bluuebunny/crossref_metadata_2025_split huggingface dataset:
Need for more evolutionary and developmental perspective on basic emotional mechanisms
Authors: Weisfeld Glenn , LaFreniere Peter 
Published: May 2012

AbstractLindquist et al.'s meta-analysis focuses on adult humans; the authors' emotion model might be strengthened by considering research on infants and animals, highlighting the importance of the limbic system. Reliance on the James–Lange theory is questionable; emotions typically occur instantaneously, with dubious dependence on bodily feedback for affect. Stronger evidence for localization might be obtained using more precise emotion terms and alterative localization methods.
Neuroscience findings are consistent with appraisal theories of emotion; but does the brain “respect” constructionism?
Authors: Scherer Klaus R. 
Published: May 2012

AbstractI reject Lindquist et al.'s implicit claim that all emotion theories other than constructionist ones subscribe to a “brain locationist” approach. The neural mechanisms underlying relevance detection, reward, attention, conceptualization, or language use are consistent with many theories of emotion, in particular componential appraisal theories. I also question the authors' claim that the meta-analysis they report provides support for thespecificassumptions of constructionist theories.
BRAZILIAN HEALTH TECHNOLOGY ASSESSMENT BULLETIN: EDITORIAL PROCESS, DISSEMINATION STRATEGIES, CRITICAL APPRAISAL, AND INITIAL IMPACT
Authors: Silva Marcus Tolentino , de Almeida Rosimary Terezinha , Gava Cintia Maria , Galvão Taís Freire , da Silva Edina Mariko Koga , Santos Vania Cristina Canuto , Ronchini Misani Akiko Kanamota , de Mesquita Aline Monte , Elias Flávia Tavares Silva , d'Oliveira Alexandre Lemgruber Portugal , Atallah Álvaro Nagib 
Published: May 2012

Objectives: This study reports on the Brazilian experience of developing a specialized bulletin, the Brazilian Health Technology Assessment Bulletin (BRATS), on health technology assessments (HTA).Methods: The editorial process, format, and dissemination strategy of the publication are presented. A critical appraisal of the available issues was made using the checklist for HTA reports of the International Network of Agencies for Health Technology Assessment. The initial impact was estimated based on a retrospective observational measurement of the types of publications that cite the bulletin as a source of information. The publications citing BRATS were identified using Google Scholar.Results: Since June 2008, fourteen issues of the bulletin have been produced. BRATS has not presented any significant limitation that would compromise generalizations of its results within the Brazilian context. The initial impact of the bulletin, however, has been small, which may be due to its exclusively electronic dissemination format and technical language. We found nine publications citing BRATS in Google Scholar.Conclusions: It is hoped that the bulletin will promote the continuity of HTA actions among health-sector managers and professionals in Brazil.
High-throughput analysis of epistasis in genome-wide association studies with BiForce
Authors: Gyenesei Attila , Moody Jonathan , Semple Colin A.M. , Haley Chris S. , Wei Wen-Hua 
Published: May 2012

AbstractMotivation: Gene–gene interactions (epistasis) are thought to be important in shaping complex traits, but they have been under-explored in genome-wide association studies (GWAS) due to the computational challenge of enumerating billions of single nucleotide polymorphism (SNP) combinations. Fast screening tools are needed to make epistasis analysis routinely available in GWAS.Results: We present BiForce to support high-throughput analysis of epistasis in GWAS for either quantitative or binary disease (case–control) traits. BiForce achieves great computational efficiency by using memory efficient data structures, Boolean bitwise operations and multithreaded parallelization. It performs a full pair-wise genome scan to detect interactions involving SNPs with or without significant marginal effects using appropriate Bonferroni-corrected significance thresholds. We show that BiForce is more powerful and significantly faster than published tools for both binary and quantitative traits in a series of performance tests on simulated and real datasets. We demonstrate BiForce in analysing eight metabolic traits in a GWAS cohort (323 697 SNPs, &gt;4500 individuals) and two disease traits in another (&gt;340 000 SNPs, &gt;1750 cases and 1500 controls) on a 32-node computing cluster. BiForce completed analyses of the eight metabolic traits within 1 day, identified nine epistatic pairs of SNPs in five metabolic traits and 18 SNP pairs in two disease traits. BiForce can make the analysis of epistasis a routine exercise in GWAS and thus improve our understanding of the role of epistasis in the genetic regulation of complex traits.Availability and implementation: The software is free and can be downloaded from http://bioinfo.utu.fi/BiForce/.Contact: wenhua.wei@igmm.ed.ac.ukSupplementary information: Supplementary data are available at Bioinformatics online.
Paraneoplastic Isaacs' Syndrome
Authors: Rana Sandeep S. , Ramanathan Ramnath Santosh , Small George , Adamovich Brenda 
Published: May 2012

Abstract

Objective:
Isaacs' syndrome is a rare disease resulting from hyperexcitability of peripheral nerves causing continuous muscle fiber activity characterized by muscle twitching and stiffness at rest and delayed muscle relaxation after voluntary contraction. Our objective was to discuss the relationship of Isaacs' syndrome to paraneoplastic syndromes as reported in the available literature and in 3 patients evaluated at our academic medical center.

Methods:
We review the literature on Isaacs' syndrome and describe 3 patients in whom Isaacs' syndrome heralded underlying malignancy or benign neoplasm, including their presenting symptoms, electrophysiologic findings, and laboratory and pathology results.

Results:
In all 3 cases, clinical and electrodiagnostic testing was suggestive of Isaacs' syndrome. Two patients tested positive, and one was negative for voltage-gated potassium channel antibodies. Two of the patients developed malignant tumors, that is, one was diagnosed with metastatic thymoma and one with lymphoplasmacytic lymphoma, ranging from 6 months to 1 year after the diagnosis of Isaacs' syndrome. One patient was diagnosed with a spinal cord hemangioblastoma 5 years after he was diagnosed with Isaacs' syndrome.

Conclusions:
Our case series highlights the association of Isaacs' syndrome with a variety of neoplasms both malignant and benign. Our report also underscores the fact that Isaacs' syndrome may be diagnosed several years before a neoplasm is discovered. In our cases, Isaacs' syndrome overlapped with other neuromuscular disorders, that is, myasthenia gravis in a patient with thymoma and chronic inflammatory demyelinating polyneuropathy in a patient with lymphoplasmacytic lymphoma with paraproteinemia. To our knowledge, this is the first report of an association between Isaacs' syndrome with lymphoplasmacytic lymphoma and a spinal cord hemangioblastoma.
What's in the Literature?
Authors: El-Dokla Ahmed , Lacomis David 
Published: May 2012

Abstract
Over the past 3 months, there was an explosion of articles describing the clinical, imaging, and pathological features of familial amyotrophic lateral sclerosis and frontotemporal dementia associated with the C9ORF72 hexanucleotide repeat expansion. A proposal for amyotrophic lateral sclerosis staging and an overview of changing utilization of noninvasive ventilation in the United Kingdom are also reviewed. There was also an interesting series of articles on generalized myasthenia gravis that is seronegative for acetylcholine receptor and muscle-specific kinase antibodies but harbors antibodies against the low-density lipoprotein receptor–related protein 4, which binds agrin on the postsynaptic cleft and seems to play a pathogenic role in myasthenia gravis. The clinically important disorder, small fiber neuropathy (SFN), is also reviewed including an important discovery of sodium channel Nav1.7 mutations in patients with previously idiopathic SFN and a treatment approach for SFN using a Nav1.7 channel blocker. Another important article expands the phenotypes of anoctamin 5 autosomal recessive limb–girdle muscular dystrophy. Presentations were variable with adult-onset sometimes asymmetric weakness with proximal and sometimes calf involvement and high creatine kinase. Females were less severely affected and often had exercise induced myalgia without weakness.
The ciprofloxacin target AUC : MIC ratio is not reached in hospitalized patients with the recommended dosing regimens
Authors: Haeseker Michiel , Stolk Leo , Nieman Fred , Hoebe Christian , Neef Cees , Bruggeman Cathrien , Verbon Annelies 
Published: May 2012

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• The efficacy target of AUC : MIC > 125 is based on the study of Forrest et al. in 1993.• Recent studies have shown that in ICU patients the ciprofloxacin efficacy target of AUC : MIC > 125 is often not reached.WHAT THIS STUDY ADDS• The efficacy targets of ciprofloxacin in patients in general wards are often not reached. Most patients have low AUC with current i.v. dosing regimens. We suggest increasing the standard dose of ciprofloxacin to 1200 mg intravenously 24 h–1.• Patients in general wards have high interindividual variability of pharmacokinetic parameters and therapeutic drug monitoring could be useful to support dosing.AIM The aim of this study was to determine the ciprofloxacin serum concentrations in hospitalized patients and to determine which percentage reached the efficacy target of AUC : MIC > 125. Additionally, the influence of demographic anthropomorphic and clinical parameters on the pharmacokinetics and pharmacodynamics of ciprofloxacin were investigated.METHODS In serum of 80 hospitalized patients ciprofloxacin concentrations were measured with reverse phase high performance liquid chromatography with fluorescence detection. The ciprofloxacin dose was 400–1200 mg day−1 i.v. in two or three doses depending on renal function and causative bacteria. Pharmacokinetic parameters were calculated with maximum a posteriori Bayesian estimation (MW\PHARM 3.60). A two compartment open model was used.RESULTS Mean (± SD) age was 66 (± 17) years, the mean clearance corrected for bodyweight was 0.24 l h−1 kg−1 and the mean AUC was 49 mg l−1 h. Ciprofloxacin clearance and thus AUC were associated with both age and serum creatinine. Of all patients, 21% and 75% of the patients, did not reach the proposed ciprofloxacin AUC : MIC > 125 target with MICs of 0.25 and 0.5 mg l−1, respectively. A computer simulated increase in the daily dose from 800 mg to 1200 mg, decreased these percentages to 1% and 37%, respectively.CONCLUSION A substantial proportion of the hospitalized patients did not reach the target ciprofloxacin AUC : MIC and are suboptimally dosed with recommended doses. Taking into account the increasing resistance to ciprofloxacin worldwide, a ciprofloxacin dose of 1200 mg i.v. daily in patients with normal renal function is necessary to reach the targeted AUC : MIC > 125.
A contrast in safety, pharmacokinetics and pharmacodynamics across age groups after a single 50 mg oral dose of the γ‐secretase inhibitor avagacestat
Authors: Tong Gary , Wang Jun‐Sheng , Sverdlov Oleksandr , Huang Shu‐Pang , Slemmon Randy , Croop Robert , Castaneda Lorna , Gu Huidong , Wong Oi , Li Hewei , Berman Robert M. , Smith Christina , Albright Charles F. , Dockens Randy 
Published: May 2012

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Under homeostatic conditions, sequential cleavage of amyloid precursor protein by β‐site cleaving enzyme and γ‐secretase forms the common Aβ isoforms, Aβ1–38, Aβ1–40, and Aβ1–42.• However, in the pathological Alzheimer's disease (AD) state, Aβ clearance is decreased nearly 30%. As such, γ‐secretase is a promising drug target for AD therapy, as a decrease in its enzymatic activity has the potential to reduce Aβ levels and modify disease.• In contrast, current treatments for AD provide only short term symptomatic relief.WHAT THIS STUDY ADDS• Unique among previous studies of γ‐secretase inhibitors (GSIs), such as semagacestat and begacestat, our results showed that avagacestat, an oral GSI in clinical development for the disease‐modifying treatment of AD, decreased Aβ1–40 plasma concentrations and was well‐tolerated in both young and elderly subjects, with adverse events being predominantly mild to moderate in severity.AIM To evaluate the single dose pharmacokinetics, pharmacodynamics, and preliminary tolerability of the γ‐secretase inhibitor BMS‐708163 (avagacestat) in young and elderly men and women.METHODS All subjects received double‐blinded administration of a single 50 mg dose of avagacestat in capsule form or matching placebo. Main evaluations included pharmacokinetics, safety, plasma amyloid‐β (Aβ)1–40 concentratios and exploration of Notch biomarkers.RESULTS Avagacestat 50 mg capsule was well tolerated and rapidly absorbed among young and elderly subjects, with a median tmax between 1 and 2 h post dose and an average half‐life between 41 and 71 h. In general, subjects aged 75 years or more had higher AUC(0,∞) values than those aged less than 75 years. An exploratory analysis of Aβ1–40 serum concentrations showed a pattern of decreasing concentrations over the first 4–6 h followed by a rise above baseline that was maintained until the end of the assessment period. Adverse events were generally mild, occurring more frequently in elderly subjects, with no observed difference between subjects receiving avagacestat and placebo. No dose limiting gastrointestinal effects of avagacestat were observed and exploratory biomarkers of Notch inhibition did not change significantly.CONCLUSIONS The favourable safety profile and pharmacokinetic effects of avagacestat in this study support its continued development, especially in the target population of elderly subjects with mild cognitive impairment or Alzheimer's disease.
Illumination properties and imaging promises of blended, multiple‐scattering seismic data: a tutorial
Authors: Berkhout A.J. , Verschuur D.J. , Blacquière G. 
Published: May 2012

ABSTRACTIn traditional seismic surveys the firing time between shots is such that the shot records do not interfere in time. In the concept of blended acquisition, however, shot records do overlap, allowing denser source sampling and wider azimuths in an economic way. A denser shot sampling and wider azimuths make that each subsurface gridpoint is illuminated from a larger number of angles and will therefore improve the image quality in terms of signal‐to‐noise ratio and spatial resolution. In this tutorial, we show that, even with very simple blending parameters like time delays, the incident wavefield at a specific subsurface gridpoint represents a dispersed time series with a complex code. For shot record migration purposes, this time series should be designed such that it facilitates a stable inversion process. In a next step, we explain how the illumination property of the incident wavefield can be further improved by utilizing the surface‐related multiples. This means that these multiples can be exploited to improve the incident wavefield by filling angle gaps in the illumination and/or by extending the range of angles (‘natural blending’). In this way the energy contained in the multiples now contributes to the image, rather than decreasing its quality. One remarkable consequence of this property is that the benefits to be obtained from the improved illumination depend on the detector locations in acquisition geometries as well. We explain how to quantify the contribution of the blended surface multiples to the incident wavefield for a blended source configuration. In addition, we explain how blended measurements can be directly used in an angle‐dependent migration process with a bifocal, least‐squares imaging condition. The result is a densely sampled reflectivity function in the ray parameter domain, also improving the capability of velocity estimation. We will show examples to illustrate the theory.
Parenting under Pressure: a grounded theory of parenting young children with life‐threatening congenital heart disease
Authors: Rempel Gwen R. , Ravindran Vinitha , Rogers Laura G. , Magill‐Evans Joyce 
Published: May 2012

rempel g.r., ravindran v., rogers l.g. & magill‐evans j. (2013) Parenting under pressure: a grounded theory of parenting young children with life‐threatening congenital heart disease. Journal of Advanced Nursing69(3), 619–630. doi: 10.1111/j.1365‐2648.2012.06044.xAbstractAim.  To report a grounded theory study to describe the process of parenting young children who have survived hypoplastic left heart syndrome to inform parent‐focused interventions.Background.  Technological advances in paediatric cardiology worldwide have improved the survival rates for young children with hypoplastic left heart syndrome who undergo staged surgical palliation. These children, however, are at risk for life‐threatening complications and parents are charged with the responsibility to monitor their children at home with minimal support and guidance from healthcare professionals once home.Design.  A constructivist grounded theory study.Method.  The study was conducted in 2006–2008. Participants were 25 parents (15 mothers, 10 fathers) and 28 grandparents (17 grandmothers, 11 grandfathers) of 15 young children (6 months–4·5 years) who had undergone the Sano surgical approach for hypoplastic left heart syndrome. The 53 interviews were digitally recorded, transcribed and analysed using open and focused coding, constant comparative analysis and memoing.Findings.  A process of Parenting under Pressure emerged that was characterized by four overlapping and re‐emerging phases: (1) realizing and adjusting to the inconceivable; (2) growing increasingly attached; (3) watching for and accommodating the unexpected; and (4) encountering new challenges.Conclusions.  In‐depth understanding of the phases of Parenting under Pressure provides direction for nurses to support parents of children who survive hypoplastic left heart syndrome. Interventions that help carers of children with complex health conditions move through the phases of our Parenting under Pressure process may help them safeguard the survival of their children, and their own survival as parents as they manage multiple demands.
An essential function of sphingolipids in yeast cell division
Authors: Epstein Sharon , Castillon Guillaume A. , Qin Yongmei , Riezman Howard 
Published: May 2012

SummaryCeramides are bioactive lipids and precursors to sphingolipids. They have been shown to take part in a wide variety of different physiological processes in eukaryotic organisms and are thought to be toxic at high concentrations. Ceramide is synthesized by condensation of the sphingoid base sphinganine and a fatty acyl CoA by ceramide synthases, a family of enzymes that differ in their specificity for the length of the acyl CoA substrate. We have engineered a yeast strain where the endogenous ceramide synthase has been replaced by one of the putative enzymes from cotton. As a result, the yeast strain produces C18 rather than C26 ceramides showing that the cotton protein is a bona fide ceramide synthase with specificity towards C18 acyl CoA. Strikingly, the accumulation of C18 ceramide is not toxic in Saccharomyces cerevisiae. This allows survival of the yeast after deletion of the normally essential AUR1 (inositol phosphorylceramide synthase) gene permitting us to address the essential roles of sphingolipids. Deletion of AUR1 allows cell growth, but leads to a defect in cytokinesis, which takes twice as long as in wild‐type strains. Nuclear division and recruitment of septins is apparently not affected, but cytokinesis is delayed and cell separation is incomplete.
Validation and implications of an energy‐based bedload transport equation
Authors: GAO PENG 
Published: May 2012

AbstractA recently developed bedload equation (Abrahams & Gao, 2006) has the form ib = ωG3˙4, where ib is the immersed bedload transport rate, ω is the stream power per unit area, G = 1−θc/θ, θ is the dimensionless shear stress and θc is the associated threshold value for the incipient motion of bed grains. This equation has a parsimonious form and provides good predictions of transport rate in both the saltation and sheetflow regimes (i.e. flows with low and high θ values, respectively). In this study, the equation was validated using data independent of those used for developing it. The data represent bedload of identical sizes transported in various steady, uniform, fully rough and turbulent flows over plane, mobile beds. The equation predicted ib quite well over five orders of magnitude. This equation was further compared with six classic bedload equations and showed the best performance. Its theoretical significance was subsequently examined in two ways. First, based on collision theory, the parameter G was related to the ratio of grain‐to‐grain collisions to the total collisions including both grain‐to‐grain and grain‐to‐bed collisions, Pg by Pg = G2, suggesting that G characterizes the dynamic processes of bedload transport from the perspective of granular flow, which partly accounts for the good performance of the equation. Moreover, examining the ability of two common equations to predict bedload in gravel‐bed rivers revealed that G can also be used to simplify equations for predicting transport capacities in such rivers. Second, a simple dimensionless form of the equation was created by introducing B = ib/ω. The theoretical nature of the term B was subsequently revealed by comparing this equation with both the Bagnold model and two commonly used parameters representing dimensionless bedload transport rates.
Bronchoalveolar lavage fluid exosomes contribute to cytokine and leukotriene production in allergic asthma
Authors: Torregrosa Paredes P. , Esser J. , Admyre C. , Nord M. , Rahman Q. K. , Lukic A. , Rådmark O. , Grönneberg R. , Grunewald J. , Eklund A. , Scheynius A. , Gabrielsson S. 
Published: May 2012

AbstractBackgroundLeukotrienes (LTs) are potent pro‐inflammatory mediators involved in asthma. Exosomes, nanosized vesicles released from various cells, can stimulate or down‐regulate immune responses, depending on the state and nature of the originating cell. We have recently shown an altered exosome profile in bronchoalveolar lavage fluid (BALF) of patients with sarcoidosis, but their role in asthma is unknown. Our aims were to investigate whether exosomes from BALF have LT biosynthetic capacity and to explore phenotypic and functional characteristics of BALF exosomes in asthma.MethodsBronchoalveolar lavage fluid exosomes were collected from healthy individuals (n = 13) and patients with mild allergic asthma to birch pollen (n = 12) before and after birch allergen provocation. Exosomes were characterized by flow cytometry and Western blot. Their capacity to induce IL‐8 and LT production in the human bronchial epithelial cell (BEC) line 16HB14o‐ was measured by ELISA and reverse‐phase HPLC, respectively.ResultsCompared to BALF exosomes from healthy individuals, BALF exosomes from asthmatics displayed higher levels of exosome‐associated markers, such as the tetraspanins CD63 and CD81 and the scavenger receptor CD36. No major differences were observed between BALF exosomes from before and after allergen provocation. Furthermore, we show that BALF exosomes contain enzymes for LT biosynthesis. The effect of exosomes to promote LTC4 and IL‐8 release in BEC was significantly increased for exosomes from asthmatics, and the CysLT1 receptor antagonist Montelukast reduced exosome‐induced IL‐8 secretion.ConclusionsBronchoalveolar lavage fluid exosomes from asthmatic and healthy individuals exhibit distinct phenotypes and functions. BALF exosomes from asthmatics might contribute to subclinical inflammation by increasing cytokine and LTC4 generation in airway epithelium.