0.5–3 years on T).

Conclusion:

Measures of stress that captured individuals' experiences of gender liminality were associated with diminished nocturnal decline in amBP and increased levels of CRP. There are significant differences between men grouped into different stages of the transition process. Am. J. Hum. Biol., 2012. © 2011Wiley Periodicals, Inc.
Electrospun PLA/PCL fibers with tubular nanoclay: Morphological and structural analysis
Authors: Haroosh Hazim J. , Chaudhary Deeptangshu S. , Dong Yu
Published: November 2011

Biodegradable polymers are good candidates for a wide range of applications in tissue engineering and drug delivery because of their biocompatibility, their degradation, mechanical properties, and offer a sustained release of encapsulated drugs. The electrospun polymer nanofibrous materials can be used as carriers for hydrophobic and hydrophilic drugs. This research work focused on poly(lactic acid) (PLA) and blends of PLA with poly (ε‐caprolactone) (PCL) that are reinforced with different concentrations of halloysite nanotubes (HNTs) and various cosolvents for electrospinning including chloroform : acetone, chloroform : methanol, and dichloromethane (DCM) : N,N, dimethylformamide (DFM). The fibers produced from the DCM : DMF system without HNTs were more uniform resulting in smaller fiber diameters as compared to the chloroform: methanol system due to the increased solution conductivity. The addition of HNT nanoparticles produced electrospun fibers with large diameters because the viscosity of the solution increased. Cosolvent was important in determining fiber diameters because it strongly influenced the solution viscosity and conductivity. HNTs had relatively small impact on the growth of a crystalline morphology in PCL–HNT composites. The solvent mixture of chloroform : methanol was better for PLA‐based systems since PLA was found to have slightly higher crystallinity and larger enthalpy value indicating the improved structural orderness in the PLA polymer matrix. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012
Preparation of drug‐loaded microspheres of linear and star‐shaped poly(D,L‐lactide)s and their drug release behaviors
Authors: Baimark Yodthong , Srisa‐ard Mangkorn
Published: November 2011

Linear (1‐arm) and star‐shaped (4‐, 6‐, and 16‐arm) poly(D,L‐lactide)s (PDLLs) were synthesized by ring‐opening polymerization in bulk of D,L‐lactide monomer. Hydroxyl end‐group compounds and stannous octoate were used as the initiator and catalyst, respectively. The intrinsic viscosity and glass transition temperature (Tg) of the PDLLs decreased steadily as the branch arm number increased for similar molecular weights. However, the intrinsic viscosity and Tg values of the linear PDLL were less than the star‐shaped PDLL for similar each PDLL arm lengths. Ibuprofen, a poorly water soluble model drug was entrapped in the PDLL microspheres. All drug‐loaded PDLL microspheres were prepared by the oil‐in‐water emulsion solvent evaporation method, were spherical in shape, and had a smooth surface with fine dispersibility. In vitro drug release behaviors indicated that the drug release from the microspheres with higher branch arm number was faster than from those with lower branch arm number. Moreover, the drug release from the star‐shaped PDLL microspheres was slower than that of the linear PDLL microspheres for similar PDLL arm lengths. The drug release behavior could be adjusted through both the branch arm number and arm length of PDLL. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012
Effective query generation and postprocessing strategies for prior art patent search
Authors: Cetintas Suleyman , Si Luo
Published: November 2011

Rapid increase in global competition demands increased protection of intellectual property rights and underlines the importance of patents as major intellectual property documents. Prior art patent search is the task of identifying related patents for a given patent file, and is an essential step in judging the validity of a patent application. This article proposes an automated query generation and postprocessing method for prior art patent search. The proposed approach first constructs structured queries by combining terms extracted from different fields of a query patent and then reranks the retrieved patents by utilizing the International Patent Classification (IPC) code similarities between the query patent and the retrieved patents along with the retrieval score. An extensive set of empirical results carried out on a large‐scale, real‐world dataset shows that utilizing 20 or 30 query terms extracted from all fields of an original query patent according to their log(tf)idf values helps form a representative search query out of the query patent and is found to be more effective than is using any number of query terms from any single field. It is shown that combining terms extracted from different fields of the query patent by giving higher importance to terms extracted from the abstract, claims, and description fields than to terms extracted from the title field is more effective than treating all extracted terms equally while forming the search query. Finally, utilizing the similarities between the IPC codes of the query patent and retrieved patents is shown to be beneficial to improve the effectiveness of the prior art search.
Feeding lactate for CHO cell culture processes: Impact on culture metabolism and performance
Authors: Li Jincai , Wong Chun Loong , Vijayasankaran Natarajan , Hudson Terry , Amanullah Ashraf
Published: November 2011

Lactate has long been regarded as one of the key metabolites of mammalian cell cultures. High levels of lactate have clear negative impacts on cell culture processes, and therefore, a great amount of efforts have been made to reduce lactate accumulation and/or to induce lactate consumption in the later stage of cultures. However, there is virtually no report on the impact of lactate depletion after initial accumulation. In this work, we observed that glucose uptake rate dropped over 50% at the onset of lactate consumption, and that catabolism of alanine due to lactate depletion led to ammonium accumulation. We explored the impact of feeding lactate as well as pyruvate to the cultures. In particular, a strategy was employed where CO2 was replaced by lactic acid for culture pH control, which enabled automatic lactate feeding. The results demonstrated that lactate or pyruvate can serve as an alternative or even preferred carbon source during certain stage of the culture in the presence of glucose, and that by feeding lactate or pyruvate, very low levels of ammonia can be achieved throughout the culture. In addition, low levels of pCO2 were also maintained in these cultures. This was in strong contrast to the control cultures where lactate was depleted during the culture, and ammonia and pCO2 build‐up were significant. Culture growth and productivity were similar between the control and lactate‐fed cultures, as well as various product quality attributes. To our knowledge, this work represents the first comprehensive study on lactate depletion and offers a simple yet effective strategy to overcome ammonia and pCO2 accumulation that could arise in certain cultures due to early depletion of lactate. Biotechnol. Bioeng. 2012; 109:1173–1186. © 2011 Wiley Periodicals, Inc.
Anisotropic nutrient transport in three‐dimensional single species bacterial biofilms
Authors: Van Wey A.S. , Cookson A.L. , Soboleva T.K. , Roy N.C. , McNabb W.C. , Bridier A. , Briandet R. , Shorten P.R.
Published: November 2011

The ability for a biofilm to grow and function is critically dependent on the nutrient availability, and this in turn is dependent on the structure of the biofilm. This relationship is therefore an important factor influencing biofilm maturation. Nutrient transport in bacterial biofilms is complex; however, mathematical models that describe the transport of particles within biofilms have made three simplifying assumptions: the effective diffusion coefficient (EDC) is constant, the EDC is that of water, and/or the EDC is isotropic. Using a Monte Carlo simulation, we determined the EDC, both parallel to and perpendicular to the substratum, within 131 real, single species, three‐dimensional biofilms that were constructed from confocal laser scanning microscopy images. Our study showed that diffusion within bacterial biofilms was anisotropic and depth dependent. The heterogeneous distribution of bacteria varied between and within species, reducing the rate of diffusion of particles via steric hindrance. In biofilms with low porosity, the EDCs for nutrient transport perpendicular to the substratum were significantly lower than the EDCs for nutrient transport parallel to the substratum. Here, we propose a reaction–diffusion model to describe the nutrient concentration within a bacterial biofilm that accounts for the depth dependence of the EDC. Biotechnol. Bioeng. 2012; 109:1280–1292. © 2011 Wiley Periodicals, Inc.
Surgical anatomy of the pectoral nerves and the pectoral musculature
Authors: Porzionato Andrea , Macchi Veronica , Stecco Carla , Loukas Marios , Tubbs R. Shane , De Caro Raffaele
Published: November 2011

The pectoral nerves (PNs) may be selectively injured through various traumatic mechanisms such as direct trauma, hypertrophic muscle compression, and iatrogenic injuries (breast surgery and axillary node dissection, pectoralis major muscle transfers). The PN may be surgically recovered through nerve transfers. They may also be used as donors to the musculocutaneous, axillary, long thoracic, and spinal accessory nerves and for reinnervation of myocutaneous free flaps. Thus, in this article, we reviewed the surgical anatomy of PN. A meta‐analysis of the available literature showed that the lateral pectoral nerve (LPN) arises most frequently with two branches from the anterior divisions of the upper and middle trunks (33.8%) or as a single root from the lateral cord (23.4%). The medial pectoral nerve (MPN) usually arises from the medial cord (49.3%), anterior division of the lower trunk (43.8%), or lower trunk (4.7%). The two PN are usually connected immediately distal to the thoracoacromial artery by the so‐called ansa pectoralis. The MPN may also show communications with the intercostobrachial nerve. In 50%–100% of cases, it may pass, at least with some branches, through the pectoralis minor muscle. The LPN supplies the upper portions of the pectoralis major muscle; the MPN innervates the lower parts of the pectoralis major and the pectoralis minor muscle. Among the accessory muscles of the pectoral girdle, the LPN may also innervate the tensor semivaginae articulationis humero‐scapularis, pectoralis minimus, sternoclavicularis, axillary arch, sternalis, and infraclavicularis muscles; the MPN may innervate the pectoralis quartus, chondrofascialis, axillary arch, chondroepitrochlearis, and sternalis muscles. Clin. Anat. 25:559–575, 2012. © 2011 Wiley Periodicals, Inc.
Gentiana asclepiadea protects human cells against oxidation DNA lesions
Authors: Hudecová Alexandra , Hašplová Katarína , Miadoková Eva , Magdolenová Zuzana , Rinna Alessandra , Collins Andrew R. , Gálová Eliška , Vaculčíková Dagmar , Gregáň Fridrich , Dušinská Mária
Published: November 2011

The objectives of this study were to examine whether the methanolic and aqueous extracts from the haulm and flower of Gentiana asclepiadea exhibited free radical scavenging and protective (antigenotoxic) effect against DNA oxidation induced by H2O2 in human lymphocytes and human embryonic kidney cells (HEK 293). All four extracts exhibited high scavenging effect on 1,1‐diphenyl‐2‐picrylhydrazyl radicals at concentrations 2.5 and 25 mg ml−1. The level of DNA damage was measured using the alkaline version of single‐cell gel electrophoresis (comet assay). Challenge with H2O2 shows that the pre‐treatment of the cells with non‐genotoxic doses of Gentiana extracts protected human DNA—either eliminated or significantly reduced H2O2 induced DNA damage. The genotoxic activity of H2O2 was most effectively decreased after 30 min of pre‐incubation with 0.05 mg ml−1 (range, 93.5%–96.3% of reduction in lymphocytes) and 0.25 mg ml−1 (range, 59.5%–71.4% and 52.7%–66.4% of reduction in lymphocytes and HEK 293 cells, respectively) of G. asclepiadea extracts. These results suggest that the tested G. asclepiadea extracts could be considered as an effective natural antioxidant source. Copyright © 2011 John Wiley & Sons, Ltd.
Endothelial Function and Soluble Endoglin in Smokers With Heart Failure
Authors: Heffernan Kevin S. , Kuvin Jeffrey T. , Patel Ayan R. , Karas Richard H. , Kapur Navin K.
Published: November 2011

Background:

Although cigarette smoking is a risk factor for heart failure (HF), smokers with HF have lower mortality rates during/following hospitalization compared to nonsmokers. We examined vascular endothelial function in chronic smokers and nonsmokers with HF as it relates to this smoker's paradox.

Hypothesis:

Smokers with HF will have attenuated endothelial dysfunction compared to non‐smokers with HF.

Methods:

Brachial artery flow‐mediated dilation (FMD), a measure of conduit vessel endothelial function, was measured in 33 smoking and nonsmoking patients with HF vs controls. In addition, soluble endoglin (sEng), a circulating mediator of endothelial function, was measured in a separate group of 36 smoking and nonsmoking patients with HF vs controls.

Results:

FMD was significantly lower in smokers without HF compared to the nonsmokers without HF (P < 0.05). FMD was significantly higher in smokers with HF vs nonsmokers with HF (P < 0.05) and did not differ from values seen in nonsmokers without HF (P > 0.05). There were no differences in sEng between smokers and nonsmokers without HF (P > 0.05). sEng was lower in smokers with HF vs nonsmokers with HF (P < 0.05) and did not differ from values seen in nonsmokers without HF (P > 0.05).

Conclusions:

Smokers with HF had higher brachial FMD and lower sEng than nonsmokers with HF, and values were comparable to nonsmokers without HF. These findings offer novel insight into the smoker's paradox and suggest that improved short‐term outcome in patients hospitalized with HF may in part be mediated by preservation of vascular endothelial function in this setting. © 2011 Wiley Periodicals, Inc.

The authors have no funding, financial relationships, or conflicts of interest to disclose.
A Review of Causes and Systemic Approach to Cardiac Troponin Elevation
Authors: Patil Harshal , Vaidya Omkar , Bogart Douglas
Published: November 2011

The first American College of Cardiology/European Society of Cardiology task force published recommendations for a universal definition of myocardial infarction (MI) in 2000 based on the measurement of troponin (Tn). Although this rapid and highly sensitive blood test is certainly valuable in the appropriate setting, its widespread use in variety of clinical scenarios may lead to the detection of Tn elevation in absence of thrombotic acute coronary syndrome. In 2007, the joint European Society of Cardiology/American College of Cardiology Foundation/American Heart Association/World Heart Federation task force proposed a new definition for acute MI based on detection of Tn and associated clinical evidence. The goal of this article is to review the universal definition of acute MI and to differentiate type 1 MI, type 2 MI, and non–acute coronary syndrome Tn elevations. The prognosis and a clinical approach to this differential diagnosis will be developed. © 2011 Wiley Periodicals, Inc.

The authors have no funding, financial relationships, or conflicts of interest to disclose.
How Healthy Were the Arteries of Phidippides?
Authors: Heffernan Kevin S.
Published: November 2011

Subacute and chronic cardiac adaptations to marathon running may increase risk for sudden death. Herein, it is proposed that cardiac arrhythmogenic remodeling resulting from prolonged strenuous exertion may also have a systemic vascular component. Marathon running reduces coronary perfusion pressure and causes acute endothelial damage, possibly via altering concentrations of circulating angiogenic growth factors with novel vasoregulatory properties. Marathon runners have increased arterial stiffness and augmented pressure from wave reflections contributing to a widening of pulse pressure. Pulsatile hemodynamics may contribute to target organ damage. Moreover, each of these vascular maladaptations (increased arterial stiffness, augmented pressure from wave reflections, and widened pulse pressure) has been associated with atrial fibrillation and may provide a substrate for lethal arrhythmogenesis in the marathon runner. Clin. Cardiol. 2012 DOI: 10.1002/clc.21009

The author has no funding, financial relationships, or conflicts of interest to disclose.

This article ﬁrst published online 28 November 2011. It has since changed. The term “coronary pulse pressure” has been changed to “coronary perfusion pressure.”
Computational fluid dynamics in brain aneurysms
Authors: Sforza Daniel M. , Putman Christopher M. , Cebral Juan R.
Published: November 2011

Because of its ability to deal with any geometry, image‐based computational fluid dynamics (CFD) has been progressively used to investigate the role of hemodynamics in the underlying mechanisms governing the natural history of cerebral aneurysms. Despite great progress in methodological developments and many studies using patient‐specific data, there are still significant controversies about the precise governing processes and divergent conclusions from apparently contradictory results. Sorting out these issues requires a global vision of the state of the art and a unified approach to solving this important scientific problem. Towards this end, this paper reviews the contributions made using patient‐specific CFD models to further the understanding of these mechanisms, and highlights the great potential of patient‐specific computational models for clinical use in the assessment of aneurysm rupture risk and patient management. Copyright © 2011 John Wiley & Sons, Ltd.
White lighting
Authors: Rea M. S. , Freyssinier J. P.
Published: November 2011

White is a color sensation absent hue. Manufacturers describe practical light sources used for illumination as tinted warm‐white or cool‐white, but these informal designations do not seem to be based upon measured human color perceptions of white illumination. This article describes the results of a series of psychophysical experiments that more precisely measured subjective perceptions of white illumination from light sources of different correlated color temperatures (CCTs). Generally, perceptions of untinted white illumination for sources with high CCTs (above 4000 K) are associated with chromaticities that fall above the blackbody locus. In contrast, perceptions of untinted white illumination for sources with low CCTs (below 4000 K) are associated with chromaticities that lie well below the blackbody locus. © 2011 Wiley Periodicals, Inc. Col Res Appl, 2013
Recent advances in miniaturisation – The role of microchip electrophoresis in clinical analysis
Authors: Shang Fengjun , Guihen Elizabeth , Glennon Jeremy D.
Published: November 2011

This review aims to highlight the current role of microchip CE (MCE) in clinical analysis to date, and also its future potential in this important area. One of the most notable advancements in separation science, which has accelerated in the last decade, has been the use of plastic and glass microchips to achieve high‐speed electrophoresis separations in seconds, requiring only pico or nanolitre sample volumes. So far, in the clinical laboratory, MCE has lent itself to the resolution of very complex challenging analytes such as DNA, RNA, protein analysis, cellular components and other disease biomarkers. At present, most basic clinical laboratories rely heavily upon various kinds of enzymatic immunoassays as these methods offer speed, specificity, reliability and are well established analytical methods. However, this is not always the case, as with all analytical methods there are limitations, and sometimes enzymatic‐based assays can be challenged by low‐level concentration of target analytes present in samples resulting in high RSD values and results that cannot be interpreted. In some cases, this difficulty can be exasperated when complex sample matrices are presented for analysis, and interfering components result in highly exaggerated results from unwanted extra enzymatic binding. MCE may have a role in providing alternative highly sophisticated automated clinical analysis using state‐of‐the‐art methodologies.
Haplotype variation and genotype imputation in African populations
Authors: Huang Lucy , Jakobsson Mattias , Pemberton Trevor J. , Ibrahim Muntaser , Nyambo Thomas , Omar Sabah , Pritchard Jonathan K. , Tishkoff Sarah A. , Rosenberg Noah A.
Published: November 2011

Sub‐Saharan Africa has been identified as the part of the world with the greatest human genetic diversity. This high level of diversity causes difficulties for genome‐wide association (GWA) studies in African populations—for example, by reducing the accuracy of genotype imputation in African populations compared to non‐African populations. Here, we investigate haplotype variation and imputation in Africa, using 253 unrelated individuals from 15 Sub‐Saharan African populations. We identify the populations that provide the greatest potential for serving as reference panels for imputing genotypes in the remaining groups. Considering reference panels comprising samples of recent African descent in Phase 3 of the HapMap Project, we identify mixtures of reference groups that produce the maximal imputation accuracy in each of the sampled populations. We find that optimal HapMap mixtures and maximal imputation accuracies identified in detailed tests of imputation procedures can instead be predicted by using simple summary statistics that measure relationships between the pattern of genetic variation in a target population and the patterns in potential reference panels. Our results provide an empirical basis for facilitating the selection of reference panels in GWA studies of diverse human populations, especially those of African ancestry. Genet. Epidemiol. 35:766–780, 2011. © 2011 Wiley Periodicals, Inc.
To stratify or not to stratify: power considerations for population‐based genome‐wide association studies of quantitative traits
Authors: Behrens Gundula , Winkler Thomas W. , Gorski Mathias , Leitzmann Michael F. , Heid Iris M.
Published: November 2011

Meta‐analyses of genome‐wide association studies require numerous study partners to conduct pre‐defined analyses and thus simple but efficient analyses plans. Potential differences between strata (e.g. men and women) are usually ignored, but often the question arises whether stratified analyses help to unravel the genetics of a phenotype or if they unnecessarily increase the burden of analyses. To decide whether to stratify or not to stratify, we compare general analytical power computations for the overall analysis with those of stratified analyses considering quantitative trait analyses and two strata. We also relate the stratification problem to interaction modeling and exemplify theoretical considerations on obesity and renal function genetics. We demonstrate that the overall analyses have better power compared to stratified analyses as long as the signals are pronounced in both strata with consistent effect direction. Stratified analyses are advantageous in the case of signals with zero (or very small) effect in one stratum and for signals with opposite effect direction in the two strata. Applying the joint test for a main SNP effect and SNP‐stratum interaction beats both overall and stratified analyses regarding power, but involves more complex models. In summary, we recommend to employ stratified analyses or the joint test to better understand the potential of strata‐specific signals with opposite effect direction. Only after systematic genome‐wide searches for opposite effect direction loci have been conducted, we will know if such signals exist and to what extent stratified analyses can depict loci that otherwise are missed. Genet. Epidemiol. 2011. © 2011 Wiley Periodicals, Inc.35:867‐879, 2011
Pitfalls of merging GWAS data: lessons learned in the eMERGE network and quality control procedures to maintain high data quality
Authors: Zuvich Rebecca L. , Armstrong Loren L. , Bielinski Suzette J. , Bradford Yuki , Carlson Christopher S. , Crawford Dana C. , Crenshaw Andrew T. , de Andrade Mariza , Doheny Kimberly F. , Haines Jonathan L. , Hayes M. Geoffrey , Jarvik Gail P. , Jiang Lan , Kullo Iftikhar J. , Li Rongling , Ling Hua , Manolio Teri A. , Matsumoto Martha E. , McCarty Catherine A. , McDavid Andrew N. , Mirel Daniel B. , Olson Lana M. , Paschall Justin E. , Pugh Elizabeth W. , Rasmussen Luke V. , Rasmussen‐Torvik Laura J. , Turner Stephen D. , Wilke Russell A. , Ritchie Marylyn D.
Published: November 2011

Genome‐wide association studies (GWAS) are a useful approach in the study of the genetic components of complex phenotypes. Aside from large cohorts, GWAS have generally been limited to the study of one or a few diseases or traits. The emergence of biobanks linked to electronic medical records (EMRs) allows the efficient reuse of genetic data to yield meaningful genotype–phenotype associations for multiple phenotypes or traits. Phase I of the electronic MEdical Records and GEnomics (eMERGE‐I) Network is a National Human Genome Research Institute‐supported consortium composed of five sites to perform various genetic association studies using DNA repositories and EMR systems. Each eMERGE site has developed EMR‐based algorithms to comprise a core set of 14 phenotypes for extraction of study samples from each site's DNA repository. Each eMERGE site selected samples for a specific phenotype, and these samples were genotyped at either the Broad Institute or at the Center for Inherited Disease Research using the Illumina Infinium BeadChip technology. In all, approximately 17,000 samples from across the five sites were genotyped. A unified quality control (QC) pipeline was developed by the eMERGE Genomics Working Group and used to ensure thorough cleaning of the data. This process includes examination of sample and marker quality and various batch effects. Upon completion of the genotyping and QC analyses for each site's primary study, eMERGE Coordinating Center merged the datasets from all five sites. This larger merged dataset reentered the established eMERGE QC pipeline. Based on lessons learned during the process, additional analyses and QC checkpoints were added to the pipeline to ensure proper merging. Here, we explore the challenges associated with combining datasets from different genotyping centers and describe the expansion to eMERGE QC pipeline for merged datasets. These additional steps will be useful as the eMERGE project expands to include additional sites in eMERGE‐II, and also serve as a starting point for investigators merging multiple genotype datasets accessible through the National Center for Biotechnology Information in the database of Genotypes and Phenotypes. Our experience demonstrates that merging multiple datasets after additional QC can be an efficient use of genotype data despite new challenges that appear in the process. Genet. Epidemiol. 35:887–898, 2011. © 2011 Wiley Periodicals, Inc.
Uncertainty assessment of hydrologic and climate forecast models in Northeastern Brazil
Authors: Kwon Hyun‐Han , de Assis de Souza Filho Francisco , Block Paul , Sun Liqiang , Lall Upmanu , Reis Dirceu S.
Published: November 2011

Seasonal streamflow forecasts based on climate information can guide water managers toward superior reservoir operations, leading to improved water resources management efficiency. Uncertainty, however, is always present in seasonal streamflow forecasts, affecting the forecast value. Thus, a forecast should not be considered complete without a description of its uncertainty, which is critical for climate risk and water resources management. This study investigates the uncertainties of a seasonal streamflow forecast system for Northeastern Brazil based on climate precipitation forecasts and hydrologic modeling. These two sources of uncertainty are treated independently and then compared in order to guide future investments in the forecast system. Sea surface temperature is considered to be the primary source of uncertainty for the seasonal precipitation forecasts, based upon a 10‐member climate model ensemble. Parameter uncertainty is considered to be the only source of uncertainty for the hydrologic model. Estimation of parameter uncertainty is estimated by the Shuffled Complex Evolution Metropolis algorithm, which employs a Markov Chain Monte Carlo scheme to provide the posterior distribution of the parameters and form uncertainty bounds on streamflow forecasts. Results indicate that uncertainties associated with the climate forecast are much larger than those from parameter estimation in the hydrologic model. Although model structure has not been considered in the evaluation of hydrologic uncertainties, this study indicates that future efforts to address the predominant source of uncertainty should focus on the climate prediction models. Copyright © 2011 John Wiley & Sons, Ltd.
Estimated phytanic acid intake and prostate cancer risk: A prospective cohort study
Authors: Wright Margaret E. , Bowen Phyllis , Virtamo Jarmo , Albanes Demetrius , Gann Peter H.
Published: November 2011

Phytanic acid is a saturated fatty acid found predominantly in red meat and dairy products and may contribute to increases in prostate cancer risk that are observed with higher intakes of these foods. We constructed a novel summary measure of phytanic acid intake and prospectively examined its association with prostate cancer risk in the Alpha‐Tocopherol, Beta‐Carotene Cancer Prevention Study—a cohort of Finnish male smokers aged 50–69 years. Diet was assessed at baseline in 27,111 participants using a validated 276‐item dietary questionnaire. Since phytanic acid is not currently included in food composition tables, we used the published phytanic acid content of 151 major food items to estimate total daily intake. During up to 21 years of follow‐up, a total of 1,929 incident prostate cancer cases (including 438 advanced cases) were identified. Higher phytanic acid intake, though unrelated to the risk of localized disease [relative risks (RR) and 95% confidence intervals (CI) for increasing quartiles of intake = 1.00 (ref), 0.83 (0.68–1.01), 0.76 (0.62–0.94) and 0.91 (0.74–1.13); p trend = 0.23], was associated with increased risks of advanced prostate cancer [RR and 95% CI = 1.00 (ref), 1.43 (1.09–1.89), 1.31 (0.99–1.75) and 1.38 (1.02–1.89); p trend = 0.06]. This association appeared to be driven predominantly by phytanic acid obtained from dairy products (particularly butter). Our study indicates that phytanic acid may contribute to previously observed associations between high‐fat animal foods (particularly dairy products) and prostate cancer risk, although some caution is warranted as it may be acting as a surrogate marker of dairy fat.
Using biofilms as initial inocula in animal models of biofilm‐related infections
Authors: Williams Dustin L. , Costerton J. William
Published: November 2011

One of the most practical strategies that has been undertaken to fight biofilm implant‐related infections has been the development of coatings on biomaterial devices that can elute antimicrobials into regions of patients' tissues. To date, the majority of animal studies that have been developed to model infections that accompany the use of these materials have primarily involved an initial inoculum of planktonic bacterial cells from batch cultures. Although valuable, data that have been derived from these experiments may not provide important clinical insight into how bacteria in well‐established, mature biofilms impact device‐related and other clinical infections when they contaminate a patient site or implanted device. In this review, a discussion is presented on the impact that a shift in biofilm research may have if initial inocula of well‐established, mature biofilms are used to model biomaterial device‐related infections in animal models. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2011.
A fully degradable tracheal stent: In vitro and in vivo characterization of material degradation
Authors: Ng Anthony H. C. , Ng Nelson S. P. , Zhu G. H. , Lim Lynne H. Y. , Venkatraman Subbu S.
Published: November 2011

We report on the testing of materials for a fully degradable tracheal stent. Such a stent has several advantages over currently used permanent stents made of metal or silicone polymers. However, the mode of degradation in the trachea is expected to be different from a fully submerged device, because of the uniqueness of the tracheal environment. A physical model was developed to allow an in‐depth study of degradation of bioabsorbable polymers exposed to two differing media; namely 70 wt % water (gel) on one side and humidified air on the other, simulating conditions in a tracheal passage. Longitudinal microtome slices were obtained from both polymer surfaces and degradation kinetics data were derived from size exclusion chromatography. On the basis of the data obtained, it is observed that well‐studied bulk‐degrading polymers might show surface‐eroding properties in such an environment. Generally, hydrophobic polymers retard the formation of a water concentration gradient and exhibit bulk‐degradation kinetics. However, addition of specific plasticizers can influence the water uptake gradient, and force the polymer towards a pseudo “surface‐eroding” behavior. In vivo studies in a rabbit model of degradable stents made from a selected polymer, demonstrate the feasibility of a fully bioabsorbable tracheal stent. This study aims to improve understanding of degradation of polymers under heterogeneous environments. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2012.
Association of participation in a mindfulness program with measures of PTSD, depression and quality of life in a veteran sample
Authors: Kearney David J. , McDermott Kelly , Malte Carol , Martinez Michelle , Simpson Tracy L.
Published: November 2011

Objectives: To assess outcomes of veterans who participated in mindfulness‐based stress reduction (MBSR). Design: Posttraumatic stress disorder (PTSD) symptoms, depression, functional status, behavioral activation, experiential avoidance, and mindfulness were assessed at baseline, and 2 and 6 months after enrollment. Results: At 6 months, there were significant improvements in PTSD symptoms (standardized effect size, d = ‐0.64, p< 0.001); depression (d = ‐0.70, p<0.001); behavioral activation (d = 0.62, p<0.001); mental component summary score of the Short Form‐8 (d = 0.72, p<0.001); acceptance (d = 0.67, p<0.001); and mindfulness (d = 0.78, p<0.001), and 47.7% of veterans had clinically significant improvements in PTSD symptoms. Conclusions: MBSR shows promise as an intervention for PTSD and warrants further study in randomized controlled trials. © 2011 Wiley Periodicals, Inc. J Clin Psychol 68:1–16, 2012.
Matrix metalloproteinase3 gene promoter polymorphisms and their haplotypes are associated with gastric cancer risk in eastern Indian population
Authors: Dey Sanjib , Stalin Sami , Gupta Arnab , Saha Debjit , Kesh Kousik , Swarnakar Snehasikta
Published: November 2011

Single nucleotide polymorphisms (SNPs) of matrix metalloproteinase3 (MMP3) promoter in the development and progression of gastric cancer of whole stomach has never been investigated in any population. We conducted a hospital‐based case‐control study to explore the MMP3 SNPs and their haplotypes with the risk of gastric cancer for the first time in eastern Indian population. A total of 218 gastric cancer patients and 175 healthy controls were genotyped for MMP3‐1612 5A/6A (rs3025058) by PCR–RFLP and rechecked 10% by DNA sequencing. MMP3‐707 A/G (rs522616) and MMP3‐375 C/G (rs617819) were genotyped by DNA sequencing among 209 patients and 154 controls. MMP3‐1612 5A6A genotype (P = 0.026, odds ratio (OR) = 1.756, confidence interval (CI) = 1.070–2.883), combined 5A5A and 5A6A genotype (P = 0.015, OR = 1.791, CI = 1.122–2.858) and 5A allele (P = 0.002, OR = 1.75, CI = 1.21–2.53) and; MMP3‐707 GG genotype (P = < 0.0001; OR = 9.612; 95% CI = 3.403–27.147), combined GG and AG genotype (P = 0.001, OR = 2.201, CI = 1.385–3.498) and G allele (P = <0.0001, OR = 2.189, CI = 1.582–3.033) conferred significant risk for gastric cancer development. Also, tobacco addicted individuals with combined 5A5A and 5A6A genotype (P = 0.005, OR = 2.952, CI = 1.377–6.327) at −1612 position of MMP3 promoter displayed a higher risk to gastric cancer development. The genotypic combinations of all three MMP3 promoter polymorphisms and their haplotypes with increasing risk allele in a dose‐dependent manner showed a potential risk for developing gastric cancer. The analyses suggested that the MMP3‐707 G/G and MMP3‐1612 5A/6A polymorphisms are potential independent predictors of gastric cancer risk development. © 2011 Wiley Periodicals, Inc.
Processed nerve allografts for peripheral nerve reconstruction: A multicenter study of utilization and outcomes in sensory, mixed, and motor nerve reconstructions
Authors: Brooks Darrell N. , Weber Renata V. , Chao Jerome D. , Rinker Brian D. , Zoldos Jozef , Robichaux Michael R. , Ruggeri Sebastian B. , Anderson Kurt A. , Bonatz Ekkehard E. , Wisotsky Scott M. , Cho Mickey S. , Wilson Christopher , Cooper Ellis O. , Ingari John V. , Safa Bauback , Parrett Brian M. , Buncke Gregory M.
Published: November 2011

Purpose: As alternatives to autograft become more conventional, clinical outcomes data on their effectiveness in restoring meaningful function is essential. In this study we report on the outcomes from a multicenter study on processed nerve allografts (Avance® Nerve Graft, AxoGen, Inc). Patients and Methods: Twelve sites with 25 surgeons contributed data from 132 individual nerve injuries. Data was analyzed to determine the safety and efficacy of the nerve allograft. Sufficient data for efficacy analysis were reported in 76 injuries (49 sensory, 18 mixed, and 9 motor nerves). The mean age was 41 ± 17 (18–86) years. The mean graft length was 22 ± 11 (5–50) mm. Subgroup analysis was performed to determine the relationship to factors known to influence outcomes of nerve repair such as nerve type, gap length, patient age, time to repair, age of injury, and mechanism of injury. Results: Meaningful recovery was reported in 87% of the repairs reporting quantitative data. Subgroup analysis demonstrated consistency, showing no significant differences with regard to recovery outcomes between the groups (P > 0.05 Fisher's Exact Test). No graft related adverse experiences were reported and a 5% revision rate was observed. Conclusion: Processed nerve allografts performed well and were found to be safe and effective in sensory, mixed and motor nerve defects between 5 and 50 mm. The outcomes for safety and meaningful recovery observed in this study compare favorably to those reported in the literature for nerve autograft and are higher than those reported for nerve conduits. © 2011 Wiley Periodicals, Inc. Microsurgery, 2012.
Imaging and quantification of metastatic melanoma cells in lymph nodes with a ferritin MR reporter in living mice
Authors: Choi Seung Hong , Cho Hye Rim , Kim Hoe Suk , Kim Young Hwa , Kang Keon Wook , Kim Hyeonjin , Moon Woo Kyung
Published: November 2011

Cellular MRI with a reporter gene offers the opportunity to track small numbers of tumor cells and to study metastatic processes in their earliest developmental stages in the target organs of interest. This study demonstrates the feasibility of using the MR reporter ferritin for the noninvasive imaging and quantification of metastatic melanoma cells in the lymph nodes (LNs) of living mice. A B16F10 murine melanoma cell line expressing human ferritin heavy chain (hFTH) and green fluorescent protein (GFP) was constructed to allow the detection of cells by MRI and fluorescence imaging. Stable overexpression of hFTH and GFP in B16F10 murine melanoma cells was feasible and showed no cellular toxicity. In addition, hFTH cells were detectable by 9.4‐T MRI in vitro and in vivo, yielding significant changes in T2* relative to control cells. In BALB/c nude mice, the presence of hFTH‐ and GFP‐expressing metastatic melanoma cells in deep‐seated axillary LNs was demonstrated as areas of low T2* on MRI, but the same LNs were not visible by fluorescence imaging because the light was unable to penetrate the tissue. Furthermore, the metastatic volume of each LN, which was assessed by cumulative histogram analysis of the T2* MRI data, correlated well with tumor burden, which was determined by histology (r = −0.8773, p = 0.0001). This study is the first to use MRI and an MR reporter gene for both the visualization and quantification of metastatic cancer cells in LNs. Copyright © 2011 John Wiley & Sons, Ltd.