bluuebunny/crossref_metadata_2025 huggingface dataset:
On Subtyping-Relation Completeness, with an Application to Iso-Recursive Types
Authors: Ligatti Jay , Blackburn Jeremy , Nachtigal Michael
Published: March 2017

Well-known techniques exist for proving the soundness of subtyping relations with respect to type safety. However, completeness has not been treated with widely applicable techniques, as far as we’re aware.

This article develops techniques for stating and proving that a subtyping relation is complete with respect to type safety and applies the techniques to the study of iso-recursive subtyping. A new proof technique, induction on failing derivations, is provided that may be useful in other domains as well.

The common subtyping rules for iso-recursive types—the “Amber rules”—are shown to be incomplete with respect to type safety. That is, there exist iso-recursive types τ
1
and τ
2
such that τ
1
can safely be considered a subtype of τ
2
, but τ
1
⩽ τ
2
is not derivable with the Amber rules.

New, algorithmic rules are defined for subtyping iso-recursive types, and the rules are proved sound and complete with respect to type safety. The fully implemented subtyping algorithm is optimized to run in
O
(
mn
) time, where
m
is the number of μ-terms in the types being considered and
n
is the size of the types being considered.
Discovering Archipelagos of Tractability for Constraint Satisfaction and Counting
Authors: Ganian Robert , Ramanujan M. S. , Szeider Stefan
Published: March 2017

The Constraint Satisfaction Problem (CSP) is a central and generic computational problem which provides a common framework for many theoretical and practical applications. A central line of research is concerned with the identification of classes of instances for which CSP can be solved in polynomial time; such classes are often called “islands of tractability.” A prominent way of defining islands of tractability for CSP is to restrict the relations that may occur in the constraints to a fixed set, called a
constraint language
, whereas a constraint language is conservative if it contains all unary relations. Schaefer’s famous Dichotomy Theorem (STOC 1978) identifies all islands of tractability in terms of tractable constraint languages over a Boolean domain of values. Since then, many extensions and generalizations of this result have been obtained. Recently, Bulatov (TOCL 2011, JACM 2013) gave a full characterization of all islands of tractability for CSP and the counting version #CSP that are defined in terms of conservative constraint languages.

This article addresses the general limit of the mentioned tractability results for CSP and #CSP, that they only apply to instances where all constraints belong to a single tractable language (in general, the union of two tractable languages is not tractable). We show that we can overcome this limitation as long as we keep some control of how constraints over the various considered tractable languages interact with each other. For this purpose, we utilize the notion of a
strong backdoor
of a CSP instance, as introduced by Williams et al. (IJCAI 2003), which is a set of variables that when instantiated, moves the instance to an island of tractability, that is, to a tractable class of instances. We consider strong backdoors into
scattered classes
, consisting of CSP instances where each connected component belongs entirely to some class from a list of tractable classes. Figuratively speaking, a scattered class constitutes an
archipelago of tractability
. The main difficulty lies in finding a strong backdoor of given size
k
; once it is found, we can try all possible instantiations of the backdoor variables and apply the polynomial time algorithms associated with the islands of tractability on the list component-wise. Our main result is an algorithm that, given a CSP instance with
n
variables, finds in time
f
(
k
)
n

O
(1)

a strong backdoor into a scattered class (associated with a list of finite conservative constraint languages) of size
k
or correctly decides that there is not such a backdoor. This also gives the running time for solving (#)CSP, provided that (#)CSP is polynomial-time tractable for the considered constraint languages. Our result makes significant progress towards the main goal of the backdoor-based approach to CSPs—the identification of maximal base classes for which small backdoors can be detected efficiently.
Surviving the Web
Authors: Calzavara Stefano , Focardi Riccardo , Squarcina Marco , Tempesta Mauro
Published: March 2017

In this article, we survey the most common attacks against web sessions, that is, attacks that target honest web browser users establishing an authenticated session with a trusted web application. We then review existing security solutions that prevent or mitigate the different attacks by evaluating them along four different axes: protection, usability, compatibility, and ease of deployment. We also assess several defensive solutions that aim at providing robust safeguards against multiple attacks. Based on this survey, we identify five guidelines that, to different extents, have been taken into account by the designers of the different proposals we reviewed. We believe that these guidelines can be helpful for the development of innovative solutions approaching web security in a more systematic and comprehensive way.
SPL
Authors: Hirzel Martin , Schneider Scott , Gedik Buğra
Published: March 2017

Big data is revolutionizing how all sectors of our economy do business, including telecommunication, transportation, medical, and finance. Big data comes in two flavors: data at rest and data in motion. Processing data in motion is
stream processing
. Stream processing for big data analytics often requires scale that can only be delivered by a distributed system, exploiting parallelism on many hosts and many cores. One such distributed stream processing system is IBM Streams. Early customer experience with IBM Streams uncovered that another core requirement is extensibility, since customers want to build high-performance domain-specific operators for use in their streaming applications. Based on these two core requirements of distribution and extensibility, we designed and implemented the Streams Processing Language (SPL). This article describes SPL with an emphasis on the language design, distributed runtime, and extensibility mechanism. SPL is now the gateway for the IBM Streams platform, used by our customers for stream processing in a broad range of application domains.
Time vs. Information Tradeoffs for Leader Election in Anonymous Trees
Authors: Glacet Christian , Miller Avery , Pelc Andrzej
Published: March 2017

Leader election is one of the fundamental problems in distributed computing. It calls for all nodes of a network to agree on a single node, called the
leader
. If the nodes of the network have distinct labels, then agreeing on a single node means that all nodes have to output the label of the elected leader. If the nodes of the network are anonymous, the task of leader election is formulated as follows: every node
v
of the network must output a simple path, which is coded as a sequence of port numbers, such that all these paths end at a common node, the leader. In this article, we study deterministic leader election in anonymous trees.

Our aim is to establish tradeoffs between the allocated time τ and the amount of information that has to be given
a priori
to the nodes to enable leader election in time τ in all trees for which leader election in this time is at all possible. Following the framework of
algorithms with advice
, this information (a single binary string) is provided to all nodes at the start by an oracle knowing the entire tree. The length of this string is called the
size of advice
. For a given time τ allocated to leader election, we give upper and lower bounds on the minimum size of advice sufficient to perform leader election in time τ.

For most values of τ, our upper and lower bounds are either tight up to multiplicative constants, or they differ only by a logarithmic factor. Let
T
be an
n
-node tree of diameter
diam
⩽
D
. While leader election in time
diam
can be performed without any advice, for time
diam
− 1 we give tight upper and lower bounds of Θ(log
D
). For time
diam
− 2 we give tight upper and lower bounds of Θ(log
D
) for even values of
diam
, and tight upper and lower bounds of Θ(log
n
) for odd values of
diam
. Moving to shorter time, in the interval [β ·
diam
,
diam
− 3] for constant β > 1/2, we prove an upper bound of
O
(
n
log
n
/
D
) and a lower bound of Ω(
n
/
D
), the latter being valid whenever
diam
is odd or when the time is at most
diam
− 4. Hence, with the exception of the special case when
diam
is even and time is exactly
diam
− 3, our bounds leave only a logarithmic gap in this time interval. Finally, for time α ·
diam
for any constant α < 1/2 (except for the case of very small diameters), we again give tight upper and lower bounds, this time Θ(
n
).
A New CMOS Controllable Impedance Multiplier with Large Multiplication Factor
Authors: Al-Absi Munir A.
Published: March 2017

This paper presents a new compact controllable impedance multiplier using CMOS technology. The design is based on the use of the translinear principle using MOSFETs in subthreshold region. The value of the impedance will be controlled using the bias currents only. The impedance can be scaled up and down as required. The functionality of the proposed design was confirmed by simulation using BSIM3V3 MOS model in Tanner Tspice 0.18 μm TSMC CMOS process technology. Simulation results indicate that the proposed design is functioning properly with a tunable multiplication factor from 0.1- to 100-fold. Applications of the proposed multiplier in the design of low pass and high pass filters are also included.
Regional Frequency Analysis of Extremes Precipitation Using L-Moments and Partial L-Moments
Authors: Khan Said Arab , Hussain Ijaz , Hussain Tajammal , Faisal Muhammad , Muhammad Yousaf Shad , Mohamd Shoukry Alaa
Published: March 2017

Extremes precipitation may cause a series of social, environmental, and ecological problems. Estimation of frequency of extreme precipitations and its magnitude is vital for making decisions about hydraulic structures such as dams, spillways, and dikes. In this study, we focus on regional frequency analysis of extreme precipitation based on monthly precipitation records (1999–2012) at 17 stations of Northern areas and Khyber Pakhtunkhwa, Pakistan. We develop regional frequency methods based on L-moment and partial L-moments (L- and PL-moments). The L- and PL-moments are derived for generalized extreme value (GEV), generalized logistic (GLO), generalized normal (GNO), and generalized Pareto (GPA) distributions. TheZ-statistics and L- and PL-moments ratio diagrams of GNO, GEV, and GPA distributions were identified to represent the statistical properties of extreme precipitation in Northern areas and Khyber Pakhtunkhwa, Pakistan. We also perform a Monte Carlo simulation study to examine the sampling properties of L- and PL-moments. The results show that PL-moments perform better than L-moments for estimating large return period events.
Development and In Vitro Evaluation of an Innovative “Dietary Flavonoid Supplement” on Osteoarthritis Process
Authors: Lauro Maria Rosaria , Crascí Lucia , Sansone Francesca , Cardile Venera , Panico Anna Maria , Puglisi Giovanni
Published: March 2017

The aim of this study was to evaluate the antidegenerative effect in osteoarthritis damage of eriocitrin alone and eriocitrin formulated as innovative “dietary flavonoid supplement.” A complexation between eriocitrin and hydroxypropyl β‐cyclodextrin by solubilization/freeze‐drying method was performed. The complex in solution was evaluated by phase solubility studies and the optimal 1 : 2 flavanone/cyclodextrin molar ratio was selected. Hydroxypropyl β‐cyclodextrin was able to complex eriocitrin as confirmed by UV‐Vis absorption, DSC, and FTIR studies. The complex formed increased the eriocitrin water solubility (from 4.1 ± 0.2 g·L−1 to 11.0 ± 0.1 g·L−1) and dissolution rate (from 37.0% to 100%) in 30 min. The in vitro studies exhibit the notion that eriocitrin and its complex inhibit AGEs in a similar manner because hydroxypropyl β‐cyclodextrin does not interfere with the flavanone intrinsic property. Instead, the presence of cyclodextrin improves eriocitrin antioxidant stability maintaining a high fluorescence value until 8 hours with respect to the pure materials. Moreover, hydroxypropyl β‐cyclodextrin showed moderate GAGs restoration acting synergistically with the complexed compound to maintain the structural chondrocytes integrity. The results point out that ERT/HP‐betaCD complex possesses technological and biological characteristics able to obtain an easily soluble nutraceutical product, which reduces the degenerative and oxidative damage which occurs in osteoarthritis, and improve the patient compliance.
Characterization of the Anti–PD-1 Antibody REGN2810 and Its Antitumor Activity in HumanPD-1Knock-In Mice
Authors: Burova Elena , Hermann Aynur , Waite Janelle , Potocky Terra , Lai Venus , Hong Seongwon , Liu Matt , Allbritton Omaira , Woodruff Amy , Wu Qi , D’Orvilliers Amanda , Garnova Elena , Rafique Ashique , Poueymirou William , Martin Joel , Huang Tammy , Skokos Dimitris , Kantrowitz Joel , Popke Jon , Mohrs Markus , MacDonald Douglas , Ioffe Ella , Olson William , Lowy Israel , Murphy Andrew , Thurston Gavin
Published: March 2017

The Programmed Death-1 (PD-1) receptor delivers inhibitory checkpoint signals to activated T cells upon binding to its ligands PD-L1 and PD-L2 expressed on antigen-presenting cells and cancer cells, resulting in suppression of T-cell effector function and tumor immune evasion. Clinical antibodies blocking the interaction between PD-1 and PD-L1 restore the cytotoxic function of tumor antigen-specific T cells, yielding durable objective responses in multiple cancers. This report describes the preclinical characterization of REGN2810, a fully human hinge-stabilized IgG4(S228P) high-affinity anti–PD-1 antibody that potently blocks PD-1 interactions with PD-L1 and PD-L2. REGN2810 was characterized in a series of binding, blocking, and functional cell-based assays, and preclinical in vivo studies in mice and monkeys. In cell-based assays, REGN2810 reverses PD-1–dependent attenuation of T-cell receptor signaling in engineered T cells and enhances responses of human primary T cells. To test the in vivo activity of REGN2810, which does not cross-react with murine PD-1, knock-in mice were generated to express a hybrid protein containing the extracellular domain of human PD-1, and transmembrane and intracellular domains of mouse PD-1. In these mice, REGN2810 binds the humanized PD-1 receptor and inhibits growth of MC38 murine tumors. As REGN2810 binds to cynomolgus monkey PD-1 with high affinity, pharmacokinetic and toxicologic assessment of REGN2810 was performed in cynomolgus monkeys. High doses of REGN2810 were well tolerated, without adverse immune-related effects. These preclinical studies validate REGN2810 as a potent and promising candidate for cancer immunotherapy. Mol Cancer Ther; 16(5); 861–70. ©2017 AACR.
The Nature of Phonetic Gradience across a Dialect Continuum: Evidence from Modern Greek Vowels
Authors: Themistocleous Charalambos
Published: March 2017

This study investigates the acoustic properties of vowels in 2 Modern Greek varieties: Standard Modern Greek (SMG) and Cypriot Greek (CG). Both varieties contain in their phonetic inventories the same 5 vowels. Forty-five female speakers between 19 and 29 years old participated in this study: 20 SMG speakers and 25 CG speakers, born and raised in Athens and Nicosia, respectively. Stimuli consisted of a set of nonsense CVCV and VCV words, each containing 1 of the 5 Greek vowels in stressed and unstressed position. Gaining insights from the controlled experimental design, the study sheds light on the gradient effects of vowel variation in Modern Greek. It shows that (1) stressed vowels are more peripheral than unstressed vowels, (2) SMG unstressed /i a u/ vowels are more raised than the corresponding CG vowels, (3) SMG unstressed vowels are shorter than CG unstressed vowels, and (4) SMG /i·u/ are more rounded than the corresponding CG vowels. Moreover, it shows that variation applies to specific subsystems, as it is the unstressed vowels that vary cross-varietally whereas the stressed vowels display only minor differences. The implications of these findings with respect to vowel raising and vowel reduction are discussed.
Identifying Epithelial Endocytotic Mechanisms of the Peanut Allergens Ara h 1 and Ara h 2
Authors: Price Dwan , Ackland M. Leigh , Suphioglu Cenk
Published: March 2017

Background: Peanuts are still one of the highest contributors to anaphylactic deaths after ingestion of a food allergen. At the molecular level, interactions between peanut allergens and the intestinal epithelium are largely unexplored. Previous findings by our research group demonstrated that the major peanut allergens, i.e., Ara h 1, Ara h 2, Ara h 3, and Ara h 6, were able to cross the Caco-2 human cell culture model of the intestinal epithelium. This research broadened our investigation to identify the mechanisms by which the Caco-2 monolayers uptake peanut allergens, specifically by endocytosis. Here, we aim to increase our understanding of allergen-epithelial interactions and, more broadly, the pathway from allergen to allergy. Methods: The human Caco-2 cell culture model was exposed to peanut extract and a combination of confocal microscopy and inhibition studies were used to identify the endocytotic mechanisms of peanut allergens in intestinal epithelia. Results: Our findings demonstrate that the peanut allergens Ara h 1 and Ara h 2 are transported through intestinal epithelia initially via early endosomes using multiple endocytotic mechanisms. From there, they are then transported to late endosomes and ultimately to lysosomes. Conclusions: These novel findings provide insight into the allergen-epithelial interactions of peanut allergens with the intestinal epithelium. Consequently, this opens the possibility of the use of these endocytotic pathways as targets for inhibitors in therapeutic development and preventative measures for peanut allergy in the future.
Nonnative Accent Discrimination with Words and Sentences
Authors: Atagi Eriko , Bent Tessa
Published: March 2017

Background: Accent detection studies have shown native listeners to be highly sensitive to the presence of nonnative accents. This study examined the robustness of this sensitivity. Methods: We evaluated listeners' accent discrimination performance when presented with a stimulus set consisting of multiple nonnative accents, as well as words and sentences that were unique in each trial. Listeners heard pairs of talkers reading the same word or sentence and indicated whether the talkers' native languages were the same or different. Talkers included two native talkers and six nonnative talkers from three native language backgrounds. Results: Listeners were highly sensitive to the difference between native and nonnative accents, confirming earlier findings, but were much less sensitive to the difference between two nonnative accents. Furthermore, while stimulus length affected listeners' sensitivity to the difference between native and nonnative accents, this factor had a minimal effect on their sensitivity to the difference between two nonnative accents. Conclusion: The findings suggest that task and stimulus characteristics have a significant effect on the degree of sensitivity to nonnative accents.
Patterns of Eye Movement Impairment Correlate with Regional Brain Atrophy in Neurodegenerative Parkinsonism
Authors: Vintonyak Olga , Gorges Martin , Müller Hans-Peter , Pinkhardt Elmar H. , Ludolph Albert C. , Huppertz Hans-Jürgen , Kassubek Jan
Published: March 2017

Background: One common feature of neurodegenerative parkinsonism including Parkinson's disease (PD), multisystem atrophy (MSA), and progressive supranuclear palsy (PSP) is altered eye movement control. Characteristic regional structural atrophy patterns in MRI can be observed in PD, MSA, and PSP. Objective: To investigate the association between eye movement disturbances and regional brain atrophy in patients with PD, MSA, and PSP. Methods: High-resolution 3-dimensional T1-weighted MRI images and video-oculographic recordings (EyeLink®) were obtained from 39 PD, 32 PSP, and 18 MSA patients and 24 matched healthy control subjects. Automatic regional volumetric assessment was performed using atlas-based volumetry (ABV). Results: The prevalence of saccadic intrusions as a measure of inhibitory control was significantly increased in PD patients compared to controls (p < 0.001) and negatively correlated with whole brain volume, cerebral brain volume, and occipital lobe volume (p = 0.0057, p = 0.0049, and p = 0.0059, respectively; all p values are false discovery rate corrected). In MSA, smooth pursuit was disturbed by characteristic “catch-up” saccades (p < 0.001) and it was significantly correlated with cerebellar volume (p = 0.004) and pontine volume (p < 0.001). The hallmark of PSP was pathologically slowed vertical peak eye velocities (p < 0.001); the lower the peak eye velocity, the more marked midbrain atrophy (p = 0.007). Conclusions: Foci of regional atrophy correlated with disease-specific eye movement alterations in all investigated parkinsonian syndromes. Oculomotor impairment in PD, predominantly the result of executive dysfunction, was linked to cerebral atrophy. Impairment in the corresponding oculomotor pathways was associated with atrophy of pontocerebellar oculomotor structures in MSA and midbrain atrophy in PSP.
Pattern of Nitrergic Neuronal System Organization in the Brain of Two Holostean Fishes (Actinopterygii: Ginglymodi)
Authors: López Jesús M. , Lozano Daniel , Morales Lorena , González Agustín
Published: March 2017

The study of the nitrergic system, formed by the networks of neurons containing the enzyme nitric oxide synthase (NOS), has been extremely useful in unraveling neuroanatomical features of the organization of the central nervous system of vertebrates. Thus, data are available for representatives of most vertebrate classes and, in particular, several studies have detailed the organization of this system in teleosts. In contrast, no information is available regarding this neurotransmission system in the brains of holosteans, an early diverged and poorly understood group of actinopterygian fishes, currently considered a sister group of teleosts that contains only 8 species. The present study provides the first detailed information on the distribution of nitrergic cell bodies and fibers in 2 holostean species of the genus Lepisosteus, the spotted gar L. oculatus and the Florida gar L. platyrhincus. NOS immunohistochemistry and the NADPH diaphorase (NADPH-d) histochemical reaction were used, and both techniques yielded identical results, with the exception of the primary olfactory and terminal nerve fibers, which only labeled for NADPH-d exclusively in L. oculatus. Double immunohistochemistry was conducted for the simultaneous detection of NOS with tyrosine hydroxylase, choline acetyltransferase, calbindin, calretinin, and serotonin to accurately establish the localization of the nitrergic neurons and fibers in the brain of holosteans, the neuroanatomy of which has been mostly neglected, and to assess possible interactions between these neuroactive substances. Distinct groups of nitrergic cells were located in subpallial areas, the basal hypothalamus, posterior tubercle, optic tectum and mesencephalic tegmentum, reticular formation, solitary tract nucleus, spinal cord, and amacrine cells in the retina. In addition, low numbers of nitrergic cells were observed in the pallium, suprachiasmatic nucleus, prethalamic and thalamic areas, torus lateralis and torus semicircularis, cerebellar and laterodorsal tegmental nuclei, and the ventral octavolateral area. Comparison of these results with those from other classes of vertebrates, and including a segmental analysis to correlate cell populations, reveals that the pattern of the nitrergic system in holosteans is very close to that in ancestral actinopterygian fishes and highlights conserved and derived traits.
Reactions of Buckwheat-Hypersensitive Patients during Oral Food Challenge Are Rare, but Often Anaphylactic
Authors: Yanagida Noriyuki , Sato Sakura , Takahashi Kyohei , Nagakura Ken-ichi , Ogura Kiyotake , Asaumi Tomoyuki , Ebisawa Motohiro
Published: March 2017

Background: Buckwheat (BW) is a common cause of life-threatening allergy in Asia. Few have examined oral food challenges (OFCs) using BW. We here describe the OFC outcomes for the diagnosis or confirmation of tolerance acquisition and clarify risk factors for positive OFCs. Methods: Between July 2005 and March 2014, we retrospectively reviewed data from children who underwent OFCs using 3,072 mg of BW protein at Sagamihara National Hospital. Children were suspected of having BW allergy because of positive results for BW-specific IgE or because they had been previously diagnosed with BW allergy owing to immediate reactions to BW. Results: Of 476 such patients, we analyzed 419 aged 1-17 years (median age 6.7 years). Forty-four (10.5%) reacted to the BW OFC and 24 (54.5%) experienced anaphylaxis. Among patients with suspected BW allergies (n = 369), 30 (8.1%) reacted to OFC. However, among patients with definitive BW allergies (n = 50) who underwent OFCs a median of 7.0 years after their last immediate reaction, 14 (28.0%) reacted to OFC. Among 12 patients with past anaphylactic reactions to BW, 8 exhibited tolerance to BW. A history of immediate reaction to BW and high BW-specific IgE levels were significant risk factors for a positive OFC. Conclusions: BW allergies are rare among children suspected of having BW allergies due to positivity for BW-specific IgE. Most children with definitive BW allergies can tolerate BW, even after anaphylactic reactions. Nevertheless, careful observation is needed when performing BW OFCs, considering the high incidence of anaphylactic reactions.
Corneal Cross-Linking as a Treatment for Fungal Keratitis Associated with Corneal Melting
Authors: Igal Vadim  , Pikkel Igal Yael Sara , Pikkel Yoav Yechezkel 
Published: March 2017

We present the case of a young male that suffered from fungal corneal abscess and corneal melting. The patient was treated successfully by corneal cross-linking. Taking into account our experience from this case, we offer to consider corneal cross-linking as a therapeutic option in cases of fungal keratitis.
Intravitreal Anti-Vascular Endothelial Growth Factor for Macular Edema due to Complex Retinal Arterial Macroaneurysms
Authors: Bormann Caroline , Heichel Jens , Hammer Ute , Habermann Anke , Hammer Thomas
Published: March 2017

Introduction: Complex retinal arterial macroaneurysms (RAM) are often accompanied by hemorrhage and/or affect the macula. We evaluated the effect of intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy using ranibizumab or aflibercept with or without laser photocoagulation in the treatment of macular edema due to RAM. Methods: A case report of two patients with secondary macular edema caused by RAM is presented. The first case was a 76-year-old female treated with two 0.5-mg injections of ranibizumab and additional focal laser photocoagulation. This patient presented a solely intraretinal exudation. The second patient was a 96-year-old female, who received one 2.0-mg injection of aflibercept. She showed sub- and intraretinal edema. We documented the clinical courses of these patients based on fundus photography, fluorescein angiography, and spectral-domain optical coherence tomography. Patients were followed-up for 12 months. Results: Patients were treated successfully using anti-VEGF therapy (ranibizumab or aflibercept) with or without laser photocoagulation. In both cases, we observed a complete regression of the macular edema and an increase in visual acuity. Conclusion: RAM can manifest with heterogeneous findings. Intravitreal anti-VEGF therapy with or without laser photocoagulation may be an effective treatment option in cases of macular edema due to RAM. Aflibercept and ranibizumab seem to be a potent anti-VEGF therapy for RAM. Individualized patient care is needed.
Dermoscopy in the Evaluation of Nail Disorders
Authors: Alessandrini Aurora , Starace Michela , Piraccini Bianca Maria
Published: March 2017

Nail dermoscopy was initially used only in the assessment of nail pigmentation, but now it is widely utilized for the evaluation of many nail disorders. In daily practice, dermoscopy may confirm clinical diagnoses and guides in the management of nail diseases and treatments, permitting a better visualization of symptoms. Dry dermoscopy is required for evaluation of the nail plate surface, while gel as an interface is necessary for assessment of nail pigmentation and onycholysis, as well as for the evaluation of the distal nail margin. In this review, we describe the dermoscopic features of the most important nail disorders, looking at the different areas of the nail. Dermatoscopic changes that usually accompany specific nail diseases are also reviewed.
Leveraging Big Data and Electronic Health Records to Enhance Novel Approaches to Acute Kidney Injury Research and Care
Authors: Sutherland Scott M. , Goldstein Stuart L. , Bagshaw Sean M.
Published: March 2017

While acute kidney injury (AKI) has been poorly defined historically, a decade of effort has culminated in a standardized, consensus definition. In parallel, electronic health records (EHRs) have been adopted with greater regularity, clinical informatics approaches have been refined, and the field of EHR-enabled care improvement and research has burgeoned. Although both fields have matured in isolation, uniting the 2 has the capacity to redefine AKI-related care and research. This article describes how the application of a consistent AKI definition to the EHR dataset can accurately and rapidly diagnose and identify AKI events. Furthermore, this electronic, automated diagnostic strategy creates the opportunity to develop predictive approaches, optimize AKI alerts, and trace AKI events across institutions, care platforms, and administrative datasets.
Inhibition of Ceramide Decreased the Expression of ATP-Binding Cassette Transporter G5/8 mRNA in an Animal Model of Cholesterol Gallstone
Authors: Kim Hyo Jung , Kim Jae Seon , Oh Seikwan , Yoo Hwan-Soo
Published: March 2017

Background: The increased risk of gallstone has been reported in patients with ATP-binding cassette (ABC) transporter polymorphism. The half-transporters ABCG5 and ABCG8 mediate the efflux of cholesterol in hepatocytes and the intestine. We investigated whether ceramide plays a role in cholesterol efflux through the ABC transporters. Methods: Six-week-old C57BL/6J mice were assigned to 3 groups. The normal group (n = 5) was fed a normal chow diet, the cholesterol group (n = 10) was fed a lithogenic diet, and the myriocin group (n = 15) was fed the lithogenic diet and myriocin, a specific inhibitor of serine-palmitoyl transferase. After 6 weeks, the ABCG5 and ABCG8 transporters were analyzed. Results: The rate of cholesterol gallstone formation in cholesterol group was also higher than that in normal and myriocin groups (0, 70, and 40%, respectively). ABCG5 and ABCG8 mRNA levels were significantly increased in cholesterol group and less increased in myriocin group, relative to that in normal group (p < 0.05). Conclusions: The inhibition of ceramide biosynthesis by myriocin suppressed gallstone formation and ABCG5/8 mRNA expression. We expect that ceramide's role as a regulator of the ABCG5/8 transporter might be linked to cholesterol gallstone formation.
МЕТАБОЛІЗМ ПРИ ГІПО- ТА ГІПЕРТИРЕОЗІ
Authors: Nechyporuk V. M , Korda M. M.
Published: March 2017

Гормони щитоподібної залози необхідні для нормальної життєдіяльності всіхорганів і систем організму та впливають на клітини усіх тканин. Тиреоїдні гормони мають анаболічний ефект на білковий обмін, катаболічний – на жировий, опосередковано регулюють метаболізм вуглеводів, забезпечують енергетичні процеси, поглинання кисню клітинами, впливають на водно-сольовий баланс, скоротливу здатність міокарда, частоту серцевих скорочень, тонус судин. Дисфункція щитоподібної залози (гіпо- або гіперфункція) належить до числа найпоширеніших ендокринних захворювань у медичній практиці. В даному огляді літератури головну увагу приділено поясненню механізмів виникнення гіпо- та гіпертиреозу та їх впливу на процеси обміну вуглеводів, ліпідів та білків.
Continuing or Temporarily Stopping Prestroke Antihypertensive Medication in Acute Stroke
Authors: Woodhouse Lisa J. , Manning Lisa , Potter John F. , Berge Eivind , Sprigg Nikola , Wardlaw Joanna , Lees Kennedy R. , Bath Philip M. , Robinson Thompson G.
Published: March 2017

Over 50% of patients are already taking blood pressure–lowering therapy on hospital admission for acute stroke. An individual patient data meta-analysis from randomized controlled trials was undertaken to determine the effect of continuation versus temporarily stopping preexisting antihypertensive medication in acute stroke. Key databases were searched for trials against the following inclusion criteria: randomized design; stroke onset ≤48 hours; investigating the effect of continuation versus stopping prestroke antihypertensive medication; and follow-up of ≥2 weeks. Two randomized controlled trials were identified and included in this meta-analysis of individual patient data from 2860 patients with ≤48 hours of acute stroke. Risk of bias in each study was low. In adjusted logistic regression and multiple regression analyses (using random effects), we found no significant association between continuation of prestroke antihypertensive therapy (versus stopping) and risk of death or dependency at final follow-up: odds ratio 0.96 (95% confidence interval, 0.80–1.14). No significant associations were found between continuation (versus stopping) of therapy and secondary outcomes at final follow-up. Analyses for death and dependency in prespecified subgroups revealed no significant associations with continuation versus temporarily stopping therapy, with the exception of patients randomized ≤12 hours, in whom a difference favoring stopping treatment met statistical significance. We found no significant benefit with continuation of antihypertensive treatment in the acute stroke period. Therefore, there is no urgency to administer preexisting antihypertensive therapy in the first few hours or days after stroke, unless indicated for other comorbid conditions.
Adipocyte‐Specific Enhancement of Angiotensin II Type 1 Receptor‐Associated Protein Ameliorates Diet‐Induced Visceral Obesity and Insulin Resistance
Authors: Azushima Kengo , Ohki Kohji , Wakui Hiromichi , Uneda Kazushi , Haku Sona , Kobayashi Ryu , Haruhara Kotaro , Kinguchi Sho , Matsuda Miyuki , Maeda Akinobu , Toya Yoshiyuki , Yamashita Akio , Umemura Satoshi , Tamura Kouichi
Published: March 2017

Background

The renin–angiotensin system has a pivotal role in the pathophysiology of visceral obesity. Angiotensin
II
type 1 receptor (
AT
1R) is a major player in the signal transduction of the renin–angiotensin system, and the overactivation of this signaling contributes to the progression of visceral obesity. We have shown that the
AT
1R‐associated protein (
ATRAP
) promotes
AT
1R internalization from the cell surface into cytoplasm along with the suppression of overactivation of tissue
AT
1R signaling. In this study, we examined whether the enhancement of adipose
ATRAP
expression could efficiently prevent diet‐induced visceral obesity and insulin resistance.

Methods and Results

We generated adipocyte‐specific
ATRAP
transgenic mice using a 5.4‐kb adiponectin promoter, and transgenic mice and littermate control mice were fed either a low‐ or high‐fat diet for 10 weeks. Although the physiological phenotypes of the transgenic and control mice fed a low‐fat diet were comparable, the transgenic mice exhibited significant protection against high‐fat diet–induced adiposity, adipocyte hypertrophy, and insulin resistance concomitant with an attenuation of adipose inflammation, macrophage infiltration, and adipokine dysregulation. In addition, when mice were fed a high‐fat diet, the adipose expression of glucose transporter type 4 was significantly elevated and the level of adipose phospho‐p38 mitogen‐activated protein kinase was significantly attenuated in the transgenic mice compared with control mice.

Conclusions

Results presented in this study suggested that the enhancement in adipose
ATRAP
plays a protective role against the development of diet‐induced visceral obesity and insulin resistance through improvement of adipose inflammation and function via the suppression of overactivation of adipose
AT
1R signaling. Consequently, adipose tissue
ATRAP
is suggested to be an effective therapeutic target for the treatment of visceral obesity.
Physical Activity and Sedentary Behavior in Children With Congenital Heart Disease
Authors: Voss Christine , Duncombe Stephanie L. , Dean Paige H. , de Souza Astrid M. , Harris Kevin C.
Published: March 2017

Background

Children with congenital heart disease (
CHD
) are thought to have low levels of physical activity (
PA
), but few studies have used objective measures of
PA
in this population.

Methods and Results

We recruited patients with mild, moderate, and severe
CHD
and cardiac transplant recipients, aged 8 to 19 years, from pediatric cardiology clinics throughout British Columbia and Yukon, Canada. Participants were fitted with an ActiGraph accelerometer to be worn over the right hip for 7 days. Daily means were estimated for a variety of accelerometry‐derived metrics, including moderate‐to‐vigorous
PA
and percentage of sedentary time if they had at least 3 valid days of accelerometry data. Participants also completed a
PA
questionnaire. We included 90 participants (aged 13.6±2.7 years; 54% male), of which 26 had mild
CHD
, 26 had moderate
CHD
, 29 had severe
CHD
, and 9 were cardiac transplant recipients. Median daily moderate‐to‐vigorous PA was 43 min/day (interquartile range: 28.9–56.9 min/day), and 8% met
PA
guidelines of 60 minutes of moderate‐to‐vigorous PA at least 6 days a week. There were no significant differences in any accelerometry‐derived metric according to
CHD
severity. Boys were significantly more active and less sedentary than girls. Activity declined and sedentary behaviors increased with age in both sexes. Sports participation was common, including competitive out‐of‐school clubs (57%).
PA
restrictions from cardiologists were rare (15%).

Conclusions

We found normal age–sex patterns of
PA
in children with
CHD
. There were no differences in
PA
by
CHD
severity, suggesting that sociocultural factors are likely important determinants of
PA
in these children.
Embolic Stroke of Undetermined Source
Authors: Hart Robert G. , Catanese Luciana , Perera Kanjana S. , Ntaios George , Connolly Stuart J.
Published: March 2017

Background and Purpose—

Embolic stroke of undetermined source (ESUS) designates patients with nonlacunar cryptogenic ischemic strokes in whom embolism is the likely stroke mechanism. It has been hypothesized that anticoagulation is more efficacious than antiplatelet therapy for secondary stroke prevention in ESUS patients. We review available information about ESUS.

Methods—

Systematic literature review to assess the frequency of ESUS, patient features, and prognosis using PubMed from 2014 to present, unrestricted by language.

Results—

On the basis of 9 studies, the reported frequency of ESUS ranged from 9% to 25% of ischemic strokes, averaging 17%. From 8 studies involving 2045 ESUS patients, the mean age was 65 years and 42% were women; the mean NIH stroke score was 5 at stroke onset (4 studies, 1772 ESUS patients). Most (86%) ESUS patients were treated with antiplatelet therapy during follow-up, with the annualized recurrent stroke rate averaging 4.5% per year during a mean follow-up of 2.7 years (5 studies, 1605 ESUS patients).

Conclusions—

ESUS comprises about 1 ischemic stroke in 6. Patients with ischemic stroke meeting criteria for ESUS were relatively young compared with other ischemic stroke subtypes and had, on average, minor strokes, consistent with small emboli. Retrospective methods of available studies limit confidence in stroke recurrence rates but support a substantial (>4% per year) rate of stroke recurrence during (mostly) antiplatelet therapy. There is an important need to define better antithrombotic prophylaxis for this frequently occurring subtype of ischemic stroke.
Overview of Ice Nucleating Particles
Authors: Kanji Zamin A. , Ladino Luis A. , Wex Heike , Boose Yvonne , Burkert-Kohn Monika , Cziczo Daniel J. , Krämer Martina
Published: March 2017

Ice particle formation in tropospheric clouds significantly changes cloud radiative and microphysical properties. Ice nucleation in the troposphere via homogeneous freezing occurs at temperatures lower than −38°C and relative humidity with respect to ice above 140%. In the absence of these conditions, ice formation can proceed via heterogeneous nucleation aided by aerosol particles known as ice nucleating particles (INPs). In this chapter, new developments in identifying the heterogeneous freezing mechanisms, atmospheric relevance, uncertainties, and unknowns about INPs are described. The change in conventional wisdom regarding the requirements of INPs as new studies discover physical and chemical properties of these particles is explained. INP sources and known reasons for their ice nucleating properties are presented. The need for more studies to systematically identify particle properties that facilitate ice nucleation is highlighted. The atmospheric relevance of long-range transport, aerosol aging, and coating studies (in the laboratory) of INPs are also presented. Possible mechanisms for processes that change the ice nucleating potential of INPs and the corresponding challenges in understanding and applying these in models are discussed. How primary ice nucleation affects total ice crystal number concentrations in clouds and the discrepancy between INP concentrations and ice crystal number concentrations are presented. Finally, limitations of parameterizing INPs and of models in representing known and unknown processes related to heterogeneous ice nucleation processes are discussed.
Western Boundary Sea Level: A Theory, Rule of Thumb, and Application to Climate Models
Authors: Minobe Shoshiro , Terada Mio , Qiu Bo , Schneider Niklas
Published: March 2017

To better understand coastal sea level variability and changes, a theory that predicts sea levels along a curved western boundary using interior ocean sea level information is proposed. The western boundary sea level at a particular latitude is expressed by the sum of contributions from interior sea levels propagating onto the western boundary by long Rossby waves between that latitude and a higher latitude, and from the western boundary sea level at the higher latitude. This theory is examined by using a linear, reduced gravity model. A comparison between the theory and the model shows good agreement. A simple scaling law (or rule of thumb) derived from the theory provides a measure of the higher-latitude sea level and ocean interior sea level contributions. The theory is then tested using data from 34 climate models in phase 5 of the Coupled Model Intercomparison Project (CMIP5) for dynamic sea level changes between the end of the twentieth and twenty-first centuries. The theory captures the nearly uniform sea level rise from the Labrador Sea to New York City (NYC), with a reduction in the increase of sea level farther south toward the equator, qualitatively consistent with the CMIP5 multimodel ensemble, even though the theory underestimates the equatorward reduction rate. Along the South American east coast, the theory successfully reproduced the spatial pattern of the sea level change. The theory suggests a strong link between a sea level rise hot spot along the northeastern coast of North America and the sea level increase in the Labrador Sea, consistent with the result that rates of NYC sea level rise are highly correlated to those in the Labrador Sea in CMIP5 models.
Does Canada need trade adjustment assistance?
Authors: Lysenko Dmitry , Mills Lisa , Schwartz Saul
Published: March 2017

Trade adjustment assistance (TAA) is government aid to those affected by trade agreements. We review the history of TAA in Canada and ask whether Canada needs to reintroduce it in response to the recent intensification of trade negotiations. In light of the compensation offered by the federal government in connection with the Canada–European Union Comprehensive Economic and Trade Agreement (CETA), we examine how TAA fits in with the evolution of Canadian federalism in the trade policy area. Based in part on interviews with provincial trade negotiators, we conclude, first, that the compensation is an outcome of Canadian federalism. Second, we argue that while there is no reason to reintroduce a federal TAA program for workers, compensation for provinces is necessary to facilitate their cooperation with the implementation of trade treaty provisions. Third, we suggest that a more transparent rationale for such compensation would be superior to the ad hoc compensation observed in CETA.
The challenges of federalism to Canada’s international trade relations: The Canada–European Union Comprehensive Economic and Trade Agreement
Authors: Tejpar Ali
Published: March 2017

As one of the first “second-generation” free trade agreements that address indirect and non-tariff barriers, the Canada–European Union Comprehensive Economic and Trade Agreement (CETA) is likely to serve as an international model. CETA, however, highlights significant challenges for Canadian federalism in both the negotiation and implementation processes of this and any such future trade agreements. While the inclusion of sub-federal governments allows for provinces/territories to help shape the provisions that fall within their jurisdictions, this paper argues that subsequent challenges arise in conveying a unified Canadian commitment to implement the agreement. Overall, the CETA negotiations demonstrated the significant institutional weaknesses of current federal–provincial/territorial relations with respect to international trade agreements. In the Canadian context, this suggests a need for “summit federalism” to ensure that all federal–provincial/territorial governments align their terms and interests and convey a unified commitment to fulfilling Canada’s current and future international trade agreements.
Taiwan’s international visibility in the twenty-first century: A suggestive note
Authors: Cho Young Chul , Ahn Mun Suk
Published: March 2017

This paper provides a critical check to the ongoing, dominant blue/green debate about Taiwan’s identity vis-à-vis China. The colour blue is associated with those who support closer ties with China and green with those who support Taiwanese independence. The state-centric debate over unification, independence, or the status quo in cross-strait relations is closely tied to Taiwan’s national aspirations to enhance its international standing in the twenty-first century, a standing which is arguably diplomatically under-recognized. Based on a critical discussion of the blue/green debate, this paper presents two pragmatic ways of augmenting Taiwan’s international visibility through global recognition without jeopardizing national security or regional stability in East Asia.