bluuebunny/crossref_metadata_2025 huggingface dataset:
Stenotrophomonas maltophila cellulitis in an immunocompromised patient presenting with purpura, diagnosed on skin biopsy
Authors: Gao Yi , Minca Eugen C. , Procop Gary W. , Bergfeld Wilma F.
Published: July 2016

Stenotrophomas maltophilia is an opportunistic Gram‐negative bacillus and an important cause of nosocomial infections, particularly in immunosuppressed individuals. Although infections with this organism are most often in the form of pneumonia, bacteremia and endocarditis, awareness of the impact of S. maltophilia skin infections has been increasing. Here we describe a case of S. maltophilia cellulitis in a 65‐year‐old man with severe neutropenia and purpuric skin lesions to highlight the critical histopathological findings and correlate them with the clinical manifestations of the skin infection with this organism. Because identification of S. maltophilia can be challenging and infections are difficult to manage, this case illustrates essential considerations regarding the multifaceted histopathological, dermatological, clinical and microbiological aspects of the diagnosis and treatment of S. maltophilia cellulitis in a severely immunocompromised patient. Cognizance of the increasing incidence of nosocomial infections with uncommon microorganisms such as S. maltophilia is necessary when presented with atypical cutaneous manifestations, particularly in immunocompromised patients.
Seizure‐onset patterns in focal cortical dysplasia and neurodevelopmental tumors: Relationship with surgical prognosis and neuropathologic subtypes
Authors: Lagarde Stanislas , Bonini Francesca , McGonigal Aileen , Chauvel Patrick , Gavaret Martine , Scavarda Didier , Carron Romain , Régis Jean , Aubert Sandrine , Villeneuve Nathalie , Giusiano Bernard , Figarella‐Branger Dominique , Trebuchon Agnès , Bartolomei Fabrice
Published: July 2016

Objectives

The study of intracerebral electroencephalography (EEG) seizure‐onset patterns is crucial to accurately define the epileptogenic zone and guide successful surgical resection. It also raises important pathophysiologic issues concerning mechanisms of seizure generation. Until now, several seizure‐onset patterns have been described using distinct recording methods (subdural, depth electrode), mostly in temporal lobe epilepsies or with heterogeneous neocortical lesions.

Methods

We analyzed data from a cohort of 53 consecutive patients explored by stereoelectroencephalography (SEEG) and with pathologically confirmed malformation of cortical development (MCD; including focal cortical dysplasia [FCD] and neurodevelopmental tumors [NDTs]).

Results

We identified six seizure‐onset patterns using visual and time‐frequency analysis: low‐voltage fast activity (LVFA); preictal spiking followed by LVFA; burst of polyspikes followed by LVFA; slow wave/DC shift followed by LVFA; theta/alpha sharp waves; and rhythmic spikes/spike‐waves. We found a high prevalence of patterns that included LVFA (83%), indicating nevertheless that LVFA is not a constant characteristic of seizure onset. An association between seizure‐onset patterns and histologic types was found (p = 001). The more prevalent patterns were as follows: (1) in FCD type I LVFA (23.1%) and slow wave/baseline shift followed by LVFA (15.4%); (2) in FCD type II burst of polyspikes followed by LVFA (31%), LVFA (27.6%), and preictal spiking followed by LVFA (27.6%); (3) in NDT, LVFA (54.5%). We found that a seizure‐onset pattern that included LVFA was associated with favorable postsurgical outcome, but the completeness of the EZ resection was the sole independent predictive variable.

Significance

Six different seizure‐onset patterns can be described in FCD and NDT. Better postsurgical outcome is associated with patterns that incorporate LVFA.
Fail but Try Again? The Effects of Age, Gender, and Multiple–Owner Experience on Failed Entrepreneurs’ Reentry
Authors: Baù Massimo , Sieger Philipp , Eddleston Kimberly A. , Chirico Francesco
Published: July 2016

We investigate what leads failed entrepreneurs to reenter entrepreneurship by taking a developmental career perspective. Specifically, we hypothesize that the age of failed entrepreneurs has a nonlinear relationship with the likelihood of reentering entrepreneurship that follows different career stages (early, middle, and late). The gender of failed entrepreneurs and multiple–owner experience in the failed firm are hypothesized to be moderators of this relationship. We test our hypotheses using a database consisting of the Swedish population, including 4,761 entrepreneurs who failed between 2000 and 2004. Analyzing their career paths over the years following their failure offers support for our theoretical expectations.
Glycerolipid synthesis and lipid trafficking in plant mitochondria
Authors: Michaud Morgane , Prinz William A. , Jouhet Juliette
Published: July 2016

Lipid trafficking between mitochondria and other organelles is required for mitochondrial membrane biogenesis and signaling. This lipid exchange occurs by poorly understood nonvesicular mechanisms. In yeast and mammalian cells, this lipid exchange is thought to take place at contact sites between mitochondria and the ER or vacuolar membranes. Some proteins involved in the tethering between membranes or in the transfer of lipids in mitochondria have been identified. However, in plants, little is known about the synthesis of mitochondrial membranes. Mitochondrial membrane biogenesis is particularly important and noteworthy in plants as the lipid composition of mitochondrial membranes is dramatically changed during phosphate starvation and other stresses. This review focuses on the principal pathways involved in the synthesis of the most abundant mitochondrial glycerolipids in plants and the lipid trafficking that is required for plant mitochondria membrane biogenesis.
State of the art: von Willebrand disease
Authors: James A. H. , Eikenboom J. , Federici A. B.
Published: July 2016

The State of the Art in von Willebrand disease (VWD) has been impacted not only by discoveries in the field of haemostasis, but also by changes in practice in other fields. The development of bleeding assessment tools has led to the clarification of bleeding symptoms and phenotype in VWD. New discoveries in the biology and genetics of von Willebrand factor (VWF) are challenging our existing diagnostics and classification(s). An improved understanding of reproductive physiology and the pathology of VWD along with changing obstetric, gynaecologic and haemostatic therapies necessitate an evolving response to the care of women with VWD. The survival of patients with autoimmune disease, malignancies and congenital heart disease along with increasing use of circulatory support devices and extracorporeal membrane oxygenation is increasing the prevalence of acquired von Willebrand syndrome. In each of these challenges, there are opportunities to improve the care of our patients with VWD.
Diagnostic laboratory for bleeding disorders ensures efficient management of haemorrhagic disorders
Authors: Riddell A. , Chuansumrit A. , El‐Ekiaby M. , Nair S. C.
Published: July 2016

Haemorrhagic disorders like Postpartum haemorrhage and Dengue haemorrhagic fever are life threatening and requires an active and efficient transfusion service that could provide the most appropriate blood product which could be effective in managing them. This would essentially require prompt identification of the coagulopathy so that the best available product can be given to the bleeding patient to correct the identified haemostatic defect which will help control the bleeding. This would only be possible if the transfusion service has a laboratory to correctly detect the haemostatic defect and that too with an accuracy and precision which is ensured by a good laboratory quality assurance practices. These same processes are necessary for the transfusion services to ensure the quality of the blood products manufactured by them and that it contains adequate amounts of haemostasis factors which will be good to be effective in the management of haemorrhagic disorders. These issues are discussed in detail individually in the management of postpartum haemorrhage and Dengue haemorrhagic fever including when these can help in the use of rFVIIa in Dengue haemorrhagic fever. The requirements to ensure good‐quality blood products are made available for the management of these disorders and the same have also been described.
Innovating immune tolerance induction for haemophilia
Authors: Batsuli G. , Meeks S. L. , Herzog R. W. , Lacroix‐Desmazes S.
Published: July 2016

Introduction

Haemophilia A is an X‐linked bleeding disorder characterized by a deficiency of coagulation protein factor VIII (FVIII). A challenging complication of therapeutic FVIII infusions is the formation of neutralizing alloantibodies against the FVIII protein defined as inhibitors. The development of FVIII inhibitors drastically alters the quality of life of the patients and is associated with tremendous increases in morbidity as well as treatment costs.

Aim

Current clinical immune tolerance induction protocols to reverse inhibitors are lengthy, costly and not effective in all patients. Prophylactic protocols to prevent inhibitor formation have not yet been developed in the clinical setting. However, there has been ample progress towards this goal in recent years in preclinical studies using animal models of haemophilia.

Methods

Here, we review the mechanisms that lead to inhibitor formation against FVIII and two promising new strategies for antigen‐specific tolerance induction.

Results

CD4+ T cells play an important role in the FVIII‐specific B cell response. Immune tolerance can be induced based on transplacental delivery of FVIII domains fused to Fc or on oral delivery of leaf cells from chloroplast transgenic crop plants.

Conclusions

Recent literature suggests that prophylactic tolerance induction protocols for FVIII may be feasible in haemophilia A patients.
Quality laboratory issues in bleeding disorders
Authors: Adcock D. M. , Mammen J. , Nair S. C. , de Lima Montalvão S. A.
Published: July 2016

Selected quality issues pertinent to the determination of accurate results in the haemostasis laboratory are discussed. Specifically, the implementation of a successful external quality‐assessment scheme is described, including its impact on result accuracy as well as the programme's unique challenges and opportunities. Errors in the preanalytical phase of laboratory testing represent the greatest source for reporting incorrect test results. Some of the most common preanalytical errors are described including those that necessitate sample rejection. Analytical means to identify potential sources of error and analytical means to overcome particular interferences are described. Representing the most important clinical complication in the treatment of patients with haemophilia, quality issues related to determination of the presence of inhibitory antibodies against factor VIII (FVIII) are reviewed. Heat treatment of patient plasma prior to testing, particularly in patients receiving replacement FVIII concentrate or during induction of immune tolerance to achieve more accurate results is recommended, while screening activated partial thromboplastin time‐based mixing tests to rule out inhibitor presence is discouraged. The initiatives presented in this review can be implemented in robust and resource restricted settings to improve the quality of laboratory testing in patients with bleeding disorders.
Medical co‐morbidities of patients with haemophilia: pain, obesity and hepatitis C
Authors: Witkop M. L. , Peerlinck K. , Luxon B. A.
Published: July 2016

Clinical care of patients with haemophilia (PWH) has progressed rapidly over the past decade. Current therapy has allowed patients with haemophilia to live longer and many patients are now experiencing the co‐morbidities of the general population. In this review article, we focus on three common diseases states that affect PWH: chronic pain, obesity and hepatitis C. Pain has been a co‐morbidity for many years and PWH often have unusual needs for chronic pain relief compared to the general population. Obesity is not only increasing in the general population but also in patients with hereditary bleeding disorders. The co‐morbidity of obesity not only causes increased pain progression and joint damage but also affects the dosing of factor concentrates. Finally, hepatitis C is known to have infected the majority of patients who received non‐virally inactivated pooled factor concentrates in the past. New treatment regimens have been developed that allow the nearly uniform cure of chronic hepatitis C with a short course of oral medications.
State of the art: gene therapy of haemophilia
Authors: Spencer H. T. , Riley B. E. , Doering C. B.
Published: July 2016

Clinical gene therapy has been practiced for more than a quarter century and the first products are finally gaining regulatory/marketing approval. As of 2016, there have been 11 haemophilia gene therapy clinical trials of which six are currently open. Each of the ongoing phase 1/2 trials is testing a variation of a liver‐directed adeno‐associated viral (AAV) vector encoding either factor VIII (FVIII) or factor IX (FIX) . As summarized herein, the clinical results to date have been mixed with some perceived success and a clear recognition of the immune response to AAV as an obstacle to therapeutic success. We also attempt to highlight promising late‐stage preclinical activities for AAV‐FVIII where, due to inherent challenges with manufacture, delivery and transgene product biosynthesis, more technological development has been necessary to achieve results comparable to what has been observed previously for AAV‐FIX. Finally, we describe the development of a stem cell‐based lentiviral vector gene therapy product that has the potential to provide lifelong production of FVIII and provide a functional ‘cure’ for haemophilia A. Integral to this program has been the incorporation of a blood cell‐specific gene expression element driving the production of a bioengineered FVIII designed for optimal efficiency. As clearly outlined herein, haemophilia remains at the forefront of the rapidly advancing clinical gene therapy field where there exists a shared expectation that transformational advances are on the horizon.
Impact of enzyme preparation and degree of hydrolysis on peptide profile and nitrogen solubility of sodium caseinate hydrolysates
Authors: Rajarathnam Ebenezer , Nongonierma Alice B. , O'Sullivan Dara , Flynn Cal , FitzGerald Richard J.
Published: July 2016

The solubility of casein ingredients is limited under certain pH conditions. Therefore, sodium caseinate (NaCN) was hydrolysed at laboratory scale with four enzyme preparations (Alcalase, Prolyve, FlavorPro Whey and pepsin) yielding hydrolysates having degree of hydrolysis (DH) values between 0.19 ± 0.11 and 19.25 ± 0.73%. The nitrogen solubility index (NSI) over the pH range 2.0–8.0 was affected by (i) the specificity of the enzyme preparation, (ii) the DH and (iii) the presence of unhydrolysed NaCN within the hydrolysate. The trends observed at laboratory scale (<5 L) were also seen with the semi‐pilot‐scale (300 L) hydrolysates generated with Alcalase and FlavorPro Whey. Removal of unhydrolysed NaCN from the FlavorPro Whey hydrolysate using a 5‐kDa ultrafiltration (UF) membrane increased NSI. This study has highlighted the importance of carefully selecting the proteolytic preparation along with the DH to design casein‐based ingredients with enhanced technofunctional properties.
Sofosbuvir plus simeprevir for the treatment of HCV genotype 4 patients with advanced fibrosis or compensated cirrhosis is highly efficacious in real life
Authors: Willemse S. B. , Baak L. C. , Kuiken S. D. , van der Sluys Veer A. , Lettinga K. D. , van der Meer J. T. M. , Depla A. C. T. M. , Tuynman H. , van Nieuwkerk C. M. J. , Schinkel C. J. , Kwa D. , Reesink H. W. , van der Valk M.
Published: July 2016

Chronic hepatitis C virus (HCV) infection is a major cause of chronic liver disease and liver‐related death. Recently, multiple regimens of different direct‐acting antiviral agents (DAAs) have been registered. Although treatment with sofosbuvir (SOF) and simeprevir (SMV) is registered for the treatment of genotype 4 patients in some countries, data on efficacy of this combination are lacking. We aimed to assess the efficacy of SOF and SMV with or without RBV during 12 weeks in a real‐life cohort of genotype 4 HCV patients. A retrospective multicentre observational study was conducted in 4 hospitals in Amsterdam, the Netherlands, including patients with advanced liver fibrosis or liver cirrhosis treated with SOF plus SMV with or without RBV during 12 weeks for a genotype 4 chronic HCV infection from 1 January 2015 to 1 August 2015. Sustained viral response (SVR) was established at week 12 after end of treatment. A total of 53 patients with genotype 4 HCV infection, treatment naïve and experienced, were included. SVR was achieved in 49 of 53 patients (92%). The four failures all had a virological relapse and did not receive ribavirin. Three were nonresponder to earlier interferon‐based treatment, and one was treatment naive. In this real‐life cohort of patients with HCV genotype 4 infection and advanced liver fibrosis/cirrhosis, we show that treatment with SOF and SMV is effective. The addition of RBV could be considered in treatment‐experienced patients as recommended in guidelines.
Anti‐envelope antibody responses in individuals at high risk of hepatitis C virus who resist infection
Authors: Swann R. E. , Mandalou P. , Robinson M. W. , Ow M. M. , Foung S. K. H. , McLauchlan J. , Patel A. H. , Cramp M. E.
Published: July 2016

Injection drug users uninfected by hepatitis C virus (HCV) despite likely repeated exposure through high‐risk behaviour are well documented. Factors preventing infection in these individuals are incompletely understood. Here, we looked for anti‐HCV‐envelope antibody responses in a cohort of repeatedly exposed but uninfected subjects. Forty‐two hepatitis C diagnostic antibody‐ and RNA‐negative injection drug users at high risk of exposure were studied and findings compared to healthy controls and cases with chronic HCV infection. Purified IgGs from sera were tested by ELISA for binding to genotype 1a and 3a envelope glycoproteins E1E2 with further testing for IgG and IgM reactivity against soluble E2. Virus‐neutralizing activity was assessed using an HCV pseudoparticle system. Uninfected subjects demonstrated significantly greater IgG and IgM reactivities to envelope glycoproteins than healthy controls with IgG from 6 individuals additionally showing significant neutralization. This study is the first to describe humoral immunological responses targeting the HCV envelope, important for viral neutralization, in exposed uninfected individuals. A subset of these cases also had evidence of viral neutralization via anti‐envelope antibodies. In addition to confirming viral exposure, the presence of specific anti‐envelope antibodies may be a factor that helps these individuals resist HCV infection.
A Pedagogical Model for Computational Linguistics across Curricular Boundaries
Authors: Alm Cecilia Ovesdotter , Womack Kathryn , Haake Anne , Engström Timothy
Published: July 2016

As techniques in computational linguistics become more widely used in scholarship and application in diverse fields, strategies for attracting students and practitioners to this area, for collaborating across disciplinary boundaries, as well as the pedagogical approaches to teaching it, will also shift. This pedagogical concept paper reports on an educational example providing a high‐level introduction of computational linguistics to students across curricular levels and disciplines. Specifically, it focuses on an interdisciplinary summer workshop in which the topic of computational natural language processing (NLP) was a key theme, illustrating the workshop's provision of exposure to computational linguistics for students in both technical and non‐technical majors. Including NLP modules as a major theme could bring together students from various backgrounds, encourage intellectual curiosity beyond their respective fields of study, and foster critical thinking about modeling practices and computational epistemologies. The interdisciplinary approach provided opportunities to reach out to emerging scholars and practitioners across fields, to expose them to NLP concepts, and to let them consider the benefits of considering natural language data in their own work or in future interdisciplinary collaborations.
Enhanced Memory as a Common Effect of Active Learning
Authors: Markant Douglas B. , Ruggeri Azzurra , Gureckis Todd M. , Xu Fei
Published: July 2016

Despite widespread consensus among educators thatactive learningleads to better outcomes than comparatively passive forms of instruction, it is often unclear why these benefits arise. In this article, we review research showing that the opportunity to control the information experienced while learning leads to improved memory relative to situations where control is absent. By integrating findings from a wide range of experimental paradigms, we identify a set of distinct mechanisms that mediate these effects, including the formation of distinctive sensorimotor associations, elaborative encoding due to goal‐directed exploration, improved co‐ordination of selective attention and encoding, adaptive selection of material based on existing memory, and metacognitive monitoring. Examining these mechanisms provides new insights into the effects of active learning, including how different forms of active control lead to improved outcomes relative to more traditional, passive instruction.
Recalling modernity: how nationalist memories shape religious diversity in Quebec and Catalonia
Authors: Burchardt Marian
Published: July 2016

In this article, I explore how nations without states, or ‘stateless nations’ respond to new forms of religious diversity. Drawing on the cases of Quebec and Catalonia, I do so by tracing the historical emergence of the cultural narratives that are mobilized to support institutional responses to diversity and the way they bear on contemporary controversies. The article builds on recent research and theorizations of religious diversity and secularism, which it expands and specifies by spelling out how pre‐existing cultural anxieties stemming from fears over national survival are stored in collective memories and, if successfully mobilized, feed into responses to migration‐driven religious diversification. I show that while Quebec and Catalonia were in many ways similarly positioned before the onset of powerful modernization processes and the resurgence of nationalism from the 1960s onwards, their responses to religious diversity differ dramatically.
Visions of Albion: ancient landscapes, Glastonbury and alternative forms of nationalism
Authors: Gemie Sharif
Published: July 2016

Nationalist visions are often connected with a cult of the land. This article considers some of the cultural‐nationalist ideas linked to the Somerset town of Glastonbury, a prominent New Age centre. It discusses the legacy of British pastoralism as shown in the work of H. V. Morton and Cecil Sharp. It considers the evolution of an English–Celtic tradition, drawing on the legacy of the Arthurian legend, but being re‐formulated in the late twentieth century as a vehicle for New Age conceptions of British society. The article concludes by evaluating the political values inherent in the New Age.
Can evolutionary constraints explain the rarity of nitrogen‐fixing trees in high‐latitude forests?
Authors: Menge Duncan N. L. , Crews Timothy E.
Published: July 2016

The rarity of symbiotic nitrogen (N)‐fixing trees in temperate and boreal (‘high‐latitude’) forests is curious. One explanation – the evolutionary constraints hypothesis – posits that high‐latitude N‐fixing trees are rare because few have evolved. Here, we consider traits necessary for high‐latitude N‐fixing trees. We then use recent developments in trait evolution to estimate that > 2000 and > 500 species could have evolved from low‐latitude N‐fixing trees and high‐latitude N‐fixing herbs, respectively. Evolution of N‐fixing from nonfixing trees is an unlikely source of diversity. Dispersal limitation seems unlikely to limit high‐latitude N‐fixer diversity. The greater number of N‐fixing species predicted to evolve than currently inhabit high‐latitude forests suggests a greater role for ecological than evolutionary constraints.

Contents

Summary
1195

I.
Introduction
1196

II.
The role of diversity
1196

III.
An evolutionary framework for the success of high‐latitude N‐fixing woody symbioses
1196

IV.
Conclusions
1200

Acknowledgements
1200

References
1200
Gap expansion in old‐growth subarctic forests: the climate–pathogen connection
Authors: Vézeau Corinne , Payette Serge
Published: July 2016

We tested the hypothesis considering old‐growth subarctic woodlands, free of fire, insect and stand‐scale blowdown disturbances, to be at equilibrium with the climate. To do so, we explored the status of Hudsonian woodlands based on the natality/mortality ratio.

The gap history of the woodland was reconstructed based on mapping and dating of dead gap‐spruces (Picea mariana). Among the 25 gaps studied, 763 dead trees and only 14 saplings were recorded. The center of some gaps remained treeless over the last 1000 yr, and gap area doubled over the last 100 yr. The status of the tree population is in a demographic disequilibrium caused by the small replacement of dead spruces in all of the gaps.

Episodes of ‘mass’ mortality occurred during several decades corresponding to years of favorable tree‐ring growth. The natural process of gap‐filling appears to be ineffective under current conditions. Good tree‐ring growth of dying trees suggests abundant precipitation during the mortality episodes, but precipitation appears to be involved indirectly in the mortality process.

The main cause of the widespread tree mortality during the last centuries of gap expansion appears to be biotic in origin. The impact of pathogenic fungal disease linked to late‐lying snow cover is proposed for the mortality events.
Effect of plant‐based diets on obesity‐related inflammatory profiles: a systematic review and meta‐analysis of intervention trials
Authors: Eichelmann F. , Schwingshackl L. , Fedirko V. , Aleksandrova K.
Published: July 2016

Plant‐based dietary interventions have been proposed to reduce obesity induced chronic low‐grade inflammation and hence prevent chronic disease risk; however, human evidence remains unclear. This systematic review and meta‐analysis of intervention trials aimed to assess the effect of plant‐based diets on obesity‐related inflammatory biomarker profiles. Medline, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for articles published until January 2016 and mean differences in biomarkers of inflammatory status were assessed for: C‐reactive protein (CRP), interleukin‐6 (IL‐6), tumour necrosis factor‐alpha (TNF‐ɑ), soluble intercellular adhesion molecule 1 (sICAM), leptin, adiponectin and resistin. Of initially identified 2,583 publications, 29 met the meta‐analysis inclusion criteria [a total of 2,689 participants]. Consumption of plant‐based diets was associated with a reduction in the mean concentrations of the following biomarkers: CRP [effect size, −0.55 mg/l, 95% confidence intervals (CI): −0.78; −0.32, I2 = 94.4%], IL‐6 [effect size, −0.25 ng/l, 95% CI: −0.56; 0.06, I2 = 74%], and, to some degree, sICAM (−25.07 ng/ml [95% CI: −52.32; 2.17, I2 = 93.2%]). No substantial effects were revealed for TNF‐ɑ, resistin, adiponectin and leptin. Plant‐based diets are associated with an improvement in obesity‐related inflammatory profiles and could provide means for therapy and prevention of chronic disease risk.
Political appointees in executive government: Exploring and explaining roles using a large‐N survey in Norway
Authors: Askim Jostein , Karlsen Rune , Kolltveit Kristoffer
Published: July 2016

Political appointees in executive government have received increased scholarly attention in recent years. However, few studies have covered non‐Westminster systems, and apart from classifications that systemize variation in assignments, theorizing about appointees has been limited. Using large‐N survey data, the article finds three distinct roles among political appointees in Norway: ‘stand in’, ‘media adviser’ and ‘political coordinator’. The article then combines insights from research on political appointees with insights from core executive studies (CES) to explain why political appointees perform one role or another. The empirical results support the notion that roles of appointees within the core executive depend on where they sit, supporting the asymmetric power model within CES. The results also show that appointees’ roles within the executive depend on their personal experience, supporting the notion of a resource exchange between ministers and their appointees in the mould of the resource‐dependency perspective within CES.
Inhibition of FGF Signalling Pathway Augments the Expression of Pluripotency and Trophoblast Lineage Marker Genes in Porcine Parthenogenetic Blastocyst
Authors: Li LY , Li MM , Yang SF , Zhang J , Li Z , Zhang H , Zhu L , Zhu X , Verma V , Liu Q , Shi D , Huang B
Published: July 2016

Contents

The consistent failure to isolate bona fide pluripotent cell lines from livestock indicates that the underlying mechanisms of early lineage specification are poorly defined. Unlike other species, the contrivances of segregation have been comprehensively studied in the mouse. In mouse, FGF/MAPK signalling pathway dictates the segregation of hypoblast (primitive endoderm). However, it is not evident whether this mechanism is also conserved in livestock. Here, in this study, we examined the roles of FGF/MAP kinase signalling pathways in porcine parthenogenetic embryos during the early development. Porcine parthenogenetic embryos were cultured in the medium addition with FGFR inhibitor BGJ398 (10 μm) or DEMOS. Pluripotency‐ and lineage‐related gene expressions in the early porcine embryos were determined. Compared to control, total cell numbers on day 7 were significantly higher (55 ± 5.96 vs 47 ± 1.97, p < 0.05) in embryos cultured in the presence of BGJ398, but had no significant effect on the rate of blastocyst development (47% vs 44%, p > 0.05). Nonetheless, BGJ398 treatment significantly augmented the expression of pluripotency and trophoblast marker genes (SOX2, OCT4, KLF4 and CDX2), but did not significantly change the expression of NANOG and hypoblast marker gene (GATA4). Furthermore, the addition of FGF signalling agonist (FGF2) during the embryo development significantly decreased the expression of pluripotency and trophoblast marker genes (SOX2, NANOG, KLF4 and CDX2), but no significant effect on the expression of OCT4 and GATA4 was observed. Here, we exhibit that inhibition of FGF signalling could improve the quality of the porcine embryo and escalate the chance to capture pluripotency. Besides, it also promotes the trophoblast development of porcine parthenogenetic embryo. In addition, the data suggested that FGF signalling pathway is dispensable for the segregation of hypoblast and epiblast lineages in porcine embryo during the early development.
Recognition criteria, characteristics and implications of the fluvial to marine transition zone in ancient deltaic deposits (Lajas Formation, Argentina)
Authors: Gugliotta Marcello , Flint Stephen S. , Hodgson David M. , Veiga Gonzalo D.
Published: July 2016

The seaward end of modern rivers is characterized by the interactions of marine and fluvial processes, a tract known as the fluvial to marine transition zone, which varies between systems due to the relative strength of these processes. To understand how fluvial and tidal process interactions and the fluvial to marine transition zone are preserved in the rock record, large‐scale outcrops of deltaic deposits of the Middle Jurassic Lajas Formation (Neuquén Basin, Argentina) have been investigated. Fluvial–tidal indicators consist of cyclically distributed carbonaceous drapes in unidirectional, seaward‐oriented cross‐stratifications, which are interpreted as the result of tidal modulation of the fluvial current in the inner part of the fluvial to marine transition zone. Heterolithic deposits with decimetre‐scale interbedding of coarser‐grained and finer‐grained facies with mixed fluvial and tidal affinities are interpreted to indicate fluvial discharge fluctuations (seasonality) and subordinate tidal influence. Many other potential tidal indicators are argued to be the result of fluvial–tidal interactions with overall fluvial dominance or of purely fluvial processes. No purely tidal or tide‐dominated facies were recognized in the studied deposits. Moreover, fluvial–tidal features are found mainly in deposits interpreted as interflood (forming during low river stage) in distal (delta front) or off‐axis (interdistributary) parts of the system. Along major channel axes, the interpreted fluvial to marine transition zone is mainly represented by the fluvial‐dominated section, whereas little or no tide‐dominated section is identified. The system is interpreted to have been hyposynchronous with a poorly developed turbidity maximum. These conditions and the architectural elements described, including major and minor distributary channels, terminal distributary channels, mouth bars and crevasse mouth bars, are consistent with an interpretation of a fluvial‐dominated, tide‐influenced delta system and with an estimated short backwater length and inferred microtidal conditions. The improved identification of process interactions, and their preservation in ancient fluvial to marine transition zones, is fundamental to refining interpretations of ancient deltaic successions.
Recognition of a novel HLA‐A*11 variant, HLA‐A*11:196, in a Taiwanese unrelated bone marrow stem cell donor
Authors: Yang K.L. , Hung J.H. , Lin P.Y.
Published: July 2016

One nucleotide substitution at residue 484 of HLA‐A*11:01:01:01 results in a novel allele, HLA‐A*11:196.
Double red blood cell collection: comparison of three apheresis systems
Authors: Burgstaler Edwin A. , Duffy Kimberly J. , Gandhi Manish J.
Published: July 2016

BACKGROUND

We compared three instruments for double red blood cell (DRBC) collection to efficiently optimize our RBC inventory.

STUDY DESIGN AND METHODS

Instruments compared were the TerumoBCT Trima Accel (Trima), the Fenwal Alyx (Alyx), and the Haemonetics MCS+ 8150 (MCS+). Forty consecutive collections (80 products) per instrument were evaluated for hemoglobin (Hb) content, leukoreduction, collection time, instrument efficiency, donor acceptance, and reactions. The total number of whole blood donors who could be eligible for DRBC collection was analyzed. All collections were as per the manufacturer recommendations with target volume of 360 or 400mL. Leukoreduction was integral to the collection procedure for the Alyx and Trima, while it was a separate process for the MCS+.

RESULTS

The total numbers of whole blood donors who could be eligible for DRBC collection were 10,116 for the MCS+, 9378 for the Alyx, and 8573 for the Trima. All units collected had more than 42.5 g of Hb. Mean Hb levels were as follows: Trima, 59.2 g; Alyx, 56.8 g; and MCS+, 51.5 g. Donor times for the Trima, Alyx, and MCS+ were 52, 45, and 52 minutes, respectively. Technician times for the Trima, Alyx, and MCS+ (without filtration) were 87, 73, and 64 minutes. All collected products had fewer than 5 × 106 white blood cells.

CONCLUSIONS

All three instruments would be capable of collecting an acceptable leukoreduced DRBC product. The Alyx was most portable, with the shortest donor time and total technician time (considering filtration time) and highest collection efficiency and would collect from more donors than the Trima. We thus chose the Alyx as it best fits the specific needs of our center.
Does therapeutic plasma exchange have a role in the treatment of prosthetic hip–associated cobalt toxicity? A case report and literature review
Authors: Grant Michelle L. , Karp Julie K. , Palladino Michele , Le Nguyet , Hall Nancy , Herman Jay H.
Published: July 2016

BACKGROUND

Prosthetic hip–associated cobalt toxicity (PHACT) is an uncommon, but potentially devastating, complication for patients with metal‐on‐metal hip implants (MoMs). Clinical management of PHACT is poorly defined, with primary intervention being MoM explant followed by chelation therapy. Therapeutic plasma exchange (TPE) in cobalt toxicity has not been previously described. Given that cobalt is predominantly albumin bound, it should theoretically be removed by TPE. Here we report a case of PHACT and our experience using TPE to lower plasma cobalt levels.

CASE REPORT

A 61‐year‐old woman developed deafness, blindness, ambulatory dysfunction, and endocrinopathies after MoM implant. Cobalt levels on admission were greater than 1500 µg/L. In an attempt to rapidly lower cobalt levels before MoM explant, hemodialysis and TPE were performed. Hemodialysis removed negligible amounts of cobalt. One session of TPE temporarily removed approximately two‐thirds of measurable cobalt, but levels rebounded to pre‐TPE values after 8 hours. It was only after MoM removal that cobalt levels plateaued below 300 µg/L and clinical symptoms improved.

DISCUSSION

TPE removed cobalt from a PHACT patient, but a durable decrease in cobalt was only achieved after MoM explant. These findings are comparable to reports where chelation was employed in PHACT patients before MoM explant. The observed rebound phenomenon is likely from rapid equilibration between the immense extravascular tissue source (the MoM) and the intravascular compartment.

CONCLUSION

TPE may serve as adjunctive therapy for PHACT patients whose cobalt levels remain high after explant, especially in patients with renal failure, in whom chelation is contraindicated.
Identifying Uncertainty in Laser Powder Bed Fusion Additive Manufacturing Models
Authors: Lopez Felipe , Witherell Paul , Lane Brandon
Published: July 2016

As additive manufacturing (AM) matures, models are beginning to take a more prominent stage in design and process planning. A limitation frequently encountered in AM models is a lack of indication about their precision and accuracy. Often overlooked, model uncertainty is required for validation of AM models, qualification of AM-produced parts, and uncertainty management. This paper presents a discussion on the origin and propagation of uncertainty in laser powder bed fusion (L-PBF) models. Four sources of uncertainty are identified: modeling assumptions, unknown simulation parameters, numerical approximations, and measurement error in calibration data. Techniques to quantify uncertainty in each source are presented briefly, along with estimation algorithms to diminish prediction uncertainty with the incorporation of online measurements. The methods are illustrated with a case study based on a thermal model designed for melt pool width predictions. Model uncertainty is quantified for single track experiments, and the effect of online estimation in overhanging structures is studied via simulation.
Reliability Analysis in the Presence of Aleatory and Epistemic Uncertainties, Application to the Prediction of a Launch Vehicle Fallout Zone
Authors: Brevault Loïc , Lacaze Sylvain , Balesdent Mathieu , Missoum Samy
Published: July 2016

The design of complex systems often requires reliability assessments involving a large number of uncertainties and low probability of failure estimations (in the order of 10−4). Estimating such rare event probabilities with crude Monte Carlo (CMC) is computationally intractable. Specific numerical methods to reduce the computational cost and the variance estimate have been developed such as importance sampling or subset simulation. However, these methods assume that the uncertainties are defined within the probability formalism. Regarding epistemic uncertainties, the interval formalism is particularly adapted when only their definition domain is known. In this paper, a method is derived to assess the reliability of a system with uncertainties described by both probability and interval frameworks. It allows one to determine the bounds of the failure probability and involves a sequential approach using subset simulation, kriging, and an optimization process. To reduce the simulation cost, a refinement strategy of the surrogate model is proposed taking into account the presence of both aleatory and epistemic uncertainties. The method is compared to existing approaches on an analytical example as well as on a launch vehicle fallout zone estimation problem.
The Effects of Gender and Idea Goodness on Ownership Bias in Engineering Design Education
Authors: Toh Christine A. , Strohmetz Andrew A. , Miller Scarlett R.
Published: July 2016

Concept selection is a critical stage of the engineering design process because of its potential to influence the direction of the final design. While formalized selection methods have been developed to increase its effectiveness and reduce human decision-making biases, research that understands these biases in more detail can provide a foundation for improving the selection process. One important bias that occurs during this process is ownership bias or an unintentional preference for an individual's own ideas over the ideas of others. However, few studies have explored ownership bias in a design setting and the influence of other factors such as the gender of the designer or the “goodness” of an idea. In order to understand the impact of these factors in engineering design education, a study was conducted with 110 engineering students. The results from this study show that male students tend to show ownership bias during concept selection by selecting more of their own ideas while female students tend to show the opposite bias, the Halo Effect, by selecting more of their team members' concepts. In addition, participants exhibited ownership bias for ideas that were considered good or high quality, but the opposite bias for ideas that were not considered good or high quality. These results add to our understanding of the factors that impact team concept selection and provide empirical evidence of the occurrence of ownership bias and the effects of gender and idea goodness in engineering design education.
Propagation of Modeling Uncertainty by Polynomial Chaos Expansion in Multidisciplinary Analysis
Authors: Dubreuil S. , Bartoli N. , Gogu C. , Lefebvre T.
Published: July 2016

Multidisciplinary analysis (MDA) is nowadays a powerful tool for analysis and optimization of complex systems. The present study is interested in the case where MDA involves feedback loops between disciplines (i.e., the output of a discipline is the input of another and vice versa). When the models for each discipline involve non-negligible modeling uncertainties, it is important to be able to efficiently propagate these uncertainties to the outputs of the MDA. The present study introduces a polynomial chaos expansion (PCE)-based approach to propagate modeling uncertainties in MDA. It is assumed that the response of each disciplinary solver is affected by an uncertainty modeled by a random field over the design and coupling variables space. A semi-intrusive PCE formulation of the problem is proposed to solve the corresponding nonlinear stochastic system. Application of the proposed method emphasizes an important particular case in which each disciplinary solver is replaced by a surrogate model (e.g., kriging). Three application problems are treated, which show that the proposed approach can approximate arbitrary (non-Gaussian) distributions very well at significantly reduced computational cost.
Extension Effects in Compliant Joints and Pseudo-Rigid-Body Models
Authors: Venkiteswaran Venkatasubramanian Kalpathy , Su Hai-Jun
Published: July 2016

Compliant members come in a variety of shapes and sizes. While thin beam flexures are commonly used in this field, they can be replaced by soft members with lower aspect ratio. This paper looks to study the behavior of such elements by analyzing them from the view of beam theory for 2D cases. A modified version of the Timoshenko beam theory is presented which incorporates extension and Poisson's effects. The utility and validity of the new approach are demonstrated by comparing against Euler–Bernoulli beam theory, Timoshenko beam theory, and finite-element analysis (FEA). The results from this are then used to study the performance of pseudo-rigid-body models (PRBMs) for the analysis of low aspect ratio soft compliant joints for 2D quasi-static applications. A parallel-guiding mechanism comprised of similar compliant elements is analyzed using the new results to validate the contribution of this work.
Robustness Metrics: Consolidating the Multiple Approaches to Quantify Robustness
Authors: Moritz Göhler Simon , Eifler Tobias , Howard Thomas J.
Published: July 2016

The robustness of a design has a major influence on how much the product's performance will vary and is of great concern to design, quality, and production engineers. While variability is always central to the definition of robustness, the concept does contain ambiguity, and although subtle, this ambiguity can have significant influence on the strategies used to combat variability, the way it is quantified and ultimately, the quality of the final design. In this contribution, the literature for robustness metrics was systematically reviewed. From the 108 relevant publications found, 38 metrics were determined to be conceptually different from one another. The metrics were classified by their meaning and interpretation based on the types of the information necessary to calculate the metrics. Four different classes were identified: (1) sensitivity robustness metrics; (2) size of feasible design space robustness metrics; (3) functional expectancy and dispersion robustness metrics; and (4) probability of compliance robustness metrics. The goal was to give a comprehensive overview of robustness metrics and guidance to scholars and practitioners to understand the different types of robustness metrics and to remove the ambiguities of the term robustness. By applying an exemplar metric from each class to a case study, the differences between the classes were further highlighted. These classes form the basis for the definition of four specific subdefinitions of robustness, namely the “robust concept,” “robust design,” “robust function,” and “robust product.”
Predicting binaural speech intelligibility using the signal-to-noise ratio in the envelope power spectrum domain
Authors: Chabot-Leclerc Alexandre , MacDonald Ewen N. , Dau Torsten
Published: July 2016

This study proposes a binaural extension to the multi-resolution speech-based envelope power spectrum model (mr-sEPSM) [Jørgensen, Ewert, and Dau (2013). J. Acoust. Soc. Am. 134, 436–446]. It consists of a combination of better-ear (BE) and binaural unmasking processes, implemented as two monaural realizations of the mr-sEPSM combined with a short-term equalization-cancellation process, and uses the signal-to-noise ratio in the envelope domain (SNRenv) as the decision metric. The model requires only two parameters to be fitted per speech material and does not require an explicit frequency weighting. The model was validated against three data sets from the literature, which covered the following effects: the number of maskers, the masker types [speech-shaped noise (SSN), speech-modulated SSN, babble, and reversed speech], the masker(s) azimuths, reverberation on the target and masker, and the interaural time difference of the target and masker. The Pearson correlation coefficient between the simulated speech reception thresholds and the data across all experiments was 0.91. A model version that considered only BE processing performed similarly (correlation coefficient of 0.86) to the complete model, suggesting that BE processing could be considered sufficient to predict intelligibility in most realistic conditions.