bluuebunny/crossref_metadata_2025 huggingface dataset:
Rac1 GTPase Promotes Interaction of Hematopoietic Stem/Progenitor Cell with Niche and Participates in Leukemia Initiation and Maintenance in Mouse
Authors: Chen Shuying , Li Huan , Li Shouyun , Yu Jing , Wang Min , Xing Haiyan , Tang Kejing , Tian Zheng , Rao Qing , Wang Jianxiang
Published: March 2016

Interaction between hematopoietic stem/progenitor cells (HSPCs) with their niche is critical for HSPC function. The interaction also plays an important role in the multistep process of leukemogenesis. Rac1 GTPase has been found to be highly expressed and activated in leukemia patients. Here, by forced expression of constitutively active form of Rac1 (Rac1-V12) in HSPCs, we demonstrate that active Rac1 promotes interaction of HSPC with niche. We then established an active Rac1 associated acute myeloid leukemia (AML) model by expression of Rac1-V12 cooperated with AML1-ETO9a (AE9a) in mouse HSPCs. Compared with AE9a alone, Rac1-V12 cooperated with AE9a (AER) drives an AML with a short latency, demonstrating that activation of Rac1 GTPase in mice promotes AML development. The mechanism of this AML promotion is by a better homing and lodging of leukemia cells in niche, which further enhancing their colony formation, quiescence and preventing leukemia cells from apoptosis. Further study showed that an inhibitor targeting activated Rac1 can increase the efficacy of chemotherapeutic agents to leukemia cells. This study provides evidence that activation of Rac1 promotes leukemia development through enhancing leukemia cells' homing and retention in niche, and suggests that inhibition of Rac1 GTPase could be an effective way of eliminating AML cells.
Lineage-Specific Early Differentiation of Human Embryonic Stem Cells Requires a G2 Cell Cycle Pause
Authors: Van Oudenhove Jennifer J. , Grandy Rodrigo A. , Ghule Prachi N. , del Rio Roxana , Lian Jane B. , Stein Janet L. , Zaidi Sayyed K. , Stein Gary S.
Published: March 2016

Human embryonic stem cells (hESCs) have an abbreviated G1 phase of the cell cycle that allows rapid proliferation and maintenance of pluripotency. Lengthening of G1 corresponds to loss of pluripotency during differentiation. However, precise mechanisms that link alterations in the cell cycle and early differentiation remain to be defined. We investigated initial stages of mesendodermal lineage commitment in hESCs, and observed a cell cycle pause. Transcriptome profiling identified several genes with known roles in regulation of the G2/M transition that were differentially expressed early during lineage commitment. WEE1 kinase, which blocks entry into mitosis by phosphorylating CDK1 at Y15, was the most highly expressed of these genes. Inhibition of CDK1 phosphorylation by a specific inhibitor of WEE1 restored cell cycle progression by preventing the G2 pause. Directed differentiation of hESCs revealed that cells paused during commitment to the endo- and mesodermal, but not ectodermal, lineages. Functionally, WEE1 inhibition during meso- and endodermal differentiation selectively decreased expression of definitive endodermal markers SOX17 and FOXA2. Our findings identify a novel G2 cell cycle pause that is required for endodermal differentiation and provide important new mechanistic insights into early events of lineage commitment.
Pubertal exposure to ethinylestradiol promotes different effects on the morphology of the prostate of the male and female gerbil during aging
Authors: Perez Ana P. S. , Biancardi Manoel F. , Caires Cássia R. S. , Falleiros Luiz R. , Góes Rejane M. , Santos Fernanda C. A. , Taboga Sebastião R.
Published: March 2016

In rodents, the final growth and maturation of the prostate occur at puberty, a crucial period for prostate development. The present study is a serological, morphological, morphometric, and immunohistochemical analysis of the effects of exposure to ethinylestradiol (EE) (15 µg/kg/day) during puberty (EE/PUB group) on the male ventral and female prostate in senile gerbils. In the study, male and female gerbils (Meriones unguiculatus) (42 days) received by gavage 15 μg/kg/day of EE (a component of the contraceptive pill), diluted in 100 µL of Nujol® for 1 week (EE/PUB group). In the control group, males and females were not treated. Animals were killed (n = 5) after 12 months in the experimental groups. In the senile male in the EE/PUB group, we observed a reduction in testosterone levels and a decrease in the prostatic epithelial thickness, as well as in the thickness of the muscle layer. In addition, an increase in PIN multiplicity and prostatic inflammation was observed. In the senile female in the EE/PUB group, we observed increased testosterone and estradiol levels, an enhanced prostatic epithelial thickness and an increase in the thickness of the muscle layer. Immunohistochemical analysis revealed an increase in positive cells (%) for AR and PCNA in the male prostate and an increase in positive basal cells for p63 in the female prostate of the EE/PUB group. Exposure to EE during puberty resulted in an inhibitory action on the male ventral prostate and an anabolic effect on the female prostate in senile gerbils. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 477–489, 2017.
Focus on Methodology: Beyond paper and pencil: Conducting computer‐assisted data collection with adolescents in group settings
Authors: Raffaelli Marcela , Armstrong Jessica , Tran Steve P. , Griffith Aisha N. , Walker Kathrin , Gutierrez Vanessa
Published: March 2016

Computer‐assisted data collection offers advantages over traditional paper and pencil measures; however, little guidance is available regarding the logistics of conducting computer‐assisted data collection with adolescents in group settings. To address this gap, we draw on our experiences conducting a multi‐site longitudinal study of adolescent development. Structured questionnaires programmed on laptop computers using Audio Computer Assisted Self‐Interviewing (ACASI) were administered to groups of adolescents in community‐based and afterschool programs. Although implementing ACASI required additional work before entering the field, we benefited from reduced data processing time, high data quality, and high levels of youth motivation. Preliminary findings from an ethnically diverse sample of 265 youth indicate favorable perceptions of using ACASI. Using our experiences as a case study, we provide recommendations on selecting an appropriate data collection device (including hardware and software), preparing and testing the ACASI, conducting data collection in the field, and managing data.
Hepatocellular Carcinoma Post Embolotherapy: Imaging Appearances and Pitfalls on Computed Tomography and Magnetic Resonance Imaging
Authors: Chiu Rita Y.W. , Yap Wan W. , Patel Roshni , Liu David , Klass Darren , Harris Alison C.
Published: March 2016

Embolotherapies used in the treatment of hepatocellular carcinoma (HCC) include bland embolization, conventional transarterial chemoembolization (cTACE) using ethiodol as a carrier, TACE with drug-eluting beads and super absorbent polymer microspheres (DEB-TACE), and selective internal radiation therapy (SIRT). Successfully treated HCC lesions undergo coagulation necrosis, and appear as nonenhancing hypoattenuating or hypointense lesions in the embolized region on computed tomography (CT) and magnetic resonance. Residual or recurrent tumours demonstrate arterial enhancement with portal venous phase wash-out of contrast, features characteristic of HCC, in and/or around the embolized area. Certain imaging features that result from the procedure itself may limit assessment of response. In conventional TACE, the high-attenuating retained ethiodized oil may obscure arterially-enhancing tumours and limit detection of residual tumours; thus a noncontrast CT on follow-up imaging is important post-cTACE. Hyperenhancement within or around the treated zone can be seen after cTACE, DEB-TACE, or SIRT due to physiologic inflammatory response and may mimic residual tumour. Recognition of these pitfalls is important in the evaluation embolotherapy response.
A comparison of the usage of anal verge and dentate line in measuring distances within the rectum
Authors: Chang K.H. , Johnson J.A. , Waldron D. , Condon E.T. , El-Bassiouni M. , Coffey J.C.
Published: March 2016

ABSTRACT

Introduction:

The anal verge is key in determining measurement-based suitability for neoadjuvant radiotherapy in rectal cancer. The dentate line is a distinct anatomic landmark and may permit more accurate measurement for rectal lesions. This study aimed to establish measurative ranges for distances of the rectal valves from the dentate line and the anal verge and to compare variability between the two.

Methods:

Patients (n = 104) undergoing colonoscopy and sigmoidoscopy were prospectively accrued. The distances of rectal valves were measured from the anal verge and the dentate line respectively by using a vector subtraction-based approach. Distances were correlated with gender, age and body mass index. Standard deviation was the measure of variability.

Results:

The gross topography of the rectum was remarkably consistent with three valves identifiable in the majority (99 of 104) of patients. The median distance between the dentate line and the anal verge was 2.0 cm. The distances of each rectal valve (proximal to distal) to the anal verge and dentate line were 11.4 ± 2.0 cm, 8.6 ± 2.0 cm, 6.0 ± 1.7 cm and 9.1 ± 1.6 cm, 6.3 ± 1.6 cm, 3.7 ± 1.5 cm, respectively. Between-group variability was minimally reduced when using the dentate line as a reference point. Obesity was associated with an increased distance of the proximal rectal valve from the anal verge and the dentate line (p = 0.004 and 0.015 respectively).

Conclusions:

Rectal valve anatomy is remarkably consistent. Both dentate line and anal verge are reliable landmarks from which distances can be measured within the rectum.

Highlights:
Overview of smartphone applications for sleep analysis
Authors: Ong Adrian A. , Gillespie M. Boyd
Published: March 2016

Objective

To review and assess the current selection of sleep analysis smartphone applications (apps) available for download.

Methods

The iOS and Google Play mobile app store were searched for sleep analysis apps targeted for consumer use. Alarm clock, sleep‐aid, snoring and sleep‐talking recorder, fitness tracker apps, and apps geared towards health professionals were excluded. App information and features were obtained from in‐store descriptions, and the app developer website.

Results

A total of 51 unique sleep apps in both iOS and Google Play stores were included. The apps were rated 3.8/5 in both stores, and had an average price of $1.12 in the iOS store and $0.58 in the Google Play store. >65% of sleep apps report on sleep structure, including duration, time awake, and time in light/deep sleep, while reporting of REM was limited. The availability of extra features was variable, ranging from 4% to 73% of apps.

Conclusions

There are a variety of sleep analysis apps with a range of functionality. The apps with the most reviews from the each store are featured. Many apps provide data on sleep structure; however the algorithms are not validated by scientific literature or studies. Since patients may inquire about their sleep habits from these apps, it is necessary for physicians to be aware of the most common apps and the features offered and their limitations in order to properly counsel patients.
Writing Performative Shakespeares
Authors: Conkie Rob
Published: March 2016

This innovative study offers a genuinely groundbreaking approach to Shakespeare in performance. Six chapters work like case studies, each highly creative in terms of visual form and structure – including puzzles, comics and pinboards – inviting the reader into playful engagement with the performative dimensions of Shakespearean production. The case studies include discussion of training and rehearsal processes; the materiality of the performance event and its various embodiments; the intertextual citations through which productions make meaning; and, in response to all of this, the multiplicity and variety of audience perspectives and interpretations. Conkie's production choices range from original practices to politicised adaptations, small-scale workshops to multimedia spectacles, offering inventive analyses of what Shakespeare might mean, or can be made to mean, at particular times and in specific places, at the start of the twenty-first century.
Government as Practice
Authors: Bhattacharyya Dwaipayan
Published: March 2016

The democratic Left in India is in crisis. During the first decade of this century it slid from its highest parliamentary presence to virtual irrelevance. A key to its retrieval, this book argues, lies in its ability to imagine a new popular politics for reinventing its democratic credentials beyond electoral posturing. In this respect, much can be learnt from the Left's governmental practices as they have evolved since the late 1960s, crafting a unique blend of politics, policy, idealism, practicality, vision and delivery. By looking at the problematics of government from the days of deft land reforms to messy land acquisition, this book situates 'government as practice' as a prism for critical thinking on democratic politics in postcolonial India. Grounded in empirical and archival research, the book will be useful for those who are passionate as well as sceptical about the revival potentials of a new Left in India's fast-changing political economy.
The Rise of Modern Science Explained
Authors: Cohen H. Floris
Published: March 2016

For centuries, laymen and priests, lone thinkers and philosophical schools in Greece, China, the Islamic world and Europe reflected with wisdom and perseverance on how the natural world fits together. As a rule, their methods and conclusions, while often ingenious, were misdirected when viewed from the perspective of modern science. In the 1600s thinkers such as Galileo, Kepler, Descartes, Bacon and many others gave revolutionary new twists to traditional ideas and practices, culminating in the work of Isaac Newton half a century later. It was as if the world was being created anew. But why did this recreation begin in Europe rather than elsewhere? This book caps H. Floris Cohen's career-long effort to find answers to this classic question. Here he sets forth a rich but highly accessible account of what, against many odds, made it happen and why.
The Geometry of Celestial Mechanics
Authors: Geiges Hansjörg
Published: March 2016

Celestial mechanics is the branch of mathematical astronomy devoted to studying the motions of celestial bodies subject to the Newtonian law of gravitation. This mathematical introductory textbook reveals that even the most basic question in celestial mechanics, the Kepler problem, leads to a cornucopia of geometric concepts: conformal and projective transformations, spherical and hyperbolic geometry, notions of curvature, and the topology of geodesic flows. For advanced undergraduate and beginning graduate students, this book explores the geometric concepts underlying celestial mechanics and is an ideal companion for introductory courses. The focus on the history of geometric ideas makes it perfect supplementary reading for students in elementary geometry and topology. Numerous exercises, historical notes and an extensive bibliography provide all the contextual information required to gain a solid grounding in celestial mechanics.
Samuel Richardson and the Art of Letter-Writing
Authors: Curran Louise
Published: March 2016

This fascinating study examines Samuel Richardson's letters as important works of authorial self-fashioning. It analyses the development of his epistolary style; the links between his own letter-writing practice and that of his fictional protagonists; how his correspondence is highly conscious of the spectrum of publicity; and how he constructed his letter collections to form an epistolary archive for posterity. Looking backwards to earlier epistolary traditions, and forwards, to the emergence of the lives-in-letters mode of biography, the book places Richardson's correspondence in a historical continuum. It explores how the eighteenth century witnesses a transition, from a period in which an author would rarely preserve personal papers to a society in which the personal lives of writers become privileged as markers of authenticity in the expanded print market. It argues that Richardson's letters are shaped by this shifting relationship between correspondence and publicity in the mid-eighteenth century.
In Defense of Pluralism
Authors: Montpetit Éric
Published: March 2016

The work of early pluralist thinkers, from Arthur Bentley to Robert Dahl, inspired much optimism about democracy. They argued that democracy was functioning well, despite disagreements arising among the diversity of interests represented in policy-making processes. Yet it is unlikely that anyone paying attention to news coverage today would share such optimism. The media portray current policy-making processes as intractably polarized, devoid of any opportunity to move forward and adopt essential policy changes. This book aims to revive our long-lost sense of optimism about policy-making and democracy. Through original research into biotechnology policy-making in North America and Europe, Éric Montpetit shows that the depiction of policy-making offered by early pluralist thinkers is not so far off the present reality. Today's policy decision-making process - complete with disagreement among the participants - is consistent with what might be expected in a pluralist society, in sharp contrast with the negative image projected by the media.
Practical Foundations for Programming Languages
Authors: Harper Robert
Published: March 2016

This text develops a comprehensive theory of programming languages based on type systems and structural operational semantics. Language concepts are precisely defined by their static and dynamic semantics, presenting the essential tools both intuitively and rigorously while relying on only elementary mathematics. These tools are used to analyze and prove properties of languages and provide the framework for combining and comparing language features. The broad range of concepts includes fundamental data types such as sums and products, polymorphic and abstract types, dynamic typing, dynamic dispatch, subtyping and refinement types, symbols and dynamic classification, parallelism and cost semantics, and concurrency and distribution. The methods are directly applicable to language implementation, to the development of logics for reasoning about programs, and to the formal verification language properties such as type safety. This thoroughly revised second edition includes exercises at the end of nearly every chapter and a new chapter on type refinements.
Expression of 17β-hydroxysteroid dehydrogenase and the effects of LH, FSH and prolactin on oestrone and 17β-oestradiol secretion in the endometrium of pigs during early pregnancy and the oestrous cycle
Authors: Wojciechowicz B. , Kotwica G. , Zglejc K. , Waszkiewicz E. , Franczak A.
Published: March 2016

The endometrium of pregnant and cyclic pigs is a source of oestrone (E1) and 17β-oestradiol (E2). However, the roles of LH, FSH and prolactin (PRL) as regulators of endometrial steroidogenesis, and the presence of 17β-hydroxysteroid dehydrogenase (17β-HSD) in the porcine endometrium, remain unknown. Therefore, in the present study we examined 17β-HSD expression and the effects of LH, FSH and PRL on E1 and E2 release in vitro in endometrial explants harvested from gravid pigs on Days 10–11 (embryo migration within the uterus), 12–13 (maternal recognition of pregnancy) and 15–16 (beginning of implantation) and compared them with results obtained in non-gravid pigs. The results show that: (1) endometrial 17β-HSD activity was decreased on Days 15–16 in pregnant and cyclic pigs compared with the preceding days; (2) LH, FSH and PRL increased endometrial E1 secretion on Days 10–11 and 15–16 of pregnancy and on Days 12–13 and 15–16 of the oestrous cycle; and (3) LH, FSH and PRL increased endometrial E2 secretion on Days 15–16 of pregnancy and during the days studied in the oestrous cycle. In conclusion, data suggest that LH, FSH and PRL affect endometrial secretion of estrogens in pigs.
The Universe Had One Chance
Authors: Demarest Heather
Published: March 2016

In a deterministically evolving world, the usefulness of nontrivial probabilities can seem mysterious. I use the ‘Mentaculus’ machinery developed by David Albert and Barry Loewer to show how all probabilities in such a world can be derived from a single, initial chance event. I go on to argue that this is the only genuine chance event. Perhaps surprisingly, we have good evidence of its existence and nature. I argue that the existence of this chance event justifies our epistemic reliance on nontrivial probabilities.
Sufficient Conditions for Causality to Be Transitive
Authors: Halpern Joseph Y.
Published: March 2016

Natural conditions are provided that are sufficient to ensure that causality as defined by approaches that use counterfactual dependence and structural equations will be transitive.
Beyond Empathy for Pain
Authors: de Vignemont Frédérique , Jacob Pierre
Published: March 2016

Here we address four objections raised by Julien Deonna, John Michael, and Francesca Fardo against a recent account of empathy for pain (by Frédérique de Vignemont and Tania Singer and Vignemont and Pierre Jacob). First, to what extent must the empathizer share her target’s affective state? Second, how can one interpret neuroscientific findings on vicarious pain in light of recent results challenging the notion of a pain matrix? Third, can one offer a simpler account of how empathy makes one aware of another’s emotion? Finally, to what extent can this account of empathy for pain be generalized to empathy for emotions?
Search for soft X-ray flashes at the fireball phase of classical/recurrent novae using MAXI/GSC data
Authors: Morii Mikio , Yamaoka Hitoshi , Mihara Tatehiro , Matsuoka Masaru , Kawai Nobuyuki
Published: March 2016

We searched for precursive soft X-ray flashes (SXFs) associated with optically discovered classical or recurrent novae in the data of five years’ all-sky observations with the Gas Slit Camera (GSC) of the Monitor of All-sky X-ray Image (MAXI). We first developed a tool to measure the fluxes of point sources by fitting the event distribution with a model that incorporates the point-spread function (PSF-fit) to minimize the potential contamination from nearby sources. Then we applied the PSF-fit tool to 40 classical/recurrent novae that were discovered in optical observations from 2009 August to 2014 August. We found no precursive SXFs with significance above the 3 σ level in the energy range of 2–4 keV between td − 10 d and td, where td is the date when each nova was discovered. We obtained the upper limits for the bolometric luminosity of SXFs, and compared them with the theoretical prediction and that observed for MAXI J0158−744. This result could constrain the population of massive white dwarfs with a mass of roughly 1.40 solar mass, or larger, in binary systems.
Molecular Mechanisms Linking Autonomic Dysfunction and Impaired Cardiac Contractility in Critical Illness*
Authors: Ackland Gareth L. , Whittle John , Toner Andrew , Machhada Asif , Del Arroyo Ana Gutierrez , Sciuso Alberto , Jenkins Nicholas , Dyson Alex , Struthers Richard , Sneyd J. Robert , Minto Gary , Singer Mervyn , Shah Ajay M. , Gourine Alexander V.
Published: March 2016

Objectives:

Molecular mechanisms linking autonomic dysfunction with poorer clinical outcomes in critical illness remain unclear. We hypothesized that baroreflex dysfunction alone is sufficient to cause cardiac impairment through neurohormonal activation of (nicotinamide adenine dinucleotide phosphate oxidase dependent) oxidative stress resulting in increased expression of G-protein–coupled receptor kinase 2, a key negative regulator of cardiac function.

Design:

Laboratory/clinical investigations.

Setting:

University laboratory/medical centers.

Subjects:

Adult rats; wild-type/nicotinamide adenine dinucleotide phosphate oxidase subunit-2–deficient mice; elective surgical patients.

Interventions:

Cardiac performance was assessed by transthoracic echocardiography following experimental baroreflex dysfunction (sino-aortic denervation) in rats and mice. Immunoblots assessed G-protein–coupled receptor recycling proteins expression in rodent cardiomyocytes and patient mononuclear leukocytes. In surgical patients, heart rate recovery after cardiopulmonary exercise testing, time/frequency measures of parasympathetic variables were related to the presence/absence of baroreflex dysfunction (defined by spontaneous baroreflex sensitivity of <6 ms mm Hg–1). The associations of baroreflex dysfunction with intraoperative cardiac function and outcomes were assessed.

Measurements and Main Results:

Experimental baroreflex dysfunction in rats and mice resulted in impaired cardiac contractility and upregulation of G-protein–coupled receptor kinase 2 expression. In mice, genetic deficiency of gp91 nicotinamide adenine dinucleotide phosphate oxidase subunit-2 prevented upregulation of G-protein–coupled receptor kinase 2 expression in conditions of baroreflex dysfunction and preserved cardiac function. Baroreflex dysfunction was present in 81 of 249 patients (32.5%) and was characterized by lower parasympathetic tone and increased G-protein–coupled receptor kinase 2 expression in mononuclear leukocytes. Baroreflex dysfunction in patients was also associated with impaired intraoperative cardiac contractility. Critical illness and mortality were more frequent in surgical patients with baroreflex dysfunction (relative risk, 1.66 [95% CI, 1.16–2.39]; p = 0.006).

Conclusions:

Reduced baroreflex sensitivity is associated with nicotinamide adenine dinucleotide phosphate oxidase subunit-2–mediated upregulation of G-protein–coupled receptor kinase 2 expression in cardiomyocytes and impaired cardiac contractility. Autonomic dysfunction predisposes patients to the development of critical illness and increases mortality.
Assessment of Depression, Anxiety, and Quality of Life in Singaporean Patients With Glaucoma
Authors: Lim Nigel C.S. , Fan Chara H.J. , Yong Michael K.H. , Wong Elizabeth P.Y. , Yip Leonard W. Y.
Published: March 2016

Purpose:

To determine the prevalence and risk factors for anxiety disorder and depression among glaucoma patients in Singapore, and to assess the relationship between quality of life (QOL) and depression/anxiety.

Methods:

In this cross-sectional study, glaucoma patients aged 21 and above with a known diagnosis of primary open-angle glaucoma or primary angle-closure glaucoma were recruited from a tertiary care hospital. Patients with other types of glaucoma, and coexisting ocular or psychiatric disorders were excluded.

Ophthalmic examination was carried out on all participants, which included best-corrected visual acuity (BCVA), intraocular pressure (IOP), gonioscopy, standard automated perimetry, and optic disc evaluation. Sociodemographic information and treatment histories were also collected.

The Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), and Visual Function Questionnaire (VFQ25) were administered to evaluate for depression, anxiety, and impact on QOL, respectively.

Results:

A total of 100 patients were included in this study. The mean age was 67.1±12.0 years (range, 24 to 90 y). The frequency of depression and anxiety among our patients was 30% and 64%, respectively. The mean HAM-D score was 4.37±4.17 (range, 0 to 17), whereas the mean HAM-A score was 2.38±2.80 (range, 0 to 13). The mean VFQ25 score was 78.8±16.0 (range, 42.4 to 97.0). The poorest subscale on the VFQ25 was driving, with a mean score of 42.4±42.6 (range, 0.0 to 100.0).

We did not find any significant difference between the presence of depression/anxiety between patients with primary open-angle glaucoma (P=0.263) and primary angle-closure glaucoma (P=0.830). Risk factors for depression included: female sex (P=0.020), higher logMAR BCVA in the worse eye (P=0.004), higher cup-disc ratio (P=0.016), lower MD in the better and worse eye (P=0.022 and 0.001, respectively), and lower mean VFQ25 score (P<0.001). Risk factors for anxiety included: lower MD in the worse eye (P=0.004) and lower mean VFQ25 score (P=0.004). There was also no significant association between the use of topical β-blockers/carbonic anhydrase inhibitors with depression (P=0.793) or anxiety (P=0.282).

Conclusions:

There is a relatively high prevalence of depression (30%) and anxiety disorders (64%) among glaucoma patients in Singapore. Female glaucoma patients are more likely to suffer from depression. Other risk factors for depression include higher cup-disc ratio, higher logMAR BCVA, lower MD, and a lower mean VFQ25 score. Risk factors for anxiety disorder include lower MD and lower mean VFQ25 score. Ophthalmologists could consider use of the VFQ25 as an assessment for impairments in QOL in a glaucoma patient. If a glaucoma patient is at high risk of depression or anxiety disorder, a multidisciplinary management approach involving ophthalmology and psychiatry may be required.
Comparison of the Deep Optic Nerve Structures in Superior Segmental Optic Nerve Hypoplasia and Primary Open-Angle Glaucoma
Authors: Lee Eun Ji , Lee Kyoung Min , Lee Seung Hyen , Kim Tae-Woo
Published: March 2016

Purpose:

The purpose of this study was to characterize the microstructure of the deep optic nerve tissues in eyes with superior segmental optic nerve hypoplasia (SSOH) in comparison with that in primary open-angle glaucoma (POAG).

Methods:

Thirty-five eyes with SSOH, 37 eyes with POAG, and 54 healthy control eyes underwent enhanced depth imaging (EDI) volume scanning of the optic nerve using spectral-domain optical coherence tomography (SD-OCT). POAG patients were matched with SSOH patients in terms of the thickness of the neuroretinal rim and the retinal nerve fiber layer in the superior sector. The lamina cribrosa thickness (LCT) was determined in 3 equidistant planes, and anterior lamina cribrosa surface depth (LCD) was determined in 5 equidistant planes. The measurements were compared between groups, and the areas under the receiver operating characteristic curves (AUC) were obtained for each parameter.

Results:

Eyes with SSOH had larger LCT and smaller LCD than POAG eyes at all locations (all P<0.001). The largest LCT was observed at the superior midperiphery in the SSOH group, but at central locations in both the POAG and control groups. The best parameters for discriminating the SSOH from glaucoma and healthy eyes were the superior midperipheral LCT (AUC=0.973) and inferior and inferior midperipheral LCD (AUCs=0.906), respectively.

Conclusions:

The LCT and LCD exhibited characteristic features in eyes with SSOH that were distinctive from those of POAG and healthy eyes. Investigation of the deep optic nerve structure using EDI SD-OCT may be beneficial for differentiating between SSOH and glaucoma, which may help to avoid both overtreatment and undertreatment.
A New Expander for Schlemm Canal Surgery in Primary Open-angle Glaucoma—Interim Clinical Results
Authors: Grieshaber Matthias C. , Grieshaber Hans R. , Stegmann Robert
Published: March 2016

Purpose:

To evaluate a new canal expander in circumferential viscocanalostomy (canaloplasty) for whites with primary open-angle glaucoma (POAG).

Design:

Prospective, single-center, noncomparative study.

Participants:

Twenty-two eyes of 22 consecutive patients with medically uncontrolled POAG underwent primary viscocanalostomy and implantation of the Stegmann Canal Expander into Schlemm canal with a follow-up time of at least 1 year.

Materials and Methods:

Schlemm canal was unroofed ab externo, and dilated with viscoelastic material and microcatheter. The Stegmann Canal Expander is a flexible, fenestrated hollow implant of 9 mm in length. One expander was implanted into either side of the surgically created of ostium to keep the Schlemm canal permanently open. The superficial scleral flap was closed watertight. Laser goniopuncture of the trabeculo-Descemet membrane window was performed if postoperative intraocular pressure (IOP) exceeded 16 mm Hg.

Main Outcome Measures:

Complete successes were defined as a confirmed IOP≤21, ≤18, and ≤16 mm Hg without medications, respectively, combined with a 30% IOP reduction. Number of antiglaucomatous medications, best-corrected visual acuity, and intraoperative and postoperative complications were recorded.

Results:

The mean IOP dropped from 27.1±5.3 mm Hg preoperatively to 13.6±1.6 mm Hg at 6 months, 13.0±1.5 mm Hg at 9 months, and 13.1±2.2 mm Hg at 12 months (P<0.001). The complete success rates for an IOP≤21, ≤18, and ≤16 mm Hg combined with a 30% IOP reduction were 91% [95% confidence interval (CI), 0.80-1.0], 91% (95% CI, 0.80-1.0), and 91.0% (95% CI, 0.80-1.0) at 6 months, and 86% (95% CI, 0.73-1.0), 82% (95% CI, 0.67-1.0), and 82.0% (95% CI, 0.67-1.0) at 12 months. The success rate of an IOP≤16 mm Hg without medications did not depend on age [hazard ratios (HR) 1.02; 95% CI, 0.85-1.12; P=0.74], preoperative IOP (HR 0.97; 95% CI, 0.83-1.23; P=0.89), and mean visual defect (HR 1.05; 95% CI, 0.72-1.27; P=0.76). Laser goniopuncture was performed on 2 eyes (9%) 4.1 months postoperatively; the mean IOP was 19.5 mm Hg before and 13.6 mm Hg after goniopuncture. The number of medications dropped from 2.9±0.6 before surgery to 0.05±0.2 after surgery (P<0.001). The postoperative best-corrected visual acuity at last visit (0.12±0.09; range, 0 to 0.39) was comparable to preoperative values (mean±SD, 0.16±0.10; range, 0 to 0.39) (P=0.35). Minor intraoperative or postoperative complications included microhyphema (8 eyes) and transient elevated IOP (steroid responder; 2 eyes).

Conclusions:

Implantation of the Stegmann Canal Expander in canaloplasty lowered IOP significantly in POAG without complications related to the device in this 1-year observation period.
Goldmann Applanation Tonometry Versus Dynamic Contour Tonometry After Vitrectomy
Authors: Mamas Nikolaos , Fuest Matthias , Koutsonas Antonios , Roessler Gernot , Mazinani Babac E. , Walter Peter , Plange Niklas
Published: March 2016

Purpose:

The aim of the study was to investigate the agreement of intraocular pressure (IOP) measurement using dynamic contour tonometry (DCT) and Goldmann applanation tonometry (GAT) in eyes after vitrectomy with intraocular gas endotamponade, in eyes after vitrectomy with no tamponade, and in controls.

Methods:

In this prospective comparative study IOP was measured with GAT and DCT in 41 eyes with gas endotamponade (sulfur hexafluoride 20%) 1 to 3 days after vitrectomy, in 32 postvitrectomy eyes with intraocular water, and in 46 control eyes with no history of glaucoma or intraocular surgery. Corneal pachymetry and axial length measurements were additionally performed.

Results:

The mean difference between GAT and DCT (GAT-DCT) in gas-filled eyes was 3.1 mm Hg [SD=6.2 mm Hg], that in eyes after vitrectomy with no tamponade was 0.4 mm Hg (SD=4.8 mm Hg), and in control eyes was 0.4 mm Hg (SD=3.8 mm Hg). No significant correlation was found between the differences of GAT and DCT (GAT-DCT) and the mean IOP of GAT and DCT in water-filled eyes (r=−0.25, P=0.18) and control eyes (r=0.23, P=0.13), but a significant correlation was found in the gas-filled eyes (r=0.71, P<0.0001). A significant correlation between central corneal thickness and the mean difference of both methods was seen only in the control group (r=0.36, P=0.03).

Conclusions:

IOP as determined by DCT underestimates IOP in gas-filled eyes compared with GAT, as GAT values were on average 3.1 mm Hg higher compared with those of DCT. The extent of IOP underestimation using DCT increases with higher IOP values. In the group of eyes after vitrectomy and in normal eyes we found a generally good agreement between the 2 methods, although high interindividual discrepancies were present. Our findings suggest that the 2 devices should not be used interchangeably in IOP evaluation after vitrectomy with gas endotamponade, which remains a difficult challenge.
The Economic Burden of Childhood Glaucoma
Authors: Liu Dan , Huang Linda , Mukkamala Lekha , Khouri Albert S.
Published: March 2016

Purpose:

To date, there are limited data on the economic burden of childhood glaucoma, a relatively rare but visually debilitating disease. The purpose of this study is to evaluate the immediate costs of illness associated with childhood glaucoma during the first 4 years after presentation.

Methods:

Data on age, sex, surgical interventions, visits, examinations under anesthesia, and medications were collected yearly following presentation in patients with childhood glaucoma. Inclusion criteria included diagnosis of primary or secondary childhood glaucoma, age less than 21 years, and follow-up of 4 years. A total of 23 patients (39 eyes) were included. Cost analysis used 2013 hospital-specific charges and US average hourly wage to calculate outcomes of total, direct, and indirect costs (significance level P<0.05).

Results:

The annual cost of care of childhood glaucoma averaged $21,441.61 per patient, representing 1100% of annual costs in adult glaucoma and an increase of 800% in annual costs of health care per pediatric patient. The average total 4-year cost of care was $85,074.96 per patient. Surgical interventions and examinations under anesthesia were the greatest contributors to costs, representing 69.0% and 23.2% of total 4-year costs, respectively. The annual costs of care for childhood glaucoma were highest in the first year compared with subsequent years, averaging $46,293.62 per patient (P<0.05).

Conclusions:

Childhood glaucoma carries a substantial economic burden with the highest costs occurring in the first year after presentation. The greatest contributors to cost of illness are surgical interventions and examinations and anesthesia.
Paediatric workload of an adult retrieval service in Scotland
Authors: Harry Christina L. , Mccormack Jon , Donald Michael , Corfield Alasdair R.
Published: March 2016

The Emergency Medical Retrieval Service (EMRS) provides adults with life-threatening conditions in remote areas with timely interventions and rapid access to definitive medical care, including a primary response service. Paediatric patients are managed under a separate network. Despite this, there has been an increase in paediatric retrievals by EMRS. We aim to inform future service development and ascertain how EMRS can serve the needs of this cohort. This is a retrospective, observational study. Raw data were retrieved from the database of paediatric patients retrieved by EMRS for 9 years. A total of 112 paediatric patients were retrieved; 46% were primary retrievals. The most common injuries were head injuries (n=29) and orthopaedic injuries (n=16). Common interventions include fluid resuscitation (n=34), ventilation (n=22) and sedation/paralysis (n=22).This study describes the evolution of an adult retrieval service to cover paediatric patients in Scotland outside the remit of the paediatric retrieval service.
Comparative Analysis of Methods for Detecting Isocitrate Dehydrogenase 1 and 2 Mutations and Their Metabolic Consequence, 2-Hydroxyglutarate, in Different Neoplasms
Authors: Babakoohi Shahab , Lapidus Rena G. , Faramand Rawan , Sausville Edward A. , Emadi Ashkan
Published: March 2016

Isocitrate dehydrogenase (IDH) mutations have been recognized in a few neoplasms including glioma, acute myeloid leukemia, chondrosarcoma, cholangiocarcinoma, and angioimmunoblastic T-cell lymphoma. The direct methods to detect IDH mutations include DNA sequencing, immunohistochemistry (IHC), or by measuring its byproduct, 2-hydroxyglutarate (2-HG), in the blood or urine. Moreover, conventional magnetic resonance imaging can be modified to magnetic resonance spectroscopy (MRS) to measure 2-HG in tumor. By conducting a search in Medline/PubMed and ISI/Web of Science for the published articles in English related to the methods for detection of IDH mutations and its byproduct 2-HG, we compared different methodologies to detect these mutations and discuss advantages and limitations of each method. Studies in which a methodology of detection was compared with another modality were included. Multiple studies have shown that both DNA sequencing and IHC are reliable methods for detecting IDH mutations in glioma and other solid neoplasms. IHC appeared to be less costly, easier to perform, and may be slightly more accurate than DNA sequencing. 2-HG has also been measured in bone marrow aspirate, serum and urine of patients with mutant IDH acute myeloid leukemia, and correlated very well with sequencing and IHC. Lastly, in some glioma patients, MRS detected IDH mutations noninvasively and reliably with excellent correlations with other modalities such as IHC and sequencing. In conclusion, IHC, MRS, and 2-HG detection all are clinically useful and comparable with DNA sequencing in identifying IDH mutations in different neoplasms. 2-HG and MRS can be utilized for monitoring treatment response in a variety of neoplasms.
GRB7 Expression and Correlation With HER2 Amplification in Invasive Breast Carcinoma
Authors: Bivin William W. , Yergiyev Oleksandr , Bunker Mark L. , Silverman Jan F. , Krishnamurti Uma
Published: March 2016

Growth factor receptor-bound protein 7 (GRB7) gene is located adjacent to the HER2 gene on the 17q12-21 amplicon, is often coamplified with HER2 in a subset of breast cancers, and has been implicated in resistance to anti-HER2 and antiestrogen therapy. This study investigated the correlation of GRB7 expression by immunohistochemistry with HER2 expression, HER2 amplification, increased chromosome 17 copy number, and other prognostic and predictive factors in invasive breast cancer, including histologic grade, pathologic stage, and ER, PR, and p53 status. Paraffin-embedded samples of 188 invasive breast carcinomas with documented HER2, ER, and PR testing were collected and divided into 3 groups: cases positive for HER2 overexpression/gene amplification (n=60), negative for HER2 overexpression (n=97), and cases with increased chromosome 17 copy number without HER2 amplification (n=31). GRB7 expression was evaluated on all 188 cases. In addition, p53 immunohistochemistry was performed on 13 HER2+/GRB7+ cases and 39 HER2+/GRB7− cases. GRB7 expression correlated strongly with HER2 overexpression. GRB7 expression was present in 20/60 (33.33%) of HER2+ cases, compared with 1/97 (1.03%) HER2− cases, and 1/31 (3.22%) increased chromosome 17 copy number cases (P<0.0001). In HER2+ cases, GRB7 expression was found to correlate significantly with a greater degree of HER2 amplification. The mean±SEM HER2 copy number was 21.14±2.59 in GRB7+ cases, compared with 9.8±1.38 in GRB7− cases (P=0.0001). GRB7 expression correlated significantly with ER negativity (P=0.012) and p53 positivity (P=0.03). GRB7 expression did not correlate with histologic grade, pathologic stage, or PR expression. Our data shows that GRB7 expression in invasive breast cancer correlates with markers of a more aggressive phenotype, including HER2 overexpression, a greater degree of HER2 amplification, ER negativity, and p53 positivity.
Phylogeny-aware Identification and Correction of Taxonomically Mislabeled Sequences
Authors: Kozlov Alexey M. , Zhang Jiajie , Yilmaz Pelin , Glöckner Frank Oliver , Stamatakis Alexandros
Published: March 2016

Molecular sequences in public databases are mostly annotated by the submitting authors without further validation. This procedure can generate erroneous taxonomic sequence labels. Mislabeled sequences are hard to identify, and they can induce downstream errors because new sequences are typically annotated using existing ones. Furthermore, taxonomic mislabelings in reference sequence databases can bias metagenetic studies which rely on the taxonomy. Despite significant efforts to improve the quality of taxonomic annotations, the curation rate is low because of the labour-intensive manual curation process.

Here, we present SATIVA, a phylogeny-aware method to automatically identify taxonomically mislabeled sequences (“mislabels”) using statistical models of evolution. We use the Evolutionary Placement Algorithm (EPA) to detect and score sequences whose taxonomic annotation is not supported by the underlying phylogenetic signal, and automatically propose a corrected taxonomic classification for those. Using simulated data, we show that our method attains high accuracy for identification (96.9% sensitivity / 91.7% precision) as well as correction (94.9% sensitivity / 89.9% precision) of mislabels. Furthermore, an analysis of four widely used microbial 16S reference databases (Greengenes, LTP, RDP and SILVA) indicates that they currently contain between 0.2% and 2.5% mislabels. Finally, we use SATIVA to perform an in-depth evaluation of alternative taxonomies for Cyanobacteria.

SATIVA is freely available athttps://github.com/amkozlov/sativa.
Oomycetes during 120,000 years of temperate rainforest ecosystem development
Authors: Dickie Ian A. , Wakelin Angela M. , Martinez-Garcia Laura , Richardson Sarah J. , Makiola Andreas , Tylianakis Jason M.
Published: March 2016

The occurrence of plant-associated oomycetes in natural ecosystems and particularly during long-term ecosystem development is largely unknown, despite the importance of many oomycetes as plant pathogens. Using DNA sequencing from roots, we investigated the frequency and host relationships of plant-associated oomycete communities along a 120 000 year glacial chronosequence, comprising site ages with rapid compositional change (“early succession”; 5, 15, and 70 years old soil); relatively stable higher-diversity sites (“mature”, 280, 500, 1000, 5000, 12000 years); and ancient, nutrient-limited soils with declining plant diversity and stature (“retrogression”, 60 000, 120 000 years). Plant-associated oomycetes were frequent in all three early successional sites, occurring in 38 – 65% of plant roots, but rare (average 3%) in all older ecosystems. Oomycetes were highly host specific, and more frequent on those plant species that declined most strongly in abundance between ecosystem ages. The results support the particular importance of plant-associated oomycetes in early succession (up to 70 years). High host specificity and correlations of abundance of oomycete inside roots with declining plant species are consistent with oomycete-driven successional change.
Have coral snake mimics diversified more than non-mimics?
Authors: Caetano Daniel S. , Alencar Laura R. V. , Passos Paulo , Grazziotin Felipe G. , Zaher Hussam , Martins Marcio
Published: March 2016

Dipsadidae is the most diversified family of snakes, composed of species showing an impressive variety of color patterns. Some species are cryptic whereas others have contrasting patterns comprised by bright colors alternated with darker shades, including particular combinations of vivid colors characteristic of coral snakes (Elapidae). Species with such patterns are thought to be mimics of coral snakes based on their color pattern similarity, predator avoidance of such patterns in field experiments, and the geographical concordance between models and mimics. Here we test whether color patterns associated with coral snake mimicry and contrasting color patterns in general influenced the diversification dynamics of the group. We compile the largest database of color patterns among reptiles to date, with color descriptions for the majority (594 species) of dipsadids. We used trait-dependent diversification models along with extensive simulations to deal with the recently described statistical bias associated with such methods. Despite the apparent survival advantage associated with coral snake mimicry, we show that there is no detectable influence of color types in the dynamics of diversification in Dipsadidae. We discuss insights into the function of color patterns and argue that non-mimic contrasting patterns might serve as pre-adaptations to mimicry of coral snakes.

Data archival location

BEAST XML file and BiSSE MCMC results:http://dx.doi.org/10.6084/m9.figshare.831493

R code for analyses and simulations:https://github.com/Caetanods/Dipsadidae_color_evolution