bluuebunny/crossref_metadata_2025 huggingface dataset:
Queering violence and narrative
Authors: Lewis Elizabeth Sara , Bastos Liliana Cabral
Published: October 2017

This chapter argues that it is useful to take a queer stance on studying narratives about violence in marginalized communities, considering “queer” a position countering any type of normalization that produces stigmatized margins (Halperin 1995; Louro 2004), not limited to gender and sexuality. Normative, marginalizing discourses, (re)produced by the media, “the talk of crime” (Caldeira 2000) and hate speech (Butler 1997) tend to characterize Brazilian favelas as dangerous places filled with violent criminals, homogenizing and further stigmatizing their residents (Kokoreff 2003; Valladares 2005). We examine how experiences of violence and daily life are constructed in adolescent favela residents’ narratives, focusing on how they destabilize certain aspects of the normative, marginalizing and homogenizing discourses of the media, and how violence and narrative itself are queered in their constructions.
Discursive constructions of deviance in the narratives of a prison inmate
Authors: Biar Liana
Published: October 2017

This chapter aims at identifying a specific type of discourse about violence: the stories of adherence to drug trafficking, their emergence in the research context and the processes of identity construction resulting from said context. The data comes from fieldwork done during 2009 in one of the main prison institutions in Brazil. Interviews were realized with inmate members of Rio de Janeiro criminal gangs who attended the prison school. These interviews were then qualitatively analyzed, from a micro-perspective approach, in light both of studies on oral narratives, based on interactional sociolinguistics, and of identity studies, especially those which consider narrative discourse as a privileged locus for social identity construction and analysis. From the analysis of the narratives’ structure systems of coherence, it was possible to understand the way in which inmates neutralize the force of values and of accepting order so as to give new meaning to deviant actions, as being pleasant or respectable.
Towards an operational category of discourse markers
Authors: Crible Ludivine
Published: October 2017

The field of discourse markers (DMs) studies suffers from lack of consensus on the limits and definition of the category. There seems to be a crucial need for onomasiological studies that account for every kind of DM in cross-linguistic data. This study presents a proposal for an operational, corpus-based definition of DMs that addresses several theoretical and methodological shortcomings in the field. I claim that any categorical definition is only useful insofar as it is endorsed by an empirical model of identification and annotation. Such a model will be described and illustrated by relevant authentic examples from a pilot study on a comparable corpus of French and English interviews.
Discourse markers and discourse relations
Authors: Costăchescu Adriana
Published: October 2017

We investigate if and how Discourse Markers (DMs) can be integrated into a dynamic semantic framework (in the SDRT variant, cf. Asher & Lascarides 2003, 2008, 2009) in order to study the relationships between discursive markers and rhetoric relations in a dialogue. We assume that short answers (Schlangen & Lascarides 2003) and DMs have the same basic characteristics: (i) both are semantically under-specified; (ii) in both cases, the receiver adds, by deduction, significant elements, in order to narrow, or even eliminate the semantic under-specification. We illustrate the possibility of integrating the DMs in the SDRT by examining the behaviour of the French DM quoi ‘what’ in a corpus in expressing rhetorical relations, such as:

Explanation(α, β) (A: – Le curé est arrivé à pied, ou quoi
? B: – Il est venu dans la voiture de Mathurin. ‘A : – The priest arrived on foot, or what? B: – He came in Mathurin’s car’)

Contrast(α, β) (A: – Je vais attendre. B: - Attendre quoi? Ils viennent de sortir. ‘A : I am going to wait. B: – What for? They have just left’);

Phatic(α, β), when the channel is not functioning (A: -Coco! B (who is hard of hearing): –
Quoi
? A: (screaming) – Ils te disent au revoir. ‘A: – Coco! B : -What? A: – They are saying ‘good bye’ to you’).

The study of DMs within SDRT tells us a lot about the deductive processes implied by the good functioning the human communication.
Italian non-canonical negations as modal particles
Authors: Squartini Mario
Published: October 2017

This chapter will focus on the role of information state as a major factor in the development of modal particles derived from negative minimizers. By capitalizing on previous research on Romance non-canonical negations (see especially Schwenter 2003, 2005, 2006), the analysis will describe the special discursive function of the Italian negative operator mica (etym. ‘crumb’) in direct questions, where the textual dynamics ‘given’ vs. ‘new’ interacts with the speaker’s mirative reactions. The occurrence of distinct regional patterns in the use of mica in direct questions indicates different combinations of polarity with the mirative role of the speaker, who, apart from managing information flow, also reacts to unexpected information by matching previous knowledge with new information acquired in discourse.
Vocatives as a source category for pragmatic markers
Authors: Kleinknecht Friederike , Souza Miguel
Published: October 2017

This paper considers familiarizers, a special class of vocatives denoting solidarity and intimacy, as possible sources for pragmatic markers and discourse markers. We argue that affectivity plays a crucial role in the use of vocatives in general and especially in this functional development. More precisely, terms of address have the potential to intensify the affectivity displayed by the speaker. In this quality, they may be employed as linguistic strategies to enhance the expressive and illocutionary force of utterances. These expressive uses may be the source of several more peculiar functions related to turn and information management. While this holds for familiarizers as well as for vocatives in general, not interferring with the deictic force of addressing contained in the vocative form, in several languages there are familiarizers which undergo an inflationary use and end up as mere elements of discourse marking, emphasizing and delimiting sequential units such as turns, utterances, and intonation units. The deictic reference to the collocutor is virtually lost, which is shown by the typical fossilization of the masculine singular form in the newly derived functions. We illustrate this development with vocative-based markers in different languages with special focus on the familiarizers güey in Mexican Spanish and alter in German. Although their sociopragmatic indexicalities are far from identical, this comparative approach reveals some interesting similarities. In our view, a definition as ‘pragmatic markers’ is justified for vocative-based markers at any point of their evolution, while the term ‘discourse marker’ should be restricted to functions that are no longer directly inferable from the vocative’s deictic and expressive qualities.
Paths of development of English DMs
Authors: Mazzon Gabriella
Published: October 2017

Starting from notions of conversational dominance as a locus for face-work, and of the crucial role of specific language items in managing conflict and (dis)agreement in dialogue, the paper will look at some case studies in the development and pragmaticalization stages of various English Discourse Markers (such as now, pray, please, I’m afraid, and well). Beginning with the source forms, the paper will discuss the gradual emergence of subjective and intersubjective meanings, as well as the phenomenon of layering and the tendency toward the development of deontic meanings that some English discourse markers show, possibly indicating a form of cyclical development of functions. The specific case studies presented include both a synchronic and a diachronic perspective.
On the pragmatic expansion of Polish gdzieś tam ‘somewhere (there)/about’
Authors: Adamczyk Magdalena
Published: October 2017

In standard usage gdzieś tam functions as an adverbial adding approximation/indeterminacy to expressions of place, time and number/amount/measure, and as such it is semantically equivalent to English ‘somewhere (there) in some contexts and ‘about’ in others. In conversational speech, however, its use sometimes diverges, more or less markedly, from the standard one, which is manifested both formally and functionally. The present study sets out to examine, locally, the lexico-syntactic cotext of gdzieś tam (to see how it differs depending on whether the expression is used conventionally or otherwise) and, globally, novel, context-sensitive functions that the phrase is capable of performing in a communicative act. A broader issue the paper attempts to address is the extent, if any, to which the canonical meaning of gdzieś tam is reflected in the pragmatically expanded use of the expression.
A pragmatic approach to Joseph Wright’s English Dialect Dictionary
Authors: Giuliani Stephan
Published: October 2017

Joseph Wright’s English Dialect Dictionary (EDD; 1898–1905) represents a landmark publication in Late Modern English dialectology. This article explores the potential of the EDD and its digital version (EDD Online) for historical pragmatic research and discusses essential theoretical and methodological considerations that arise from taking a pragmatic approach towards this complex historical document of non-standard English varieties. Besides traditional lexicographic information, the EDD also contains evidence of a great variety of different dialectal documents that are written to mimic spoken language. Three exemplary discourse markers (DM) – aweel, lor-a-massy and arrah – will be introduced and analysed from a pragmatic perspective.
Just a suggestion
Authors: Beeching Kate
Published: October 2017

This article aims to illustrate what a contrastive perspective, combined with sociolinguistic and corpus approaches, can bring to the investigation of the evolution of pragmatic functions which emerge through language contact (Ingham 2012a) and pragmatic borrowing (Andersen 2014). A recent collection of articles (Lauwers, Vanderbauwhede & Verleyen (eds) 2012) draws attention to the light which cognate forms and ‘false friends’ can shed on pragmaticalisation and semantic change. Sociolinguistic studies drawing on corpora of spoken interaction, which are tagged for demographic features, particularly speakers’ age and gender, coupled with modified matched-guise attitudinal studies, show that the use of new functions of pragmaticalising items reflects the incrementation model, posited by Labov (2001), with concomitant indexical obsolescence (Eckert 2014) of the older functions. The approach is illustrated for juste/just, and the conclusions confirm Dostie’s (2009) thesis that items whose meaning predisposes them to become pragmaticalised may do so to a greater extent in one region/language than in another.
Dramatherapy and Psychodrama with Looked-After Children and Young People
Authors: Moore Joan , Andersen-Warren Madeline , Kirk Kate
Published: October 2017

This paper provides the results of a questionnaire constructed to solicit information about the creative structures that dramatherapists and psychodramatists are using in therapy with Looked-After children (LAC) and young people. After a brief account of the research itself the results are presented; this starts by defining the assessment and evaluation tools that are used by the practitioners. The particular needs of this client group are examined and what follows is the analysis and explanation of the creative ways in which the practitioners meet the needs of LAC and young people.
A probabilistic pathway score (PROPS) for classification with applications to inflammatory bowel disease
Authors: Han Lichy , Maciejewski Mateusz , Brockel Christoph , Gordon William , Snapper Scott B , Korzenik Joshua R , Afzelius Lovisa , Altman Russ B
Published: October 2017

Gene-based supervised machine learning classification models have been widely used to differentiate disease states, predict disease progression and determine effective treatment options. However, many of these classifiers are sensitive to noise and frequently do not replicate in external validation sets. For complex, heterogeneous diseases, these classifiers are further limited by being unable to capture varying combinations of genes that lead to the same phenotype. Pathway-based classification can overcome these challenges by using robust, aggregate features to represent biological mechanisms. In this work, we developed a novel pathway-based approach, PRObabilistic Pathway Score, which uses genes to calculate individualized pathway scores for classification. Unlike previous individualized pathway-based classification methods that use gene sets, we incorporate gene interactions using probabilistic graphical models to more accurately represent the underlying biology and achieve better performance. We apply our method to differentiate two similar complex diseases, ulcerative colitis (UC) and Crohn’s disease (CD), which are the two main types of inflammatory bowel disease (IBD). Using five IBD datasets, we compare our method against four gene-based and four alternative pathway-based classifiers in distinguishing CD from UC. We demonstrate superior classification performance and provide biological insight into the top pathways separating CD from UC.

Availability and Implementation

PROPS is available as a R package, which can be downloaded at http://simtk.org/home/props or on Bioconductor.

Supplementary information

Supplementary data are available at Bioinformatics online.
PyBEL: a computational framework for Biological Expression Language
Authors: Hoyt Charles Tapley , Konotopez Andrej , Ebeling Christian
Published: October 2017

Biological Expression Language (BEL) assembles knowledge networks from biological relations across multiple modes and scales. Here, we present PyBEL; a software package for parsing, validating, converting, storing, querying, and visualizing networks encoded in BEL.

Availability and implementation

PyBEL is implemented in platform-independent, universal Python code. Its source is distributed under the Apache 2.0 License at https://github.com/pybel.

Supplementary information

Supplementary data are available at Bioinformatics online.
Cancer progression models and fitness landscapes: a many-to-many relationship
Authors: Diaz-Uriarte Ramon
Published: October 2017

Motivation

The identification of constraints, due to gene interactions, in the order of accumulation of mutations during cancer progression can allow us to single out therapeutic targets. Cancer progression models (CPMs) use genotype frequency data from cross-sectional samples to identify these constraints, and return Directed Acyclic Graphs (DAGs) of restrictions where arrows indicate dependencies or constraints. On the other hand, fitness landscapes, which map genotypes to fitness, contain all possible paths of tumor progression. Thus, we expect a correspondence between DAGs from CPMs and the fitness landscapes where evolution happened. But many fitness landscapes—e.g. those with reciprocal sign epistasis—cannot be represented by CPMs.

Results

Using simulated data under 500 fitness landscapes, I show that CPMs’ performance (prediction of genotypes that can exist) degrades with reciprocal sign epistasis. There is large variability in the DAGs inferred from each landscape, which is also affected by mutation rate, detection regime and fitness landscape features, in ways that depend on CPM method. Using three cancer datasets, I show that these problems strongly affect the analysis of empirical data: fitness landscapes that are widely different from each other produce data similar to the empirically observed ones and lead to DAGs that infer very different restrictions. Because reciprocal sign epistasis can be common in cancer, these results question the use and interpretation of CPMs.

Availability and implementation

Code available from Supplementary Material.

Supplementary information

Supplementary data are available at Bioinformatics online.
Lifeways and territorial innovation: values and practices for promoting collective appropriation of territory
Authors: Herrera Obeimar B , Parra Manuel , Livscovsky Iris , Ramos Pedro , Gallardo Daniela
Published: October 2017

In recent decades, most multilateral organizations and other agents of change have used the theoretical approach of sustainable livelihoods to guide their work. This approach has been criticized in recent years for promoting a short-term materialist focus in development projects, thus limiting its practical usefulness and feasibility. Due to the necessity for renewed proposals, a group of community cargos and researchers have developed a long-term comparative retrospective study that goes beyond the conventional approach. It provides a framework with a broader theoretical scope and applied utility grounded on local self-management: lifeways and territorial innovation. Our constructivist approach, based on Bourdieu´s Social Reproduction theory, is aimed at promoting and triggering a sense of territoriality within the communities and further onto the more extensive territory. Since the work was developed along with people from rural communities, we utilized the concept of Social Learning as to enrich the former theoretical principle.
Hierarchical attention networks for information extraction from cancer pathology reports
Authors: Gao Shang , Young Michael T , Qiu John X , Yoon Hong-Jun , Christian James B , Fearn Paul A , Tourassi Georgia D , Ramanthan Arvind
Published: October 2017

Objective

We explored how a deep learning (DL) approach based on hierarchical attention networks (HANs) can improve model performance for multiple information extraction tasks from unstructured cancer pathology reports compared to conventional methods that do not sufﬁciently capture syntactic and semantic contexts from free-text documents.

Materials and Methods

Data for our analyses were obtained from 942 deidentiﬁed pathology reports collected by the National Cancer Institute Surveillance, Epidemiology, and End Results program. The HAN was implemented for 2 information extraction tasks: (1) primary site, matched to 12 International Classification of Diseases for Oncology topography codes (7 breast, 5 lung primary sites), and (2) histological grade classiﬁcation, matched to G1–G4. Model performance metrics were compared to conventional machine learning (ML) approaches including naive Bayes, logistic regression, support vector machine, random forest, and extreme gradient boosting, and other DL models, including a recurrent neural network (RNN), a recurrent neural network with attention (RNN w/A), and a convolutional neural network.

Results

Our results demonstrate that for both information tasks, HAN performed signiﬁcantly better compared to the conventional ML and DL techniques. In particular, across the 2 tasks, the mean micro and macroF-scores for the HAN with pretraining were (0.852,0.708), compared to naive Bayes (0.518, 0.213), logistic regression (0.682, 0.453), support vector machine (0.634, 0.434), random forest (0.698, 0.508), extreme gradient boosting (0.696, 0.522), RNN (0.505, 0.301), RNN w/A (0.637, 0.471), and convolutional neural network (0.714, 0.460).

Conclusions

HAN-based DL models show promise in information abstraction tasks within unstructured clinical pathology reports.
A bequest to Christine of Lorraine from Catherine de’ Medici
Authors: Michahelles Kerrie-rue
Published: October 2017

The French royal family was living in exile at Blois when the Queen Mother of France, Catherine de’ Medici (b. 1519), dictated her will on the morning of her death, on 5 January 1589. She bequeathed to her granddaughter, Christine of Lorraine (1565–1637), one half of her movable possessions. This paper explores the nature and meanings embedded in the testamentary bequest and the corresponding inventory of the movable goods acquired by Christine through this gift and eventually brought to Florence on the occasion of her marriage in 1589 to Ferdinando de’ Medici, Grand Duke of Tuscany (1549–1609). A translation of the inventory is provided in an online appendix.
Ventriculoscopic Surgery for Cystic Retrochiasmatic Craniopharyngiomas: Indications, Surgical Technique, and Short-Term Patient Outcomes
Authors: Hollon Todd C , Savastano Luis E , Altshuler David , Barkan Ariel L , Sullivan Stephen E
Published: October 2017

BACKGROUND

Attempted gross-total resection for the management of cystic retrochiasmatic craniopharyngiomas can cause severe hypothalamic dysfunction and decrease overall survival. Ventriculoscopic surgery is a minimally invasive alternative; however, potential indications and technique have not been well defined.

OBJECTIVE

To present our indications and technique for the ventriculoscopic treatment of cystic retrochiasmatic craniopharyngiomas.

METHODS

We evaluated all patients with retrochiasmatic craniopharyngiomas for ventriculoscopic surgery. Indications and operative technique were developed to minimize operative morbidity, relieve mass effect, and optimize functional outcome. Cyst size and functional outcomes were statistically evaluated to determine radiographic and short-term clinical outcome.

RESULTS

Indications for ventriculoscopic surgery included (1) radiographic evidence of hypothalamic involvement and (2) major cystic component. Ten patients met indications, and mean follow-up was 2.5 ± 1.6 yr. The surgical technique included wide cyst fenestration at the foramen of Monro, and fenestration of inferior cyst wall/third ventriculostomy (“through-and-through” technique). Preoperative Karnofsky performance status was 70 ± 15 and was inversely correlated with preoperative cyst size (13 ± 13 cm3). A statistically significant reduction in cyst size was found on early postoperative imaging (2.1 ± 4.3 cm3). Seven patients received postoperative radiotherapy. Postoperative performance scores (81 ± 8.3) had improved; no patient suffered functional decline. Pre- and postoperative body mass indices were similar. No patient had short-term hypothalamic obesity.

CONCLUSION

Ventriculoscopic surgery, with or without adjuvant treatments, can reduce early postoperative tumor volume and improve short-term functional status in cystic retrochiasmatic craniopharyngiomas with hypothalamic involvement; it should be considered a minimally invasive option in the multimodal treatment of craniopharyngiomas. Further studies are needed to determine long-term efficacy.
Inherited and acquired clinical phenotypes associated with neuroendocrine tumors
Authors: Nicholaides Rory E. , de la Morena M. Teresa
Published: October 2017

Purpose of review

Overview of neuroendocrine neoplasms in the context of their associations with primary and secondary immunodeficiency states.

Recent findings

Malignancies of neuroendocrine origin are well known to be associated with hereditary syndromes, including multiple endocrine neoplasia type 1, von Hippel–Lindau syndrome, neurofibromatosis type 1, and tuberous sclerosis. This review includes the X-linked form of hyper-IgM syndrome (XHIGM), due to mutations in the CD40Ligand gene (CD40LG), as an additional inherited disorder with susceptibility to such malignancies, and discusses neuroendocrine tumors (NETs) arising in other immunocompromised states. Of all primary immune deficiency diseases, NETs appear to be unique to XHIGM patients. Outcomes for XHIGM patients with NETs is poor, and the mechanism behind this association remains unclear. In secondary immune deficiency states, NET occurrences were primarily in patients with HIV or AIDS, the autoimmune disease systemic lupus erythematosus and solid organ transplant recipients. Gastroenteropancreatic NETs were most frequent in XHIGM patients, whereas nongastroenteropancreatic–NETs, like Merkel cell carcinoma and small-cell lung carcinoma, affected HIV/AIDS patients. Possible mechanisms as to the nature of these associations are discussed, including chronic infections and inflammation, and CD40–CD40L interactions. Many questions remain, and further studies are needed to clarify the predisposition of patients with XHIGM to the development of NETs. Given that many of these patients present late in their disease state and have poor outcomes, it is imperative to keep a high index of suspicion at the advent of early signs and symptoms. Regular monitoring with laboratory or imaging studies, including tumor markers, may be warranted, for which further studies are needed.

Of all primary immunodeficiency diseases, NETs appear to be unique to XHIGM, and the mechanism behind this association remains unclear. Outcome for XHIGM patients with NETs is poor, and it is imperative to keep a high index of suspicion at the advent of early signs and symptoms.
The complexities of fibromyalgia and its comorbidities
Authors: Lichtenstein Adi , Tiosano Shmuel , Amital Howard
Published: October 2017

Purpose of review

Fibromyalgia syndrome (FMS) is defined as chronic, widespread musculoskeletal pain and tenderness with concomitant mood and cognitive dysfunction. Several comorbidities have been reported to be associated with FMS. We reviewed the literature concerning the most noteworthy chronic conditions associated with FMS.

Recent findings

There is mounting evidence displaying the concurrence of fibromyalgia and coexisting medical and psychiatric conditions. Such comorbidities may blur the classical clinical presentations and erroneously lead to misinterpretation of disease activity. The recognition of this fact should be underlined, as misrecognition may lead to excessive therapy and avoidable side-effects of medications on the one hand and to a better handling of FMS on the other hand, leading to improved clinical outcomes.

A greater proportion of psychiatric and rheumatologic disorders are associated with FMS patients than the population. Consequently, physicians treating patients with either condition should keep in mind that these patients may have such comorbidities and should be treated accordingly.
In Vitro Effect of Vancomycin on the Viability of Articular Chondrocytes
Authors: Shaw K. Aaron , Eichinger Josef K. , Nadig Nischal , Parada Stephen A.
Published: October 2017

Objectives:

To characterize the in vitro toxicity of vancomycin on articular cartilage.

Methods:

Osteochondral samples extracted from fresh, juvenile porcine stifle (knee) joints were exposed to vancomycin saline concentrations of 2, 5, and 10 mg/mL and compared with a saline and nonsaline treated control. Comparison of chondrocyte viability was assessed with histology examination of chondrocyte degeneration using the Mankin criteria and a live/dead staining using ethidium homodimer-2 and calcien acetoxymethylester stain and confocal laser scanning microscopy.

Results:

A comparison of chondrocyte viability in the control sample and 2 mg/mL group showed no statistical difference (P = 0.38). The chondrocyte toxicity was statistically significantly higher in both the 5 mg/mL (P = 0.003) and 10 mg/mL (P < 0.001) experimental groups in comparison to the control sample. Chondrocyte death increased in a statistically significant dose-dependent fashion. Histologically, the Mankin scores were higher for the saline-treated group in comparison to the untreated control group.

Conclusions:

Vancomycin is toxic to articular chondrocytes in concentrations of 5 mg/mL and greater. Strategies for controlling concentration must be developed before routine application of topical antibiotics around synovial joints is performed.
Sex Differences in Vascular Reactivity to Angiotensin II During the Evolution of Myocardial Infarction
Authors: Flores-Monroy Jazmin , Ramirez-Hernández Diana , Samano-Hernández Citali , Lezama-Martínez Diego , Sampieri-Cabrera Raul , Martínez-Aguilar Luisa
Published: October 2017

The influence of sex on the vascular response during the progression of myocardial infarction (MI) has not been extensively studied. In this work, we analyzed the differences of the vasoconstriction induced by angiotensin II (Ang II) in the absence and presence of valsartan (200 nM) on the aortic rings of male and female Wistar rats at 2, 4, 24, and 48 hours and 1, 2, 3, and 4 weeks after induction of MI. In the aortic rings of males, an increase was observed in the contractile response that lasts up to 4 weeks; on females, this effect is diminished since 48 hours until reaching sham group values at 2 weeks of coronary occlusion. The incubation of valsartan generated greater reduction on vasoconstriction in males than females. In relation to the determination of infarct areas, we found them between 30% and 40% in all experimental groups. In addition, the index of hypertrophy was determined and no significant changes were observed in female rats, while in males we reported an increase at 2, 3, and 4 weeks. In conclusion, we found differences in vascular reactivity due to sex, as well as on the response of Ang II via AT1 during the evolution of MI.
TESTOSTERONE SUPPLEMENTATION AND RETINAL VASCULAR DISEASE
Authors: Dedania Vaidehi S. , Zacks David N. , Pan Wei , VanderBeek Brian L.
Published: October 2017

Purpose:

To determine whether testosterone supplementation is associated with retinal artery occlusion (RAO) or retinal vein occlusion (RVO).

Methods:

Retrospective matched cohort study using data from a large national U.S. insurance database. The testosterone cohort consisted of all male patients who filled a prescription for testosterone from 2000 to 2013. Five controls were matched on age (±3 years), sex, race, and similar time in plan (±3 months) for every exposed patient. Exclusion occurred for <2 years in the plan, <1 eye care visit, medications known to affect androgen levels, and systemic diseases associated with occlusions or increased testosterone. Cox proportional hazard regression assessed the hazard of a new diagnosis of RAO or RVO while controlling for age, race, diabetes mellitus, and hypertension.

Results:

A total of 35,784 incident testosterone users were compared with 178,860 matched controls. Ninety-three (0.3%) RAOs and 50 (0.1%) RVOs were found in the testosterone cohort and contrasted with 316 (0.2%) RAOs and 232 (0.1%) RVOs in the control group. After multivariate analysis, testosterone supplementation significantly increased the hazard of RAO (hazard ratio: 1.43, 95% confidence interval: 1.12–1.81, P = 0.004), but not of RVO (hazard ratio: 1.03, 95% confidence interval: 0.74–1.42, P = 0.86).

Conclusion:

Although the incidence of RAO and RVO is low in users of testosterone, supplementation therapy is associated with an increased hazard of RAO, but apparently not of RVO.
Outcomes and Rationale of Excision and Mucous Membrane Grafting in Palpebral Vernal Keratoconjunctivitis
Authors: Iyer Geetha , Agarwal Shweta , Srinivasan Bhaskar
Published: October 2017

Purpose:

To report outcomes of mucous membrane grafting (MMG) for refractory giant papillae in vernal keratoconjunctivitis.

Methods:

Eleven eyes of 6 patients having giant papillae and recurrent shield ulcers refractory to topical medications, cryotherapy, and supratarsal steroid injections and shave excision of papillae underwent surgical resection of the giant papillae with MMG. Average occurrence of shield ulcers was twice per eye per year before the procedure with 50% of eyes having steroid-induced cataract and glaucoma.

Results:

No recurrence of the shield ulcer in any eye was observed over a mean follow-up period of 38.2 (range 9–106) months. The papillae recurred beyond the graft junction in one eye.

Conclusions:

Surgical excision of refractory giant papillae followed by MMG does have its advantages in reducing their corneal complications, and it should be considered early in the management of exuberant refractory giant papillae.
Factors Limiting the Visual Outcome After Descemet Stripping Automated Endothelial Keratoplasty: Comprehensive Analysis Including the Graft Position and Irregularity
Authors: Iwama Yasuaki , Soma Takeshi , Maeda Naoyuki , Sasamoto Yuzuru , Oie Yoshinori , Koh Shizuka , Nishida Kohji
Published: October 2017

Purpose:

To investigate factors affecting best postoperative corrected distance visual acuity (CDVA) in patients who have undergone Descemet stripping automated endothelial keratoplasty (DSAEK).

Methods:

Forty-two eyes of 42 patients with predominantly non-Fuchs endothelial corneal dystrophy after DSAEK were retrospectively evaluated. All patients were examined using anterior segment optical coherence tomography when their best postoperative CDVA had been achieved. We analyzed the relationship between best postoperative CDVA and preoperative, intraoperative, and postoperative factors, including corneal higher-order aberrations (HOAs), corneal backward scattering, graft irregularity, and graft decentration. Variables with P < 0.2 in univariate analysis were entered into a multivariate linear regression model to determine the factors affecting best postoperative CDVA.

Results:

Mean CDVA improved from 1.16 ± 0.46 preoperatively to 0.22 ± 0.19 logarithm of the minimum angle of resolution equivalents postoperatively (P < 0.0001). Best postoperative CDVA was achieved 11.6 ± 7.7 months after DSAEK. Multivariate analysis showed that anterior corneal coma-like HOAs and venting incisions inside the pupil area were significantly correlated with best postoperative CDVA (t = 2.90, P = 0.006; t = 2.62, P = 0.01, respectively). No significant relationship was found between the visual outcome and any other factor, including posterior corneal HOAs, corneal backward scattering, graft decentration, and graft irregularity.

Conclusions:

Irregularity of the anterior corneal surface and venting incisions inside the pupil area are important factors that impair best postoperative CDVA in patients who have undergone DSAEK. In contrast, our results indicate that the graft position and irregularity might not have a strong influence on the visual outcome after DSAEK.
Sutureless Deep Sclerectomy: A Preliminary Report
Authors: Abdelrahman Ahmed M. , ElTanamly Rasha , Sabry Mohamed
Published: October 2017

This study describes a modification of deep sclerectomy, making it completely sutureless, with a 6-month follow-up period. This was a prospective pilot phase that included 24 eyes of 16 patients, 13 male individuals and 3 female individuals, with medically uncontrolled open-angle glaucomas despite maximally tolerated medical therapy. After excising the deep flap, no sutures are added to the superficial scleral flap or to the conjunctiva. A statistically significant reduction of the intraocular pressure was reported during all the follow-up visits without serious complications.
Test Conditions in Macular Visual Field Testing in Glaucoma
Authors: Eura Mariko , Matsumoto Chota , Hashimoto Shigeki , Okuyama Sachiko , Takada Sonoko , Nomoto Hiroki , Tanabe Fumi , Shimomura Yoshikazu
Published: October 2017

Purpose:

The purpose of this study is to evaluate the suitable visual field (VF) test conditions (target size, test type, and eccentricity) for the macular region, we investigated the correlations between the ganglion cell layer (GCL) thickness and 6 VF test results.

Methods:

We tested 32 eyes of patients (61.1±9.2 y) with preperimetric (6), early-stage (16), and moderate-stage (10) glaucoma. The VF tests included 3 SAP (the 10-2 HFA using SITA with target size III [HFA SITA (III)], full threshold with size III [HFA FULL (III)] and size I [HFA FULL (I)]) and 3 visual function-specific perimetry tests (the 10-2 SWAP, 10-2 flicker, and 10-2 Humphrey Matrix). The GCL and inner plexiform layer (GCL+IPL) thickness was measured by Spectral Domain Optical Coherence Tomography (SD-OCT) with a macular 7×7 mm2 cube scan (3D OCT-2000, Topcon). The coefficient of determination (r
2) for the correlation between visual sensitivity and the GCL+IPL thickness was calculated for each test at eccentricities 0 to 5 degrees, 5 to 7 degrees, and 7 to 10 degrees using linear and quadratic regressions.

Results:

All 6 tests showed the strongest correlation with the GCL+IPL thickness at 5 to 7 degrees. The respective r
2 (linear) and R
2 (quadratic) for HFA SITA (III), HFA FULL (III), HFA FULL (I), SWAP, Flicker, and Matrix were (0.40, 0.50), (0.43, 0.53), (0.44, 0.46), (0.51, 0.51), (0.33, 0.34), and (0.52, 0.52).

Conclusions:

As compared with the frequently-used SAP with a size III, SAP with size I and the function-specific perimetry tests (especially the Matrix) could be more suitable for testing the macular region.
Reversible Venting Stitch for Fenestrating Valve-less Glaucoma Shunts
Authors: Akil Handan , Vu Priscilla Q. , Nguyen Anhtuan H. , Nugent Alexander , Chopra Vikas , Francis Brian A. , Tan James C.
Published: October 2017

Purpose:

The purpose of this is to describe a venting stitch modification for valveless glaucoma aqueous shunts and characterize early postoperative intraocular pressure (IOP) and glaucoma medication use following the modification.

Materials and Methods:

Retrospective chart review of 61 sequential patients undergoing Baerveldt glaucoma implant (BGI)-350 implantation at the Doheny Eye Institute. Twenty-four patients received a glaucoma shunt with venting stitch modification (modified BGI) and 37 patients received an unmodified shunt (BGI-only). IOP, number of glaucoma medications, and number of hypotony cases (intraocular pressure ≤5 mm Hg) were compared between the groups. T-tests were used for statistical analysis.

Results:

At postoperative-day 1, mean IOP was significantly lower compared with preoperatively in the modified BGI group (14 mm Hg; reduced by 51%; P<0.0001) but not the BGI-only group (27 mm Hg; P=0.06). IOP difference between groups persisted till immediately before tube opening (P=0.005) and fewer IOP-lowering medications needed in the modified BGI group (P<0.0001). One case (4.2%) of postoperative hypotony was encountered with BGI modification, which resolved after the stitch was removed in clinic.

Conclusions:

The venting stitch valveless shunt modification allows for effective, reliable, and safe control of early postoperative IOP.
New Approach for Differentiation of Bone Marrow Mesenchymal Stem Cells Toward Chondrocyte Cells With Overexpression of MicroRNA-140
Authors: Mahboudi Hossein , Soleimani Masoud , Hanaee-Ahvaz Hana , Ghanbarian Hossein , Bandehpour Mojgan , Enderami Seyed Ehsan , Kazemi Bahram
Published: October 2017

Mesenchymal stem cells are widely stimulated by transforming growth factor beta-3 (TGFβ3) for chondrocyte differentiation. The objective of our study was to establish a new method for differentiation of human mesenchymal stem cells toward chondrocyte by overexpression of MicroRNA-140 (miR-140), and also this method was compared with method of induction with TGFβ3 in high-cell density culture systems. Mesenchymal stem cells were harvested from bone marrow of human. We prepared vectors and then was used for recombinant Lenti virus production in HEK-293 cell. Transducted cells were cultured in monolayer culture system and were harvested after days 7, 14, and 21. Real time polymerase chain reaction (RT-PCR) was performed to evaluate the cartilage-specific genes in the mRNA levels. Also, in order to confirm our results, we have done immunocytochemistry technique. Bone marrow mesenchymal stem cells (BMSCs) were transducted with recombinant Lenti virus, and miR-140 was expressed. Immunocytochemical method confirmed the differentiation of BMSC toward chondrocyte with handling cartilage matrix genes. Also real-time PCR showed that after expression of miR-140 in transducted BMSCs significantly increased gene expression of collagen type II and aggrecan and downregulated expression of collagen type I when compared with the mRNA levels measured in nontransducted BMSCs. These results were compatible compared with TGFβ3 induction method as control positive. In this study, we described a new approach and technique that may be applied for differentiation of BMSCs to chondrocyte instead of stimulation with TGFβ3. Our data implies that miR-140 is a potent chondrogenic differentiation inducer for BMSCs, and we have shown increasing chondrogenic differentiation by using miR-140 overexpression.
Choice of Endoscopic Procedure in Children With Clinically Suspected Gastrointestinal Graft‐versus‐host Disease
Authors: Mårtensson Thomas , Szakos Attila , Mellgren Karin , Toporski Jacek , Arvidson Johan , Casswall Thomas H. , Gustafsson Britt
Published: October 2017

Objectives:

Gastrointestinal graft‐versus‐host disease (GI‐GVHD) is a potentially life‐threatening complication after hematopoietic stem cell transplantation. Symptoms indicating GI‐GVHD motivates endoscopy with biopsy sampling and histopathological confirmation. Optimal extent of endoscopy in children is, however, presently unknown. Therefore, we aimed to evaluate whether biopsies from the rectosigmoid area versus the rest of the colon/ileocolon with or without biopsies from simultaneous upper endoscopy, were equally reliable for detection of GI‐GVHD and relevant differential diagnoses.

Methods:

Retrospective multicenter study based on histopathological re‐evaluation of biopsies and hospital record data, collected from children with suspected GI‐GVHD.

Results:

Forty‐four children with 51 endoscopic occasions (81 procedures) were included. Thirty‐nine of 51 (76.5%) were diagnosed as GI‐GVHD, 14 (27.4%) received a differential diagnosis and 7 (13.7%) had normal histology findings. Comorbidity, that is, simultaneous detection of a differential diagnosis and GI‐GVHD, was observed in 9 (23.1%) cases. Cytomegalovirus infection was the most frequent differential diagnosis, 6 of 7 were detected in biopsies from rectosigmoid and esophagogastroduodenal areas. Sensitivity for detection of GI‐GVHD in biopsies collected from rectosigmoid‐ileocolonic‐, rectosigmoid‐, or esophagogastroduodenal areas were 97.4%, 84.6%, 83.3%, respectively, and 97.4% when the latter 2 were merged. The difference, nondetected GI‐GVHD in the rectosigmoid area versus detected elsewhere in the GI tract, was statistically significant (P = 0.03).

Conclusions:

Biopsies collected from the rectosigmoid area solely were not optimal for detection of pediatric GI‐GVHD. When biopsy sampling from rectosigmoid and upper GI tract areas was combined, the sensitivity for GI‐GVHD was, however, equally high as for ileocolonoscopy or full upper and lower endoscopy.
Awareness and Implementation of the 2014 ESPGHAN/NASPGHAN Guideline for Childhood Functional Constipation
Authors: Koppen Ilan J.N. , Vriesman Mana H. , Tabbers Merit M. , Di Lorenzo Carlo , Benninga Marc A.
Published: October 2017

Objective:

The aim of the study was to assess whether physicians approach children with functional constipation according to the 2014 European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN)/North American Society of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) guideline.

Methods:

We invited pediatricians and pediatric gastroenterologists in the Netherlands and the United States to participate in this anonymous survey using a self‐developed questionnaire containing 19 multiple choice questions concerning evaluation and treatment of children with constipation.

Results:

We included 328 physicians (67% from the United States, 34% from the Netherlands). The majority of US responders (53%) worked in primary care, whereas all Dutch responders worked in a hospital. In total, 31% of responders were not familiar with the guideline (38% US responders vs 16% Dutch responders, P < 0.001). Perianal inspection was frequently (“often” or “always” on a 5‐point Likert scale) conducted by 78% of responders. Digital rectal examination was frequently done by 42%. Inquiry about sexual abuse was made by 18%. Commonly reported reasons for omitting these items were perceived patient or parental discomfort. Most frequently implemented initial nonpharmacological interventions included a toilet training program (89%), optimizing fluid and fiber intake (86% and 81%), a defecation diary (62%), and a reward system (60%). Polyethylene glycol was the most prescribed medication for disimpaction (68%) and maintenance treatment (57% for infants, 97% for children ≥1 year).

Conclusions:

Many responders were not familiar with the ESPGHAN/NASPGHAN guideline for functional constipation. Nonetheless, therapeutic decisions correlated fairly well with recommendations from the guideline, especially for children 1 year of age or older. Guideline awareness and adherence remain to be improved. Future studies should focus on exploring strategies to improve guideline implementation through the development of digital learning tools.
Impaired IL‐10 Receptor‐mediated Suppression in Monocyte From Patients With Crohn Disease
Authors: Nunberg Moran Y. , Werner Lael , Kopylov Uri , Haberman Yael , Lahad Avishay , Weiss Batia , Shouval Dror S.
Published: October 2017

Objectives:

Interleukin‐10 (IL‐10) is an immunoregulatory cytokine that has a central role in suppressing proinflammatory responses. Patients with deleterious mutations in interleukin (IL)‐10 or IL‐10 receptor (IL‐10R) genes develop severe colitis and perianal disease in the first months of life. Whether IL‐10R expression and signaling in pediatric‐ or adult‐onset Crohn disease (CD) are altered is unknown. The objective of this study was to characterize IL‐10R expression and IL‐10R‐mediated suppression in patients with CD.

Methods:

Monocytes were sorted from peripheral blood mononuclear cells of patients with CD and control subjects. IL‐10R expression was determined by flow cytometry. Monocytes were stimulated with lipopolysaccharide (LPS) for 3 hours in the presence of different concentrations of IL‐10 to determine IL‐10‐mediated suppression of tumor necrosis factor α production. Signaling through the IL‐10R was evaluated by quantifying STAT3 phosphorylation in response to IL‐10 stimulation.

Results:

Forty‐two subjects were enrolled in this study: 19 with CD and 23 controls. Stimulation of monocytes with LPS markedly increased IL‐10R expression in both groups but to a much lower extent in patients with CD. In addition, IL‐10‐mediated suppression of TNFα production upon LPS stimulation and IL‐10‐induced STAT3 phosphorylation were attenuated in patients with CD versus controls. Finally, LPS‐stimulated monocytes from patients with CD secreted significantly lower quantities of IL‐10, compared with control monocytes.

Conclusions:

IL‐10R expression and signaling are decreased in monocytes from patients with CD. Additional studies are required to assess whether similar patterns occur in other innate immune cells, especially in the gut, and whether disease activity, medical therapy, and genetic factors modulate these findings.
Early Nutrition Intervention Attenuates Weight Gain for Pediatric Acute Lymphoblastic Leukemia Patients in Maintenance Therapy
Authors: Hill Rachel , Hamby Tyler , Bashore Lisa , Rapisand Stefanie , Galipp Kari , Heym Kenneth , Bowman W. Paul
Published: October 2017

Obesity following treatment of pediatric acute lymphoblastic leukemia (ALL) has become a significant long-term concern. Excessive weight gain often occurs during treatment, particularly during induction and the first 6 months of maintenance therapy, and it may be potentially modifiable. This retrospective study aimed to evaluate the impact of an early, 3-visit nutrition intervention on weight gain during maintenance therapy in ALL patients. Medical records of the intervention group were compared with historical controls who were treated on the same ALL treatment protocols during an earlier time period. Anthropometrics were collected throughout intensive therapy and at every monthly visit during the first 12 months of maintenance therapy. In total, 67 patients were evaluated (33 in the intervention group and 34 in the control group). After controlling for significant predictors of body mass index (BMI) z-scores in maintenance therapy—including higher BMI at diagnosis and weight gain throughout intensive therapy—the intervention group demonstrated more controlled weight gain during maintenance therapy (P<0.0001). A 3-visit nutrition intervention was effective in attenuating weight gain trends during ALL maintenance therapy.