bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolution of anterior segment reconstruction after live donor adult liver transplantation: a single‐center experience
Authors: Pomposelli James J. , Akoad Mohamed , Khwaja Khalid , Lewis W. D. , Cheah Yee L. , Verbesey Jennifer , Jenkins Roger L. , Pomfret Elizabeth A.
Published: October 2011

Pomposelli JJ, Akoad M, Khwaja K, Lewis WD, Cheah YL, Verbesey J, Jenkins RL, Pomfret EA. Evolution of anterior segment reconstruction after live donor adult liver transplantation: a single‐center experience.  Clin Transplant 2011 DOI: 10.1111/j.1399‐0012.2011.01529.x.  © 2011 John Wiley & Sons A/S.

Abstract:  Controversy exists regarding the best method for venous outflow reconstruction after live donor liver transplantation using right lobe grafts. Some authors advocate routine inclusion of the middle hepatic vein with the graft, whereas others favor a more selective approach. In this report, we examine the evolution of our decision making and technique of selective anterior venous segment reconstruction during live donor adult liver transplantation performed in 226 recipients. We have developed a simplified back‐bench procedure using sequential‐composite anastomosis using various vascular conduits with syndactylization to the right hepatic vein creating a single large‐outflow anastomosis in the recipient. Conduits used include iliac artery or vein allograft, recanalized umbilical vein, cryopreserved iliac artery allograft, and 6‐mm synthetic expanded polytetrafluoroethylene vascular graft. This technique can be performed quickly, safely, and under cold storage conditions and results in excellent outcome while minimizing donor risk.
Effect of early EBV and/or CMV viremia on graft function and acute cellular rejection in pediatric liver transplantation
Authors: Indolfi Giuseppe , Heaton Nigel , Smith Melvyn , Mieli‐Vergani Giorgina , Zuckerman Mark
Published: October 2011

Indolfi G, Heaton N, Smith M, Mieli‐Vergani G, Zuckerman M. Effect of early EBV and/or CMV viremia on graft function and acute cellular rejection in pediatric liver transplantation.  Clin Transplant 2012: 26: E55–E61.  © 2011 John Wiley & Sons A/S.

Abstract:  Background:  The clinical impact of Epstein–Barr virus (EBV) and cytomegalovirus (CMV) infections in the early post‐transplantation period are poorly documented. We investigated the prevalence and timing of EBV and CMV infections during the first 21 d post‐transplantation in relation to graft function and acute cellular rejection in a large cohort of pediatric liver transplantation recipients.

Patients and methods:  Clinical, biochemical, virological, and histopathological data of 62 consecutive children who received a liver transplant were reviewed retrospectively.

Results:  Seventeen patients (27%) developed EBV and 11 (18%) CMV viremia (mean interval from surgery: 7.6 d, SD 3.6 and 8.7 d, SD 6.4, respectively). EBV and CMV viremia were more common as a consequence of reactivation than of primary infection. EBV viremic recipients had more often abnormal bilirubin levels [p = 0.01; OR 5.8: 95% CI 1.3–25.5]. Acute rejection was diagnosed in 20 recipients (32.3%). No correlation was found between rejection and EBV and CMV serology before transplantation and viremia after transplantation (mean interval between the diagnosis of rejection and the detection of EBV DNA and CMV DNA: one d, SD 4.4 and five d, SD 9.2, respectively).

Conclusion:  EBV and CMV viremia occur at a very early‐stage post‐transplantation and do not appear to affect the short‐term outcome of the transplant.
Lack of association of IL6R rs2228145 and IL6ST/gp130 rs2228044 gene polymorphisms with cardiovascular disease in patients with rheumatoid arthritis
Authors: López‐Mejías R. , García‐Bermúdez M. , González‐Juanatey C. , Castañeda S. , Miranda‐Filloy J. A. , Gómez‐Vaquero C. , Fernández‐Gutiérrez B. , Balsa A. , Pascual‐Salcedo D. , Blanco R. , González‐Álvaro I. , Llorca J. , Martín J. , González‐Gay M. A.
Published: October 2011

Interleukin‐6 (IL‐6) is a key mediator of inflammation in rheumatoid arthritis (RA) and its actions may be controlled by the IL‐6 receptor (IL‐6R). IL‐6 transducer (IL‐6ST/ gp130) is the signal transducing subunit of the IL‐6R. We assessed the influence of the IL6R and the IL6ST/gp130 genes in the risk of cardiovascular (CV) disease in RA. For this purpose, 1250 Spanish patients with RA were genotyped for the IL6R rs2228145 and IL6ST/gp130 rs2228044 functional gene polymorphisms. Patients were stratified according to the presence or absence of CV events. Also, a subgroup of patients without CV events was assessed for the presence of subclinical atherosclerosis using two surrogate markers of atherosclerosis (flow‐mediated endothelium‐dependent vasodilatation and carotid intima‐media thickness). No significant differences in the genotype and allele frequencies for both gene polymorphisms between patients with and without CV events were observed. It was also the case when values of surrogate markers of atherosclerosis were compared according to IL6R and IL6ST genotype frequencies. In conclusion, our results do not confirm an association of IL6R rs2228145 and IL6ST/gp130 rs2228044 polymorphisms with CV disease in RA.
Probes for activity‐based profiling of plant proteases
Authors: van der Hoorn Renier A. L. , Kaiser Markus
Published: October 2011

Proteases are key players in plant development and immunity. When and where these proteases act during these processes is difficult to predict from proteomic or transcriptomic data because proteases are tightly regulated by post‐translational mechanisms such as processing, phosphorylation and the presence of cofactors or inhibitors. Protease activities can be displayed using activity‐based probes that react with the catalytic site of proteases in a mechanism‐dependent manner. Plant proteomes have been labeled with probes for caspases, vacuolar processing enzymes, papain‐like cysteine proteases, the proteasome, subtilases, prolyloligopeptidases, serine carboxypeptidases and matrix metalloproteases. Here, we review these protease probes with a focus on the specificity determinants that reside in the probe and the detection methods dictated by the reporter tag.
Leflunomide for cytomegalovirus: bench to bedside
Authors: Chacko B. , John G.T.
Published: October 2011

Cytomegalovirus (CMV) remains a major cause of morbidity and mortality among transplant recipients, frequently engaging the clinician in a struggle to balance graft preservation with control of CMV disease. Leflunomide has been shown to have immunosuppressive activity in experimental allograft models together with antiviral activity inhibiting CMV both in vitro and in vivo. Data are emerging about its potential role in ganciclovir‐sensitive and ‐resistant CMV, primarily by virtue of a unique mechanism inhibiting virion assembly, as opposed to inhibition of viral DNA synthesis by current agents. This review aims to put in perspective, the knowledge acquired in the last decade or so on leflunomide for CMV. Evidence suggests that it might have activity against human CMV with good oral bioavailability and, more importantly in the resource‐poor setting, is economical. Although the data presented here are not from randomized trials, several relevant observations have been made that could influence future, more structured assessments of the drug. An immune suppressive compound with antiviral features and experimental activity in chronic rejection is an attractive combination for organ transplantation, and it appears that leflunomide may just fit that niche.
Optimising μCT Imaging of the Middle and Inner Cat Ear
Authors: Seifert H. , Röher U. , Staszyk C. , Angrisani N. , Dziuba D. , Meyer‐Lindenberg A.
Published: October 2011

With 9 figures and 4 tables

This study’s aim was to determine the optimal scan parameters for imaging the middle and inner ear of the cat with micro‐computertomography (μCT). Besides, the study set out to assess whether adequate image quality can be obtained to use μCT in diagnostics and research on cat ears. For optimisation, μCT imaging of two cat skull preparations was performed using 36 different scanning protocols. The μCT‐scans were evaluated by four experienced experts with regard to the image quality and detail detectability. By compiling a ranking of the results, the best possible scan parameters could be determined. From a third cat’s skull, a μCT‐scan, using these optimised scan parameters, and a comparative clinical CT‐scan were acquired. Afterwards, histological specimens of the ears were produced which were compared to the μCT‐images. The comparison shows that the osseous structures are depicted in detail. Although soft tissues cannot be differentiated, the osseous structures serve as valuable spatial orientation of relevant nerves and muscles. Clinical CT can depict many anatomical structures which can also be seen on μCT‐images, but these appear a lot less sharp and also less detailed than with μCT.
Replacement of fish meal protein by surimi by‐product protein in the diet of blue gouramiTrichogaster trichopterusfingerlings
Authors: Mohanta K. N. , Subramanian S. , Korikanthimath V. S.
Published: October 2011

Based on the nutrient requirement ofTrichogaster trichopterus, a fish meal–based basal diet with 350 g/kg diet crude protein and 16.7 MJ/kg energy was formulated, in which the fish meal protein was replaced by surimi by‐product protein at 0.0 (control), 12.5, 25, 50, 75 and 100% levels. The formulated diets were fedad libitumtoT. trichopterusfingerlings (4.80 ± 0.03 g) in triplicate groups for 45 days in a closed water system. Eighteen fibre‐reinforced plastic tanks with 200 l of water were used for rearing the fish. Weight gain, specific growth rate, feed/gain ratio, protein efficiency ratio, nutrient retention and digestibility (protein and energy) of fish were not affected (p > 0.05) up to 50% fish meal protein replacement level by surimi by‐product protein. While whole‐body protein content of fish was marginally decreased, the lipid content was increased with increase in surumi by‐product incorporation level in the diet. The study results suggest that the fish meal protein, which is scarce and costly nowadays, could be replaced up to 50% by surimi by‐product protein in the diet of blue gourami without hampering the growth and nutrient utilization of fish.
JC virus granular neuronopathy and rhombencephalic progressive multifocal leukoencephalopathy: Case report and review of the literature
Authors: Keith Julia , Bilbao Juan , Baskind Roy
Published: October 2011

JC virus (JCV) granular neuronopathy remains an under‐appreciated phenomenon whereby JCV inhabits neurons in the granular layer of the cerebellum causing neuronal loss, gliosis and a clinical cerebellar syndrome. The following case describes a man with sarcoidosis and idiopathic leukopenia who developed a clinical cerebellar syndrome due to JCV granular neuronopathy, followed by neurological decline due to rhombencephalic progressive multifocal leukoencephalopathy. This case reminds us of the ability of JCV to produce dual neuropathology which includes JCV granular neuronopathy, and the pathogenesis and clinical implications for this phenomenon are discussed.
Phosphorylated Syk expression is enhanced in Nasu‐Hakola disease brains
Authors: Satoh Jun‐ichi , Tabunoki Hiroko , Ishida Tsuyoshi , Yagishita Saburo , Jinnai Kenji , Futamura Naonobu , Kobayashi Michio , Toyoshima Itaru , Yoshioka Toshiaki , Enomoto Katsuhiko , Arai Nobutaka , Saito Yuko , Arima Kunimasa
Published: October 2011

Nasu‐Hakola disease (NHD) is a rare autosomal recessive disorder, characterized by progressive presenile dementia and formation of multifocal bone cysts, caused by a loss‐of‐function mutation of DNAX‐activation protein 12 (DAP12) or triggering receptor expressed on myeloid cells 2 (TREM2). TREM2 and DAP12 constitute a receptor/adaptor complex on myeloid cells. The post‐receptor signals are transmitted via rapid phosphorylation of the immunoreceptor tyrosine‐based activating motif (ITAM) of DAP12, mediated by Src protein tyrosine kinases, followed by binding of phosphorylated ITAM to Src homology 2 (SH2) domains of spleen tyrosine kinase (Syk), resulting in autophosphorylation of the activation loop of Syk. To elucidate the molecular mechanism underlying the pathogenesis of NHD, we investigated Syk expression and activation in the frontal cortex and the hippocampus of three NHD and eight control brains by immunohistochemistry. In NHD brains, the majority of neurons expressed intense immunoreactivities for Syk and Y525/Y526‐phosphorylated Syk (pSyk) chiefly located in the cytoplasm, while more limited populations of neurons expressed Src. The levels of pSyk expression were elevated significantly in NHD brains compared with control brains. In both NHD and control brains, substantial populations of microglia and macrophages expressed pSyk, while the great majority of reactive astrocytes and myelinating oligodendrocytes did not express pSyk, Syk or Src. These observations indicate that neuronal expression of pSyk was greatly enhanced in the cerebral cortex and the hippocampus of NHD brains, possibly via non‐TREM2/DAP12 signaling pathways involved in Syk activation.
Fatigue crack propagation into the residual stress field along and perpendicular to laser beam butt‐weld in aluminium alloy AA6056
Authors: VAIDYA W. V. , STARON P. , HORSTMANN M.
Published: October 2011

Laser beam butt welds in Al‐alloys are very narrow and are accompanied by steep residual stress gradients. In such a case, how the initial crack orientation and the distance of the notch tip relative to the weld affect fatigue crack propagation has not been investigated. Therefore, this investigation was undertaken with two different crack orientations: along the mid‐weld and perpendicular to the weld. Fatigue crack propagation ‘along the mid‐weld’ was found to be faster in middle crack tension specimens than in compact tension specimens. For the crack orientation ‘perpendicular to the weld’, the relative distance between the notch tip and the weld was varied using compact tension specimens to generate either tensile or compressive residual stresses near the notch tip. When tensile residual stresses were generated near the notch tip, fatigue crack propagation was found to be faster than that in the base material, irrespective of the difference in the initial residual stress level and whether the crack propagated along the mid‐weld or perpendicular to the weld. In contrast, when compressive weld residual stresses were generated near the notch tip, fatigue crack arrest, slow crack propagation, multiple crack branching and out of plane deviation occurred. The results are discussed by considering the superposition principle and possible practical implications are mentioned.
The flexural strength and fracture toughness of reactive powder concrete in response to changing fibre size and pre‐setting pressure
Authors: İPEK M.
Published: October 2011

In this study, steel fibre mixtures having different compositions of fibres with various sizes were used in reactive powder concrete. The mixture composition, which would present the best performance during the flexural tests, was determined. Pre‐setting pressure tests at six different magnitudes (0, 5, 10, 15, 20, 25 MPa) were conducted on the freshly prepared reactive powder concrete mixture having the determined mixture composition. The 30‐mm‐long steel fibres mixed at a ratio of 4.5% provided the highest flexure strength and the fracture toughness during these tests. The highest pre‐setting pressure was attained at 25 MPa and the flexural strength of the sample increased by 117% reaching 28.07 MPa at that pre‐setting pressure.
A model of cumulative fatigue strengthening effect due to coaxing
Authors: JUN C. , SONG‐LIN Z. , JIN‐ZHI F. , XIN‐TIAN L.
Published: October 2011

In this paper, a fatigue experiment of auto drive shaft smooth specimen is studied in details. Through the analysis of load amplitude and load cycles, which influenced on the residual fatigue strength of structure, we find a mathematical model of strengthening effect due to coaxing. Based on the auto drive shaft work load spectrum, a cumulative fatigue strengthening model is suggested. Then, a new method of lightweight design that can maximise cumulative strengthening effect is proposed. Our model and method can provide a theoretical basis for lightweight design on structural parts of automobiles.
Transcriptional responses of surface water marine microbial assemblages to deep‐sea water amendment
Authors: Shi Yanmei , McCarren Jay , DeLong Edward F.
Published: October 2011

Deep‐water nutrient injection in the North Pacific Subtropical Gyre provides an aperiodic yet significant source of inorganic nutrients to the nutrient‐limiting surface waters, and has been implicated in phytoplankton bloom formation. Here we examined short‐term transcriptional responses of surface water picoplankton assemblages in a deep‐sea water (DSW) mixing experiment. Both flow cytometric and transcriptomic analysis indicated stimulation of an Alteromonas‐like population in the DSW‐amended treatment after 12 h, relative to the control. Among the highly expressed alteromonad transcripts in DSW‐treated samples, those encoding genes associated with chemotaxis, cell motility and carbon metabolism were most highly represented, relative to the control. Similarly, Prochlorococcus showed significantly higher levels of transcripts associated with carbon fixation and photosynthesis, as well as slightly increased cell density, relative to the control. Although other microbial taxa did not exhibit enhanced growth, DSW‐stimulated changes in their genome‐wide transcriptional profiles were still readily detectable. Cell‐associated cyanophage DNA and cDNA profiles suggested DSW stimulation of phage‐mediated cell lysis, in previously infected cells. Comparison of the DSW‐responsive Alteromonas populations, to previously reported dissolved organic matter (DOM)‐responding alteromonads (McCarren et al., 2010), revealed differential transcript abundances, predominantly among genes encoding mobile elements and phage‐related genes. Transcript representation in other metabolic pathways differed significantly between Alteromonas populations in the two different treatments, suggesting perturbation‐specific metabolic responses to DSW and DOM. In total, the results provide new insight into short‐term responses of picoplankton to DSW mixing, which occur prior to the more well‐studied, longer‐term growth responses of larger phytoplankton species.
Synergistic metabolism of a broad range of C1 compounds in the marine methylotrophic bacterium HTCC2181
Authors: Halsey Kimberly H. , Carter Amy E. , Giovannoni Stephen J.
Published: October 2011

The 1.3 Mbp genome of HTCC2181, a member of the abundant OM43 clade of coastal bacterioplankton, suggested it is an obligate methylotroph. Preliminary experiments demonstrated that methanol and formaldehyde, but not other common C1 compounds such as methylamine, could support growth. Methanol concentrations in seawater are reportedly < 100 nM, suggesting either that the flux of methanol through plankton pools is very rapid, or that methanol may not be the primary growth substrate for HTCC2181. Therefore, we investigated the apparent extreme substrate range restriction of HTCC2181 in greater detail. Growth rate and maximum cell density of HTCC2181 increased with methanol concentration, yielding a Ks value of 19 µM. In contrast, no growth was observed in the presence of the methylated (C1) compounds, methyl chloride, trimethylamine‐oxide (TMAO) or dimethylsulfoniopropionate (DMSP) when they were the sole substrates. However, growth rate, maximum cell density and cellular ATP content were significantly enhanced when any of these methylated compounds were provided in the presence of a limiting concentration of methanol. These observations fit a model in which the metabolic intermediate formaldehyde is required for net carbon assimilation, allowing C1 substrates that do not produce a formaldehyde intermediate to be oxidized for energy, but not assimilated into biomass. Rates of methanol and TMAO oxidation and assimilation were measured with 14C‐radiolabelled compounds in cultures of HTCC2181 and seawater microbial communities collected off the Oregon coast. The results indicated that in nature as well as in culture, C1 substrates are partitioned between those that are mainly oxidized to produce energy and those that are assimilated. These findings indicate that the combined fluxes of C1 compounds in coastal systems are sufficient to support significant populations of obligate methyltrophs by a metabolic strategy that involves the synergistic metabolism of multiple C1 compounds.
Isolation and characterization of the unicellular diazotrophic cyanobacterium Group C TW3 from the tropical western Pacific Ocean
Authors: Taniuchi Yukiko , Chen Yuh‐ling Lee , Chen Houng‐Yung , Tsai Mei‐Ling , Ohki Kaori
Published: October 2011

A unicellular diazotrophic cyanobacterium strain of Group C, designated TW3, was isolated from the oligotrophic Kuroshio Current of the western Pacific Ocean. To our knowledge, this represents the first successful laboratory culture of a Group C unicellular diazotroph from oceanic water. TW3 cells are green rods, 2.5–3.0 µm in width and 4.0–6.0 µm in length. Phylogenetic analyses of both 16S rRNA and nifH gene fragments indicated that the TW3 sequences were over 98% identical to those of the previously isolated Cyanothece sp. ATCC51142 and Gloeocapsa sp., suggesting that TW3 is a member of the Group C unicellular diazotrophs. In addition, both TW3 and Cyanothece sp. ATCC51142 share morphological characteristics; both strains are sheathless and rod‐shaped, display binary fission in a single plane, and possess dispersed thylakoids. TW3 grows aerobically in nitrogen‐deficient artificial seawater, and exhibited the highest observed growth rate of 0.035 h−1 when cultured at 30°C and 140 µmol m−2 s−1 of light intensity. The nitrogen fixation rate, when grown optimally using a 12 h/12 h light–dark cycle, was 7.31 × 10−15 mol N cell−1 day−1. Immunocytochemical staining using Trichodesmium sp. NIBB1067 nitrogenase antiserum revealed the existence of diazotrophic cells sharing morphological characteristics of TW3 in the Kuroshio water from which TW3 was isolated.
A Full Scale Approximation of Covariance Functions for Large Spatial Data Sets
Authors: Sang Huiyan , Huang Jianhua Z.
Published: October 2011

Gaussian process models have been widely used in spatial statistics but face tremendous computational challenges for very large data sets. The model fitting and spatial prediction of such models typically require O(n3) operations for a data set of size n. Various approximations of the covariance functions have been introduced to reduce the computational cost. However, most existing approximations cannot simultaneously capture both the large- and the small-scale spatial dependence. A new approximation scheme is developed to provide a high quality approximation to the covariance function at both the large and the small spatial scales. The new approximation is the summation of two parts: a reduced rank covariance and a compactly supported covariance obtained by tapering the covariance of the residual of the reduced rank approximation. Whereas the former part mainly captures the large-scale spatial variation, the latter part captures the small-scale, local variation that is unexplained by the former part. By combining the reduced rank representation and sparse matrix techniques, our approach allows for efficient computation for maximum likelihood estimation, spatial prediction and Bayesian inference. We illustrate the new approach with simulated and real data sets.
New Consistent and Asymptotically Normal Parameter Estimates for Random-Graph Mixture Models
Authors: Ambroise Christophe , Matias Catherine
Published: October 2011

Random-graph mixture models are very popular for modelling real data networks. Parameter estimation procedures usually rely on variational approximations, either combined with the expectation–maximization (EM) algorithm or with Bayesian approaches. Despite good results on synthetic data, the validity of the variational approximation is, however, not established. Moreover, these variational approaches aim at approximating the maximum likelihood or the maximum a posteriori estimators, whose behaviour in an asymptotic framework (as the sample size increases to ∞) remains unknown for these models. In this work, we show that, in many different affiliation contexts (for binary or weighted graphs), parameter estimators based either on moment equations or on the maximization of some composite likelihood are strongly consistent and √n convergent, when the number n of nodes increases to ∞. As a consequence, our result establishes that the overall structure of an affiliation model can be (asymptotically) caught by the description of the network in terms of its number of triads (order 3 structures) and edges (order 2 structures). Moreover, these parameter estimates are either explicit (as for the moment estimators) or may be approximated by using a simple EM algorithm, whose convergence properties are known. We illustrate the efficiency of our method on simulated data and compare its performances with other existing procedures. A data set of cross-citations among economics journals is also analysed.
Kalman Filter Initialization for Integrated Population Modelling
Authors: Besbeas Panagiotis , Morgan Byron J. T.
Published: October 2011

In integrated population modelling in ecology, where data from multiple surveys are analysed simultaneously, the Kalman filter may be used to approximate a component likelihood for a state space model of population count data. We evaluate a new method for initiating this Kalman filter, based on a stable age distribution. The new method is illustrated and compared with alternative approaches by application to data on the grey heron. The new method is simple to use, extends naturally to the case of multivariate time series of count data and performs well in a simulation study.
Two-Level Designs of Strength 3 and up to 48 Runs
Authors: Schoen Eric D. , Mee Robert W.
Published: October 2011

The paper will help practitioners to select strength 3 designs that are useful for screening both main effects and two-factor interactions. We calculated word length patterns, correlations of four-factor interaction contrast vectors with the intercept and ranks of the two-factor interaction matrices for all non-equivalent two-level orthogonal arrays of strength 3 and run sizes up to 48. On the basis of these characteristics, there are a limited number of designs that can be recommended for practical use.
Predicting Treatment Efficacy via Quantitative Magnetic Resonance Imaging: A Bayesian Joint Model
Authors: Wu Jincao , Johnson Timothy D. , Galbán Craig J. , Chenevert Thomas L. , Meyer Charles R. , Rehemtulla Alnawaz , Hamstra Daniel A. , Ross Brian D.
Published: October 2011

The prognosis for patients with high grade gliomas is poor, with a median survival of 1 year. Treatment efficacy assessment is typically unavailable until 5–6 months post diagnosis. Investigators hypothesize that quantitative magnetic resonance imaging can assess treatment efficacy 3 weeks after therapy starts, thereby allowing salvage treatments to begin earlier. The purpose of this work is to build a predictive model of treatment efficacy by using quantitative magnetic resonance imaging data and to assess its performance. The outcome is 1-year survival status. We propose a joint, two-stage Bayesian model. In stage I, we smooth the image data with a multivariate spatiotemporal pairwise difference prior. We propose four summary statistics that are functionals of posterior parameters from the first-stage model. In stage II, these statistics enter a generalized non-linear model as predictors of survival status. We use the probit link and a multivariate adaptive regression spline basis. The hybrid Metropolis-within-Gibbs algorithm and reversible jump Markov chain Monte Carlo methods are applied iteratively between the two stages to estimate the posterior distribution. Through both simulation studies and model performance comparisons we find that we can achieve higher overall correct classification rates by accounting for the spatiotemporal correlation in the images and by allowing for a more complex and flexible decision boundary provided by the generalized non-linear model.
Artistic productivity and creative thinking in Parkinson’s disease
Authors: Canesi M. , Rusconi M. L. , Isaias I. U. , Pezzoli G.
Published: October 2011

Background and purpose:  Creative drive and enhanced artistic‐like production may emerge in patients with Parkinson’s disease (PD) during dopaminergic therapy. However, it has not been described to date whether this artistic‐like production results from dopaminergic drugs triggering innate skills or it could be considered as a repeated behavior possibly associated with impulse control disorders (ICDs).

Methods:  We investigated creative drive in a cohort of cognitively preserved patients with PD by means of the Torrance Test of Creative Thinking (TTCT). We also investigated a putative association between creative drive and ICDs in 36 PD patients with (PD‐c) or without (PD‐nc) increased artistic‐like production and 36 healthy controls (HC). We considered artistic‐like productivity to be enhanced if patients reported working on any form of art more than 2 h per day after the introduction of dopaminergic treatment. The TTCT, the Barratt Impulsiveness Scale (BIS‐11A), the Minnesota Impulsive Disorders Interview (MIDI), and the Punding Rating Scale were applied.

Results:  Mean TTCT score of PD‐c was found to be similar to HC (169.4 ± 51.6 vs. 170.2 ± 69.7, respectively), and both PD‐c and HC had significantly higher TTCT scores than patients with PD‐nc (125.4 ± 46.1 P < 0.05). TTCT did not correlate with any demographic or clinical data in both PD subgroups. No correlation was found between TTCT, BIS‐11A, and MIDI.

Conclusions:  Our study suggests that newly acquired artistic‐like production in patients with PD is not associated with impulsivity or ICDs. Artistic‐like production might represent the emerging of innate skills in a subset of predisposed patients with PD on dopaminergic therapy.
Jerusalem in Athens: On the Biblical Epigraphs to Leo Strauss's Natural Right and History
Authors: O'Mahoney Paul
Published: October 2011

The Old Testament epigraphs used by Leo Strauss for his study Natural Right and History tend invariably to vex his readers. In the book itself and in other of his writings, Strauss explicitly states that the Old Testament tradition does not know ‘nature’ in the philosophical sense, and hence the concept of ‘natural right’ is unknown or alien to that tradition. Another, more obvious problem they present has been seemingly universally passed over by commentators: neither epigraph tells the reader anything explicitly about right, natural or otherwise. One cannot claim them to contain lessons about right, because such lessons are not directly extractable from the epigraphs as they stand. Here I wish to argue that Strauss's choice of epigraph does two things: first, it points to the fact that Old Testament stories can be given a political reading, or used to illustrate political lessons. In implying this, Strauss is following Machiavelli, who is the most important figure in Natural Right and History. Second, the epigraphs point to the deeply problematic nature of the concept of natural right, primarily the equivocal nature of the term, a difficulty never made explicit by Strauss but the awareness of which permeates his study.
Parenting by anxious mothers: effects of disorder subtype, context and child characteristics
Authors: Murray Lynne , Lau Pui Yi , Arteche Adriane , Creswell Cathy , Russ Stephanie , Zoppa Letizia Della , Muggeo Michela , Stein Alan , Cooper Peter
Published: October 2011

Background:  There has been increasing research interest in parenting by anxious adults; however, little is known about anxiety‐subtype effects, or effects of the context in which parenting is assessed.

Methods:  Two groups of anxious mothers, social phobia (N = 50), generalised anxiety disorder (N = 38), and nonanxious controls (N = 62) were assessed with their 4.9‐year‐old children in three tasks: two presented threat specifically relevant to each maternal disorder, namely, a social threat task where the child had to give a speech, and a nonsocial threat task where the child had to explore potentially scary objects; the third was a nonthreat task (playing with play dough). Seven parenting dimensions were scored. Effects on parenting of maternal anxiety subgroup and task, and their interactions, were examined, as were effects of earlier child behavioural inhibition and currently manifest anxiety.

Results:  There were no parenting differences between maternal groups in the nonthreat play‐dough task; parenting difficulties in the two anxious groups were principally evident in the disorder‐specific challenge. Parenting differences between nonanxious and anxious mothers occurred independently of child characteristics. There was little evidence for particular forms of parenting difficulty being unique to maternal disorder.

Conclusions:  Anxious mothers’ parenting difficulties emerge when occurring under challenge, especially when this is disorder‐specific. These effects should be considered in research and clinical practice.
Training and learning robotic surgery, time for a more structured approach: a systematic review
Authors: Schreuder HWR , Wolswijk R , Zweemer RP , Schijven MP , Verheijen RHM
Published: October 2011

Please cite this paper as: Schreuder H, Wolswijk R, Zweemer R, Schijven M, Verheijen R. Training and learning robotic surgery, time for a more structured approach: a systematic review. BJOG 2012;119:137–149.

Background  Robotic assisted laparoscopic surgery is growing rapidly and there is an increasing need for a structured approach to train future robotic surgeons.

Objectives  To review the literature on training and learning strategies for robotic assisted laparoscopic surgery.

Search strategy  A systematic search of MEDLINE, EMBASE, the Cochrane Library and the Journal of Robotic Surgery was performed.

Selection criteria  We included articles concerning training, learning, education and teaching of robotic assisted laparoscopic surgery in any specialism.

Data collection and analysis  Two authors independently selected articles to be included. We categorised the included articles into: training modalities, learning curve, training future surgeons, curriculum design and implementation.

Main results  We included 114 full text articles. Training modalities such as didactic training, skills training (dry lab, virtual reality, animal or cadaver models), case observation, bedside assisting, proctoring and the mentoring console can be used for training in robotic assisted laparoscopic surgery. Several training programmes in general and specific programmes designed for residents, fellows and surgeons are described in the literature. We provide guidelines for development of a structured training programme.

Authors’ conclusions  Robotic surgical training consists of system training and procedural training. System training should be formally organised and should be competence based, instead of time based. Virtual reality training will play an import role in the near future. Procedural training should be organised in a stepwise approach with objective assessment of each step. This review aims to facilitate and improve the implementation of structured robotic surgical training programmes.
Catecholamines up integrates dopamine synthesis and synaptic trafficking
Authors: Wang Zhe , Ferdousy Faiza , Lawal Hakeem , Huang Zhinong , Daigle J. Gavin , Izevbaye Iyare , Doherty Olugbenga , Thomas Jerrad , Stathakis Dean G , O’Donnell Janis M.
Published: October 2011

J. Neurochem. (2011) 10.1111/j.1471‐4159.2011.07517.x

The highly reactive nature of dopamine renders dopaminergic neurons vulnerable to oxidative damage. We recently demonstrated that loss‐of‐function mutations in the Drosophila gene Catecholamines up (Catsup) elevate dopamine pools but, paradoxically, also confer resistance to paraquat, an herbicide that induces oxidative stress‐mediated toxicity in dopaminergic neurons. We now report a novel association of the membrane protein, Catsup, with GTP cyclohydrolase rate‐limiting enzyme for tetrahydrobiopterin (BH4) biosynthesis and tyrosine hydroxylase, rate‐limiting enzyme for dopamine biosynthesis, which requires BH4 as a cofactor. Loss‐of‐function Catsup mutations cause dominant hyperactivation of both enzymes. Elevated dopamine levels in Catsup mutants coincide with several distinct characteristics, including hypermobility, minimal basal levels of 3,4‐dihydroxy‐phenylacetic acid, an oxidative metabolite of dopamine, and resistance to the vesicular monoamine transporter inhibitor, reserpine, suggesting that excess dopamine is synaptically active and that Catsup functions in the regulation of synaptic vesicle loading and release of dopamine. We conclude that Catsup regulates and links the dopamine synthesis and transport networks.
Neuronal Nogo‐A regulates glutamate receptor subunit expression in hippocampal neurons
Authors: Peng Xiangmin , Kim Jeeyong , Zhou Zhigang , Fink David J. , Mata Marina
Published: October 2011

J. Neurochem. (2011) 10.1111/j.1471‐4159.2011.07520.x

Nogo‐A and its cognate receptor NogoR1 (NgR1) are both expressed in neurons. To explore the function of these proteins in neurons of the CNS, we carried out a series of studies using postnatal hippocampal neurons in culture. Interfering with the binding of Nogo‐A to NgR1 either by adding truncated soluble fragment of NgR1 (NgSR) or by reducing NgR1 protein with a specific siRNA, resulted in a marked reduction in Nogo‐A expression. Inhibition of Rho‐ROCK or MEK‐MAPK signaling resulted in a similar reduction in neuronal Nogo‐A mRNA and protein. Reducing Nogo‐A protein levels by siRNA resulted in an increase in the post‐synaptic scaffolding protein PSD95, as well as increases in GluA1/GluA2 AMPA receptor and GluN1/GluN2A/GluN2B NMDA glutamate receptor subunits. siRNA treatment to reduce Nogo‐A resulted in phosphorylation of mTOR; addition of rapamycin to block mTOR signaling prevented the up‐regulation in glutamate receptor subunits. siRNA reduction of NgR1 resulted in increased expression of the same glutamate receptor subunits. Taken together the results suggest that transcription and translation of Nogo‐A in hippocampal neurons is regulated by a signaling through NgR1, and that interactions between neuronal Nogo‐A and NgR1 regulate glutamatergic transmission by altering NMDA and AMPA receptor levels through an rapamycin‐sensitive mTOR‐dependent translation mechanism.
HspB8 mutation causing hereditary distal motor neuropathy impairs lysosomal delivery of autophagosomes
Authors: Kwok Alice S. , Phadwal Kanchan , Turner Bradley J. , Oliver Peter L. , Raw Annie , Simon Anna Katharina , Talbot Kevin , Agashe Vishwas R.
Published: October 2011

J. Neurochem. (2011) 10.1111/j.1471‐4159.2011.07521.x

HspB8, a small heat‐shock protein implicated in autophagy, is mutated in patients with distal hereditary motor neuropathy type II (dHMNII). Autophagy is essential for maintaining protein homeostasis in the central nervous system, but its role has not been investigated in peripheral motor neurons. We used a novel, multispectral‐imaging flow cytometry assay to measure autophagy in cells. This assay revealed that over‐expression of wild‐type HspB8 in motor neuron‐like NSC34 cells led to an increased co‐localisation of autophagosomes with the lysosomes. By contrast, over‐expression of mutant HspB8 resulted in autophagosomes that co‐localised with protein aggregates but failed to co‐localise with the lysosomes. A similar impairment of autophagy could also be demonstrated in peripheral blood mononuclear cells from two dHMNII patients with the HspB8K141E mutation. We conclude that defects in HspB8‐mediated autophagy are likely to contribute to dHMNII pathology and their detection in peripheral blood mononuclear cells could be a useful, accessible biomarker for the disease.
Increased dosage of tumor suppressors limits the tumorigenicity of iPS cells without affecting their pluripotency
Authors: Menendez Sergio , Camus Suzanne , Herreria Aida , Paramonov Ida , Morera Laura B. , Collado Manuel , Pekarik Vlad , Maceda Iago , Edel Michael , Consiglio Antonella , Sanchez Adriana , Li Han , Serrano Manuel , Belmonte Juan C. I.
Published: October 2011

Embryonic stem (ES) cells and induced pluripotent stem (iPS) cells represent a promising therapeutic tool for many diseases, including aged tissues and organs at high risk of failure. However, the intrinsic self‐renewal and pluripotency of ES and iPS cells make them tumorigenic, and hence, the risk of tumor development hinders their clinical application. Here, we present a novel approach to limit their tumorigenicity and increase their safety through increased copy number of tumor suppressors. iPS containing an extra copy of the p53 or Ink4a/ARF locus show normal pluripotency, as determined by in vitro and in vivo differentiation assays. Yet, while retaining full pluripotency, they also possess an improved engagement of the p53 pathway during teratocarcinoma formation, which leads to a reduced tumorigenic potential in various in vitro and in vivo assays. Furthermore, they show an improved response to anticancer drugs, which could aid in their elimination in case tumors arise with no adverse effects on cell function or aging. Our system provides a model for studying tumor suppressor pathways during reprogramming, differentiation, and cell therapy applications. This offers an improved understanding of the pathways involved in tumor growth from engrafted pluripotent stem cells, which could facilitate the use of ES and iPS cells in regenerative medicine.
Everolimus‐induced loss of wound strength can be prevented by a short postoperative delay in its administration
Authors: Willems Martine C. M. , Hendriks Thijs , de Man Ben M. , Lomme Roger M. L. M. , van der Vliet J. Adam
Published: October 2011

The use of mammalian target of rapamycin inhibitors coincides with an increased incidence of surgical complications. In previous experiments, serious negative effects of postoperative everolimus on anastomotic strength were found. This study aims to investigate if delayed drug administration can prevent loss of wound strength. Ten groups of Wistar rats each received daily oral doses of 1.0 or 2.0 mg/kg everolimus, starting the day of anastomotic construction in both ileum and colon, or 1, 2, 3, or 4 days later. The 11th group received saline. Seven days later, wound strength in anastomoses and in the abdominal wall and wound hydroxyproline levels were measured. Mean wound strength was significantly and dose‐dependently reduced if everolimus was started on the day of operation. In ileum and colon, strength was not affected if drug administration was delayed until the third or second day, respectively. In abdominal fascia, this was the case only if everolimus was withheld until day 4. In general, changes in wound hydroxyproline content showed similarities to changes in wound strength. Thus, delaying administration of everolimus for 2–4 days after operation can prevent a serious loss of wound strength, both in the intestine and in the abdominal fascia.
Collagen matrix‐bound clotting factors (CMBCF) promote healing‐associated events independent of factor XIII in an in vitro model
Authors: Pohle Thorsten , Becker Jan C. , Lügering Andreas
Published: October 2011

We have previously explored in vitro as well as in vivo models of the biological effects of liquid fibrin glue (FG) containing factor XIII. The fixed combination of a collagen matrix and coagulation factors I and IIa (TachoSil®, Nycomed, Linz, Austria) is void of factor XIII. We aimed to determine whether (1) this preparation exerts similar effects to liquid FG on cells in an in vitro system, or (2) this effect is modulated by factor XIII. In an in vitro model, the effect of the fixed combination of collagen matrix and coagulation factors I and IIa (collagen matrix‐bound clotting factor [CMBCF]) on the expression and secretion of growth factors (vascular endothelial growth factor, platelet‐derived growth factor, fibroblast growth factor‐2) by gastric epithelial (AGS) and mesenchymal cells (fibroblasts), as well as their proliferative response (WST‐test), was compared in the presence and absence of factor XIII. The use of CMBCF compared with collagen type I matrix resulted in an increased proliferation rate of fibroblasts; there was an increased secretion of fibroblast growth factor‐2. Gastric epithelial cells secreted more vascular endothelial growth factor and platelet‐derived growth factor into the culture supernatant in the presence of CMBCF. All responses remained unaltered by the addition of factor XIII in different concentrations. In conclusion, CMBCF exerted effects similar to liquid FG in an in vitro model of healing. The addition of factor XIII did not alter the response of mesenchymal or epithelial cells, with respect to proliferation and growth factor secretion.
Metamorphic evolution of lawsonite eclogites from the southern Motagua fault zone, Guatemala: insights from phase equilibria and Raman spectroscopy
Authors: ENDO S. , WALLIS S. R. , TSUBOI M. , TORRES DE LEÓN R. , SOLARI L. A.
Published: October 2011

Lawsonite eclogite (metabasalt and metadolerite) and associated metasedimentary rocks in a serpentinite mélange from an area just south of the Motagua fault zone (SMFZ), Guatemala, represent excellent natural records of the forearc slab–mantle interface. Pseudosection modelling of pristine lawsonite eclogite reproduces the observed predominant mineral assemblages, and garnet compositional isopleths intersect within the phase fields, yielding a progradeP–Tpath that evolves from 20 kbar, 470 °C (M1) to 25 kbar, 520 °C (M2). The dominant penetrative foliation within the eclogite blocks is defined by minerals developed during the prograde evolution, and the associated deformation, therefore, took place during subduction. Thermometry using Raman spectra of carbonaceous material in metasedimentary rocks associated with the SMFZ eclogites gives estimates of peak‐Tof ∼520 °C. Barometry using Raman spectroscopy shows unfractured quartz inclusions in garnet rims retain overpressures of up to ∼10 kbar, implying these inclusions were trapped at conditions just below the quartz/coesite transition, in agreement with the results of phase equilibrium analysis. Additional growth of Ca‐rich garnet indicates initial isothermal decompression to 20 kbar (M3) followed by hydration and substantial cooling to the lawsonite–blueschist facies (M4). Further decompression of the hydrated eclogite blocks to the pumpellyite–actinolite facies (3–5 kbar, 230–250 °C) is associated with dehydration and veining (M5). The presence of eclogite as m‐ to 10 m‐sized blocks in a serpentinite matrix, lack of widespread deformation developed during exhumation and derived progradeP–Tpath associated with substantial dehydration of metabasites within the antigorite stability field suggest that the SMFZ eclogites represent the uppermost part of the forearc slab crust sampled by an ascending serpentinite diapir in an active, moderate‐Tsubduction zone.