bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intestinal clostridial counts have no diagnostic value in the diagnosis of enterotoxaemia in veal calves
Authors: Valgaeren B. R. , Pardon B. , Verherstraeten S. , Goossens E. , Timbermont L. , Haesebrouck F. , Ducatelle R. , Deprez P. R. , Van Immerseel F. 
Published: January 2013

Enterotoxaemia is an important cause of sudden death in veal calves. This study aimed to evaluate intestinal Clostridium perfringens counts as a diagnostic tool for enterotoxaemia. Field necropsies were conducted on 48 sudden death cases in Belgian Blue veal farms. In 31/48 suddenly deceased calves, the diagnosis of enterotoxaemia was made based on haemorrhagic lesions in the small intestines, while in seven of these cases, no clear‐cut diagnosis could be made based on macroscopic appearance of the gut. In the 10 remaining calves, a definitive cause of death other than enterotoxaemia could be identified. Samples of the intestinal content were taken for quantification of C perfringens. After matching cases and controls for diet, and the interval between death and sampling, no significant differences could be detected between the mean C perfringens counts of the small intestines in enterotoxaemia cases and counts in the matching segments in the control group. These results indicate that intestinal C perfringens counts cannot be advised as a discriminative postmortem diagnostic tool for enterotoxaemia in veal calves, not even when sampled within three hours after death.
ON THE EDGE OF DECIDABILITY IN COMPLEXITY ANALYSIS OF LOOP PROGRAMS
Authors: BEN-AMRAM AMIR M. , KRISTIANSEN LARS 
Published: January 2013

We investigate the decidability of the feasibility problem for imperative programs with bounded loops. A program is called feasible if all values it computes are polynomially bounded in terms of the input. The feasibility problem is representative of a group of related properties, like that of polynomial time complexity. It is well known that such properties are undecidable for a Turing-complete programming language. They may be decidable, however, for languages that are not Turing-complete. But if these languages are expressive enough, they do pose a challenge for analysis. We are interested in tracing the edge of decidability for the feasibility problem and similar problems. In previous work, we proved that such problems are decidable for a language where loops are bounded but indefinite (that is, the loops may exit before completing the given iteration count). In this paper, we consider definite loops. A second language feature that we vary, is the kind of assignment statements. With ordinary assignment, we prove undecidability of a very tiny language fragment. We also prove undecidability with lossy assignment (that is, assignments where the modified variable may receive any value bounded by the given expression, even zero). But we prove decidability with max assignments (that is, assignments where the modified variable never decreases its value).
Serum Antibodies to Blood Group A Predict Survival on PROSTVAC-VF
Authors: Campbell Christopher T. , Gulley James L. , Oyelaran Oyindasola , Hodge James W. , Schlom Jeffrey , Gildersleeve Jeffrey C. 
Published: January 2013

AbstractPurpose: There is evidence that therapeutic cancer vaccines can lengthen survival for some patients with cancer, but responses vary widely from one person to another. Methods to predict clinical outcomes will advance the field and provide new insights into critical determinants of in vivo efficacy.Experimental Design: This retrospective study included 141 subjects from phase II trials of PROSTVAC-VF, a poxvirus-based cancer vaccine currently in phase III clinical trials for advanced prostate cancer. A glycan microarray was used to profile prevaccination antiglycan antibody populations in sera as potential biomarkers for PROSTVAC-VF. The screen for predictive biomarkers identified antiglycan antibodies that consistently stratified subjects into groups with different Kaplan–Meier survival estimates. Because of the potential for overfitting, a permutation test was used to estimate the false discovery rate.Results: Prevaccination antibody levels to blood group A trisaccharide (BG-Atri) were found to have a statistically significant correlation with survival. Long-term survival was approximately doubled in subjects with abundant anti-BG-Atri immunoglobulin M (IgM) relative to subjects with little or no preexisting IgM for BG-Atri. This survival correlation was specific to vaccine treatment, as no correlation was observed in control patients immunized with wild-type poxviruses lacking the key tumor antigen, prostate-specific antigen (PSA). Moreover, anti-BG-Atri IgM levels were not correlated with general measures of disease severity, such as PSA levels, Gleason score, or Halabi predicted survival.Conclusion: In addition to reporting a new potentially predictive biomarker for PROSTVAC-VF, this study highlights the use of glycan microarray technology for improving our understanding of vaccine immunology. Clin Cancer Res; 19(5); 1290–9. ©2012 AACR.
Relief of Feedback Inhibition of HER3 Transcription by RAF and MEK Inhibitors Attenuates Their Antitumor Effects in BRAF-Mutant Thyroid Carcinomas
Authors: Montero-Conde Cristina , Ruiz-Llorente Sergio , Dominguez Jose M. , Knauf Jeffrey A. , Viale Agnes , Sherman Eric J. , Ryder Mabel , Ghossein Ronald A. , Rosen Neal , Fagin James A. 
Published: January 2013

Abstract
The RAF inhibitor vemurafenib (PLX4032) increases survival in patients with BRAF-mutant metastatic melanoma, but has limited efficacy in patients with colorectal cancers. Thyroid cancer cells are also comparatively refractory to RAF inhibitors. In contrast to melanomas, inhibition of mitogen-activated protein kinase (MAPK) signaling by PLX4032 is transient in thyroid and colorectal cancer cells. The rebound in extracellular signal-regulated kinase (ERK) in thyroid cells is accompanied by increased HER3 signaling caused by induction of ERBB3 (HER3) transcription through decreased promoter occupancy by the transcriptional repressors C-terminal binding protein 1 and 2 and by autocrine secretion of neuregulin-1 (NRG1). The HER kinase inhibitor lapatinib prevents MAPK rebound and sensitizes BRAF-mutant thyroid cancer cells to RAF or MAP-ERK kinase inhibitors. This provides a rationale for combining ERK pathway antagonists with inhibitors of feedback-reactivated HER signaling in this disease. The determinants of primary resistance to MAPK inhibitors vary between cancer types, due to preferential upregulation of specific receptor tyrosine kinases, and the abundance of their respective ligands.
Significance: Thyroid cancer cell lines with mutant BRAF are resistant to PLX4032. RAF inhibitors transiently inhibit the ERK pathway and de-repress HER3 transcription. In the context of constitutive NRG1 secretion, this results in an ERK and AKT rebound that diminishes the antitumor effects of RAF inhibitors, which is overcome by combination with lapatinib. Cancer Discov; 3(5); 520–33. ©2013 AACR.
See related commentary by Girotti and Marais, p. 487
This article is highlighted in the In This Issue feature, p. 471
Cardiovascular risk among patients on clopidogrel anti-platelet therapy after placement of drug-eluting stents is modified by genetic variants in both the CYP2C19 and ABCB1 genes
Authors: Knight Stacey , Horne Benjamin D. , Huntinghouse John A. , Rollo Jeffrey S. , Muhlestein J. Brent , May Heidi , Anderson Jeffrey L. , Carlquist John F. 
Published: January 2013

SummaryLong-term (at least one year) dual anti-platelet therapy incorporating aspirin and clopidogrel is currently recommended following percutaneous coronary intervention with placement of a drug-eluting stent (DES). Genetic variants in both the ABCB1 and CYP2C19 genes have been associated with cardiovascular events among patients on clopidogrel. We examined the concurrent contribution of the CYP2C19 *2 and *17 alleles and the ABCB1 3435 alleles to one-year clinical risk among patients (n=1,034 on clopidogrel therapy following the placement of a DES. For CYP2C19*2, event rates were 8.4%, 10.9% and 44.4% for patients with 0, 1 and 2 *2 alleles, respectively (p=0.016). ABCB1 3435 was not associated with events in univariate analysis. However, 72% of patients with a *2 variant also possessed the ABCB1 3435 C allele; among these patients (*2/C genotype) the event rate for myocardial infarction (MI) was 14.2% vs. 6.9% for those lacking both *2 and C alleles (p=0.027) and for MI/death, 16.9% vs. 9.6% (p=0.046). Overall for all genotypes, the presence of the gain-of-function (protective) *17 allele significantly reduced the one-year rate of MI from 11.1% to 7.0% (p=0.045) and trended to reduce the combined rate of MI/death from 13.8% to 10.5% (p=0.182). In conclusion, the ABCB1 3435 locus and the *2 allele combine to impart a significant trend toward increased risk. This trend was largely reversed by the simultaneous carriage of one or two *17 alleles. These findings suggest that assessment of a combined genotype may improve risk assessment.
The role of innate immune cells in obese adipose tissue inflammation and development of insulin resistance
Authors: Chavakis Triantafyllos , Chmelar Jindrich , Chung Kyoung-Jin 
Published: January 2013

SummaryObesity is characterised by a chronic state of low-grade inflammation in different tissues including the vasculature. There is a causal link between adipose tissue (AT) inflammation and obesity-related metabolic complications, such as the development of insulin resistance and subsequently of type 2 diabetes. Intense efforts in the recent years have aimed at dissecting the pathophysiology of AT inflammation. The role of both innate and adaptive immune cells, such as macrophages or cytotoxic T cells in AT inflammation has been demonstrated. Besides these cells, more leukocyte subpopulations have been recently implicated in obesity, including neutrophils and eosinophils, mast cells, natural killer cells or dendritic cells. The involvement of multiple leukocyte subpopulations underlines the complexity of obesity-associated AT inflammation. In this review, we discuss the role of innate immune cells in AT inflammation, obesity and related metabolic disorders.
Prophylactic Radiofrequency Ablation in Asymptomatic Patients With Wolff–Parkinson–White Is Not Yet a Good Strategy
Authors: Chevalier Philippe , Cadi France , Scridon Alina , Girerd Nicolas , Bejan-Angoulvan Theodora , Morel Elodie , Hot Isabelle Jaisson , Di Filippo Sylvie , Ganne Christell , Colin Cyrille 
Published: January 2013

Background—
Therapeutic management of asymptomatic patients with a Wolff–Parkinson–White (WPW) pattern is controversial. We compared the risk:benefit ratios between prophylactic radiofrequency ablation and no treatment in asymptomatic patients with WPW.

Methods and Results—
Decision analysis software was used to construct a risk–benefit decision tree. The target population consisted of 20- to 40-year-old asymptomatic patients with WPW without structural fatal heart disease or a family history of sudden cardiac death. Baseline estimates of sudden death and radiofrequency ablation complication rates were obtained from the literature, an empirical data survey, and expert opinion. The outcome measure was death within 10 years. Sensitivity analyses determined the variables that significantly impacted the decision to ablate or not. Threshold analyses evaluated the effects of key variables and the optimum policy. At baseline, the decision to ablate resulted in a reduction of mortality risk of 8.8 patients for 1000 patients compared with abstention. It is necessary to treat 112 asymptomatic patients with WPW to save one life over 10 years. Sensitivity analysis showed that 3 variables significantly impacted the decision to ablate: (1) complication of radiofrequency ablation, (2) success of radiofrequency ablation, and (3) sudden death in asymptomatic patients with WPW.

Conclusions—
This study provides a decision aid for treating asymptomatic patients with the WPW ECG pattern. Using the model and the population we tested, prophylactic catheter ablation is not yet ready for widespread clinical use.
Dopaminergic Gene Polymorphisms Affect Long-term Forgetting in Old Age: Further Support for the Magnification Hypothesis
Authors: Papenberg Goran , Bäckman Lars , Nagel Irene E. , Nietfeld Wilfried , Schröder Julia , Bertram Lars , Heekeren Hauke R. , Lindenberger Ulman , Li Shu-Chen 
Published: January 2013

AbstractEmerging evidence from animal studies suggests that suboptimal dopamine (DA) modulation may be associated with increased forgetting of episodic information. Extending these observations, we investigated the influence of DA-relevant genes on forgetting in samples of younger (n = 433, 20–31 years) and older (n = 690, 59–71 years) adults. The effects of single nucleotide polymorphisms of the DA D2 (DRD2) and D3 (DRD3) receptor genes as well as the DA transporter gene (DAT1; SLC6A3) were examined. Over the course of one week, older adults carrying two or three genotypes associated with higher DA signaling (i.e., higher availability of DA and DA receptors) forgot less pictorial information than older individuals carrying only one or no beneficial genotype. No such genetic effects were found in younger adults. The results are consistent with the view that genetic effects on cognition are magnified in old age. To the best of our knowledge, this is the first report to relate genotypes associated with suboptimal DA modulation to more long-term forgetting in humans. Independent replication studies in other populations are needed to confirm the observed association.
A quantitative analysis of the state of knowledge of turtles of the United States and Canada
Authors: Lovich Jeffrey E. , Ennen Joshua R. 
Published: January 2013

The “information age” ushered in an explosion of knowledge and access to knowledge that continues to revolutionize society. Knowledge about turtles, as measured by number of published papers, has been growing at an exponential rate since the early 1970s, a phenomenon mirrored in all scientific disciplines. Although knowledge about turtles, as measured by number of citations for papers in scientific journals, has been growing rapidly, this taxonomic group remains highly imperiled suggesting that knowledge is not always successfully translated into effective conservation of turtles. We reviewed the body of literature on turtles of the United States and Canada and found that: 1) the number of citations is biased toward large-bodied species, 2) the number of citations is biased toward wide-ranging species, and 3) conservation status has little effect on the accumulation of knowledge for a species, especially after removing the effects of body size or range size. The dispersion of knowledge, measured by Shannon Weiner diversity and evenness indices across species, was identical from 1994 to 2009 suggesting that poorly studied species remained poorly-studied species while well-studied species remained well studied. Several species listed as threatened or endangered under the U.S. Endangered Species Act (e.g., Pseudemys alabamensis, Sternotherus depressus, and Graptemys oculifera) remain poorly studied with the estimated number of citations for each ranging from only 13-24. The low number of citations for these species could best be explained by their restricted distribution and/or their smaller size. Despite the exponential increase in knowledge of turtles in the United States and Canada, no species of turtle listed under the Endangered Species Act has ever been delisted for reason of recovery. Therefore, increased knowledge does not necessarily contribute appreciably to recovery of threatened turtles.
An introduction to package evolution and criticality research studies relevant to the UK disposal programme
Authors: Padovani C. , Williams S. J. , Wood P. 
Published: January 2013

AbstractIn the UK, radioactive wastes currently planned for disposal in a geological disposal facility (GDF) include intermediate level waste, some low level waste and high level waste. Disposal of other materials, including spent fuel, uranium and plutonium is also being evaluated to inform the safety case for a GDF, if such materials were to be classified as wastes in the future. This paper describes the generic safety functions through which waste packages can contribute to the safety case of a GDF in the UK. It describes the engineering approach used or envisaged, in the UK and internationally, to ensure that waste packages retain their safety functions for the required periods of time and summarizes the scientific basis underpinning the current understanding of relevant evolution processes. Where gaps in the knowledge exist, the Nuclear Decommissioning Authority Radioactive Waste Management Directorate has identified specific research activities needed to close out such gaps to a level of maturity sufficient for this stage of the disposal programme (generic). This paper describes the latest results from their R&D programme and presents a summary of the research activities planned to meet the current needs of the disposal programme with specific reference to the topics of package evolution and criticality safety.
Three-dimensional imaging of inhomogeneous lithologies using X-ray computed tomography: characterization of drill core from the Borrowdale Volcanic Group
Authors: Engelberg D. L. , Pattrick R. A. D. , Wilson C. , McCrae R. , Withers P. J. 
Published: January 2013

AbstractX-ray computed tomography augmented by elemental microanalysis has been used to characterize two drill cores from the Borrowdale Volcanic Group, west Cumbria, UK. Information about the three-dimensional (3D) distribution of mineral phases was obtained non-destructively, and regions of interest were extracted for thin sectioning and elemental analysis. This revealed the presence of pyrite and other iron- and iron-titanium-bearing minerals. X-ray computed tomography is a very useful tool for 3D visualization, but the limitations of the tomography system used made it difficult to distinguish between regions with similar compositions, such as the different layers within the calcite veins. Methods by which these limitations might be overcome are briefly discussed.
Initial studies on the effects of radiation, thermal ageing and aqueous environments on the stability and structure of candidate polymeric encapsulant materials
Authors: Dawson J. , Smith V. , Clifford J. , Williams S. J. 
Published: January 2013

AbstractThe current route in the UK for the conditioning and immobilization of most intermediate level waste for interim storage and geological disposal is to encapsulate in a cementitious matrix. However, certain waste materials, such as those containing reactive metals (e.g. uranium and aluminium), can corrode in the presence of the highly alkaline water in a cementitious environment. In their initial, undegraded form, polymeric materials can provide the appropriate, unreactive environment needed for the encapsulation of chemically active metals.This study examines the effects of gamma radiation on the stability of six candidate polymeric encapsulants, including a vinyl ester styrene resin (VES) and five epoxy resin formulations. The polymeric encapsulants were exposed to radiation doses up to 10 MGy using AMEC's cobalt-60 gamma irradiation facility and their radiation and chemical stability characterized by the use of a number of analytical techniques. These included flexural and compressive testing, Fourier transform infrared spectroscopy (FTIR), gel fraction, leach testing and gas evolution. The results show that the most stable resin in terms of radiation resistance and chemical stability was VES. Most of the epoxy resin materials also showed good generic stability, but the FTIR analysis showed the potential for dose-rate effects in one formulation.
Coupled hydro-mechanical–chemical process modelling in argillaceous formations for DECOVALEX-2011
Authors: Bond A. E. , Benbow S. , Wilson J. , McDermott C. , English M. 
Published: January 2013

AbstractThe Nuclear Decommissioning Authority Radioactive Waste Management Directorate have been participating in the current DECOVALEX-2011 project (development of coupled models and their validation against experiments) one task of which has been examining the Mont Terri Ventilation Experiment (VE). This long-term (>9 years), field-scale experiment in the Opalinus Clay near the Swiss–French border, was designed to examine the coupled hydraulic–mechanical–chemical changes caused in the tunnel and in the surrounding geology, by the controlled ventilation of a 1.65 m diameter micro-tunnel.In contrast to many conventional benchmarking and validation exercises, a key aspect of the VE as examined in DECOVALEX was that some data were held back and participants were required to make predictions of key metrics for the future evolution of the system. This paper presents an overview of the work conducted by the Quintessa and University of Edinburgh team including selected results. The coupled models developed include multiphase flow, elastic deformation and chemical processes in both detailed and upscaled geometries.The models have been able to replicate the observed desaturation around the tunnel, tunnel deformation and localized failure, vapour migration in the tunnel, and the transition in redox conditions into the host rock.
Representation of the biosphere in post-closure assessments for the UK geological disposal programme
Authors: Kowe R. , Norris S. 
Published: January 2013

AbstractThis paper gives an overview of the Nuclear Decommissioning Authority, Radioactive Waste Management Directorate approach to representing the biosphere in post-closure safety assessment studies. The assessments consider potential releases of radionuclides and chemically toxic substances from a geological disposal facility that may reach the biosphere by transport in groundwater and gas. It gives an outline of the key processes and understanding underpinning the representation of the biosphere and how the biosphere may evolve over the long timescales of relevance to post-closure safety. The current biosphere assessment approach and associated models are supported by research studies and collaboration that ensure they are consistent with international recommendations. Research studies are also commissioned to reduce uncertainty surrounding key contaminants and potential exposure pathways and to help ensure that the approach and models are adaptable and flexible enough to incorporate future developments, as the geological disposal programme moves towards site selection.
Comparison of microbiological influences on the transport properties of intact mudstone and sandstone and its relevance to the geological disposal of radioactive waste
Authors: Wragg J. , Harrison H. , West J. M. , Yoshikawa H. 
Published: January 2013

AbstractThe role of the microbial activity on the transport properties of host rocks for geological repositories, particularly in the far-field, is an area of active research. This paper compares results from experiments investigating changes in transport properties caused by microbial activity in sedimentary rocks in Japan (mudstones) and sandstone (UK).These experiments show that both Pseudomonas denitrificans and Pseudomonas aeruginosa appear to survive and thrive in pressurized flow-through column experiments which utilized host rock materials of relevance to radioactive waste disposal. Indeed, despite there being a difference in the numbers of organisms introduced into both biotic experiments, numbers appear to stabilize at ∼105 ml−1 at their completion. Post experimental imaging has highlighted the distinct differences in biofilm morphology, for the chosen rock types and bacteria, with Pseudomonas aeruginosa derived biofilms completely covering the surface of the sandstone host and Pseudomonas denitrificans forming biofilament structures. Regardless of substrate host or choice of microbe, microbial activity results in measurable changes in permeability. Such activity appears to influence changes in fluid flow and suggests that the transport of radionuclides through the far-field will be complicated by the presence of microbes.