bluuebunny/crossref_metadata_2025 huggingface dataset:
Cross-hemispheric dopamine projections have functional significance
Authors: Fox Megan E. , Mikhailova Maria A. , Bass Caroline E. , Takmakov Pavel , Gainetdinov Raul R. , Budygin Evgeny A. , Wightman R. Mark
Published: June 2016

Significance

Decades of research have described dopamine’s importance in reward-seeking behavior and motor control. Although numerous investigations have focused on dopamine’s mechanisms in modulating behavior, the long-standing belief that dopamine neurons project solely unilaterally has limited the exploration of interhemispheric dopamine signaling. Here we resolve disparate descriptions of unilateral vs. bilateral projections by reporting that dopamine neurons can release dopamine in the contralateral hemisphere. Using voltammetry in awake and anesthetized rats, we reveal an unprecedented synchrony of dopamine fluctuations between hemispheres. Via stimulation with amphetamine, we demonstrate functional cross-hemispheric projections in a hemiparkinsonian model. This previously undescribed capacity for interhemispheric dopamine signaling can precipitate new areas of inquiry. Future work may exploit properties of bilateral dopamine release to improve treatments for Parkinson’s disease, including deep brain stimulation.
Speaking, Gesturing, Reasoning
Authors: Walker Esther J. , Núñez Rafael
Published: June 2016

People use space to structure their thoughts about time (e.g. Núñez &
Cooperrider 2013). In this chapter, we first provide a brief overview of the various
ways that we use space to talk, gesture, and reason about deictic and sequence time. We then discuss the strengths and limitations of the different
methodologies used to study space-time associations. We argue that some
methods are especially useful for documenting the existence of spatial construals
of time, while others are more useful for examining their flexibility. We illustrate
this point by describing circumstances under which temporal reasoning
diverges from patterns in both language and gesture.
The cultural cognition of time
Authors: Ellen Roy
Published: June 2016

This chapter presents an overview of some recent work in anthropology on how
time cognition works and on the human measurement of time. It attempts to
demonstrate how language, mind, social process and ecology interact to underpin
the ways in which different cultural groups experience, use and understand
time. I review how time is constituted as a domain, examining different kinds of
unit by which time is divided, and thereafter consider the logics through which
the organization of time is integrated. These problems include the juxtaposition
of cyclical and linear notions; the intrinsic complementarity of idioms of
space and time; whether ‘time as such’ is a cognitive domain and conceptual
universal beyond the particularities of local culture experience; whether the
architectures of dualism and cognitive economy are integral to our understanding
of time; the extent to which memory and narrativity are crucial to human
constructions of time; and whether certain aspects of time organization depend
entirely on its encoding in language. The chapter concludes by agreeing with
Stephen Levinson that the contribution of anthropology to understanding the
language cognition of complex domains such as time is through its emphasis
on grounded ethnography, an insistence on holistic approaches, on comparison
and on the implications of integrating data from the extremes of cultural
diversity.
Marking anteriority, perfect and perfectivity in languages of mainland Southeast Asia – concepts, linguistic area
Authors: Borchers Dörte
Published: June 2016

As a result of language contact, Southeast Asian languages belonging to different
language families share features, such as phonemic tone and numeral classifiers.
Similarities between Southeast Asian languages in the frequency of explicit
temporal marking, and the reference to spatial and temporal relations with
markers related to motion verbs might be also the result of language contact.
Descriptions of markers of Southeast Asian languages that express temporal
relations, differ in the literature due to their polysemy and due to the
application of seemingly universal categories to the description of language
specific concepts.
This paper discusses universal categories and polysemy before presenting
and comparing those grammatical markers of Burmese, Lao, Thai and
Vietnamese that are associated with the marking of the categories past, anteriority,
perfect or perfectivity.
The theory of affordances
Authors: Blin Françoise
Published: June 2016

In the last decade, the term “affordance,” coined by the ecological psychologist James Gibson (1986), has become a buzzword in CALL research. Often used to denote possibilities offered by technologies, the concept has been imported into CALL from cognate domains, such as human-computer Interaction (HCI). However, the CALL community has yet to engage in in-depth discussions on its meaning and usefulness for CALL research and design. The concept remains confusing, often misunderstood, and, at times, misused. This chapter provides an introduction to the concept of affordances, with a view to clarify its meaning and potential applications within CALL. Following a brief overview of Gibson’s theory of affordance, it presents and discusses leading HCI interpretations and conceptualizations of affordance that are particularly relevant to CALL researchers and designers. More specifically, it explicates HCI cognitivist and post-cognitivist views of affordances before exploring their relation to CALL affordances and their possible place within a CALL research agenda focusing more particularly on learner-computer interactions.
A scientific methodology for researching CALL interaction data
Authors: Chanier Thierry , Wigham Ciara R.
Published: June 2016

This chapter gives an overview of one possible staged methodology for structuring LCI data by presenting a new scientific object, LEarning and TEaching Corpora (LETEC). Firstly, the chapter clarifies the notion of corpora, used in so many different ways in language studies, and underlines how corpora differ from raw language data. Secondly, using examples taken from actual online learning situations, the chapter illustrates the methodology that is used to collect, transform and organize data from online learning situations in order to make them sharable through open-access repositories. The ethics and rights for releasing a corpus as OpenData are discussed. Thirdly, the authors suggest how the transcription of interactions may become more systematic, and what benefits may be expected from analysis tools, before opening the CALL research perspective applied to LCI towards its applications to teacher-training in Computer-Mediated Communication (CMC), and the common interests the CALL field shares with researchers in the field of Corpus Linguistics working on CMC.
Rendaku in Tōhoku Japanese
Authors: Miyashita Mizuki , Irwin Mark , Wilson Ian , Vance Timothy J.
Published: June 2016

Rendaku in many Tōhoku dialects is manifested in the form of prenasalized voicing, and this paper provides a case study of rendaku in the dialect of Kahoku-chō, Yamagata Prefecture. After describing prenasalized voicing and its relationship to rendaku, the paper reports the results of a study conducted in 2012 on speakers of the Kahoku dialect. Prenasalization did not occur at all uniformly in the productions of the survey participants; there was considerable variation, both between speakers and between target words. Also, while sex and socio-economic group were not predictors, age was, with the oldest participant having the highest prenasalization rate. Given the complex social and historical situation regarding dialect use in Japan, the Kahoku dialect has undoubtedly been altered lexically, morphologically, and phonologically.
The restoration of the ergative case marking of ‘A’ in perfective clauses in New Indo-Aryan
Authors: Drocco Andrea
Published: June 2016

The development of the ergative construction in the New Indo-Aryan period is still not totally clear. In particular we don’t know the process of grammaticalization of the new analytical ergative marker, the postposition ne, found, among others, in Hindī and Pañjābī. This study tries to demonstrate that if it is true that the “macro-history” of this form suggests that the discriminatory function of case marking is clearly important in the beginning of its process of diffusion and stabilization, it is also true that there is no single interpretation as regards its high initial variability. In fact, starting from data taken from prose texts written in the old Hindī literary variety known as Braj-bhās�ā, the full set of conditions on case alternations for A in the perfective aspect is really complex.
Exploring finiteness and non-finiteness in Pima Bajo (Uto-Aztecan)
Authors: Estrada-Fernández Zarina
Published: June 2016

This paper aims to provide a proper characterization of finite and non-finite clauses in Pima Bajo, a Uto-Aztecan language from the Tepiman branch. Our main research questions are, firstly, how to address the topic of finiteness in a language without morphological tense marking? And secondly, what are the relevant features or properties that distinguish finite and non-finite constructions in a language with no obligatory agreement markers? Finiteness and non-finiteness have long been discussed and analyzed in either formal or functional terms, mostly from a Eurocentric perspective. The most traditional notion takes finiteness to be associated with tense-aspect and agreement only, whereas functional approaches, consider finiteness to be a scalar, or gradient, phenomenon not reducible to tense-aspect marking and agreement. This paper analyzes finite and non-finite constructions in Pima Bajo, taking into consideration different morphosyntactic features, among them those that express illocutionary force and those that anchor the event. These features include aspect suffixes, personal pronouns, modals, and scope particles, among others. The analysis of finite and non-finite constructions in Pima Bajo shows that finiteness is a construction and language-particular phenomenon that cannot be reduced to morphological properties of the verb such as person and number agreement or tense marking.
Finiteness in Haruai
Authors: Comrie Bernard
Published: June 2016

Haruai, a non-Austronesian (“Papuan”) language of Papua New Guinea distinguishes, in terms of the indexing of person-number in the verb, between finite, semi-finite, and non-finite verb forms. There is a high, though not absolute, correlation between this scale and the scale running from main clause to dependent clause.
The role of nominalization in theticity
Authors: Queixalós Francesc
Published: June 2016

When speakers need to communicate a piece of information in which they allocate all the components the same degree of informational density – especially the components expressing the state of the world described and the entities associated with it – they rely on linguistic mechanisms that may differ radically from those employed in speech-acts that involve a rhematic element (rather dense informationally) linked to a thematic element (rather thin informationally). In languages where existential predication does not require a verb of existence with the subject as the thematic element, this type of construction is well adapted to the thetic communicative intention, since it is organized around a noun phrase conveying rhematic information that is not connected to any thematic element apart from the world, or the situation. Since this element is not instantiated linguistically, or at least not by expressions capable of referring, the structure of this kind of existential predication is monadic. This is the most striking difference between the formal correlates of thetic constructions and those of the dyadic construction with rheme and theme. The Sikuani language makes a great deal of use of verb nominalization machinery (which provides a way to combine in the most parsimonious way the state of affairs described and the entities associated with it) in order to fulfill the goal of thetic communication. In particular, by playing with these mechanisms this language manages to modulate the degree of semantic reification of the state of the world described by the nominalized verb. Consequently a nominalized form with a thetic function becomes able to express semantic configurations (events, states, etc.) similar to those normally expressed by finite verbs.
Specialised bilingual and multilingual Italian/Spanish lexicography and specialised translation teaching
Authors: Flores Acuña Estefanía
Published: June 2016

Lexicographical resources for the Italian-Spanish language combination are not as numerous as those found in other combinations, particularly as far as specialised lexicography is concerned. Against this background, this paper aims to present some of the most recent Italian-Spanish lexicographical resources with the purpose of reflecting on their contribution to solving the problems encountered in specialised translation training. With this aim in mind, the paper focuses on the world of Fashion, one of the main thematic areas tending to generate texts which are usually translated from Italian into Spanish.
Effect of current density on microstructure and properties of PEO ceramic coatings on magnesium alloy
Authors: Zhuang J. J. , Song R. G. , Xiang N. , Xiong Y. , Hu Q.
Published: June 2016

Plasma electrolytic oxidation (PEO) coatings were produced on AZ31 magnesium alloy in a phosphate-based electrolyte with current density varying from 5 to 20 A dm−2. The influences of the current density on the PEO process and resulting coating characteristics were discussed. The coating morphology and phase composition were studied by scanning electron microscopy and X-ray diffraction technique, respectively. The corrosion performance of the coatings was evaluated in 3.5 wt-% NaCl solution using potentiodynamic polarisation scans. The electrochemical corrosion results proved that the coating produced at current density of 10 A dm−2 shows the best corrosion resistance. The tribological test suggested that the ceramic coating produced at 10 A dm−2 exhibited the most superior wear resistance.
Biosynthesis of floral scent 2-phenylethanol in rose flowers
Authors: Hirata Hiroshi , Ohnishi Toshiyuki , Watanabe Naoharu
Published: June 2016

Plants emit chemically diverse volatile compounds for attracting pollinators or putting up a chemical defense against herbivores. 2-Phenylethanol (2PE) is one of the abundantly emitted scent compounds in rose flowers. Feeding experiments with l-[2H8]phenylalanine into rose flowers and subsequent analysis using gas chromatography–mass spectrometry analysis revealed the hypothetical biosynthetic intermediates to [2H8]-2PE, and the biochemical and genetic analyses elucidated the principal pathway to [2H8]-2PE. We recently found season-specific 2PE pathway producing [2H7]-2PE from l-[2H8]phenylalanine. This is a unique example where the dominant pathway to a specific compound changes with the seasons. This review focuses on the biosynthesis of floral volatiles and their regulation to adapt to the changes in the environment.
High-speed atomic force microscopy for materials science
Authors: Payton O. D. , Picco L. , Scott T. B.
Published: June 2016

Since its inception in 1986, the field of atomic force microscopy (AFM) has enabled surface analysis and characterisation with unparalleled resolution in a wide variety of environments. However, the technique is limited by very low sample throughput and temporal resolution making it impractical for materials science research on macro sized or time evolving samples such as the observation of corrosion. The potential of AFM sparked intense efforts to overcome these limitations shortly after its invention, and has led to the development of high-speed atomic force microscopes (HS-AFMs). Within the last 5 years the technology underpinning these instruments has matured to the point where routine imaging can achieve megapixels per second over scan areas of square millimetres, removing the limitations from AFM for industrial scale materials characterisation. This review explains the technology and looks to the future use of HS-AFMs in materials science.
Clonal redemption of autoantibodies by somatic hypermutation away from self-reactivity during human immunization
Authors: Reed Joanne H. , Jackson Jennifer , Christ Daniel , Goodnow Christopher C.
Published: June 2016

Clonal anergy is an enigmatic self-tolerance mechanism because no apparent purpose is served by retaining functionally silenced B cells bearing autoantibodies. Human autoantibodies with IGHV4-34*01 heavy chains bind to poly-N-acetyllactosamine carbohydrates (I/i antigen) on erythrocytes and B lymphocytes, cause cold agglutinin disease, and are carried by 5% of naive B cells that are anergic. We analyzed the specificity of three IGHV4-34*01 IgG antibodies isolated from healthy donors immunized against foreign rhesus D alloantigen or vaccinia virus. Each IgG was expressed and analyzed either in a hypermutated immune state or after reverting each antibody to its unmutated preimmune ancestor. In each case, the preimmune ancestor IgG bound intensely to normal human B cells bearing I/i antigen. Self-reactivity was removed by a single somatic mutation that paradoxically decreased binding to the foreign immunogen, whereas other mutations conferred increased foreign binding. These data demonstrate the existence of a mechanism for mutation away from self-reactivity in humans. Because 2.5% of switched memory B cells use IGHV4-34*01 and >43% of these have mutations that remove I/i binding, clonal redemption of anergic cells appears efficient during physiological human antibody responses.
Sexting
Authors: Bond Emma
Published: June 2016

Sexting has recently attracted both media and academic attention. Mostly associated with adolescents, sexting, broadly speaking, refers to the production of and sharing of a naked or semi-naked image or a sexualized message via digital technology. Understanding sexting behaviors, however, is rather more complex and current commonly used definitions do not adequately address the different types of sexting and the different motivations and consequences that sexting behaviors have. Both media and public discourse have centered on the risks of sexting in relation to children and young people, as have policy responses to sexting activity. Concerns over a child being groomed online and being coerced or threatened into sending a naked or semi-naked picture by someone seeking sexual gratification has been the focus of policy debate and many public educational campaigns across the globe. Similarly, other campaigns have depicted the child or young person as a victim who sends a sexualized image to a peer that is then posted on a social media site or shared widely among a peer group causing the sender humiliation and distress. While these are both clear examples of digital abuse that have been the center of public awareness campaigns, it is often argued that current legal frameworks are insufficient to provide an adequate and appropriate response in many sexting cases, as there is considerable diversity in the circumstances and the contexts of sexting behaviors. As such it is argued that the (il)legality of sexting is such that it fails to recognize young people’s agency and that they may be choosing to produce and share images of themselves by choice. While it is legal to have sex with consent in many countries at age 16, it is still illegal to take a photo of either one’s own body or that of another if they are under 18 (even if over 16 and, thus, over the age of consent to have sex in many countries). As a consequence, some young people are being criminalized by the very laws designed to protect them. In reality many young people view sexting (although they do not use such terminology) as a mundane, fairly everyday thing to do, especially when they are in a romantic, intimate relationship and they are sharing the images with each other within the context of a trusting relationship. However, it is usually when that relationship breaks down that the image is more likely to be shared with others or published online with often harmful psychological and emotional consequences for the person depicted in the image. Sadly, some young people have committed suicide as a result of an image being publically shared. While the media, public, and, indeed, academic attention has focused on sexting in relation to children and young people, such behaviors are also experienced by adults who are similarly victims of digital abuse; yet many adult victims fail to receive protection from the criminal justice system when an image or video is published online without their consent. This is more commonly known as revenge pornography.
Decolonial Philosophy and Education
Authors: Noroozi Nassim
Published: June 2016

“Decolonial philosophy of education” is an almost nonexistent term. Consequently, rigorous intellectual and scholarly conversations on education tend to be centered around a specific set of concepts and discourses that were (and still are) generated, picked up or analyzed by thinkers from a specific geographical and political space, such as Socrates, Rousseau, Dewey, Heidegger, and Foucault. This has led to the systemic ignoring and violating concepts and ideas generated from other spaces and lived through by other people.

This legacy can also be related to some philosophical aspirations for gaining total, hegemonic, and universal perceptions and representations often formulated by male Euro-American philosophers; when this intellectual passion for universality becomes coupled with or stays silent about imperial and expansionist ambitions, it can see itself implicated in creating assimilationist or genocidal practices: in education, the manifestation of universality associated with imperialism is observed in Indian residential schools. While the words education, literacy, curriculum, learning of languages, acquiring knowledge, school, school desks, and school buildings might normally echo positive vibes for many, it can make an aboriginal survivor of an Indian residential school shudder. It is furthermore hard to ignore the aspirations for a European/Universalist definition of human and man in the famous “Kill the Indian to save the child” policy of Indian Residential Schools. However, the likelihood of deeming such assimilationist attempts as benign acts of trial and error and as events external to philosophy is generally high. Therefore, the “colonial edge” of these philosophies are, more often than not, left unexamined.

This is the plane where decolonial philosopher dwell. They deliberate on essential key moments and discussions in philosophical thought that have either not been paused at enough or paused at all, and thereby question this lack of attention. There is an important reason for these intellectual halts practiced by decolonial philosophers. While these might seem to be abstract epistemic endeavors, decolonial philosophers see their work as practices of liberation that aim beyond disrupting the eminence of mainstream Euro-American philosophical thought. Through these interrogative pauses, they hope to intervene, overturn and restructure the philosophical, political and social imaginations in favor of the silenced, the ignored, the colonized, and the (epistemologically and physically) violated.

This article engages with certain key decolonial theses and is concerned with the hope of initiating and further expanding the dialogues of decolonization in the philosophy of education. The article will, however, stay away from adding new theses or theories to decolonial education. The author believes that this field, much like other paradigms, either can or will at some point suffer from theoretical exhaustion. Instead, it directs the readers to pause at some of the decisive moments discussed in decolonial theories.
Contemporary Pagan, Wiccan, and Native Faith Movements
Authors: Clifton Chas S.
Published: June 2016

Paganism is based largely in an Enlightenment-era rejection of Christianity and Romantic-era ideas of the individual experience, emotion, and creativity, combined with a search for true ethnic culture in the lore and practices of the pre-Christian past and a rejection of universal transcendental religion, in favor of the local, the particular, the polytheistic, and the animist. Particularly in the United States, Pagans have challenged governmental accommodations for existing religions by demanding equal status in public spaces. Contemporary Pagan groups began forming in the 1930s, but the largest, Wicca, emerged in the United Kingdom in the early 1950s.
Blocking
Authors: Rainer Franz
Published: June 2016

Blocking can be defined as the non-occurrence of some linguistic form, whose existence could be expected on general grounds, due to the existence of a rival form. *Oxes, for example, is blocked by oxen, *stealer by thief. Although blocking is closely associated with morphology, in reality the competing “forms” can not only be morphemes or words, but can also be syntactic units. In German, for example, the compound Rotwein ‘red wine’ blocks the phrasal unit *roter Wein (in the relevant sense), just as the phrasal unit rote Rübe ‘beetroot; lit. red beet’ blocks the compound *Rotrübe. In these examples, one crucial factor determining blocking is synonymy; speakers apparently have a deep-rooted presumption against synonyms. Whether homonymy can also lead to a similar avoidance strategy, is still controversial. But even if homonymy blocking exists, it certainly is much less systematic than synonymy blocking.

In all the examples mentioned above, it is a word stored in the mental lexicon that blocks a rival formation. However, besides such cases of lexical blocking, one can observe blocking among productive patterns. Dutch has three suffixes for deriving agent nouns from verbal bases, -er, -der, and -aar. Of these three suffixes, the first one is the default choice, while -der and -aar are chosen in very specific phonological environments: as Geert Booij describes in The Morphology of Dutch (2002), “the suffix -aar occurs after stems ending in a coronal sonorant consonant preceded by schwa, and -der occurs after stems ending in /r/” (p. 122). Contrary to lexical blocking, the effect of this kind of pattern blocking does not depend on words stored in the mental lexicon and their token frequency but on abstract features (in the case at hand, phonological features).

Blocking was first recognized by the Indian grammarian Pāṇini in the 5th or 4th century bc, when he stated that of two competing rules, the more restricted one had precedence. In the 1960s, this insight was revived by generative grammarians under the name “Elsewhere Principle,” which is still used in several grammatical theories (Distributed Morphology and Paradigm Function Morphology, among others). Alternatively, other theories, which go back to the German linguist Hermann Paul, have tackled the phenomenon on the basis of the mental lexicon. The great advantage of this latter approach is that it can account, in a natural way, for the crucial role played by frequency. Frequency is also crucial in the most promising theory, so-called statistical pre-emption, of how blocking can be learned.
Computational Semantics
Authors: Erk Katrin
Published: June 2016

Computational semantics performs automatic meaning analysis of natural language. Research in computational semantics designs meaning representations and develops mechanisms for automatically assigning those representations and reasoning over them. Computational semantics is not a single monolithic task but consists of many subtasks, including word sense disambiguation, multi-word expression analysis, semantic role labeling, the construction of sentence semantic structure, coreference resolution, and the automatic induction of semantic information from data.

The development of manually constructed resources has been vastly important in driving the field forward. Examples include WordNet, PropBank, FrameNet, VerbNet, and TimeBank. These resources specify the linguistic structures to be targeted in automatic analysis, and they provide high-quality human-generated data that can be used to train machine learning systems. Supervised machine learning based on manually constructed resources is a widely used technique.

A second core strand has been the induction of lexical knowledge from text data. For example, words can be represented through the contexts in which they appear (called distributional vectors or embeddings), such that semantically similar words have similar representations. Or semantic relations between words can be inferred from patterns of words that link them. Wide-coverage semantic analysis always needs more data, both lexical knowledge and world knowledge, and automatic induction at least alleviates the problem.

Compositionality is a third core theme: the systematic construction of structural meaning representations of larger expressions from the meaning representations of their parts. The representations typically use logics of varying expressivity, which makes them well suited to performing automatic inferences with theorem provers.

Manual specification and automatic acquisition of knowledge are closely intertwined. Manually created resources are automatically extended or merged. The automatic induction of semantic information is guided and constrained by manually specified information, which is much more reliable. And for restricted domains, the construction of logical representations is learned from data.

It is at the intersection of manual specification and machine learning that some of the current larger questions of computational semantics are located. For instance, should we build general-purpose semantic representations, or is lexical knowledge simply too domain-specific, and would we be better off learning task-specific representations every time? When performing inference, is it more beneficial to have the solid ground of a human-generated ontology, or is it better to reason directly with text snippets for more fine-grained and gradual inference? Do we obtain a better and deeper semantic analysis as we use better and deeper manually specified linguistic knowledge, or is the future in powerful learning paradigms that learn to carry out an entire task from natural language input and output alone, without pre-specified linguistic knowledge?
Unbiased probabilistic taxonomic classification for DNA barcoding
Authors: Somervuo Panu , Koskela Sonja , Pennanen Juho , Henrik Nilsson R. , Ovaskainen Otso
Published: June 2016

Motivation: When targeted to a barcoding region, high-throughput sequencing can be used to identify species or operational taxonomical units from environmental samples, and thus to study the diversity and structure of species communities. Although there are many methods which provide confidence scores for assigning taxonomic affiliations, it is not straightforward to translate these values to unbiased probabilities. We present a probabilistic method for taxonomical classification (PROTAX) of DNA sequences. Given a pre-defined taxonomical tree structure that is partially populated by reference sequences, PROTAX decomposes the probability of one to the set of all possible outcomes. PROTAX accounts for species that are present in the taxonomy but that do not have reference sequences, the possibility of unknown taxonomical units, as well as mislabeled reference sequences. PROTAX is based on a statistical multinomial regression model, and it can utilize any kind of sequence similarity measures or the outputs of other classifiers as predictors.

Results: We demonstrate the performance of PROTAX by using as predictors the output from BLAST, the phylogenetic classification software TIPP, and the RDP classifier. We show that PROTAX improves the predictions of the baseline implementations of TIPP and RDP classifiers, and that it is able to combine complementary information provided by BLAST and TIPP, resulting in accurate and unbiased classifications even with very challenging cases such as 50% mislabeling of reference sequences.

Availability and implementation: Perl/R implementation of PROTAX is available at http://www.helsinki.fi/science/metapop/Software.htm.

Contact:  panu.somervuo@helsinki.fi

Supplementary information:  Supplementary data are available at Bioinformatics online.
The Effect of the
APOE4
Gene on Accumulation of Aβ
40
After Brain Injury Cannot Be Reversed by Increasing apoE4 Protein
Authors: Washington Patricia M. , Burns Mark P.
Published: June 2016

The apolipoprotein E (apoE) protein is involved in clearance of β-amyloid (Aβ) from the brain; and the APOE4 gene is associated with Aβ plaque formation in humans following traumatic brain injury (TBI). Here, we examined the association between apoE and Aβ 40 after experimental TBI and the effects of APOE alleles on this relationship. We report a biphasic response of soluble apoE protein after TBI with an acute reduction at 1 day postinjury followed by an increase at 7 days postinjury. TBI-induced Aβ 40 levels decreased as soluble apoE levels increased. In APOE4 mice there was a diminished apoE response to TBI that corresponded to prolonged accumulation of TBI-induced Aβ 40 versus that in APOE3 mice. Amyloid precursor protein processing was similar in APOE3 and APOE4 mice suggesting that impaired clearance was responsible for the abnormal accumulation of Aβ 40 in the latter. Treatment of APOE4 mice with bexarotene for 7 days increased apoE4 protein levels but was not sufficient to reduce TBI-induced Aβ 40 . Thus, rapid clearance of TBI-induced Aβ 40 occurs in mice but these pathways are impaired in APOE4 carriers. These data may help explain the deposition of Aβ in APOE4 carriers and the increased incidence of brain Aβ plaques following TBI.
Risk Factors for Herpes Zoster Among Adults
Authors: Marin Mona , Harpaz Rafael , Zhang John , Wollan Peter C. , Bialek Stephanie R. , Yawn Barbara P.
Published: June 2016

Background.  The causes of varicella-zoster virus reactivation and herpes zoster (HZ) are largely unknown. We assessed potential risk factors for HZ, the data for which cannot be obtained from the medical sector.

Methods.  We conducted a matched case-control study. We established active surveillance in Olmsted County, Minnesota to identify HZ occurring among persons age ≥50 years during 2010–2011. Cases were confirmed by medical record review. Herpes zoster-free controls were age- and sex-matched to cases. Risk factor data were obtained by telephone interview.

Results.  We enrolled 389 HZ case patients and 511 matched controls; the median age was 65 and 66 years, respectively. Herpes zoster was associated with family history of HZ (adjusted odds ratio [aOR] = 1.65); association was highest with first-degree or multiple relatives (aOR = 1.87 and 3.08, respectively). Herpes zoster was also associated with prior HZ episodes (aOR = 1.82), sleep disturbance (aOR = 2.52), depression (aOR = 3.81), and recent weight loss (aOR = 1.95). Stress was a risk factor for HZ (aOR = 2.80), whereas a dose-response relationship was not noted. All associations indicated were statistically significant (P < .05). Herpes zoster was not associated with trauma, smoking, tonsillectomy, diet, or reported exposure to pesticides or herbicides (P > .1).

Conclusions.  We identified several important risk factors for HZ; however, the key attributable causes of HZ remain unknown.
Diagnosis and treatment of restless legs syndrome
Authors: Sales Samantha , Sanghera Manjit K. , Klocko David J. , Stewart R. Malcolm
Published: June 2016

Restless legs syndrome (RLS) is a disorder characterized by an irresistible urge to move the legs during rest, usually accompanied by uncomfortable sensations in the affected extremity or extremities. RLS can manifest at any age but prevalence increases with advancing age. This article describes the symptoms of RLS, associated comorbidities, and how to diagnose and manage RLS.
Physician assistant specialty choice
Authors: Morgan Perri , Everett Christine M. , Humeniuk Katherine M. , Valentin Virginia L.
Published: June 2016

Objectives:

To describe trends in physician assistant (PA) specialty distribution, compare these trends with physicians, and quantify the relationship of PA specialty prevalence with both PA and physician salary.

Methods:

PA specialty and salary data were obtained from the 2013 American Academy of PAs' Annual Survey; physician specialty and salary data from the American Medical Association Physician Masterfile and the Medical Group Management Association. Analyses included descriptive statistics and linear regression.

Results:

The proportion of PAs working in primary care decreased from 50% in 1997 to 30% in 2013. Substantial growth in PA proportions occurred in surgical and medical subspecialties. Regression models showed a higher prevalence of PAs in specialties with higher PA salary, higher physician salary, and higher physician-to-PA salary ratio (P<0.05).

Conclusions:

PAs are moving toward subspecialty practice. Our study suggests that demand for PAs may be an important factor driving the trend toward specialization.
Influence of SULT1A1 genetic variation on age at menopause, estrogen levels, and response to hormone therapy in recently postmenopausal white women
Authors: Moyer Ann M. , de Andrade Mariza , Weinshilboum Richard M. , Miller Virginia M.
Published: June 2016

Objective:

Onset and symptoms of menopause, and response to hormone therapy (HT) show large interindividual variability. SULT1A1 encodes for a highly expressed enzyme that metabolizes estrogens. We evaluated the relationship between genetic variation in SULT1A1, menopause age, symptoms, and response to HT.

Methods:

Women enrolled in the Kronos Early Estrogen Prevention Study at Mayo Clinic were randomized to 48 months of treatment with oral conjugated equine estrogen (n = 34), transdermal 17β-estradiol (E2) (n = 33), or placebo (n = 35). Linear regression models and ANOVA were used to test for association of SULT1A1 copy number, rs3760091, rs750155, and rs9282861 (SULT1A1

∗

2), with age at menopause and symptoms, levels of estrogens (estrone [E1], estrone sulfate [E1S], E2, and estradiol sulfate [E2S]), before and after HT.

Results:

SULT1A1 gene copy number affected the minor allele frequency for each single nucleotide polymorphisms tested. Before administration of exogenous hormones, increasing number of G alleles at rs9282861 was associated with earlier age at menopause (P = 0.014), lower frequency of night sweats (P = 0.009), and less severe insomnia (P = 0.046). After 48 months of treatment, SULT1A1 genotype was not associated with the presence of menopausal symptoms. In women randomized to oral conjugated equine estrogen, increasing number of the A allele at rs750155 was associated with lower E1S and E2S (P = 0.004 and 0.017), whereas increasing number of the C allele at rs3760091 was associated with lower E2S/E2 (P = 0.044).

Conclusions:

Interindividual variability in onset of menopause and symptoms before initiation of HT is explained in part by genetic variation in SULT1A1 and may represent a step toward individualizing HT treatment decisions.
Caprini Scores, Risk Stratification, and Rivaroxaban in Plastic Surgery: Time to Reconsider Our Strategy
Authors: Swanson Eric
Published: June 2016

Limited data are available regarding the pathophysiology of venous thromboembolism in plastic surgery patients. In an effort to identify patients at greater risk, some investigators promote individual risk assessment using Caprini scores. However, these scores do not correlate with relative risk values. Affected patients cannot be reliably predicted (97% false positive rate). Caprini scores make many body contouring patients candidates for chemoprophylaxis, an intervention that introduces risks related to anticoagulation. Caprini has financial conflicts with several companies that manufacture products such as enoxaparin, commonly used for chemoprophylaxis. Rivaroxaban, taken orally, has been used by some plastic surgeons as an alternative to enoxaparin injections. However, this medication is not United States Food and Drug Administration approved for venous thromboembolism prophylaxis in plastic surgery patients, and a reversal agent is unavailable. This article challenges the prevailing wisdom regarding individual risk stratification and chemoprophylaxis. Alternative methods to reduce risk for all patients include safer anesthesia methods and Doppler ultrasound surveillance. Clinical findings alone are unreliable in diagnosing deep venous thromboses. Only by using a reliable diagnostic tool such as Doppler ultrasound are we able to learn more about the natural history of this problem in our patients. Such knowledge is likely to better inform our treatment recommendations.
Increased Global DNA Methylation and Decreased TGFβ1 Promoter Methylation in Glaucomatous Lamina Cribrosa Cells
Authors: McDonnell Fiona S. , McNally Sara A. , Clark Abbot F. , O’Brien Colm J. , Wallace Deborah M.
Published: June 2016

Background:

Glaucoma is an optic neuropathy that affects 60 million people worldwide. There is an underlying fibrosis associated with the lamina cribrosa (LC) in glaucoma. DNA methylation is well established in regulating fibrosis and may be a therapeutic target for glaucoma. The purpose of this study was to compare global DNA methylation levels in primary human normal (NLC) and glaucomatous (GLC) cells, and to investigate DNA methylation in driving fibrosis through regulation of transforming growth factor β1 (TGFβ1).

Materials and Methods:

LC cells were cultured from normal and glaucomatous human donors. Global methylation was assessed by ELISA. qPCR was conducted for DNA methyltransferases (DNMTs), methyl-CpG-binding protein 2 (MeCP2), TGFβ 1 and 2, collagen 1α1 (COL1A1), and α-smooth muscle actin (αSMA). TGFβ1 and DNMT1 were examined by immunofluorescence. Methylation of the TGFβ1 promoter was determined by methylation-specific PCR (MSP).

Results:

Global DNA methylation demonstrated an increase in GLC compared with NLC cells (P<0.05). The previously mentioned methylation and matrix genes were increased in GLC compared with NLC cells (P<0.05). Immunofluorescence showed increased TGFβ1 and DNMT1 in GLC compared with NLC cells. MSP showed increased unmethylated DNA in the TGFβ1 promoter of GLC compared with NLC cells.

Conclusions:

We found increased expression of fibrotic genes in GLC cells and demonstrated an increase in global DNA methylation and in associated enzymes in GLC cells. Furthermore, we showed decreased promoter methylation of TGFβ1 in GLC cells. Determining a role for methylation in glaucoma and in regulating TGFβ1 may provide a novel therapeutic approach.
Ocular Adnexal Lymphoma Presenting as Refractory Unilateral Open-angle Glaucoma
Authors: Sears Nathaniel C. , Singh Annapurna , Singh Arun D.
Published: June 2016

We report a single case of masquerade glaucoma caused by increased episcleral venous pressure from adnexal lymphoma. The patient presented as a referral for unilateral glaucoma with intraocular pressures (IOPs) consistently >40 mm Hg (right eye). We present data conclusively demonstrating extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue in the involved eye, and provide an account of the treatment of the tumor with sustained regression and complete resolution of his elevated IOP. We conclude with a discussion of the proposed mechanism. This case serves as a reminder that unilateral open-angle glaucoma can be a sign of indolent ocular adnexal lymphoma. The case also provides a useful model for increased IOP with orbital lesions.
Retinal Nerve Fiber Layer Damage in Young Myopic Eyes With Optic Disc Torsion and Glaucomatous Hemifield Defect
Authors: Lee Jong Eun , Lee Jin Young , Kook Michael S.
Published: June 2016

Purpose:

To investigate retinal nerve fiber layer (RNFL) status at the opposite hemiretinas of optic disc torsion (ODT) in young myopic subjects with glaucomatous visual field (VF) defects and correlation between its thickness and VF defects using spectral-domain optical coherence tomography (SD-OCT).

Patients and Methods:

We assessed the frequency and characteristics of glaucomatous RNFL defects at the opposite hemiretinas of ODT location (ODT-unaffected hemiretinas) in 59 young myopic subjects presenting with glaucomatous VF defects confined to 1 hemifield, and compared the peripapillary RNFL thickness (pRNFLT) in ODT-unaffected hemiretinas of study eyes with that of 60 myopic controls without ODT using Cirrus HD SD-OCT. Linear regression analyses were performed between the pRNFLT measurements at ODT-unaffected hemiretinas and Humphrey field analyzer VF indices.

Results:

Approximately 42% of study eyes with ODT showed glaucomatous RNFL defects at ODT-unaffected hemiretinas. The mean width of RNFL defects was significantly greater in ODT-affected hemiretinas than in ODT-unaffected hemiretinas (P<0.001). The mean pRNFLT in ODT-unaffected hemiretinas of study group (99.9±12.1 μm) was significantly lower than that in the matched hemiretinas of control group (109.8±14.9 μm; P<0.001). Significant correlations were observed between pRNFLT parameters and Humphrey field analyzer indices for each hemiretina with or without ODT in the study group.

Conclusions:

Young myopic eyes with ODT and hemifield VF loss often show glaucomatous RNFL defects at both hemiretinas and significantly lower pRNFLT in the ODT-unaffected hemiretinas compared with matched hemiretinas of control eyes. Greater VF loss is associated with more advanced pRNFT loss in ODT-unaffected hemiretinas.
Clinical Engineers Increasingly Appointed as Medical Equipment Safety Managers in Japan
Authors: Atarashi Hidenao , Ide Hiroo , Koike Soichi
Published: June 2016

To ensure the safety of medical equipment, appointing medical equipment safety managers (MESMs) in medical institutions was made compulsory in Japan in 2007. This study aimed to describe the current status of clinical engineers (CEs) and analyze changes in the specialties of those selected as MESMs in Japan. We analyzed 2008 and 2011 government census data on hospitals. The proportion of hospitals where CEs were MESMs increased significantly, from 16.6% in 2008 to 18.5% in 2011. Although CEs are optimal as MESMs in terms of expertise, only one-third of hospitals (2,743/8,157) employed CEs.
The Impact of Reported Hospice Preferred Practices on Hospital Utilization at the End of Life
Authors: Aldridge Melissa D. , Epstein Andrew J. , Brody Abraham A. , Lee Eric J. , Cherlin Emily , Bradley Elizabeth H.
Published: June 2016

Background:

The Affordable Care Act requires hospices to report quality measures across a range of processes and practices. Yet uncertainties exist regarding the impact of hospice preferred practices on patient outcomes.

Objective:

Assess the impact of 6 hospice preferred practices and hospice organizational characteristics on hospital utilization and death using the first national data on hospice preferred practices.

Design:

Longitudinal cohort study (2008–2011) of Medicare beneficiaries (N=149,814) newly enrolled in a national random sample of hospices (N=577) from the National Hospice Survey (84% response rate) and followed until death.

Outcome Measures:

The proportion of patients at each hospice admitted to the hospital, emergency department (ED), and intensive care unit (ICU), and who died in the hospital after hospice enrollment.

Results:

Hospices that reported assessing patient preferences for site of death at admission had lower odds of being in the highest quartile for hospital death (AOR=0.36; 95% CI, 0.14–0.93) and ED visits (AOR=0.27; 95% CI, 0.10–0.76). Hospices that reported more frequently monitoring symptoms had lower odds of being in the highest quartile for ICU stays (AOR=0.48; 95% CI, 0.24–0.94). In adjusted analyses, a higher proportion of patients at for-profit compared with nonprofit hospices experienced a hospital admission (15.3% vs. 10.9%, P<0.001), ED visit (21.8% vs. 15.6%, P<0.001), and ICU stay (5.1% vs. 3.0%, P<0.001).

Conclusions:

Hospitalization of patients following hospice enrollment varies substantially across hospices. Two of the 6 preferred practices examined were associated with hospitalization rates and for-profit hospices had persistently high hospitalization rates regardless of preferred practice implementation.