bluuebunny/crossref_metadata_2025 huggingface dataset:
Randomized Trial of a Hypofractionated Radiation Regimen for the Treatment of Localized Prostate Cancer
Authors: Catton Charles N. , Lukka Himu , Gu Chu-Shu , Martin Jarad M. , Supiot Stéphane , Chung Peter W.M. , Bauman Glenn S. , Bahary Jean-Paul , Ahmed Shahida , Cheung Patrick , Tai Keen Hun , Wu Jackson S. , Parliament Matthew B. , Tsakiridis Theodoros , Corbett Tom B. , Tang Colin , Dayes Ian S. , Warde Padraig , Craig Tim K. , Julian Jim A. , Levine Mark N.
Published: March 2017

Purpose

Men with localized prostate cancer often are treated with external radiotherapy (RT) over 8 to 9 weeks. Hypofractionated RT is given over a shorter time with larger doses per treatment than standard RT. We hypothesized that hypofractionation versus conventional fractionation is similar in efficacy without increased toxicity.

Patients and Methods

We conducted a multicenter randomized noninferiority trial in intermediate-risk prostate cancer (T1 to 2a, Gleason score ≤ 6, and prostate-specific antigen [PSA] 10.1 to 20 ng/mL; T2b to 2c, Gleason ≤ 6, and PSA ≤ 20 ng/mL; or T1 to 2, Gleason = 7, and PSA ≤ 20 ng/mL). Patients were allocated to conventional RT of 78 Gy in 39 fractions over 8 weeks or to hypofractionated RT of 60 Gy in 20 fractions over 4 weeks. Androgen deprivation was not permitted with therapy. The primary outcome was biochemical-clinical failure (BCF) defined by any of the following: PSA failure (nadir + 2), hormonal intervention, clinical local or distant failure, or death as a result of prostate cancer. The noninferiority margin was 7.5% (hazard ratio, < 1.32).

Results

Median follow-up was 6.0 years. One hundred nine of 608 patients in the hypofractionated arm versus 117 of 598 in the standard arm experienced BCF. Most of the events were PSA failures. The 5-year BCF disease-free survival was 85% in both arms (hazard ratio [short v standard], 0.96; 90% CI, 0.77 to 1.2). Ten deaths as a result of prostate cancer occurred in the short arm and 12 in the standard arm. No significant differences were detected between arms for grade ≥ 3 late genitourinary and GI toxicity.

Conclusion

The hypofractionated RT regimen used in this trial was not inferior to conventional RT and was not associated with increased late toxicity. Hypofractionated RT is more convenient for patients and should be considered for intermediate-risk prostate cancer.
The Achilles tendon is mechanosensitive in older adults: adaptations following 14 weeks versus 1.5 years of cyclic strain exercise
Authors: Epro Gaspar , Mierau Andreas , Doerner Jonas , Luetkens Julian A. , Scheef Lukas , Kukuk Guido M. , Boecker Henning , Maganaris Constantinos N. , Brüggemann Gert-Peter , Karamanidis Kiros
Published: March 2017

The aging musculoskeletal system experiences a general decline in structure and function, characterized by a reduced adaptability to environmental stress. We investigated whether the older human Achilles tendon (AT) demonstrates mechanosensitivity (via biomechanical and morphological adaptations) in response to long-term mechanical loading. Thirty-four female adults (60–75 years) were allocated to either a medium-term (14 weeks; N=21) high AT strain cyclic loading exercise intervention or a control group (N=13), with 12 participants continuing with the intervention for 1.5 years. AT biomechanical properties were assessed using ultrasonography and dynamometry. Tendon cross-sectional area (CSA) was investigated by means of magnetic resonance imaging. A 22% exercise-related increment in ankle plantarflexion joint moment, along with increased AT stiffness (598.2±141.2 versus 488.4±136.9 N mm−1 at baseline), Young's modulus (1.63±0.46 versus 1.37±0.39 GPa at baseline) and about 6% hypertrophy along the entire free AT were identified after 14 weeks of strength training, with no further improvement after 1.5 years of intervention. The aging AT appears to be capable of increasing its stiffness in response to 14 weeks of mechanical loading exercise by changing both its material and dimensional properties. Continuing exercise seems to maintain, but not cause further adaptive changes in tendons, suggesting that the adaptive time–response relationship of aging tendons subjected to mechanical loading is nonlinear.
Selective attention in peacocks during assessment of rival males
Authors: Yorzinski Jessica L. , Patricelli Gail L. , Bykau Siarhei , Platt Michael L.
Published: March 2017

Males in many species compete intensely for access to females. In order to minimize costly interactions, they can assess their rivals’ competitive abilities by evaluating traits and behaviors. We know little about how males selectively direct their attention to make these assessments. Using Indian peafowl (Pavo cristatus) as a model system, we examined how males visually assess their competitors by continuously tracking the gaze of freely moving peacocks during the mating season. When assessing rivals, peacocks selectively gazed toward the lower display regions of their rivals, including the lower eyespot and fishtail feathers, dense feathers, body and wings. Their attention was modified based on the rivals’ behavior such that they spent more time looking at rivals when rivals were shaking their wings and moving. The results indicate that peacocks selectively allocate their attention during rival assessment. The gaze patterns of males assessing rivals were largely similar to those of females evaluating mates, suggesting that some male traits serve a dual function in both intra- and intersexual selection. However, males spent more time than females looking at the upper eyespots and this could indicate that the upper eyespots function more in close-up rival assessment than mate choice.
Respiratory mechanics of eleven avian species resident at high and low altitude
Authors: York Julia M. , Chua Beverly A. , Ivy Catherine M. , Alza Luis , Cheek Rebecca , Scott Graham R. , McCracken Kevin G. , Frappell Peter B. , Dawson Neal J. , Laguë Sabine L. , Milsom William K.
Published: March 2017

The metabolic cost of breathing at rest has never been successfully measured in birds, but has been hypothesized to be higher than in mammals of a similar size because of the rocking motion of the avian sternum being encumbered by the pectoral flight muscles. To measure the cost and work of breathing, and to investigate whether species resident at high altitude exhibit morphological or mechanical changes that alter the work of breathing, we studied 11 species of waterfowl: five from high altitudes (>3000 m) in Perú, and six from low altitudes in Oregon, USA. Birds were anesthetized and mechanically ventilated in sternal recumbency with known tidal volumes and breathing frequencies. The work done by the ventilator was measured, and these values were applied to the combinations of tidal volumes and breathing frequencies used by the birds to breathe at rest. We found the respiratory system of high-altitude species to be of a similar size, but consistently more compliant than that of low-altitude sister taxa, although this did not translate to a significantly reduced work of breathing. The metabolic cost of breathing was estimated to be between 1 and 3% of basal metabolic rate, as low or lower than estimates for other groups of tetrapods.
Concentration-Dependent Fluorescence Color Tuning of the Difluoroboron Avobenzone Complex in Polymer Films
Authors: Ito Fuyuki , Kikuchi Chika
Published: March 2017

We have investigated concentration-dependent fluorescence color tuning of BF2AVB in a poly(methyl methacrylate) film. BF2AVB exhibits a color change from purple-blue to orange via green, and then crystals segregate from the polymer matrix. We analyzed the fluorescence and fluorescence excitation spectral change as a function of the BF2AVB concentration in the film. We also obtained fluorescence microscope images to confirm the miscibility and crystallization properties in the films. This originates from the aggregated state formed in the polymer matrix depending on the stacking structure of the parallel (B-phase), antiparallel (G-phase), and amorphous states. The emissive species change with increasing BF2AVB concentration. The polymer matrix isolation method enables not only directly visualization of the dynamics of the crystal formation process and Ostwald’s rule of stages by fluorescence changes, but it also enables device fabrication, such as fabrication of organic light-emitting diodes and luminescent solar concentrators.
pH-Responsive Cotton Effects in the d–d Transition Band of Self-Assembling Copper(II) Complexes with a Cholesteryl-Armed Ligand
Authors: Sagami Takuya , Umemoto Shota , Tahara Yuhei O , Miyata Makoto , Yonamine Yusuke , Ishikawa Daisuke , Mori Taizo , Ariga Katsuhiko , Miyake Hiroyuki , Shinoda Satoshi
Published: March 2017

New amphiphilic transition metal complexes with helical structures self-assembled to form disk-like units in 20 wt % EtOH/water. d–d transition bands in the visible-near IR region were used to probe conformational changes during the assembly process. Self-assembly resulted in dynamic conformational changes and considerable enhancement of circular dichroism (CD) in the d–d transition bands due to steric interaction among neighboring complexes. A copper(II) complex showed the most dramatic CD changes upon self-assembly, including sign inversion of the CD signal. The self-assembled Cu(II) complexes also showed pH-responsive Cotton effects between pH 6 and pH 7 due to deprotonation. The Cotton effects of the Cu(II) complex could be finely tuned by varying the pH and ethanol content of the aqueous solvent.
Bound-Constrained Polynomial Optimization Using Only Elementary Calculations
Authors: de Klerk Etienne , Lasserre Jean B. , Laurent Monique , Sun Zhao
Published: March 2017

We provide a monotone nonincreasing sequence of upper bounds [Formula: see text] converging to the global minimum of a polynomial f on simple sets like the unit hypercube in ℝn. The novelty with respect to the converging sequence of upper bounds in Lasserre [Lasserre JB (2010) A new look at nonnegativity on closed sets and polynomial optimization, SIAM J. Optim. 21:864–885] is that only elementary computations are required. For optimization over the hypercube [0, 1]n, we show that the new bounds [Formula: see text] have a rate of convergence in [Formula: see text]. Moreover, we show a stronger convergence rate in O(1/k) for quadratic polynomials and more generally for polynomials having a rational minimizer in the hypercube. In comparison, evaluation of all rational grid points with denominator k produces bounds with a rate of convergence in O(1/k2), but at the cost of O(kn) function evaluations, while the new bound [Formula: see text] needs only O(nk) elementary calculations.
Modeling and Measuring the Consumer Activities Associated with Value Cocreation: An Exploratory Test in the Context of Education
Authors: Botti Antonio , Grimaldi Mara , Tommasetti Aurelio , Troisi Orlando , Vesci Massimiliano
Published: March 2017

The goal of the current work is to introduce a model for the identification and measurement of consumers’ behavioral and cognitive value cocreation activities in the light of service-dominant logic (SDL) assumptions. The individuation of tools for the measurement of users’ conduct has a fundamental role in the modeling of service consumer needs and in guiding suppliers to improve relationships with their counterparts. A framework identifying eight dimensions of consumer value cocreation behavior is proposed and empirically validated through an exploratory factor analysis, which confirms the existence of six out of the eight dimensions initially postulated. To develop an instrument for measuring consumer value cocreation activities and behavior, we tested our scale in the education field. In particular, the 42-item scale was tested on a sample of 180 students attending their third (last) year of their business management degree. This paper produces two main outcomes: the theoretical outcome specifies and assesses the activities and dimensions of consumers’ value cocreation, while the managerial outcome allows managers to devise new methods of delivery and new practical measures to stimulate the involvement of users at each level.
‘I wonder who chose the colour scheme, it’s very nice...’: Mike Coles, Malicious Damage and Forty Years in the Wilderness
Authors: Bestley Russ
Published: March 2017

A broad range of radical, new art and design approaches came about during the punk and post-punk boom of the late 1970s and early 1980s, though as is the nature of the profession, the graphic designer’s anonymity often kept them out of the limelight and away from wider public acknowledgement or recognition. In an age of ‘anyone can do it’, punk inspired not just musicians, but also artists, designers, filmmakers, photographers, writers and a whole array of new creatives. Some simply took the opportunity to make something immediate and of the moment, without the need for any kind of formal education, training and guidance, while others found their way into a new career as a result. A colossal new book by Mike Coles, Forty Years in the Wilderness: A Graphic Voyage of Art, Design & Stubborn Independence, charts a pictorial history of the designer’s work under the Malicious Damage banner, from early record sleeves, posters and flyers promoting Killing Joke alongside label-mates Ski Patrol and Red Beat, to the ambient house experimentation of The Orb, and more recent music graphics for Shriekback, Headcount and Vertical Smile. Part autobiography, part personal reflection, part celebration, this publication may lead to a critical reappraisal of the designer’s work alongside more widely acknowledged contemporaries, though such considerations are far from being a driving force for the project, and the title ironically sums up Coles’ attitude towards independent and autonomous production.
Book Reviews
Authors: Bestley Russ , Worley Matthew , Dale Pete
Published: March 2017

PRODUCT 45: AUSTRALIAN PUNK/POST-PUNK RECORD COVERS, MURRAY BENNETT (2016) Sydney: Inner City Sound, 360pp., ISBN: 0994360207, h/bk, AU$120.00

ACTION TIME VISION: PUNK AND POST-PUNK 7” RECORD SLEEVES, TONY BROOK AND ADRIAN SHAUGHNESSY (EDS) (2016) London: Unit Editions, 320 pp., ISBN: 0993231667, p/bk, £35.00

POST-PUNK, POLITICS AND PLEASURE IN BRITAIN, DAVID WILKINSON (2016) London: Palgrave, 228pp., ISBN: 1137497802, h/bk, £66.99
The Ethics of Authors in Scientific Publications
Authors: Oliveira Gislene Farias de
Published: March 2017

In this editorial, I will refer to an issue that has been commonplace in discussions between editors around the world: the ethical conduct of academics and scientists at the time of publishing their articles and scientific findings. In general, it is to be expected of these actors, the completeness, indispensable condition for the said professional of higher level.
Sistemática para análise de risco de saúde e segurança do trabalho em estações elevatórias de água
Authors: Cavalcanti Giseli Lopes Correia , Lago Eliane Maria Gorga , Junior Béda Barkokébas
Published: March 2017

O estudo propõe a identificação, avaliação e recomendações de controle dos riscos ocupacionais encontrados nas Estações Elevatórias de Água. Desta forma, foram realizadas visitas nas instalações escolhidas como objeto de estudo, posteriormente os agentes e os riscos foram identificados, avaliados e classificados em graus que variam de “irrelevante”, “relevante”, “de atenção”, “crítico” e “emergencial”, e por fim foram propostas medidas de tratamento para controle, minimização e eliminação dos riscos. Os dados foram obtidos em 10 (dez) Estações Elevatórias de Água, onde os operadores realizavam as atividades identificadas Posteriormente, os riscos identificados, choque elétrico, queda, picada de animais peçonhentos, prensamento, acidentes de trânsito e postura inadequada, foram avaliados e classificados de acordo com a gradação dos riscos. Foi possível concluir que as atividades realizadas nos ambientes estudados, bem como os próprios ambientes, geram riscos de segurança aos trabalhadores.
OLAK
Authors: Zhang Fan , Zhang Wenjie , Zhang Ying , Qin Lu , Lin Xuemin
Published: March 2017

In this paper, we study the problem of the anchored
k
-core. Given a graph
G
, an integer
k
and a budget
b
, we aim to identify
b
vertices in
G
so that we can determine the largest induced subgraph
J
in which every vertex, except the
b
vertices, has at least
k
neighbors in
J
. This problem was introduced by Bhawalkar and Kleinberg
e
t al. in the context of user engagement in social networks, where a user may leave a community if he/she has less than
k
friends engaged. The problem has been shown to be NP-hard and inapproximable. A polynomial-time algorithm for graphs with bounded tree-width has been proposed. However, this assumption usually does not hold in real-life graphs, and their techniques cannot be extended to handle general graphs.

Motivated by this, we propose an efficient algorithm, namely onion-layer based anchored k-core (OLAK), for the anchored
k
-core problem on large scale graphs. To facilitate computation of the anchored
k
-core, we design an
onion layer
structure, which is generated by a simple onion-peeling-like algorithm against a small set of vertices in the graph. We show that computation of the best anchor can simply be conducted upon the vertices on the
onion layers
, which significantly reduces the search space. Based on the well-organized layer structure, we develop efficient candidates exploration, early termination and pruning techniques to further speed up computation. Comprehensive experiments on 10 real-life graphs demonstrate the effectiveness and efficiency of our proposed methods.
Data tweening
Authors: Khan Meraj , Xu Larry , Nandi Arnab , Hellerstein Joseph M.
Published: March 2017

In the context of interactive query sessions, it is common to issue a succession of queries, transforming a dataset to the desired result. It is often difficult to comprehend a succession of transformations, especially for complex queries. Thus, to facilitate understanding of each data transformation and to provide continuous feedback, we introduce the concept of "data tweening", i.e., interpolating between resultsets, presenting to the user a series of incremental visual representations of a resultset transformation. We present tweening methods that consider not just the changes in the result, but also the changes in the query. Through user studies, we show that data tweening allows users to efficiently comprehend data transforms, and also enables them to gain a better understanding of the underlying query operations.
The end of a myth
Authors: Zamanian Erfan , Binnig Carsten , Harris Tim , Kraska Tim
Published: March 2017

The common wisdom is that distributed transactions do not scale. But what if distributed transactions could be made scalable using the next generation of networks and a redesign of distributed databases? There would no longer be a need for developers to worry about co-partitioning schemes to achieve decent performance. Application development would become easier as data placement would no longer determine how scalable an application is. Hardware provisioning would be simplified as the system administrator can expect a linear scale-out when adding more machines rather than some complex sub-linear function, which is highly application specific.

In this paper, we present the design of our novel scalable database system NAM-DB and show that distributed transactions with the very common Snapshot Isolation guarantee can indeed scale using the next generation of RDMA-enabled network technology without any inherent bottlenecks. Our experiments with the TPC-C benchmark show that our system scales linearly to over 6.5 million new-order (14.5 million total) distributed transactions per second on 56 machines.
Shrink
Authors: Chandramouli Badrish , Goldstein Jonathan
Published: March 2017

Streaming query deployments make up a vital part of cloud oriented applications. They vary widely in their data, logic, and statefulness, and are typically executed in multi-tenant distributed environments with varying uptime SLAs. In order to achieve these SLAs, one of a number of proposed resiliency strategies is employed to protect against failure. This paper has introduced the first, comprehensive, cloud friendly comparison between different resiliency techniques for streaming queries. In this paper, we introduce models which capture the costs associated with different resiliency strategies, and through a series of experiments which implement and validate these models, show that (1) there is no single resiliency strategy which efficiently handles most streaming scenarios; (2) the optimization space is too complex for a person to employ a "rules of thumb" approach; and (3) there exists a clear generalization of periodic checkpointing that is worth considering in many cases. Finally, the models presented in this paper can be adapted to fit a wide variety of resiliency strategies, and likely have important consequences for cloud services beyond those that are obviously streaming.
An evaluation of distributed concurrency control
Authors: Harding Rachael , Van Aken Dana , Pavlo Andrew , Stonebraker Michael
Published: March 2017

Increasing transaction volumes have led to a resurgence of interest in distributed transaction processing. In particular, partitioning data across several servers can improve throughput by allowing servers to process transactions in parallel. But executing transactions across servers limits the scalability and performance of these systems.

In this paper, we quantify the effects of distribution on concurrency control protocols in a distributed environment. We evaluate six classic and modern protocols in an in-memory distributed database evaluation framework called Deneva, providing an apples-to-apples comparison between each. Our results expose severe limitations of distributed transaction processing engines. Moreover, in our analysis, we identify several protocol-specific scalability bottlenecks. We conclude that to achieve truly scalable operation, distributed concurrency control solutions must seek a tighter coupling with either novel network hardware (in the local area) or applications (via data modeling and semantically-aware execution), or both.
Provenance for natural language queries
Authors: Deutch Daniel , Frost Nave , Gilad Amir
Published: March 2017

Multiple lines of research have developed Natural Language (NL) interfaces for formulating database queries. We build upon this work, but focus on presenting a highly detailed form of the
answers
in NL. The answers that we present are importantly based on the
provenance
of tuples in the query result, detailing not only the results but also their
explanations.
We develop a novel method for transforming provenance information to NL, by leveraging the original NL query structure. Furthermore, since provenance information is typically large and complex, we present two solutions for its effective presentation as NL text: one that is based on provenance factorization, with novel desiderata relevant to the NL case, and one that is based on summarization. We have implemented our solution in an end-to-end system supporting questions, answers and provenance, all expressed in NL. Our experiments, including a user study, indicate the quality of our solution and its scalability.
Magnetic Resonance Imaging of Coronary Arteries: Latest Technical Innovations and Clinical Experiences
Authors: Xie Yibin , Pang Jianing , Yang Qi , Li Debiao
Published: March 2017

Cardiovascular disease (CVD) is the leading cause of death and a major health care challenge globally. Coronary artery disease (CAD) is a primary underlying pathological process in the majority of cardiovascular disease cases. Magnetic resonance imaging (MRI) can play a potentially important role in the management of CAD as a noninvasive imaging modality without ionizing radiation, although its early promise has not been delivered because of several crucial technical limitations. However, recent innovations in MRI have reopened the door, with tremendous opportunities for multiparametric assessment of CAD including luminal stenosis, plaque burden and composition, and disease activities such as inflammation and hemorrhage. Novel MRI acquisition and reconstruction strategies now offer much increased spatial resolution and image quality and shortened examination times compared with conventional approaches. Recent clinical experiences of coronary MRI indicated the potential to improve the current management of coronary atherosclerosis, such as identifying the patients at the highest risk and evaluating therapeutic responses. In this review we discuss the latest technical advances and clinical insights in coronary MRI.
Functional Organization of Vestibulo-Ocular Responses in Abducens Motoneurons
Authors: Dietrich Haike , Glasauer Stefan , Straka Hans
Published: March 2017

Vestibulo-ocular reflexes (VORs) are the dominating contributors to gaze stabilization in all vertebrates. During horizontal head movements, abducens motoneurons form the final element of the reflex arc that integrates visuovestibular inputs into temporally precise motor commands for the lateral rectus eye muscle. Here, we studied a possible differentiation of abducens motoneurons into subtypes by evaluating their morphology, discharge properties, and synaptic pharmacology in semi-intactin vitropreparations of larvalXenopus laevis. Extracellular nerve recordings during sinusoidal head motion revealed a continuum of resting rates and activation thresholds during vestibular stimulation. Differences in the sensitivity to changing stimulus frequencies and velocities allowed subdividing abducens motoneurons into two subgroups, one encoding the frequency and velocity of head motion (Group I), and the other precisely encoding angular velocity independent of stimulus frequency (Group II). Computational modeling indicated that Group II motoneurons are the major contributor to actual eye movements over the tested stimulus range. The segregation into two functional subgroups coincides with a differential activation of glutamate receptor subtypes. Vestibular excitatory inputs in Group I motoneurons are mediated predominantly by NMDA receptors and to a lesser extent by AMPA receptors, whereas an AMPA receptor-mediated excitation prevails in Group II motoneurons. Furthermore, glycinergic ipsilateral vestibular inhibitory inputs are activated during the horizontal VOR, whereas the tonic GABAergic inhibition is presumably of extravestibular origin. These findings support the presence of physiologically and pharmacologically distinct functional subgroups of extraocular motoneurons that act in concert to mediate the large dynamic range of extraocular motor commands during gaze stabilization.

SIGNIFICANCE STATEMENTOutward-directed gaze-stabilizing eye movements are commanded by abducens motoneurons that combine different sensory inputs including signals from the vestibular system about ongoing head movements (vestibulo-ocular reflex). Using an amphibian model, this study investigates whether different types of abducens motoneurons exist that become active during different types of eye movements. The outcome of this study demonstrates the presence of specific motoneuronal populations with pharmacological profiles that match their response dynamics. The evolutionary conservation of the vestibulo-ocular circuitry makes it likely that a similar motoneuronal organization is also implemented in other vertebrates. Accordingly, the physiological and pharmacological understanding of specific motoneuronal contributions to eye movements might help in designing drug therapies for human eye movement dysfunctions such as abducens nerve palsy.
Nonlinear Modulation of Cutaneous Reflexes with Increasing Speed of Locomotion in Spinal Cats
Authors: Hurteau Marie-France , Thibaudier Yann , Dambreville Charline , Chraibi Anass , Desrochers Etienne , Telonio Alessandro , Frigon Alain
Published: March 2017

Cutaneous reflexes are important for responding rapidly to perturbations, correcting limb trajectory, and strengthening support. During locomotion, they are modulated by phase to generate functionally appropriate responses. The goal of the present study was to determine whether cutaneous reflexes and their phase-dependent modulation are altered with increasing speed and if this is accomplished at the spinal level. Four adult cats that recovered stable hindlimb locomotion after spinal transection were implanted with electrodes to record hindlimb muscle activity chronically and to stimulate the superficial peroneal nerve electrically to evoke cutaneous reflexes. The speed-dependent modulation of cutaneous reflexes was assessed by evoking and characterizing ipsilateral and contralateral responses in semitendinosus, vastus lateralis, and lateral gastrocnemius muscles at four treadmill speeds: 0.2, 0.4, 0.6, and 0.8 m/s. The amplitudes of ipsilateral and contralateral responses were largest at intermediate speeds of 0.4 and 0.6 m/s, followed by the slowest and fastest speeds of 0.2 and 0.8 m/s, respectively. The phase-dependent modulation of reflexes was maintained across speeds, with ipsilateral and contralateral responses peaking during the stance-to-swing transition and swing phase of the ipsilateral limb or midstance of the contralateral limb. Reflex modulation across speeds also correlated with the spatial symmetry of the locomotor pattern, but not with temporal symmetry. That the cutaneous reflex amplitude in all muscles was similarly modulated with increasing speed independently of the background level of muscle activity is consistent with a generalized premotoneuronal spinal control mechanism that could help to stabilize the locomotor pattern when changing speed.

SIGNIFICANCE STATEMENTWhen walking, receptors located in the skin respond to mechanical pressure and send signals to the CNS to correct the trajectory of the limb and to reinforce weight support. These signals produce different responses, or reflexes, if they occur when the foot is contacting the ground or in the air. This is known as phase-dependent modulation of reflexes. However, when walking at faster speeds, we do not know if and how these reflexes are changed. In the present study, we show that reflexes from the skin are modulated with speed and that this is controlled at the level of the spinal cord. This modulation could be important in preventing sensory signals from destabilizing the walking pattern.
Adult Hippocampal Neurogenesis along the Dorsoventral Axis Contributes Differentially to Environmental Enrichment Combined with Voluntary Exercise in Alleviating Chronic Inflammatory Pain in Mice
Authors: Zheng Jie , Jiang Ying-Ying , Xu Ling-Chi , Ma Long-Yu , Liu Feng-Yu , Cui Shuang , Cai Jie , Liao Fei-Fei , Wan You , Yi Ming
Published: March 2017

Cognitive behavioral therapy, such as environmental enrichment combined with voluntary exercise (EE-VEx), is under active investigation as an adjunct to pharmaceutical treatment for chronic pain. However, the effectiveness and underlying mechanisms of EE-VEx remain unclear. In mice with intraplantar injection of complete Freund's adjuvant, our results revealed that EE-VEx alleviated perceptual, affective, and cognitive dimensions of chronic inflammatory pain. These effects of EE-VEx on chronic pain were contingent on the occurrence of adult neurogenesis in the dentate gyrus in a functionally dissociated manner along the dorsoventral axis: neurogenesis in the ventral dentate gyrus participated in alleviating perceptual and affective components of chronic pain by EE-VEx, whereas neurogenesis in the dorsal dentate gyrus was involved in EE-VEx's cognitive-enhancing effects. Chronic inflammatory pain was accompanied by decreased levels of brain-derived neurotrophic factor (BDNF) in the dentate gyrus, which were reversed by EE-VEx. Overexpression of BDNF in the dentate gyrus mimicked the effects of EE-VEx. Our results demonstrate distinct contribution of adult hippocampal neurogenesis along the dorsoventral axis to EE-VEx's beneficial effects on different dimensions of chronic pain.

SIGNIFICANCE STATEMENTEnvironmental enrichment combined with voluntary exercise (EE-VEx) is under active investigation as an adjunct to pharmaceutical treatment for chronic pain, but its effectiveness and underlying mechanisms remain unclear. In a mouse model of inflammatory pain, the present study demonstrates that the beneficial effects of EE-VEx on chronic pain depend on adult neurogenesis with a dorsoventral dissociation along the hippocampal axis. Adult neurogenesis in the ventral dentate gyrus participates in alleviating perceptual and affective components of chronic pain by EE-VEx, whereas that in the dorsal pole is involved in EE-VEx's cognitive-enhancing effects in chronic pain.
Functional Connectivity of Multiple Brain Regions Required for the Consolidation of Social Recognition Memory
Authors: Tanimizu Toshiyuki , Kenney Justin W. , Okano Emiko , Kadoma Kazune , Frankland Paul W. , Kida Satoshi
Published: March 2017

Social recognition memory is an essential and basic component of social behavior that is used to discriminate familiar and novel animals/humans. Previous studies have shown the importance of several brain regions for social recognition memories; however, the mechanisms underlying the consolidation of social recognition memory at the molecular and anatomic levels remain unknown. Here, we show a brain network necessary for the generation of social recognition memory in mice. A mouse genetic study showed that cAMP-responsive element-binding protein (CREB)-mediated transcription is required for the formation of social recognition memory. Importantly, significant inductions of the CREB target immediate-early genes c-fos and Arc were observed in the hippocampus (CA1 and CA3 regions), medial prefrontal cortex (mPFC), anterior cingulate cortex (ACC), and amygdala (basolateral region) when social recognition memory was generated. Pharmacological experiments using a microinfusion of the protein synthesis inhibitor anisomycin showed that protein synthesis in these brain regions is required for the consolidation of social recognition memory. These findings suggested that social recognition memory is consolidated through the activation of CREB-mediated gene expression in the hippocampus/mPFC/ACC/amygdala. Network analyses suggested that these four brain regions show functional connectivity with other brain regions and, more importantly, that the hippocampus functions as a hub to integrate brain networks and generate social recognition memory, whereas the ACC and amygdala are important for coordinating brain activity when social interaction is initiated by connecting with other brain regions. We have found that a brain network composed of the hippocampus/mPFC/ACC/amygdala is required for the consolidation of social recognition memory.

SIGNIFICANCE STATEMENTHere, we identify brain networks composed of multiple brain regions for the consolidation of social recognition memory. We found that social recognition memory is consolidated through CREB-meditated gene expression in the hippocampus, medial prefrontal cortex, anterior cingulate cortex (ACC), and amygdala. Importantly, network analyses based on c-fos expression suggest that functional connectivity of these four brain regions with other brain regions is increased with time spent in social investigation toward the generation of brain networks to consolidate social recognition memory. Furthermore, our findings suggest that hippocampus functions as a hub to integrate brain networks and generate social recognition memory, whereas ACC and amygdala are important for coordinating brain activity when social interaction is initiated by connecting with other brain regions.
MANAGEMENT OF ENDOCRINE DISEASE: Acromegaly and pregnancy: a contemporary review
Authors: Abucham Julio , Bronstein Marcello D , Dias Monike L
Published: March 2017

Although fertility is frequently impaired in women with acromegaly, pregnancy is apparently becoming more common due to improvement in acromegaly treatment as well as in fertility therapy. As a result, several studies on pregnancy in patients with acromegaly have been published in recent years adding new and relevant information to the preexisting literature. Also, new GH assays with selective specificities and the knowledge of the expression of the various GH genes have allowed a better understanding of somatotrophic axis function during pregnancy. In this review, we show that pregnancy in women with acromegaly is generally safe, usually with tumoral and hormonal stability. Although the paucity of data limits evidence-based recommendations for preconception counseling and pregnancy surveillance, controlling tumor size and hormonal activity before pregnancy is highly recommended to ensure better outcomes, and surgical control should be attempted when feasible. Treatment interruption at pregnancy confirmation has also proven to be safe, as drugs are not formally allowed to be used during pregnancy. Drug exposure (somatostatin analogs) during early or whole pregnancy might increase the chance of a lower birth weight. Aggressive disease is uncommon and may urge individual decisions such as surgery or drug treatment during pregnancy or lactation.
Long-term safety of once-daily, dual-release hydrocortisone in patients with adrenal insufficiency: a phase 3b, open-label, extension study
Authors: Nilsson Anna G , Bergthorsdottir Ragnhildur , Burman Pia , Dahlqvist Per , Ekman Bertil , Engström Britt Edén , Ragnarsson Oskar , Skrtic Stanko , Wahlberg Jeanette , Achenbach Heinrich , Uddin Sharif , Marelli Claudio , Johannsson Gudmundur
Published: March 2017

Objective

To investigate the long-term safety and tolerability of a once-daily, dual-release hydrocortisone (DR-HC) tablet as oral glucocorticoid replacement therapy in patients with primary adrenal insufficiency (AI).

Design

Prospective, open-label, multicenter, 5-year extension study of DR-HC conducted at five university clinics in Sweden.

Methods

Seventy-one adult patients diagnosed with primary AI who were receiving stable glucocorticoid replacement therapy were recruited. Safety and tolerability outcomes included adverse events (AEs), intercurrent illness episodes, laboratory parameters and vital signs. Quality of life (QoL) was evaluated using generic questionnaires.

Results

Total DR-HC exposure was 328 patient-treatment years. Seventy patients reported 1060 AEs (323 per 100 patient-years); 85% were considered unrelated to DR-HC by the investigator. The most common AEs were nasopharyngitis (70%), fatigue (52%) and gastroenteritis (48%). Of 65 serious AEs reported by 32 patients (20 per 100 patient-years), four were considered to be possibly related to DR-HC: acute AI (n = 2), gastritis (n = 1) and syncope (n = 1). Two deaths were reported (fall from height and subarachnoid hemorrhage), both considered to be unrelated to DR-HC. From baseline to 5 years, intercurrent illness episodes remained relatively stable (mean 2.6–5.4 episodes per patient per year), fasting plasma glucose (0.7 mmol/L;P < 0.0001) and HDL cholesterol (0.2 mmol/L;P < 0.0001) increased and patient-/investigator-assessed tolerability improved. QoL total scores were unchanged but worsening physical functioning was recorded (P = 0.008).

Conclusions

In the first prospective study evaluating the long-term safety of glucocorticoid replacement therapy in patients with primary AI, DR-HC was well tolerated with no safety concerns observed during 5-year treatment.
Litoestratigrafía del Grupo Tecocoyunca (Jurásico Medio) en el área del río Ñumí (cercanías de Tlaxiaco), Oaxaca y consideraciones sobre la distribución regional de su biota
Authors: Raúl Carrasco-Ramírez S. , Ferrusquía-Villafranca Ismael , Buitrón-Sánchez Blanca E. , Ruiz-González José E.
Published: March 2017

La litoestratigrafía jurásica de la Región Mixteca es relativamente bien conocida, sin embargo, el esquema en que se basa incluye descripciones formacionales un tanto deficientes (e.g. vaguedad, caracterización por contenido fósil, delimitación cartográfica insuficiente). Con el propósito de contribuir a subsanar esta deficiencia, realizamos un estudio detallado del área Ñumí, cercanías de Tlaxiaco, donde las unidades mesojurásicas integrantes del Grupo Tecocoyunca despliegan sus atributos, permitiendo así suplementar las descripciones formacionales. Se encontró que el Grupo Tecocoyunca localmente incluye en la parte inferior a las Formaciones Asociadas Zorrillo/Taberna (Bajociano Temprano-Tardío inicial), constituidas por ~287 m de limolitas carbonosas, lodolitas y subarcosas, porta pelecípodos y plantas terrestres, así como dos zonas de carbón; se les interpreta como parte de un complejo deltaico. Estas formaciones subyacen en concordancia a la Formación Simón (Batoniano Medio-Tardío), integrada por ~270 m de subarcosas y limolitas dispuestas en estratos delgados y gruesos; se le considera un depósito transicional. Esta unidad subyace en concordancia a la Formación Otatera (Batoniano tardío), consiste en ~170 m de coquinas de pelecípodos con intercalaciones de estratos calcáreos de intraespatita; se le interpreta como un depósito nerítico somero, con un componente subordinado de playa. Esta unidad subyace concordantemente a la Formación Yucuñuti (Calloviano Medio), constituida por ~118 m de areniscas finas, coquinas, limolitas y biomicritas que portan pelecípodos y gasterópodos; se le interpreta como un depósito transicional a nerítico somero. A esta unidad le sobreyace en discordancia la Caliza con “Cidaris” del Oxfordiano, que no forma parte de este grupo. La biota del Grupo Tecocoyunca incluye una típica paleoflora mesojurásica, cuyos taxa se encuentran ampliamente distribuidos en la región centro-meridional de México y septentrional de Centroamérica; así como una paleofauna integrada por moluscos mesojurásicos comunes en la Región Mixteca. La biota en conjunto denota un clima regional cálido y húmedo. Finalmente, se considera que la descripción detallada de las formaciones que constituyen al Grupo Tecocoyunca, es de facto un avance en la redefinición de las unidades mesojurásicas de la Región Mixteca.
Radiation dose determines the method for quantification of DNA double strand breaks
Authors: BULAT TANJA , KETA OTILIJA , KORIĆANAC LELA , ŽAKULA JELENA , PETROVIĆ IVAN , RISTIĆ-FIRA ALEKSANDRA , TODOROVIĆ DANIJELA
Published: March 2017

ABSTRACT Ionizing radiation induces DNA double strand breaks (DSBs) that trigger phosphorylation of the histone protein H2AX (γH2AX). Immunofluorescent staining visualizes formation of γH2AX foci, allowing their quantification. This method, as opposed to Western blot assay and Flow cytometry, provides more accurate analysis, by showing exact position and intensity of fluorescent signal in each single cell. In practice there are problems in quantification of γH2AX. This paper is based on two issues: the determination of which technique should be applied concerning the radiation dose, and how to analyze fluorescent microscopy images obtained by different microscopes. HTB140 melanoma cells were exposed to γ-rays, in the dose range from 1 to 16 Gy. Radiation effects on the DNA level were analyzed at different time intervals after irradiation by Western blot analysis and immunofluorescence microscopy. Immunochemically stained cells were visualized with two types of microscopes: AxioVision (Zeiss, Germany) microscope, comprising an ApoTome software, and AxioImagerA1 microscope (Zeiss, Germany). Obtained results show that the level of γH2AX is time and dose dependent. Immunofluorescence microscopy provided better detection of DSBs for lower irradiation doses, while Western blot analysis was more reliable for higher irradiation doses. AxioVision microscope containing ApoTome software was more suitable for the detection of γH2AX foci.
Evaluation of the efficacy of sodium valproate in convulsive status epilepticus following to ıschemic stroke
Authors: Özdemir Hasan Hüseyin , Müngen Bülent , İlhan Selçuk
Published: March 2017

Objective : Convulsive status epilepticus (CSE) is very rarely observed after ischaemic stroke. Sodium valproate (SV) is one of the agents used in the treatment of CSE, but its role still controversial, and its degree of efficacy in treating CSE that develops following stroke is unclear. Method : We evaluated 19 patients who were treated with intravenous (IV) SV (20 mg/kg, 2 mg/kg/h-12h) after diazepam. Patients’ modified Rankin scores (mRS), SE types, and changes in biochemical parameters after treatment were assessed. Results : CSE was successfully treated in 12 (63.15%) patients. Side effects such as hypotension and allergic reactions were observed in two patients. Refractory SE development was observed in 5 (29.4%) patients with high mRS (˃ 3). No significant deterioration in patients’ laboratory evaluations, conducted before and after status, was observed. Conclusion : SV may be safe and effective in the treatment of CSE observed after ischaemic stroke, especially in patients with low mRS.
Objective short sleep duration is associated with the activity of the hypothalamic-pituitary-adrenal axis in insomnia
Authors: D’Aurea Carolina , Poyares Dalva , Piovezan Ronaldo D. , Passos Giselle Soares , Tufik Sergio , Mello Marco Tulio de
Published: March 2017

Objective To evaluate the association between objective short sleep duration in patients with insomnia and changes in blood parameters related to hypothalamic-pituitary-adrenal (HPA) axis activity.Method A cross-sectional pilot study was conducted in 30 middle-aged adults with chronic insomnia who were divided into 2 groups according to polysomnography (PSG) total sleep time (TST) (TST > 5h and < 5h). All patients underwent subjective analysis of sleep quality, anthropometric measurements, PSG, and determination off asting blood parameters.Results The results revealed lower sleep efficiency and higher sleep latency for those with a TST < 5h. The subjective sleep quality was worse in the TST < 5h. Significantly, higher glucose and cortisol levels were observed with a TST < 5h. Glucose, cortisol and ACTH levels were inversely correlated with the PSG total sleep time.Conclusion Patients with insomnia with objective short sleep duration had HPA-associated endocrine and metabolic imbalances chronically linked to increases in cardiovascular risk observed with this more severe insomnia phenotype.
Dissociative experiences in patients with epilepsy
Authors: Özdemir Osman , Cilingir Vedat , Özdemir Pınar Güzel , Milanlioglu Aysel , Hamamci Mehmet , Yilmaz Ekrem
Published: March 2017

ABSTRACT A few studies have explored dissociative experiences in epilepsy patients. We investigated dissociative experiences in patients with epilepsy using the dissociative experiences scale (DES). Ninety-eight patients with epilepsy and sixty healthy controls were enrolled in this study. A sociodemographic questionnaire and the Dissociative Experiences Scale (DES), Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI) were administered to the participants. The DES scores were significantly higher for the patients with epilepsy than the healthy individuals. The number of individuals with pathological dissociation (DES ≥ 30) was higher in the epilepsy group (n = 28) than in the control group (n = 8). Also, higher levels of dissociation were significantly associated with frequency of seizures, but were not associated with duration of epilepsy and age at onset of the disorder. These findings demonstrate that patients with epilepsy are more prone to dissociation than controls. The high rate of dissociative experiences among patients with epilepsy suggest that some epilepsy-related factors are present.