bluuebunny/crossref_metadata_2025 huggingface dataset:
Lesinurad, a Selective Uric Acid Reabsorption Inhibitor, in Combination With Febuxostat in Patients With Tophaceous Gout: Findings of a Phase III Clinical Trial
Authors: Dalbeth Nicola , Jones Graeme , Terkeltaub Robert , Khanna Dinesh , Kopicko Jeff , Bhakta Nihar , Adler Scott , Fung Maple , Storgard Chris , Baumgartner Scott , Perez‐Ruiz Fernando
Published: June 2017

Objective

To investigate the efficacy and safety of lesinurad in combination with febuxostat in a 12‐month phase III trial in patients with tophaceous gout.

Methods

Patients with serum urate (UA) ≥8.0 mg/dl (≥6.0 mg/dl with urate‐lowering therapy) and ≥1 measurable target tophus were given febuxostat 80 mg/day for 3 weeks before randomization to receive lesinurad (200 or 400 mg daily) or placebo in addition to the febuxostat. The primary end point was the proportion of patients achieving a serum UA level of <5.0 mg/dl (month 6). The key secondary end point was the proportion of patients with complete resolution of ≥1 target tophus (month 12). Other end points included the percentage change in total target tophi area. Safety assessments included adverse events and laboratory data.

Results

Patients (n = 324) were predominantly male, with a mean age of 54.1 years. Significantly more patients achieved the serum UA target by month 6 with the addition of lesinurad 400 mg (76.1%; P < 0.0001), but not 200 mg (56.6%; P = 0.13), to the febuxostat therapy as compared with febuxostat alone (46.8%). At all other time points, significantly more patients in the lesinurad 200 mg group achieved the serum UA target. The number of patients with complete tophus resolution was not different between groups. Treatment with lesinurad (200 mg and 400 mg) plus febuxostat reduced the total target tophi area as compared with febuxostat alone (50.1% and 52.9% versus 28.3%, respectively; P < 0.05). Safety was generally comparable with that of febuxostat alone, except for higher rates of predominantly reversible elevations in the serum creatinine level, particularly with lesinurad 400 mg.

Conclusion

Treatment with lesinurad in combination with febuxostat demonstrated superior lowering of serum UA levels as compared with febuxostat alone, with clinically relevant added effects on tophi and an acceptable safety profile with lesinurad 200 mg in patients with tophaceous gout warranting additional therapy.
Boundary objects in information science
Authors: Huvila Isto , Anderson Theresa Dirndorfer , Jansen Eva Hourihan , McKenzie Pam , Worrall Adam
Published: June 2017

Boundary objects (BOs) are abstract or physical artifacts that exist in the liminal spaces between adjacent communities of people. The theory of BOs was originally introduced by Star and Griesemer in a study on information practices at the Berkeley Museum of Vertebrate Zoology but has since been adapted in a broad range of research contexts in a large number of disciplines including the various branches of information science. The aim of this review article is to present an overview of the state‐of‐the‐art of information science research informed by the theory of BOs, critically discuss the notion, and propose a structured overview of how the notion has been applied in the study of information.
Doing the Research that Informs Practice: A Retrospective View of One Group's Attempt to Study The Teaching and Learning of Organic Chemistry
Authors: Bodner George M. , Ferguson Rob , Çalimsiz Selçuk
Published: June 2017

The idea that the focus of educational research should be on results that can inform the practice of teaching has been an implicit assumption for so many years that one would be hard‐pressed to trace it back to an individual source. At one time, the people doing such research in STEM disciplines were faculty in schools or colleges of education who focused on K‐12 classrooms and looked for ideas, concepts, and principles that would be valid across a range of STEM disciplines. Eventually, this research was done on college‐ or university‐level students, as well, and there was a shift toward what has been called discipline‐based educational research (DBER) that looks at the problems associated with the teaching and learning of a given discipline, such as chemistry. This paper will discuss the results of research on problem‐solving in chemistry that has been done in our research group, with particular emphasis on the challenges of teaching and learning organic chemistry. The goal of this paper is to show what can happen when one listens carefully to students and begins to appreciate the difference between what we think we have taught and what the students learned. The examples we will use have the potential for convincing those of us who teach chemistry to rethink what we do in our classes to find better ways of helping our students understand the material we are trying to teach. Although this paper will focus on results from the second‐year organic chemistry course, similar results have been observed in both inorganic and physical chemistry, as well as biochemistry courses.
Synchronization of Uncertain Complex Networks with Time‐Varying Node Delay and Multiple Time‐Varying Coupling Delays
Authors: Zhang Chuan , Wang Xingyuan , Wang Chunpeng , Zhou Wenjie
Published: June 2017

This paper investigates the synchronization problem of a class of complex dynamical networks via an adaptive control method. It differs from existing works in considering intrinsic delay and multiple different time‐varying coupling delays, and uncertain couplings. A simple approach is used to linearize the uncertainties with the norm‐bounded condition. Simple but suitable adaptive controllers are designed to drive all nodes of the complex network locally and globally synchronize to a desired state. In addition, several synchronization protocols are deduced in detail by virtue of Lyapunov stability theory and a Cauchy matrix inequality. Finally, a simulation example is presented, in which the dynamics of each node are time‐varying delayed Chua chaotic systems, to demonstrate the effectiveness of the proposed adaptive method.
Robust Stochastic Stability and Control for Uncertain Singular Markovian Jump Systems with Multiplicative Noise
Authors: Zhao Yong , Zhang Weihai , Xia Jianwei , Zhang Tianliang
Published: June 2017

This paper focuses on the problems of robust stability and stabilization and robust
control for uncertain singular Markovian jump systems with (x,v)‐dependent noise. The parameter uncertainties appearing in state, input, disturbance as well as diffusion terms are assumed to be time‐varying but norm‐bounded. Based on the approach of generalized quadratic stability, the memoryless state feedback controller is designed for the robust stabilization problem, which ensures that the resulting closed‐loop system has an impulse‐free solution and is asymptotically stable in the mean square. Furthermore, the results of robust
control problem are derived. The desired state feedback
controller is presented, which not only meets the requirement of robust stabilization but also satisfies a prescribed
performance level. The obtained results are formulated in terms of strict LMIs. What we have obtained can be viewed as corresponding extensions of existing results on uncertain singular systems. A numerical example is finally given to demonstrate the application of the proposed method.
Constrained Nonlinear‐Based Optimisation Applied to Fuzzy PID Controllers Tuning
Authors: Gil Paulo , Sebastião Ana , Lucena Catarina
Published: June 2017

This paper aims at studying the optimal Fuzzy Proportional–Integral– Derivative controllers' tuning problem by considering two different nonlinear constrained optimisation techniques. One relying on a Hessian‐based analytical approach, and the other based on a differential evolutionary method. In the case of offline implementation, two basic frameworks are under assessment, depending on the controller parameters to be adjusted. For online scaling factors and membership functions' width tuning, its implementation is based on the parallel computation paradigm. The performance index is described by a quadratic cost function, taking as arguments control errors and the increment of control actions. Constraints on the scaling factors, membership functions' width, as well as on the system inputs and outputs are also included in the optimisation problem. Experiments carried out on a benchmark system favour the offline joint optimisation based on the differential evolutionary approach of scaling factors and membership functions' width.
Boundary Control for a Vibrating String System with Bounded Input
Authors: Zhao Zhijia , Liu Yu , Luo Fei
Published: June 2017

In this study, we deal with the control problem of a vibrating string system under the condition of restricted input and external disturbance. The major objectives are the development of a boundary vibration control scheme for globally stabilizing the string system and simultaneously for compensating the effect of the input saturation, and the design of a disturbance observer for tracking the external disturbance. To this end, a boundary control is proposed based on smooth hyperbolic function to suppress the vibration and eliminate the input restriction effect, and a disturbance observer is employed to mitigate the external disturbance. The asymptotic stability of the controlled system is demonstrated employing the extended LaSalle's invariance principle. In order to verify the control performance of the proposed control, simulation results are presented by the choice of proper control design parameters.
A simple cell transport device keeps culture alive and functional during shipping
Authors: Miller Paula G. , Wang Ying I. , Swan Glen , Shuler Michael L.
Published: June 2017

Transporting living complex cellular constructs through the mail while retaining their full viability and functionality is challenging. During this process, cells often suffer from exposure to suboptimal life‐sustaining conditions (e.g. temperature, pH), as well as damage due to shear stress. We have developed a transport device for shipping intact cell/tissue constructs from one facility to another that overcomes these obstacles. Our transport device maintained three different cell lines (Caco2, A549, and HepG2 C3A) individually on transwell membranes with high viability (above 97%) for 48 h under simulated shipping conditions without an incubator. The device was also tested by actual overnight shipping of blood brain barrier constructs consisting of human induced pluripotent brain microvascular endothelial cells and rat astrocytes on transwell membranes to a remote facility (approximately 1200 miles away). The blood brain barrier constructs arrived with high cell viability and were able to regain full barrier integrity after equilibrating in the incubator for 24 h; this was assessed by the presence of continuous tight junction networks and in vivo‐like values for trans‐endothelial electrical resistance (TEER). These results demonstrated that our cell transport device could be a useful tool for long‐distance transport of membrane‐bound cell cultures and functional tissue constructs. Studies that involve various cell and tissue constructs, such as the “Multi‐Organ‐on‐Chip” devices (where multiple microscale tissue constructs are integrated on a single microfluidic device) and studies that involve microenvironments where multiple tissue interactions are of interest, would benefit from the ability to transport or receive these constructs. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:1257–1266, 2017
Hepatotoxicity after high‐dose intravenous methylprednisolone in multiple sclerosis patients
Authors: Hidalgo de la Cruz Milagros , Miranda Acuña Jahir Andrés , Lozano Ros Alberto , Vega Catalina María , Salinero Paniagua Emilio , Clemente Ricote Gerardo , De Andrés Frutos Clara Dionisia , Martínez Ginés María Luisa
Published: June 2017

Key Clinical Message

Hepatotoxicity is a rare adverse event of methylprednisolone that should be considered in clinical practice. In patients at risk, we propose liver function surveillance, by measuring hepatic enzymes concentration 15–30 days after methylprednisolone administration. Additionally, we propose ACTH, dexamethasone, or plasma exchange as alternate treatment options for these patients.
Hydrogen‐Economic Synthesis of Gasoline‐like Hydrocarbons by Catalytic Hydrodecarboxylation of the Biomass‐derived Angelica Lactone Dimer
Authors: Chang Fei , Dutta Saikat , Mascal Mark
Published: June 2017

The biomass‐derived platform molecule levulinic acid is converted into the angelica lactone dimer (ALD) in high overall yield using simple inorganic catalysts. Hydrodecarboxylation of ALD using a Pd/γ‐Al2O3 catalyst under moderate hydrogen gas pressure at high temperatures generates branched C8–C9 hydrocarbons in nearly quantitative yield consuming as little as a single equivalent of external hydrogen. These molecules are high‐octane “drop‐in” equivalents of isoalkanes used in commercial gasoline. Catalytic hydrodecarboxylation is presented as a highly effective means to reduce hydrogen demand in biomass‐to‐biofuel conversion technologies.
Autotransporter‐Based Surface Display of Hemicellulases on Pseudomonas putida: Whole‐Cell Biocatalysts for the Degradation of Biomass
Authors: Schulte Marten F. , Tozakidis Iasson E. P. , Jose Joachim
Published: June 2017

The enzymatic depolymerization of xylans into their monomeric sugars by hemicellulases is of great interest from both the ecological and the economical point of view; however, the high costs of these enzymes impede their employment on industrial scales. The utilization of whole cells displaying the enzymes on their surface could reduce costs by allowing a direct employment of the cells after cultivation and their reuse in multiple reaction cycles. Here, we present the surface display of an endo‐1,4‐β‐xylanase (XynA), a 1,4‐β‐xylosidase (XynB), and two α‐l‐arabinofuranosidases (Abf2 and AbfCelf) in the gram‐negative soil bacterium Pseudomonas putida KT2440 by fusing the enzymes to the EhaA autotransporter unit from Escherichia coli. The surface display of the enzymes was verified by flow cytometry. All four enzymes retained their functionality with hydrolytic activities of 48.5 mU mL−1 for XynA towards beechwood xylan, 6 mU mL−1 for XynB towards 4‐nitrophenyl‐β‐d‐xylopyranoside, and 8.6 mU mL−1 and 6.2 mU mL−1 for the two α‐l‐arabinofuranosidases Abf2 and AbfCelf towards 4‐nitrophenyl‐α‐l‐arabinofuranoside, respectively. Measurements were done with cell suspensions of an OD578=1. A mixture of strains displaying the three types of hemicellulases could degrade 2.5 % (w/v) raw arabinoxylan from rye bran to d‐xylose with a yield of 133.5 mg L−1 cell suspension after 24 h.
Experiences of Counselors‐as‐Clients in Counselor Education
Authors: Osborn Cynthia J. , West Erin M. , Nance William Z.
Published: June 2017

Eight professional counselors who routinely role‐play as clients in 1 counselor education program participated in a focus group investigating their portrayal experiences. Data were analyzed using interpretative phenomenological analysis, which resulted in 3 superordinate themes: missions, influential factors, and repercussions. Findings reinforce instruction of idiographic and person‐centered care in counselor education.
Experimental and Numerical Study of Grinding Media Flow in a Ball Mill
Authors: Machado Marcela V. C. , Santos Dyrney A. , Barrozo Marcos A. S. , Duarte Claudio R.
Published: June 2017

An experimental and numerical study on the grinding media dynamics inside a baffled ball mill under different solid‐flow regimes, namely, cascading, cataracting, and centrifuging, is described. The Eulerian approach was used for all simulations and the boundary condition at the drum wall was investigated by means of the specularity coefficient parameter. This effort is an important approach in representing the particle‐wall interaction in a ball mill. The restitution coefficient of the balls was experimentally measured using a video camera, and its influence was evaluated by comparing the numerical and experimental outcome of flow patterns. The simulations results proved that the specularity and restitution coefficients effects at the drum wall were more evident at high rotational speeds.
Vortex Fluidic Chemical Transformations
Authors: Britton Joshua , Stubbs Keith A. , Weiss Gregory A. , Raston Colin L.
Published: June 2017

Driving chemical transformations in dynamic thin films represents a rapidly thriving and diversifying research area. Dynamic thin films provide a number of benefits including large surface areas, high shearing rates, rapid heat and mass transfer, micromixing and fluidic pressure waves. Combinations of these effects provide an avant‐garde style of conducting chemical reactions with surprising and unusual outcomes. The vortex fluidic device (VFD) has proved its capabilities in accelerating and increasing the efficiencies of numerous organic, materials and biochemical reactions. This Minireview surveys transformations that have benefited from VFD‐mediated processing, and identifies concepts driving the effectiveness of vortex‐based dynamic thin films.
Alkali Metal Chlorine and Bromine Carbenoids: Their Thermal Stability and Structural Properties
Authors: Molitor Sebastian , Gessner Viktoria H.
Published: June 2017

The synthesis and structures of a series of M/X carbenoids of the type [Ph2P(S)]2CMX with M=Li, Na, and K and X=Cl and Br are reported, amongst the first isolated Na/Br and K/Br carbenoids. NMR spectroscopic as well as crystallographic studies showed distinct differences between the lithium carbenoids and their heavier congeners. In the solid state, all carbenoids showed no direct metal–carbon interaction, but an interaction between the metal and the halogen atom. This contact is only very weak in the case of the Li/Br carbenoid, but much more pronounced in the corresponding potassium and sodium compounds. Nevertheless, these interactions did not significantly influence the stability of the carbenoids by weakening the C−X bond and facilitating the MX elimination. As such all compounds were found to be stable up to approximately 60 °C in solution. Hence, M−X interactions—albeit being an essential feature for the structure formation of carbenoids—are not the only criterion determining the stability of such compounds. In the present systems, the stabilization by the thiophosphinoyl moieties is more important than the metal/halogen combination.
New Approach to 1,4‐Benzoxazin‐3‐ones by Electrochemical C−H Amination
Authors: Wesenberg Lars Julian , Herold Sebastian , Shimizu Akihiro , Yoshida Jun‐ichi , Waldvogel Siegfried R.
Published: June 2017

1,4‐Benzoxazin‐3‐ones are important structural motifs in natural products and bioactive compounds. Usually, the synthesis of benzoxazinones requires transition‐metal catalysts and pre‐functionalized substrates such as aryl halides. However, the anodic C−H amination of phenoxy acetates offers a very efficient and sustainable access to these heterocycles. The presented electrochemical protocol can be applied to a broad scope of alkylated substrates. Even tert‐butyl moieties or halogen substituents are compatible with this versatile method.
Tuning the Reactivity of Functionalized Diallylic Alcohols: Brønsted versus Lewis Acid Catalysis
Authors: Lempenauer Luisa , Duñach Elisabet , Lemière Gilles
Published: June 2017

The chemodivergent reactivity of bifunctional, enol thioether‐containing diallylic alcohols in acidic medium is disclosed, highlighting the difference between strong Lewis acid and mild Brønsted acid catalysis. In the presence of bismuth(III) triflate, allylic alcohol activation affords diversely substituted cyclopentenones in a Nazarov‐type electrocyclization, whereas activation of the thioenol ether by p‐toluenesulfonic acid provides an entry to α‐sulfenylated β,γ‐unsaturated ketones. Both methods represent a facile access to the corresponding products under mild conditions, using inexpensive and non‐toxic catalytic systems.
Kreativität und Chemie?
Authors: Bliersbach Markus , Reiners Christiane S.
Published: June 2017

Kreativität beschreibt das in jedem Menschen innewohnende Potenzial, mithilfe von verschiedenen metakognitiven Strategien, die vor allem auf dem Ausbrechen aus bekannten Strukturen und der Rekombination von Wissen beruhen, etwas für dessen jeweiliges Umfeld gleichsam Neues und Relevantes zu erschaffen. In der Chemie ist man vor allem beim Generieren von Forschungsfragen, bei der Hypothesenbildung, dem Planen von experimentellen Untersuchungen, dem Entwickeln von Theorien und Modellen und bei der Präsentation von Forschungsergebnissen auf Kreativität angewiesen. Jacobus Henricus van 't Hoff, der sich schon Ende des 19. Jahrhunderts mit der Rolle der Phantasie in der Wissenschaft beschäftigte, sowie Stefan Hell, der verschiedenen Widrigkeiten zum Trotz ein seit über 100 Jahren als unabänderlich geltendes wissenschaftliches Postulat umstieß, stellen Beispiele dar, die die Bedeutung von Kreativität in der Chemie verdeutlichen können.
Socioeconomic status and the development of atrial fibrillation in Hispanics, African Americans and non‐Hispanic whites
Authors: Shulman Eric , Kargoli Faraj , Aagaard Philip , Hoch Ethan , Di Biase Luigi , Fisher John , Gross Jay , Kim Soo , Ferrick Kevin J. , Krumerman Andrew
Published: June 2017

Background

Atrial fibrillation (AF) is the most common arrhythmia and is associated with significant morbidity and mortality. Despite having a higher burden of traditional AF risk factors, African American and Hispanic minorities have a lower incidence of AF when compared to non‐Hispanic whites, referred to as the “racial paradox.”

Hypothesis

Lower SES among Hispanics and African Americans may help to explain the lower incidence rates of AF compared to non‐Hispanic whites.

Methods

An electrocardiogram/electronic medical records database in New York State was interrogated for individuals free of AF for development of subsequent AF from 2000 to 2013. SES was assessed per zip code via a composite of 6 measures Z‐scored to the New York State average. SES was reclassified into decile groups. Cox regression analysis controlling for all baseline differences was used to estimate the independent predictive ability of SES for AF.

Results

We identified 48 631 persons (43% Hispanic, 37% African Americans, and 20% non‐Hispanic white; mean age 59 years; mean follow‐up of 3.2 years) of which 4556 AF cases occurred. Hispanics and African Americans had lower AF risk than whites in all SES deciles (P < 0.001 by log‐rank test). Higher SES was borderline associated with lower AF risk (hazard ratio: 0.990, 95% confidence interval: 0.980‐1.001, P = 0.061). P trend analysis was not significant by any race/ethnic group by SES deciles for AF.

Conclusions

Our study suggests that non‐Hispanic whites were at higher risk for AF compared to nonwhites, and this was independent of SES.
Relative efficacy and safety of ticagelor vs clopidogrel as a function of time to invasive management in non–ST‐segment elevation acute coronary syndrome in the PLATO trial
Authors: Pollack Charles V. , Davoudi Farideh , Diercks Deborah B. , Becker Richard C. , James Stefan K. , Lim Soo Teik , Schulte Phillip J. , Spinar Jindrich , Steg Philippe Gabriel , Storey Robert F. , Himmelmann Anders , Wallentin Lars , Cannon Christopher P. ,   on behalf of the PLATO Investigators
Published: June 2017

Background

Guidelines suggest that “upstream” P2Y12 receptor antagonists should be considered in patients with non–ST‐segment elevation acute coronary syndromes (NSTE‐ACS).

Hypothesis

Early use of ticagrelor in patients managed with an invasive strategy would be more effective than clopidogrel because of its more rapid onset of action and greater potency.

Methods

In the PLATO trial, 6792 NSTE‐ACS patients were randomized to ticagrelor or clopidogrel (started prior to angiography) and underwent angiography within 72 hours of randomization. We compared efficacy and safety outcomes of ticagrelor vs clopidogrel as a function of “early” (<3h) vs “late” (≥3h) time to angiography. Adjusted Cox proportional hazards models evaluated interaction between randomized treatment and time from randomization to angiography on subsequent outcomes.

Results

Overall, a benefit of ticagrelor vs clopidogrel for cardiovascular death/myocardial infarction/stroke was seen at day 7 (hazard ratio [HR]: 0.67, P = 0.002), day 30 (HR: 0.81, P = 0.042), and 1 year (HR: 0.80, P = 0.0045). There were no significant interactions in the <3h vs ≥3h groups at any timepoint. For major bleeding, overall there was no significant increase (HR: 1.04, 95% confidence interval: 0.85‐1.27); but there was a significant interaction with no difference between ticagrelor and clopidogrel in the early group (HR: 0.79), but higher bleeding risk with ticagrelor in the late angiography group, at 7 days (HR: 1.51, Pint = 0.002). Patterns were similar at 30 days and 1 year.

Conclusions

The benefit of ticagrelor over clopidogrel was consistent in those undergoing early and late angiography, supporting upstream use of ticagrelor.
Full runtime polyhedral optimizing loop transformations with the generation, instantiation, and scheduling of code‐bones
Authors: Martinez Caamaño Juan Manuel , Selva Manuel , Clauss Philippe , Baloian Artyom , Wolff Willy
Published: June 2017

In this paper, we present a new runtime code generation technique for speculative loop optimization and parallelization. The main benefit of this technique, compared to previous approaches, is to enable advanced optimizing loop transformations at runtime with an acceptable time overhead. The loop transformations that may be applied are those handled by the polyhedral model. The proposed code generation strategy is based on the generation of “code‐bones” at compile‐time, which are parametrized code snippets either dedicated to speculation management or to computations of the original target program. These code‐bones are then instantiated and assembled at runtime to constitute the speculatively optimized code, as soon as an optimizing polyhedral transformation has been determined. Their granularity threshold is sufficient to apply any polyhedral transformation, while still enabling fast runtime code generation. This approach has been implemented in the speculative loop parallelizing framework APOLLO.
A Study of Electrocyclic Reactions in a Molecular Junction: Mechanistic and Energetic Requirements for Switching in the Coulomb Blockade Regime
Authors: Olsen Stine T. , Brøndsted Nielsen Mogens , Hansen Thorsten , Ratner Mark A. , Mikkelsen Kurt V.
Published: June 2017

The front cover artwork was made by Dr. Stine T. Olsen. The present work involves a long term collaboration between members of the Center for Exploitation of Solar Energy at the Department of Chemistry, University of Copenhagen, Denmark and one of its international partners from the Department of Chemistry, Northwestern University, U.S.A. Read the full text of the article at 10.1002/cphc.201700140.
Resistance formulae of a multipurpose n‐step network and its application in LC network
Authors: Tan Z.‐Z. , Asad J.H. , Owaidat M.Q.
Published: June 2017

We consider a multipurpose n‐step network with cross resistors that is a profound problem that has not been resolved before. This network contains a number of different types of resistor network model. This problem is resolved by three steps: First of all, we simplify a complex graphics into a simple equivalent model; next, we use Kirchhoff's laws to analyse the network and establish a nonlinear difference equation; and finally, we construct the method of equivalent transformation to obtain the general solution of the nonlinear difference equation. In this paper, we created a new concept of negative resistance for the needs of the equivalent conversion and obtain two general resistance formulae of a multipurpose ladder network of cross resistors. As applications, several interesting specific results are produced. In particular, an n‐step impedance LC network is discussed. Our method and the results are suitable for the research of complex impedance network as well. Copyright © 2017 John Wiley & Sons, Ltd.
Metastatic neoplasms to the pancreas diagnosed by fine‐needle aspiration/biopsy cytology: A 15‐year retrospective analysis
Authors: Raymond Sasha L. T. , Yugawa Deanne , Chang Karen H. F. , Ena Brandy , Tauchi‐Nishi Pamela S.
Published: June 2017

Background

Metastatic tumors to the pancreas are rarely encountered and diagnostically challenging. We aspired to determine the incidence and origin of all metastases to the pancreas at our institution, and to examine their clinicopathologic and cytomorphologic features. We also sought to ascertain the effect of endoscopic ultrasound (EUS) guidance implementation.

Methods

A search of our database was undertaken to review all pancreatic FNA and/or CNB examined from January 2000 through December 2014.

Results

During our 15‐year study, 636 patients underwent pancreatic FNA/CNB, including 252 (40%) computerized tomography (CT) and 384 (60%) EUS‐guided biopsies. Malignancy was diagnosed in 221 (35%). Only 16 had metastases to the pancreas, comprising 2.5% of pancreatic biopsies and 7.2% of malignancies. Three (18.8%) presented with their first manifestation of cancer. EUS guidance was utilized in 50%, with rapid on‐site evaluation (ROSE) employed in 14 (88%). The most common primary site was lung (6,38%), followed by 3 (19%) each of renal and gastrointestinal malignancies. The remaining included malignant melanoma, Merkel and gallbladder small cell carcinomas, and olfactory neuroblastoma.

Conclusion

Cytologic diagnosis of metastasis to the pancreas is rare in our institution, comprising only 2.5% and 7.2% of total and malignant pancreatic FNA/CNB, respectively. FNA/CNB with ROSE proved to be an effective diagnostic modality, thereby obviating the need for more invasive procedures in the setting of pancreatic metastases. EUS‐FNA was equally effective as CT‐guided biopsies in achieving specimen adequacy and definitive diagnoses. We also present the first known case of a metastatic olfactory neuroblastoma to the pancreas diagnosed by imprint cytology.
Transmission electron microscopy of zebrafish spinal motor nerve roots
Authors: Morris Angela D. , Erisir Alev , Criswell Stacey J. , Kucenas Sarah
Published: June 2017

Background: Spinal motor nerves are essential for relaying information between the central and peripheral nervous systems. Perturbations to cell types that comprise these nerves may impair rapid and efficient transmission of action potentials and alter nerve function. Identifying ultrastructural changes resulting from defects to these cellular components via transmission electron microscopy (TEM) can provide valuable insight into nerve function and disease. However, efficiently locating spinal motor nerves in adult zebrafish for TEM is challenging and time‐consuming. Because of this, we developed a protocol that allows us to quickly and precisely locate spinal motor nerve roots in adult zebrafish for TEM processing. Results: Following fixation, a transverse slab of adult zebrafish dissected from the trunk region was mounted in embedding media, sectioned, and secondary fixation with osmium tetroxide performed. Transverse sections containing motor nerves were selected for TEM ultrathin sectioning and imaging. Conclusions: We developed an efficient protocol for locating spinal motor nerves in adult zebrafish to allow for ultrastructural characterization. Although our work focuses on spinal motor nerves, this protocol may be useful for efficiently identifying other discrete, repeated structures within the developing and mature nervous system that are difficult to find via traditional, whole organism TEM processing. Developmental Dynamics 246:956–962, 2017. © 2017 Wiley Periodicals, Inc.
Conserved signaling mechanisms in Drosophila heart development
Authors: Ahmad Shaad M.
Published: June 2017

Signal transduction through multiple distinct pathways regulates and orchestrates the numerous biological processes comprising heart development. This review outlines the roles of the FGFR, EGFR, Wnt, BMP, Notch, Hedgehog, Slit/Robo, and other signaling pathways during four sequential phases of Drosophila cardiogenesis—mesoderm migration, cardiac mesoderm establishment, differentiation of the cardiac mesoderm into distinct cardiac cell types, and morphogenesis of the heart and its lumen based on the proper positioning and cell shape changes of these differentiated cardiac cells—and illustrates how these same cardiogenic roles are conserved in vertebrates. Mechanisms bringing about the regulation and combinatorial integration of these diverse signaling pathways in Drosophila are also described. This synopsis of our present state of knowledge of conserved signaling pathways in Drosophila cardiogenesis and the means by which it was acquired should facilitate our understanding of and investigations into related processes in vertebrates. Developmental Dynamics 246:641–656, 2017. © 2017 Wiley Periodicals, Inc.
Dampening of population cycles in voles affects small mammal community structure, decreases diversity, and increases prevalence of a zoonotic disease
Authors: Ecke Frauke , Angeler David G. , Magnusson Magnus , Khalil Hussein , Hörnfeldt Birger
Published: June 2017

Long‐term decline and depression of density in cyclic small rodents is a recent widespread phenomenon. These observed changes at the population level might have cascading effects at the ecosystem level. Here, we assessed relationships between changing boreal landscapes and biodiversity changes of small mammal communities. We also inferred potential effects of observed community changes for increased transmission risk of Puumala virus (PUUV) spread, causing the zoonotic disease nephropatica epidemica in humans. Analyses were based on long‐term (1971–2013) monitoring data of shrews and voles representing 58 time series in northern Sweden. We calculated richness, diversity, and evenness at alpha, beta, and gamma level, partitioned beta diversity into turnover (species replacement) and nestedness (species addition/removal), used similarity percentages (SIMPER) analysis to assess community structure, and calculated the cumulated number of PUUV‐infected bank voles and average PUUV prevalence (percentage of infected bank voles) per vole cycle. Alpha, beta, and gamma richness and diversity of voles, but not shrews, showed long‐term trends that varied spatially. The observed patterns were associated with an increase in community contribution of bank vole (Myodes glareolus), a decrease of gray‐sided vole (M. rufocanus) and field vole (Microtus agrestis) and a hump‐shaped variation in contribution of common shrew (Sorex araneus). Long‐term biodiversity changes were largely related to changes in forest landscape structure. Number of PUUV‐infected bank voles in spring was negatively related to beta and gamma diversity, and positively related to turnover of shrews (replaced by voles) and to community contribution of bank voles. The latter was also positively related to average PUUV prevalence in spring. We showed that long‐term changes in the boreal landscape contributed to explain the decrease in biodiversity and the change in structure of small mammal communities. In addition, our results suggest decrease in small mammal diversity to have knock‐on effects on dynamics of infectious diseases among small mammals with potential implications for disease transmission to humans.
A framework for testing assumptions about foraging scales, body mass, and niche separation using telemetry data
Authors: Cumming Graeme S. , Henry Dominic A.W. , Reynolds Chevonne
Published: June 2017

Ecological theory predicts that if animals with very similar dietary requirements inhabit the same landscape, then they should avoid niche overlap by either exploiting food resources at different times or foraging at different spatial scales. Similarly, it is often assumed that animals that fall in different body mass modes and share the same body plan will use landscapes at different spatial scales. We developed a new methodological framework for understanding the scaling of foraging (i.e. the range and distribution of scales at which animals use their landscapes) by applying a combination of three well‐established methods to satellite telemetry data to quantify foraging patch size distributions: (1) first‐passage time analysis; (2) a movement‐based kernel density estimator; and (3) statistical comparison of resulting histograms and tests for multimodality. We demonstrate our approach using two sympatric, ecologically similar species of African ducks with quite different body masses: Egyptian Geese (actually a shelduck), and Red‐billed Teal. Contrary to theoretical predictions, the two species, which are sympatric throughout the year, foraged at almost identical spatial scales. Our results show how ecologists can use GPS tracking data to explicitly quantify and compare the scales of foraging by different organisms within an animal community. Our analysis demonstrates both a novel approach to foraging data analysis and the need for caution when making assumptions about the relationships among niche separation, diet, and foraging scale.
Geographically distinct patterns of reproductive isolation and hybridization in two sympatric species of theJaera albifronscomplex (marine isopods)
Authors: Ribardière Ambre , Daguin‐Thiébaut Claire , Houbin Céline , Coudret Jérôme , Broudin Caroline , Timsit Olivier , Broquet Thomas
Published: June 2017

Sympatric species that in some populations hybridize and in other populations remain reproductively isolated open interesting research possibilities for the study of hybridization and speciation. Here, we test for such a situation in two littoral isopods (Jaera albifronsandJ. praehirsuta) that occur in mixed populations and where past morphological descriptions suggested that the two species are generally reproductively isolated except in rare populations where hybridization may be happening. Using field surveys and microsatellite genetic structure analyses in two regions from France (Normandy and Brittany), we confirmed that introgressive hybridization occurs in a subset of mixedJ. albifrons/J. praehirsutapopulations (region Normandy) where the two species are found in the same habitat (pebbles on the shore). Moreover, we found that introgression in these populations is differential, 21 of 23 microsatellite markers showing little genetic divergence between species (hierarchical analysis of molecular varianceFCT = 0.017) while the remaining two loci were strongly differentiated (FCT = 0.428). By contrast,J. albifronsandJ. praehirsutain mixed populations from region Brittany occupied distinct habitats (pebbles and seaweeds, respectively) with little overlap and showed stronger genetic divergence (FCT = 0.132). In hybridizing populations, the majority of individuals show morphological traits that are characteristic of one or the other species. This raises the question of the forces that act to maintain this polymorphism, noting that hybridizing populations seem to be geographically isolated from potential source parental populations and show no detectable habitat divergence between species.
Ecohydrological disturbances associated with roads: Current knowledge, research needs, and management concerns with reference to the tropics
Authors: Wemple Beverley C. , Browning Trevor , Ziegler Alan D. , Celi Jorge , Chun Kwok Pan (Sun) , Jaramillo Fernando , Leite Nei K. , Ramchunder Sorain J. , Negishi Junjiro N. , Palomeque Ximena , Sawyer Derek
Published: June 2017

Roads are a pervasive form of disturbance with potential to negatively affect ecohydrological processes. Some of the most rapid growth in road networks is occurring in developing countries, particularly in the tropics, where political agendas are often focused on strengthening the economy, improving infrastructure, bolstering national security, achieving self‐sufficiency, and increasing citizen well‐being, often at the expense of the environment. We review what is known about road impacts on ecohydrological processes, focusing on aquatic systems, both temperate and tropical. We present seven cases that represent the broader trends of road development and impacts in tropical settings. Many of these process dynamics and impacts are not different from those experienced in temperate settings, although the magnitude of impacts in the tropics may be amplified with intense rainfall and lack of best management practices applied to road construction/maintenance. Impacts of roads in tropical settings may also be unique because of particular organisms or ecosystems affected. We outline a set of best practices to improve road network management and provide recommendations for adopting an agenda of research and road management in tropical settings. Importantly, we call for incorporation of transdisciplinary approaches to further study the effects of roads on ecohydrological processes in the tropics. Specific emphasis should also be placed on collaboration with governments and developers that are championing road development to help identify the drivers of road expansion and thresholds of negative impact, as well as methods of sustainable road construction and maintenance.
The mortality risk of deferring optimal medical therapy in heart failure: a systematic comparison against norms for surgical consent and patient information leaflets
Authors: Zaman Sameer , Zaman Saman S. , Scholtes Timothy , Shun‐Shin Matthew J. , Plymen Carla M. , Francis Darrel P. , Cole Graham D.
Published: June 2017

Aims

The prescription of optimal medical therapy for heart failure is often delayed despite compelling evidence of a reduction in mortality. We calculated the absolute risk resulting from delayed prescription of therapy. For comparison, we established the threshold applied by clinicians when discussing the risk for death associated with an intervention, and the threshold used in official patient information leaflets.

Methods and results

We undertook a meta‐analysis of randomized controlled trials to calculate the excess mortality caused by deferral of medical therapy for 1 year. Risk ratios for angiotensin‐converting enzyme inhibitors, beta‐blockers and aldosterone antagonists were 0.80, 0.73 and 0.77, respectively. In patients who might achieve a 1‐year survival rate of 90% if treated, a 1‐year deferral of treatment reduced survival to 78% (i.e. an annual absolute increase in mortality of 12 in 100 patients). This corresponds to an additional absolute mortality risk per month of 1%. A survey of clinicians carried out to establish the risk threshold at which they would obtain written consent showed the majority (85%) sought written consent for interventions associated with a 12‐fold lower mortality risk: one in 100 patients. A systematic review of UK patient information leaflets to establish the magnitude of risk considered sufficient to be stated explicitly showed that leaflets begin to mention death at a ∼18 000‐fold lower mortality risk of just 0.0007 in 100 patients.

Conclusions

Deferring heart failure treatment for 1 year carries far greater risk than the level at which most doctors seek written consent, and 18 000 times more risk than the level at which patient information leaflets begin to mention death.
Peripartum cardiomyopathy in Denmark: a retrospective, population‐based study of incidence, management and outcome
Authors: Ersbøll Anne S. , Johansen Marianne , Damm Peter , Rasmussen Steen , Vejlstrup Niels G. , Gustafsson Finn
Published: June 2017

Aim

Population‐based European studies of peripartum cardiomyopathy (PPCM) are few. We aimed to estimate the nationwide incidence and outcome of PPCM in Denmark during 2005–2014.

Methods and results

The Danish National Birth Register and the Danish National Patient Register were linked and searched for cardiomyopathy and heart failure ICD‐10 diagnoses in a period of nine months before to 12 months after a delivery from 1 January 2005 through 31 December 2014. Diagnoses were validated and additional data were extracted from patient charts. A total of 61 women met the inclusion criteria equalling 1 in 10 149 deliveries. The majority recovered left ventricular systolic function within one year, but 14.8% suffered a major adverse event with 3.3% mortality, 8.2% mechanical circulatory support requirement and/or heart transplantation and 4.9% persistent severe heart failure. Half of the women had a concomitant hypertensive disorder of pregnancy, and this subgroup had a milder course of the disease. Baseline left ventricular ejection fraction (LVEF) was the only significant predictor of LVEF 10–14 months after diagnosis, and cabergoline therapy to inhibit lactation predicted the dichotomous outcome of complete recovery (LVEF ≥55%).

Conclusion

The first validated, population‐based European estimate of PPCM incidence is 1 in 10 149 deliveries, which places Denmark between American and Japanese estimates. Clinical outcome in the cohort was similar to those reported in recent cohorts. Women with concomitant hypertensive disorder of pregnancy had a milder course of PPCM. Baseline LVEF predicted LVEF 10–14 months after diagnosis and cabergoline predicted complete recovery.
The strength of BCR signaling shapes terminal development of follicular helper T cells in mice
Authors: Sacquin Antoine , Gador Mylène , Fazilleau Nicolas
Published: June 2017

Antibody production is key for effective immune response and relies on follicular helper T (Tfh) cells. B cell‐Tfh cell interactions result either in an extra‐follicular low affinity B‐cell response or in germinal center reactions producing high‐affinity memory B cells and long‐lived plasma cells. As Tfh cells influence B‐cell commitment, it also became clear that B cells influence these interactions in ways that still remain unresolved. We observed that strong BCR signals decreased Tfh‐cell differentiation in vitro, which correlated with decreased expression of ICOS‐L at the surface of stimulated B cells. Further, we comprehensively demonstrated that ICOS‐L expression correlated with the level of Tfh differentiation irrespective of antigen presentation at the surface of activated B cells. Our in vivo experiments could show that immunization with a high‐affinity antigen for B cells resulted in much less Tfh development than immunization with low‐affinity antigen. Furthermore, blocking ICOS‐L in vivo inhibited Tfh development when using low‐affinity antigen. Altogether, these results indicate that BCR affinity shapes Tfh‐cell development in part through ICOS/ICOS‐L interactions. Ultimately, we reveal new depths in the B cell‐Tfh cell crosstalk that could eventually result in better vaccine protocols.
Synthetic Investigation toward the D‐Ring‐Functionalized Cytotoxic Oleanane‐Type Saponins Pithedulosides D and E
Authors: Ge Shi‐Jie , Tu Yuan‐Hong , Xia Jian‐Hui , Sun Jian‐Song
Published: June 2017

Leveraging on the orchestrated application of both Schmidt and Yu glycosylations, the first total syntheses of the echinocystic acid saponins pithedulosides D and E, the two antitumoral and representative D‐ring‐functionalized oleanane‐type saponins, were achieved. Benefitting from the applied convergent synthetic strategy, the echinocystic acids could be synthesized in overall yields of as high as 71 and 76 % through four linear steps.