bluuebunny/crossref_metadata_2025 huggingface dataset:
Hierarchical Modeling of the Relation Between Sequence Variants and a Quantitative Trait: Addressing Multiple Comparison and Population Stratification Issues
Authors: Kim Lee-Lian , Fijal Bonnie A. , Witte John S.
Published: July 2017

When analyzing the relation between genetic sequence information and disease traits, false‐positive associations can arise due to multiple comparisons and population stratification. In an attempt to address these issues, we incorporate into a conventional analytic model higher‐level—or “prior”—models that use additional information to improve estimates while allowing for differing population structures. We apply this hierarchical model to simulated data from the Genetic Analysis Workshop 12. We focus on the effects of common candidate gene sequence variants on quantitative risk factor 5 (Q5) levels. In particular, we compare the regression coefficients (and 95% confidence intervals) obtained from conventional (one‐stage) analyses versus the corresponding results from the hierarchical analyses. When examining either the marry‐ins or all subjects in the general and isolate populations, the conventional model detected numerous sites in candidate genes 1–5 and 7 that had statistically significant regression coefficients (alpha level = 0.05). In contrast, our hierarchical model primarily only detected associations for variants in candidate gene 2, which is the casual gene for Q5. © 2001 Wiley‐Liss, Inc.
On the Detection of Linkage in Multiple Data Sets: A Comparison of Various Statistical Approaches
Authors: Eerdewegh Paul Van , Dowd Michael , Dupuis Josée , Falls Kathleen , Hayward Brooke , Santangelo Susan L.
Published: July 2017

We contrast the pooling of multiple data sets with the compound HLOD (HLODC) and the posterior probability of linkage (PPL), two approaches that have been shown to have more power in the presence of genetic heterogeneity. We also propose and evaluate several multipoint extensions. © 2001 Wiley‐Liss, Inc.
Genome‐Wide Linkage Analysis in a General Population Sample Using σ2A Random Effects (SSARs) Fitted by Gibbs Sampling
Authors: Palmer Lyle J. , Jacobs Kevin B. , Scurrah Katrina J. , Xu Xin , Horvath Steve , Weiss Scott T.
Published: July 2017

We used variance components analysis to investigate the underlying determinants of the quantitative phenotypes (Q1–Q5) and their interrelationships in replicate 42 of the Genetic Analysis Workshop 12 simulated general population. Variance components models were fitted using Gibbs sampling in WinBUGS v1.3. Sigma‐squared‐A‐random‐effects (SSARs) were estimated for each phenotype, and were used as derived phenotypes in subsequent linkage analyses. Whole‐genome, multipoint linkage analyses were based upon a new Haseman‐Elston identity‐by descent sib‐pair method that takes a weighted combination of the trait‐sum and trait‐difference. The five quantitative traits simulated were closely correlated with each other and with affection status. The whole‐genome screen of quantitative traits associated with the simulated complex disease suggested that one or more major loci regulating Q1 localizes to chromosome 2p and that one or more major loci regulating Q5 may localize to chromosome Ip. © 2001 Wiley‐Liss, Inc.
Application of a Bayesian Method for Optimal Subset Regression to Linkage Analysis of Q1 and Q2
Authors: Ju Suh Young , Finch Stephen J. , Mendell Nancy R.
Published: July 2017

We explore an approach that allows us to consider a trait for which we wish to determine the optimal subset of markers out of a set of p ≥ 3 candidate markers being considered in a linkage analysis. The most effective analysis would find the model that only includes the q markers closest to the q major genes which determine the trait. Finding this optimal model using classical “frequentist” multiple regression techniques would require consideration of all 2p possible subsets. We apply the work of George and McCulloch [J Am Stat Assoc 88:881–9, 1993], who have developed a Bayesian approach to optimal subset selection regression, to a modification of the Baseman ‐ Elston linkage statistic [Elston et al., Genet Epidemiol 19:1–17, 2000] in the analysis of the two quantitative traits simulated in Problem 2. The results obtained using this Bayesian method are compared to those obtained using (1) multiple regression and (2) the modified Haseman‐Elston method (single variable regression analysis). We note upon doing this that for both Q1 and Q2, (1) we have extremely low power with all methods using the samples as given and have to resort to combining several simulated samples in order to have power of 50%, (2) the multivariate analysis does not have greater power than the univariate analysis for these traits, and (3) the Bayesian approach identifies the correct model more frequently than the frequentist approaches but shows no clear advantage over the multivariate approach. © 2001 Wiley‐Liss, Inc.
Quantitative Trait Linkage Analysis of the Liability Underlying a Common Oligogenic Disease
Authors: Maher Brion S. , Vanyukov Michael M. , Cooper Margaret E. , Neiwswanger Katherine , Marazita Mary L.
Published: July 2017

We utilized pedigree discriminant and factor analytic approaches to combine multivariate phenotypic information into a single liability phenotype in the isolate and general populations. We applied two‐stage relative‐pair quantitative trait linkage analysis to detect genetic contributions to variation in the resulting liability phenotypes. Linkage analysis revealed several regions of suggestive linkage in both the general and isolate populations, the majority of which appear in retrospect to be false positives. A likely explanation is an overall lack of power given that we tested hypotheses in data from only one replicate. However, it may be possible that a construct that ignores affection status when using liability‐associated characteristics as indicators of this construct is not the most effective approach in modeling the liability underlying a complex phenotype. © 2001 Wiley‐Liss, Inc.
Assessing the Effect of Sampling Strategies on the Power of Linkage Analysis to Identify Pathway‐Specific Loci Underlying a Complex Disease
Authors: Guo Xiuqing , Lin Ying-Chao , Wang Yaping , Cheng Li Shu-Chuan , Yang Huiying
Published: July 2017

Using the simulated general population data sets, we first examined the effect of sampling strategies on the power of identifying linkage by selecting samples with (A) two affected sibs in a nuclear family and (B) one affected sib and one sib with an intermediate trait value in the upper quantiles. Second, we evaluated the improvement in power when analyzing correlated traits simultaneously. Under each selection criteria, 100 replicates of 300 nuclear families were sampled and analyzed with two‐point linkage analysis for ten markers (1 cM apart) from each of the candidate regions. Different genes were identified under different sampling strategies. When a gene has a pleitropic effect, it is more powerful to analyze correlated traits simultaneously, either by using a linear combination or the larger value of standardized traits, than to analyze each trait separately. © 2001 Wiley‐Liss, Inc.
Variance Components Analysis for Genetic Linkage of Time to Onset for Disease
Authors: Amos Christopher I. , Shete Sanjay , Gu Xiangjun
Published: July 2017

We compared two variance components methods for detecting genes that influence time to onset for a complex disease using simulated data. We first divided the extended families into nuclear families. The first method fitted variance components to the martingale residuals, which were obtained from first fitting a proportional hazards model to the time to onset data for the trait, allowing for the quantitative traits Q1–Q5, sex, age, and the environmental factor. The second method treated time to onset among the affected individuals as a quantitative trait adjusting for the same factors as in the first method. Power of these analyses were similar for either approach. However, we found an excess of false‐positive results when fitting the martingale residual model or the affected‐only model to identify genetic factors linked to chromosome 6. Applying a power transformation to the martingale residuals decreased the type I error rate and increased the power of tests for genetic linkage. We also found that robust variance correction lead to tests with a slightly lower type I error rate, perhaps because the robust variance correction adjusts for the fact that we did not specifically model the effects of the mitochondrial factor in our analysis. © 2001 Wiley‐Liss, Inc.
Distribution of lod Scores in Oligogenic Linkage Analysis
Authors: Williams Jeff T. , North Karl E. , Martin Lisa J. , Comuzzie Anthony G. , Göring Harald H.H. , Blangero John
Published: July 2017

In variance component oligogenic linkage analysis it can happen that the residual additive genetic variance bounds to zero when estimating the effect of the ith quantitative trait locus. Using quantitative trait Q1 from the Genetic Analysis Workshop 12 simulated general population data, we compare the observed lod scores from oli‐gogenic linkage analysis with the empirical lod score distribution under a null model of no linkage. We find that zero residual additive genetic variance in the null model alters the usual distribution of the likelihood‐ratio statistic. © 2001 Wiley‐Liss, Inc.
A Comparison of Software Packages that Assess Linkage Using a Variance Components Approach
Authors: Atkinson Elizabeth J. , Hall Deborah , de Andrade Mariza
Published: July 2017

We report single‐point and multipoint results from three statistical genetics software packages using a variance components approach for quantitative traits. When possible, we have shown the effects of covariates. Results from GENEHUNTER, SOLAR, and ACT software packages are compared for the quantitative trait immunoglobulin E (IgE) using chromosome 5 asthma familial data from Oxfordshire (England), Perth (Australia), and Freiburg (Germany), and using the genome‐wide German data. Although few differences among variance components results for GENEHUNTER, SOLAR, and ACT were detected on a limited region of chromosome 5, these packages showed larger disagreement in the German data for chromosomes 1, 9, and 14. © 2001 Wiley‐Liss, Inc.
Should We Consider Gene×Environment Interaction in the Hunt for Quantitative Trait Loci?
Authors: Gauderman W. James , Morrison John L. , Siegmund Kimberly D.
Published: July 2017

We address the question of whether one can obtain increased power for finding a quantitative trait locus (QTL) if a gene×environment (G×E) interaction is incorporated directly into the linkage analysis. We consider both parametric and nonparametric analysis approaches to including G×E interaction. For the former, we utilize joint segregation and linkage analysis to estimate simultaneously the recombination fraction and a G×E interaction effect, as well as the remaining model parameters. The nonparametric approach is based on an extension of the Haseman‐Elston method applied to sib pairs to include a regression of the squared trait difference on marker‐identity‐by‐descent (IBD) probability (π), the sibling covariate sum (z), and π×z. We utilize 50 replicates of the simulated data and compare empirical power of the various approaches to detect MG4, a locus that is involved in a strong interaction with age for Q4 and in a weaker interaction with environmental factor E2 for Q3. Using the parametric approach, including a G×age effect does increase power for detecting linkage between MG4 and Q4 compared with ignoring the interaction (powers 58% and 38%, respectively, to exceed a lod score of 3.0). On the other hand, including a G×E2 interaction has little effect on the power to detect linkage between MG4 and Q3. The nonparametric approach leads to qualitatively similar findings. We conclude that it is beneficial to incorporate G×E interaction into a linkage analysis, provided the interaction effect is of sufficiently strong magnitude. © 2001 Wiley‐Liss, Inc.
The relationship between subcortical brain volume and striatal dopamine D2/3 receptor availability in healthy humans assessed with [11C]‐raclopride and [11C]‐(+)‐PHNO PET
Authors: Caravaggio Fernando , Ku Chung Jun , Plitman Eric , Boileau Isabelle , Gerretsen Philip , Kim Julia , Iwata Yusuke , Patel Raihaan , Chakravarty M. Mallar , Remington Gary , Graff‐Guerrero Ariel
Published: July 2017

Background

Abnormalities in dopamine (DA) and brain morphology are observed in several neuropsychiatric disorders. However, it is not fully understood how these abnormalities may relate to one another. For such in vivo findings to be used as biomarkers for neuropsychiatric disease, it must be understood how variability in DA relates to brain structure under healthy conditions. We explored how the availability of striatal DA D2/3 receptors (D2/3R) is related to the volume of subcortical brain structures in a sample of healthy humans. Differences in D2/3R availability measured with an antagonist radiotracer ([11C]‐raclopride) versus an agonist radiotracer ([11C]‐(+)‐PHNO) were examined.

Methods

Data from 62 subjects scanned with [11C]‐raclopride (mean age = 38.98 ± 14.45; 23 female) and 68 subjects scanned with [11C]‐(+)‐PHNO (mean age = 38.54 ± 14.59; 25 female) were used. Subcortical volumes were extracted from T1‐weighted images using the Multiple Automatically Generated Templates (MAGeT‐Brain) algorithm. Partial correlations were used controlling for age, gender, and total brain volume.

Results

For [11C]‐(+)‐PHNO, ventral caudate volumes were positively correlated with BPND in the dorsal caudate and globus pallidus (GP). Ventral striatum (VS) volumes were positively correlated with BPND in the VS. With [11C]‐raclopride, BPND in the VS was negatively correlated with subiculum volume of the hippocampus. Moreover, BPND in the GP was negatively correlated with the volume of the lateral posterior nucleus of the thalamus.

Conclusion

Findings are purely exploratory and presented corrected and uncorrected for multiple comparisons. We hope they will help inform the interpretation of future PET studies where concurrent changes in D2/3R and brain morphology are observed. Hum Brain Mapp 38:5519–5534, 2017. © 2017 Wiley Periodicals, Inc.
Quantifying temporal variations in water resources of a vulnerable middle eastern transboundary aquifer system
Authors: Fallatah Othman Abdurrahman , Ahmed Mohamed , Save Himanshu , Akanda Ali S.
Published: July 2017

Freshwater resources in the arid Arabian Peninsula, especially transboundary aquifers shared by Saudi Arabia, Jordan, and Iraq, are of critical environmental and geopolitical significance. Monthly Gravity Recovery and Climate Experiment (GRACE) satellite‐derived gravity field solutions acquired over the expansive Saq transboundary aquifer system were analysed and spatiotemporally correlated with relevant land surface model outputs, remote sensing observations, and field data to quantify temporal variations in regional water resources and to identify the controlling factors affecting these resources. Our results show substantial GRACE‐derived terrestrial water storage (TWS) and groundwater storage (GWS) depletion rates of −9.05 ± 0.25 mm/year (−4.84 ± 0.13 km3/year) and −6.52 ± 0.29 mm/year (−3.49 ± 0.15 km3/year), respectively. The rapid decline is attributed to both climatic and anthropogenic factors; observed TWS depletion is partially related to a decline in regional rainfall, while GWS depletions are highly correlated with increasing groundwater extraction for irrigation and observed water level declines in regional supply wells.
Glacier retreat and its impact on summertime run‐off in a high‐altitude ungauged catchment
Authors: Wang Rui , Yao Zhijun , Wu Shanshan , Liu Zhaofei
Published: July 2017

Glaciers are significant freshwater storage systems in western China and contribute substantially to the summertime run‐off of many large rivers in the Tibetan Plateau. Under the scenario of climate change, discussions of glacier variability and melting contributions in alpine basins are important for understanding the run‐off composition and ensuring that water resources are adequately managed and protected in the downstream areas. Based on the multisource spatial data and long‐term ground observation of climatic and hydrologic data, using the remote sensing interpretation, degree‐day model, and ice volume method, we presented a comprehensive study of the glacier changes in number, area, and termini and their impacts on summertime run‐off and water resource in the Tuotuo River basin, located in the source region of the Yangtze River. The results indicated that climate change, especially rising temperature, accelerated the glacier melting and consequently led to hydrological change. From 1969 to 2009, the glacier retreat showed an absolutely dominant tendency with 13 reduced glaciers and lost glacier area of 45.05 km2, accompanied by limited growing glaciers in the study area. Meanwhile, it indicated that annual glacial run‐off was averagely 0.38 × 108 m3, accounting for 4.96% of the total summertime run‐off, followed by the supply from precipitation and snowmelt. The reliability of this magnitude was assessed by the classic volume method, which also showed that the water resources from glacier melting in the Tuotuo River basin increased by approximate 17.11 × 108 m3, accounting for about 3.77% of the total run‐off over the whole period of 1969–2009. Findings from this study will serve as a reference for future research about glacier hydrology in regions where observational data are deficient. Also, it can help the planning of future water management strategies in the source region of the Yangtze River.
Mandatory waiting periods and biased abortion counseling in Central and Eastern Europe
Authors: Hoctor Leah , Lamačková Adriana
Published: July 2017

Several Central and Eastern European countries have recently enacted retrogressive laws and policies introducing new preconditions that women must fulfill before they can obtain legal abortion services. Mandatory waiting periods and biased counseling and information requirements are particularly common examples of these new prerequisites. The present article considers these requirements in light of international human rights standards and public health guidelines, and outlines the manner in which, by imposing regressive barriers on women's access to legal abortion services, these new laws and policies undermine women's health and well‐being, fail to respect women's human rights, and reinforce harmful gender stereotypes and abortion stigma.
Erythropoietin prevents the effect of chronic restraint stress on the number of hippocampal CA3c dendritic terminals—relation to expression of genes involved in synaptic plasticity, angiogenesis, inflammation, and oxidative stress in male rats
Authors: Aalling Nadia , Hageman Ida , Miskowiak Kamilla , Orlowski Dariusz , Wegener Gregers , Wortwein Gitta
Published: July 2017

Stress‐induced allostatic load affects a variety of biological processes including synaptic plasticity, angiogenesis, oxidative stress, and inflammation in the brain, especially in the hippocampus. Erythropoietin (EPO) is a pleiotropic cytokine that has shown promising neuroprotective effects. Recombinant human EPO is currently highlighted as a new candidate treatment for cognitive impairment in neuropsychiatric disorders. Because EPO enhances synaptic plasticity, attenuates oxidative stress, and inhibits generation of proinflammatory cytokines, EPO may be able to modulate the effects of stress‐induced allostatic load at the molecular level. The aim of this study was therefore to investigate how EPO and repeated restraint stress, separately and combined, influence (i) behavior in the novelty‐suppressed feeding test of depression/anxiety‐related behavior; (ii) mRNA levels of genes encoding proteins involved in synaptic plasticity, angiogenesis, oxidative stress, and inflammation; and (iii) remodeling of the dendritic structure of the CA3c area of the hippocampus in male rats. As expected, chronic restraint stress lowered the number of CA3c apical dendritic terminals, and EPO treatment reversed this effect. Interestingly, these effects seemed to be mechanistically distinct, as stress and EPO had differential effects on gene expression. While chronic restraint stress lowered the expression of spinophilin, tumor necrosis factor α, and heat shock protein 72, EPO increased expression of hypoxia‐inducible factor‐2α and lowered the expression of vascular endothelial growth factor in hippocampus. These findings indicate that the effects of treatment with EPO follow different molecular pathways and do not directly counteract the effects of stress in the hippocampus.
Conformational differentiation of α‐cyanohydroxycinnamic acid isomers: a Raman spectroscopic study
Authors: Vedad Jayson , Domaradzki Maciej E. , Mojica Elmer‐Rico E. , Chang Emmanuel J. , Profit Adam A. , Desamero Ruel Z. B.
Published: July 2017

Two α‐cyanohydroxycinnamic acid positional isomers, α‐cyano‐4‐hydroxycinnamic acid (CHCA4) and α‐cyano‐3‐hydroxycinnamic acid (CHCA3), were characterized by using Raman spectroscopy. We analysed the implications of the collected Raman spectral shifts, and verified them through other spectroscopic techniques, to arrive at plausible three dimensional structures of CHCA3 and CHCA4. The positions of these groups were mapped by systematically analysing the orientation and type of interactions functional groups make in each CHCA isomer. We determined whether or not the carboxylic moieties are forming dimeric links and ascertained the existence of ring–ring π‐stacking interactions. We also assessed the nature of the hydrogen bonding between –CN and –OH groups. The results were then taken together to model plausible three‐dimensional structures for each compound. The data revealed a structure for CHCA4 that matches the published X‐ray crystallographic structure. We then applied the same spectral analysis to CHCA3 to reveal its plausible three‐dimensional structure. The structural details revealed may account for the functional properties of the two α‐cyanohydroxycinnamic acid positional isomers. Copyright © 2017 John Wiley & Sons, Ltd.
Raman spectroscopy characterization of 10‐cash productions from the late Chinese emperors to the Republic
Authors: Montoya Noemí , Montagna Elena , Lee Yu , Doménech‐Carbó María Teresa , Doménech‐Carbó Antonio
Published: July 2017

The use of Raman spectroscopy for discriminating monetary emissions, a recurrent problem in much archaeological studies, is described. The method involves the record of Raman signatures of tenorite and crystalline and defective cuprite in the patina based on the idea that subtle, mint‐characteristic variations in the composition and metallography of the base metal during the manufacturing process are reflected in the variation in depth of the composition and crystallinity of the corrosion patina. The technique was applied to a series of 10‐cash copper coins produced around the transition between the Kuang Hsü and Hsüan T'ung last Chinese emperors and the first Republic whose averaged composition was 95 ± 1% wt Cu plus 5 ± 1% wt Zn often accompanied by traces of Sn and Pb. Raman data, corroborated by focusing ion beam‐field emission scanning electron microscopy and voltammetry of immobilized particles measurements, suggested the possibility of discerning between different provincial and regular unified currency productions.
Utility and reproducibility of 3‐dimensional printed models in pre‐operative planning of complex thoracic tumors
Authors: George Elizabeth , Barile Maria , Tang Anji , Wiesel Ory , Coppolino Antonio , Giannopoulos Andreas , Mentzer Steven , Jaklitsch Michael , Hunsaker Andetta , Mitsouras Dimitrios
Published: July 2017

Background and Objectives

3D‐printed models are increasingly used for surgical planning. We assessed the utility, accuracy, and reproducibility of 3D printing to assist visualization of complex thoracic tumors for surgical planning.

Methods

Models were created from pre‐operative images for three patients using a standard radiology 3D workstation. Operating surgeons assessed model utility using the Gillespie scale (1 = inferior to 4 = superior), and accuracy compared to intraoperative findings. Model variability was assessed for one patient for whom two models were created independently. The models were compared subjectively by surgeons and quantitatively based on overlap of depicted tissues, and differences in tumor volume and proximity to tissues.

Results

Models were superior to imaging and 3D visualization for surgical planning (mean score = 3.4), particularly for determining surgical approach (score = 4) and resectability (score = 3.7). Model accuracy was good to excellent. In the two models created for one patient, tissue volumes overlapped by >86.5%, and tumor volume and area of tissues ≤1 mm to the tumor differed by <15% and <1.8 cm2, respectively. Surgeons considered these differences to have negligible effect on surgical planning.

Conclusion

3D printing assists surgical planning for complex thoracic tumors. Models can be created by radiologists using routine practice tools with sufficient accuracy and clinically negligible variability.
Temporal variation in survival and recovery rates of lesser scaup: A response
Authors: Arnold Todd W. , Afton Alan D. , Anteau Michael J. , Koons David N. , Nicolai Chris A.
Published: July 2017

We recently analyzed long‐term (1951–2011) continental band‐recovery data from lesser scaup (Aythya affinis) and demonstrated that harvest rates declined through time, but annual survival rates exhibited no such trends; moreover, annual harvest and survival rates were uncorrelated for all age‐sex classes. We therefore concluded that declining fecundity was most likely responsible for recent population declines, rather than changes in harvest or survival. Lindberg et al. () critiqued our conclusions, arguing that we did little more than fail to reject a null hypothesis of compensatory mortality, postulated ecologically unrealistic changes in fecundity, and failed to give sufficient consideration to additive harvest mortality. Herein, we re‐summarize our original evidence indicating that harvest has been compensatory, or at most weakly additive, and demonstrate that our analysis had sufficient power to detect strongly additive mortality if it occurred. We further demonstrate that our conclusions were not confounded by population size, band loss, or individual heterogeneity, as suggested by Lindberg et al. (), and we provide additional support for our conjecture that low fecundity played a major role in declining scaup populations during 1983–2006. We therefore reiterate our original management recommendations: given low harvest rates and lack of demonstrable effect on scaup survival, harvest regulations could return to more liberal frameworks, and waterfowl biologists should work together to continue banding lesser scaup and use these data to explore alternative hypotheses to identify the true ecological causes of population change, given that it is unlikely to be excessive harvest. © 2017 The Wildlife Society.
Landscape influence on dispersal of yearling male white‐tailed deer
Authors: Peterson Brittany E. , Storm Daniel J. , Norton Andrew S. , Van Deelen Timothy R.
Published: July 2017

Landscape features can alter the transfer phase of dispersal and dispersal‐mediated disease transmission and gene flow. The transfer phase is poorly understood, but improved understanding of landscape effects on dispersal distance and direction would allow better prediction and mitigation of disease spread and improved delineation of management zones. To investigate how ecological settings influence dispersal in white‐tailed deer (Odocoileus virginianus), we captured and radio‐collared 409 juvenile male deer from 2 study areas in Wisconsin, USA, one dominated by public forest and another by row‐crop agriculture. Dispersal directions were non‐directed in the heavily forested study area, but there was a southeastern bias in the farmland study area. Individual dispersal distances were not related to forest cover, and study area average and maximum distances differed from expected, based on published relationships between forest cover and population‐average dispersal distance. Roads, rivers, and cities were semipermeable barriers to dispersal, but effects of barriers differed with respect to study area, suggesting that natural and anthropogenic features influence dispersal‐mediated disease transmission and gene flow. Our results suggest that dispersal models should consider movement barriers in more developed landscapes, and barriers can also be used to inform designation of biologically meaningful management units. © 2017 The Wildlife Society.
Changes in pore‐water chemistry and methane emission following the invasion of Spartina alterniflora into an oliogohaline marsh
Authors: Tong Chuan , Morris James T. , Huang Jiafang , Xu Hui , Wan Siang
Published: July 2017

We measured methane emissions together with acetate, DMS, sulfate, and dissolved methane concentrations in pore waters from adjacent marsh plant communities in an oligohaline marsh of the Min River estuary, southeastern China—one community dominated by a native species, Cyperus malaccensis, the other by the exotic Spartina alterniflora. The objective was to determine if the exotic species altered soil pore‐water chemistry, metabolite pools, and methane emissions. We found that the invasive S. alterniflora, significantly increased the concentration of pore‐water acetate (6.1 vs. 1.2 μM), but did not increase the pools of pore‐water DMS (54.6 vs. 45.9 nM). We observed significantly greater annual emissions of methane from the marsh areas dominated by S. alterniflora (15.1 vs. 5.1 mg m−2 h−1 annual average) and a significant correlation between annual methane emission rate and pore‐water acetate concentration at soil depths between 1 cm and 20 cm. There was no significant correlation between methane emission and the concentration of pore‐water DMS in either marsh community. The results indicate that a change in the dominant plant community can alter soil biogeochemistry. In particular, in an oligohaline environment, S. alterniflora supported higher rates of methane production than the native plant community. It probably does so through a variety of metabolic pathways, probably including acetoclastic methanongenesis.
Dendritic cells in hepatitis and liver transplantation
Authors: Soysa Radika , Wu Xia , Crispe I. Nicholas
Published: July 2017

Dendritic cells (DCs) play a key role in innate immune responses and are also the most effective cells for the activation of T cell immunity. They acquire antigen and process it; then they display it on the cell surface bound in a noncovalent complex with human leukocyte antigen molecules of class I (human leukocyte antigens A, B, and C) and class II (human leukocyte antigen DR). These cells are subdivided into 3 main subsets: 2 called myeloid dendritic cells (mDC) or classical DCs of types 1 and 2, and 1 called plasmacytoid dendritic cells (pDCs). The mDCs process and present antigen while the pDCs also strongly respond to viral signals by secreting type 1 interferon. In the liver, all of these subsets are present. However, their relative abundance is different from the peripheral blood, and it is further modified by liver disease. It appears that in relation to T cell tolerance, both mDCs and pDCs are influenced by the liver milieu and promote T cell inactivation. However, in antiviral responses and in ischemia/reperfusion injury, where innate immune functions are more important, mDCs and pDCs have distinct roles. Liver Transplantation 23 1433–1439 2017 AASLD.
The retrograde transverse cervical artery as a recipient vessel for free tissue transfer in complex head and neck reconstruction with a vessel‐depleted neck
Authors: Ciudad Pedro , Agko Mouchammed , Manrique Oscar J. , Date Shivprasad , Kiranantawat Kidakorn , Chang Wei Ling , Nicoli Fabio , Lo Torto Federico , Maruccia Michele , Orfaniotis Georgios , Chen Hung‐Chi
Published: July 2017

Background

Reconstruction in a vessel‐depleted neck is challenging. The success rates can be markedly decreased because of unavailability of suitable recipient vessels. In order to obtain a reliable flow, recipient vessels away from the zone of fibrosis, radiation, or infection need to be explored. The aim of this report is to present our experience and clinical outcomes using the retrograde flow coming from the distal transverse cervical artery (TCA) as a source for arterial inflow for complex head and neck reconstruction in patients with a vessel‐depleted neck.

Methods

Between July 2010 and June 2016, nine patients with a vessel‐depleted neck underwent secondary head and neck reconstruction using the retrograde TCA as recipient vessel for microanastomosis. The mean age was 49.6 years (range, 36 to 68 years). All patients had previous bilateral neck dissections and all, except one, had also received radiotherapy. Indications included neck contracture release (n = 3), oral (n = 1), mandibular (n = 3) and pharyngoesophageal (n = 2) reconstruction necessitating free anterolateral thigh (n = 3) and medial sural artery (n = 1) perforator flaps, fibula (n = 3) and ileocolon (n = 2) flaps respectively.

Results

There was 100% flap survival rate with no re‐exploration or any partial flap loss. One case of intra‐operative arterial vasospasm at the anastomotic suture line was managed intra‐operatively with vein graft interposition. There were no other complications or donor site morbidity during the follow‐up period.

Conclusions

In a vessel‐depleted neck, the reverse flow of the TCA may be a reliable option for complex secondary head and neck reconstruction in selected patients.
USE of arterialized saphenous vein venous flow‐through flaps as a temporizing measure for hand salvage in contaminated wounds presenting with limb ischemia: A case series
Authors: Diaz‐Abele Julian , Safa Bauback , Buntic Rudolf F. , Islur Avinash
Published: July 2017

Background

Vascular injuries resulting in limb ischemia are traditionally treated acutely with autologous or prosthetic bypass grafts. Traumatic contaminated injuries with soft tissue and vascular segmental loss are challenging as prosthetic bypasses are at risk of erosion, infection, and occlusion; and autologous bypasses are at risk of desiccation, blow‐out, infection, and clotting. We propose a novel approach to these injuries by using arterialized saphenous vein venous flow‐through free flaps (S‐VFTF) as an autologous bypass, and present the results of its application in a series of cases.

Methods

Spanning 2008 to 2015, four patients presenting with large contaminated crush/avulsion wounds with vascular injury underwent hand revascularization with S‐VFTF, allowing the contaminated wounds to be serially debrided. Definitive soft tissue reconstruction was performed once the wound was considered clean. The S‐VFTF skin paddle was de‐epithelialized and the soft tissue defect covered with a free latissimus dorsi flap or a rectus abdominis myocutaneous flap.

Results

All ischemic limbs were successfully reperfused and there were no take backs for perfusion issues. All S‐VFTF remained patent at discharge and final follow‐up. No partial or complete finger/hand amputations were required. All definitive coverage free flap survived with no complications.

Conclusion

The two‐stage reconstruction presented may help reconstructive and vascular surgeons consider alternatives to traditional vascular reconstruction methods. This technique avoids an exposed vascular graft in an extensively contaminated open wound. It allows the surgeon to perform thorough and sufficient debridement of the wound, preventing definitive reconstruction in a not yet declared zone of injury.
Convergence analysis for second‐order accurate schemes for the periodic nonlocal Allen‐Cahn and Cahn‐Hilliard equations
Authors: Guan Zhen , Lowengrub John , Wang Cheng
Published: July 2017

In this paper, we provide a detailed convergence analysis for fully discrete second‐order (in both time and space) numerical schemes for nonlocal Allen‐Cahn and nonlocal Cahn‐Hilliard equations. The unconditional unique solvability and energy stability ensures ℓ4 stability. The convergence analysis for the nonlocal Allen‐Cahn equation follows the standard procedure of consistency and stability estimate for the numerical error function. For the nonlocal Cahn‐Hilliard equation, because of the complicated form of the nonlinear term, a careful expansion of its discrete gradient is undertaken, and an H−1 inner‐product estimate of this nonlinear numerical error is derived to establish convergence. In addition, an a priori
bound of the numerical solution at the discrete level is needed in the error estimate. Such a bound can be obtained by performing a higher order consistency analysis by using asymptotic expansions for the numerical solution. Following the technique originally proposed by Strang (eg, 1964), instead of the standard comparison between the exact and numerical solutions, an error estimate between the numerical solution and the constructed approximate solution yields an O(s3+h4) convergence in
norm, in which s and h denote the time step and spatial mesh sizes, respectively. This in turn leads to the necessary bound under a standard constraint s≤Ch. Here, we also prove convergence of the scheme in the maximum norm under the same constraint.
Differential intestinal anti‐inflammatory effects of Lactobacillus fermentum and Lactobacillus salivarius in DSS mouse colitis: impact on microRNAs expression and microbiota composition
Authors: Rodríguez‐Nogales Alba , Algieri Francesca , Garrido‐Mesa Jose , Vezza Teresa , Utrilla M. Pilar , Chueca Natalia , Garcia Federico , Olivares Mónica , Rodríguez‐Cabezas M. Elena , Gálvez Julio
Published: July 2017

Scope

To compare the intestinal anti‐inflammatory effects of two probiotics Lactobacillus fermentum and Lactobacillus salivarius in mouse colitis, focusing on their impact on selected miRNAs and microbiota composition.

Methods and results

Male C57BL/6J mice were randomly assigned to four groups (n = 10): non‐colitic, DSS colitic and two colitic groups treated with probiotics (5 × 108 CFU/mouse/day). Both probiotics ameliorated macroscopic colonic damage. They improved the colonic expression of markers involved in the immune response, and the expression of miR‐155 and miR‐223. L. fermentum also restored miR‐150 and miR‐143 expression, also linked to the preservation of the intestinal barrier function. Besides, these beneficial effects were associated with the amelioration of the microbiota dysbiosis and a recovery of the SCFAs‐ and lactic acid‐producing bacterial populations, although only L. fermentum improved Chao richness, Pielou evenness and Shannon diversity. Moreover, L. fermentum also restored the Treg cell population in MLNs and the Th1/Th2 cytokine balance.

Conclusion

Both probiotics exerted intestinal anti‐inflammatory effects in DSS‐mouse colitis, maybe due to their ability to restore the intestinal microbiota homeostasis and modulate the immune response. L. fermentum showed a greater beneficial effect compared to L. salivarius, which makes it more interesting for future studies.
Folic acid modulates cancer‐associated micro RNAs and inflammatory mediators in neoplastic and non‐neoplastic colonic cells in a different way
Authors: Niemann Birgit , Nemitz Anke , Werner Josephine , Mai Ha Dong , Steinberg Pablo , Lampen Alfonso , Ehlers Anke
Published: July 2017

Scope

Scientific evidence suggests that folic acid (FA) supplementation protects the healthy colonic mucosa from neoplastic transformation but may promote the progression of precancerous lesions. The underlying molecular mechanisms are not fully understood. Therefore, we explored, if high physiological FA doses provoke changes in (i) promoter‐specific DNA methylation (ii) expression of cancer‐associated micro RNAs (miRNAs) and (iii) inflammatory mediators in human neoplastic and non‐neoplastic colonic cell lines.

Methods and results

The malignant and the non‐malignant colonic cell lines HT29 and HCEC were adapted to different near‐physiological FA concentrations. Using DNA methylation and pathway specific PCR arrays, high‐physiological FA concentrations revealed no relevant impact on promoter methylation but a number of differences between the cell lines in the expression of miRNAs and inflammatory mediators. In the HCEC cell line pro‐inflammatory genes were repressed and the miRNA expression remained nearly unaffected. In contrast, in the HT29 cell line tumour‐suppressive miRNAs were predominantly down‐regulated and the expression of genes involved in chemotaxis and immunity were modulated.

Conclusion

The different effects of high‐physiological FA concentrations in malignant and non‐malignant colonic cell lines regarding cancer‐associated miRNAs and inflammatory mediators may contribute to the different effects of FA supplementation on colonic carcinogenesis.
A Bayesian approach to solve proton stopping powers from noisy multi‐energy CT data
Authors: Lalonde Arthur , Bär Esther , Bouchard Hugo
Published: July 2017

Purpose

To propose a new formalism allowing the characterization of human tissues from multienergy computed tomography (MECT) data affected by noise and to evaluate its performance in estimating proton stopping powers (SPR).

Methods

A recently published formalism based on principal component analysis called eigentissue decomposition (ETD) is adapted to the context of noise using a Bayesian estimator. The method, named Bayesian ETD, uses the maximum a posteriori fractions of eigentissues in each voxel to determine physical parameters relevant for proton beam dose calculation. Simulated dual‐energy computed tomography (DECT) data are used to evaluate the performance of the proposed method to estimate SPR and to compare it to the initially proposed maximum‐likelihood ETD and to a state‐of‐the‐art ρe − Z formalism. To test the robustness of each method towards clinical reality, three different levels of noise are implemented, as well as variations in elemental composition and density of reference tissues. The impact of using more than two energy bins to determine SPR is also investigated by simulating MECT data using two to five energy bins. Finally, the impact of using MECT over DECT for range prediction is evaluated using a probabilistic model.

Results

For simulated DECT data of reference tissues, the Bayesian ETD approach systematically gives lower root‐mean‐square (RMS) errors with negligible bias. For a medium level of noise, the RMS errors on SPR are found to be 2.78%, 2.76% and 1.53% for ρe − Z, maximum‐likelihood ETD, and Bayesian ETD, respectively. When variations are introduced to the elemental composition and density, all implemented methods give similar performances at low noise. However, for a medium noise level, the proposed Bayesian method outperforms the two others with a RMS error of 1.94%, compared to 2.79% and 2.78% for ρe − Z and maximum‐likelihood ETD, respectively. When more than two energy spectra are used, the Bayesian ETD is able to reduce RMS error on SPR using up to five energy bins. In terms of range prediction, Bayesian ETD with four energy bins in realistic conditions reduces proton beam range uncertainties by a factor of up to 1.5 compared to ρe − Z.

Conclusion

The Bayesian ETD is shown to be more robust against noise than similar methods and a promising approach to extract SPR from noisy DECT data. In the advent of commercially available multi‐energy CT or photon‐counting CT scanners, the Bayesian ETD is expected to allow extracting more information and improve the precision of proton therapy beyond DECT.
Prediction of outcome in internet‐delivered cognitive behaviour therapy for paediatric obsessive‐compulsive disorder: A machine learning approach
Authors: Lenhard Fabian , Sauer Sebastian , Andersson Erik , Månsson Kristoffer NT , Mataix‐Cols David , Rück Christian , Serlachius Eva
Published: July 2017

Background

There are no consistent predictors of treatment outcome in paediatric obsessive–compulsive disorder (OCD). One reason for this might be the use of suboptimal statistical methodology. Machine learning is an approach to efficiently analyse complex data. Machine learning has been widely used within other fields, but has rarely been tested in the prediction of paediatric mental health treatment outcomes.

Objective

To test four different machine learning methods in the prediction of treatment response in a sample of paediatric OCD patients who had received Internet‐delivered cognitive behaviour therapy (ICBT).

Methods

Participants were 61 adolescents (12–17 years) who enrolled in a randomized controlled trial and received ICBT. All clinical baseline variables were used to predict strictly defined treatment response status three months after ICBT. Four machine learning algorithms were implemented. For comparison, we also employed a traditional logistic regression approach.

Results

Multivariate logistic regression could not detect any significant predictors. In contrast, all four machine learning algorithms performed well in the prediction of treatment response, with 75 to 83% accuracy.

Conclusions

The results suggest that machine learning algorithms can successfully be applied to predict paediatric OCD treatment outcome. Validation studies and studies in other disorders are warranted.
Stochastic and exact methods for service mapping in virtualized network infrastructures
Authors: Liberati Francesco , Giuseppi Alessandro , Pietrabissa Antonio , Suraci Vincenzo , Di Giorgio Alessandro , Trubian Marco , Dietrich David , Papadimitriou Panagiotis , Delli Priscoli Francesco
Published: July 2017

This paper presents a stochastic algorithm for virtual network service mapping in virtualized network infrastructures, based on reinforcement learning (RL). An exact mapping algorithm in line with the current state of the art and based on integer linear programming is proposed as well, and the performances of the two algorithms are compared. While most of the current works in literature report exact or heuristic mapping methods, the RL algorithm presented here is instead a stochastic one, based on Markov decision processes theory. The aim of the RL algorithm is to iteratively learn an efficient mapping policy, which could maximize the expected mapping reward in the long run. Based on the review of the state of the art, the paper presents a general model of the service mapping problem and the mathematical formulation of the 2 proposed strategies. The distinctive features of the 2 algorithms, their strengths, and possible drawbacks are discussed and validated by means of numeric simulations in a realistic emulated environment.
Directional ‐matrix compression for high‐frequency problems
Authors: Börm Steffen
Published: July 2017

Standard numerical algorithms, such as the fast multipole method or
‐matrix schemes, rely on low‐rank approximations of the underlying kernel function. For high‐frequency problems, the ranks grow rapidly as the mesh is refined, and standard techniques are no longer attractive. Directional compression techniques solve this problem by using decompositions based on plane waves. Taking advantage of hierarchical relations between these waves' directions, an efficient approximation is obtained. This paper is dedicated to directional
‐matrices that employ local low‐rank approximations to handle directional representations efficiently. The key result is an algorithm that takes an arbitrary matrix and finds a quasi‐optimal approximation of this matrix as a directional
‐matrix using a prescribed block tree. The algorithm can reach any given accuracy, and the approximation requires only
units of storage, where n is the matrix dimension, κ is the wave number, and k is the local rank. In particular, we have a complexity of
if κ is constant and
for high‐frequency problems characterized by κ2∼n. Because the algorithm can be applied to arbitrary matrices, it can serve as the foundation of fast techniques for constructing preconditioners.