bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasma and serum concentrations of cytarabine administered via continuous intravenous infusion to dogs with meningoencephalomyelitis of unknown etiology
Authors: Early P. J. , Crook K. I. , Williams L. M. , Davis E. G. , Muñana K. R. , Papich M. G. , Messenger K. M. 
Published: September 2016

The objective of this study was to evaluate the plasma and serum concentrations of cytarabine (CA) administered via constant rate infusion (CRI) in dogs with meningoencephalomyelitis of unknown etiology (MUE). Nineteen client‐owned dogs received a CRI of CA at a dose of 25 mg/m2/h for 8 h as treatment for MUE. Dogs were divided into four groups, those receiving CA alone and those receiving CA in conjunction with other drugs. Blood samples were collected at 0, 1, 8, and 12 h after initiating the CRI. Plasma (n = 13) and serum (n = 11) cytarabine concentrations were measured by high‐pressure liquid chromatography. The mean peak concentration (CMAX) and area under the curve (AUC) after CRI administration were 1.70 ± 0.66 μg/mL and 11.39 ± 3.37 h·μg/mL, respectively, for dogs receiving cytarabine alone, 2.36 ± 0.35 μg/mL and 16.91 + 3.60 h·μg/mL for dogs administered cytarabine and concurrently on other drugs. Mean concentrations for all dogs were above 1.0 μg/mL at both the 1‐ and 8‐h time points. The steady‐state achieved with cytarabine CRI produces a consistent and prolonged exposure in plasma and serum, which is likely to produce equilibrium between blood and the central nervous system in dogs with a clinical diagnosis of MUE. Other medications commonly used to treat MUE do not appear to alter CA concentrations in serum and plasma.
The Right to Left Atrial Volume Ratio Predicts Outcomes after Circumferential Pulmonary Vein Isolation of Longstanding Persistent Atrial Fibrillation
Authors: SASAKI TAKEHITO , NAKAMURA KOHKI , NAITO SHIGETO , MINAMI KENTARO , KOYAMA KEIKO , YAMASHITA EIJI , KUMAGAI KOJI , OSHIMA SHIGERU 
Published: September 2016

BackgroundWe aimed to identify the predictors of clinical outcomes after circumferential pulmonary vein isolation (CPVI) without any substrate modification for longstanding persistent atrial fibrillation (LSP‐AF).MethodsThis study retrospectively analyzed 70 consecutive LSP‐AF patients who underwent an initial CPVI and were followed‐up for more than 1 year. The right and left atrial volumes indexed to the body surface areas (right atrial volume index [RAVI] and left atrial volume index [LAVI]) were determined by preacquired contrast‐enhanced computed tomography (CT). The %RAVI/LAVI was obtained as 100 × RAVI/LAVI.ResultsDuring a median follow‐up period of 15 months (interquartile range, 13–19 months), 21 patients (30%) had arrhythmia recurrences after the CPVI. Antiarrhythmic drugs were continued in 34 patients (48%). In the Cox proportional hazard model, the %RAVI/LAVI was a significant positive predictor of arrhythmia recurrences (hazard ratio, 1.048; P = 0.039). A receiver‐operating characteristic analysis demonstrated that at an optimal cutoff of 100.1 for the %RAVI/LAVI, the sensitivity and specificity for predicting arrhythmia recurrences were 85.7% and 71.4%, respectively. The Kaplan‐Meier analysis showed that arrhythmia recurrences were less frequent in patients with a %RAVI/LAVI of <100.1 than in those with a %RAVI/LAVI of ≥100.1 (P < 0.0001), and the arrhythmia‐free survival rate at 12 months was 89.7% and 45.2%, respectively.ConclusionsThe ratio of the RAVI to LAVI on CT may be a useful predictor of clinical outcomes after CPVI of LSP‐AF. LSP‐AF patients with a less predominant right atrial enlargement relative to the left atrial enlargement may be good candidates for successful treatment with CPVI alone as the ablation strategy for LSP‐AF.
New discoveries of tetrapods (ichthyostegid‐like and whatcheeriid‐like) in the Famennian (Late Devonian) localities of Strud and Becco (Belgium)
Authors: Olive Sébastien , Ahlberg Per E. , Pernègre Vincent N. , Poty Édouard , Steurbaut Étienne , Clément Gaël 
Published: September 2016

AbstractThe origin of tetrapods is one of the key events in vertebrate history. The oldest tetrapod body fossils are Late Devonian (Frasnian–Famennian) in age, most of them consisting of rare isolated bone elements. Here we describe tetrapod remains from two Famennian localities from Belgium: Strud, in the Province of Namur, and Becco, in the Province of Liège. The newly collected material consists of an isolated complete postorbital, fragments of two maxillae, and one putative partial cleithrum, all from Strud, and an almost complete maxilla from Becco. The two incomplete maxillae and cleithrum from Strud, together with the lower jaw previously recorded from this site, closely resemble the genusIchthyostega, initially described from East Greenland. The postorbital from Strud and the maxilla from Becco do not resemble the genusIchthyostega. They show several derived anatomical characters allowing their tentative assignment to a whatcheeriid‐grade group. The new tetrapod records show that there are at least two tetrapod taxa in Belgium and almost certainly two different tetrapod taxa at Strud. This locality joins the group of Devonian tetrapod‐bearing localities yielding more than one tetrapod taxon, confirming that environments favourable to early tetrapod life were often colonized by several tetrapod taxa.
A Comparison of Genicular Nerve Treatment Using Either Radiofrequency or Analgesic Block with Corticosteroid for Pain after a Total Knee Arthroplasty: A Double‐Blind, Randomized Clinical Study
Authors: Qudsi‐Sinclair Salima , Borrás‐Rubio Enrique , Abellan‐Guillén Juan F. , Padilla del Rey María Luz , Ruiz‐Merino Guadalupe 
Published: September 2016

AbstractBackgroundKnee osteoarthritis is a disease that affects a third of the population over 65 years of age, and it is increasingly becoming a motive for consultation and a source of pain and disability. The gold standard surgical treatment is a total knee arthroplasty; however, 15% to 30% of patients who have undergone surgery continue to experience pain and functional limitation.MethodsA double‐blind, randomized clinical study compared neurolysis using traditional radiofrequency (RF) to local anesthetic and corticosteroid block of the superolateral, superomedial, and inferomedial branches of the knee genicular nerves in patients who had total knee arthroplasty but still experience pain.ResultsTwenty‐eight patients, 14 on each treatment arm, were followed for over a 1‐year period. A reduction in pain and significant joint function improvement during the first 3 to 6 months was shown, with similar results using both techniques. No adverse effects were noted. An improvement in both disability and quality of life was observed, as well as a reduction in the need for analgesics in both treatment groups.ConclusionsFurther clinical trials need to be undertaken, with a larger sample size, in order to demonstrate the efficacy of this technique and to detect the possible appearance of any long‐term adverse effects.
Monitoring 3D Vibrations in Structures using High‐resolution Blurred Imagery
Authors: McCarthy David M. J. , Chandler Jim H. , Palmeri Alessandro 
Published: September 2016

AbstractPhotogrammetry has been used in the past to monitor the laboratory testing of civil engineering structures using multiple image‐based sensors. This has been successful, but detecting vibrations during dynamic structural tests has proved more challenging because they usually depend on high‐speed cameras which often results in lower image resolutions and reduced accuracy. To overcome this limitation, a novel approach has been devised to take measurements from blurred images in long‐exposure photographs. The motion of the structure is captured in individual motion‐blurred images without dependence on imaging speed. A bespoke algorithm then determines each measurement point's motion. Using photogrammetric techniques, a model structure's motion with respect to different excitation frequencies is captured and its vibration envelope recreated in 3D. The approach is tested and used to identify changes in the model's vibration response.
A whole‐killed, blood‐stage lysate vaccine protects against the malaria liver stage
Authors: Lu X. , Liu T. , Zhu F. , Chen L. , Xu W. 
Published: September 2016

SummaryAlthough the attenuated sporozoite is the most efficient vaccine to prevent infection with the malaria parasite, the limitation of a source of sterile sporozoites greatly hampers its application. In this study, we found that the whole‐killed, blood‐stage lysate vaccine could confer protection against the blood stage as well as the liver stage. Although the protective immunity induced by the whole‐organism vaccine against the blood stage is dependent on parasite‐specific CD4+ T‐cell responses and antibodies, in mice immunized with the whole‐killed, blood‐stage lysate vaccine, CD8+, but not CD4+ effector T‐cell responses greatly contributed to protection against the liver stage. Thus, our data suggested that the whole‐killed, blood‐stage lysate vaccine could be an alternative promising strategy to prevent malaria infection and to reduce the morbidity and mortality of patients with malaria.
Gradual downhill running improves age‐related skeletal muscle and bone weakness: implication of autophagy and bone morphogenetic proteins
Authors: Kim Jeong‐Seok , Lee Young‐Hee , Yi Ho‐Keun 
Published: September 2016

New Findings
What is the central question of this study?
Exercise training by running has an effect on age‐related muscle and bone wasting that improves physical activity and quality of life in the elderly. However, the effect of downhill running on age‐related muscle and bone wasting, and its mechanisms, are unclear.

What is the main finding and its importance?
Gradual downhill running can improve skeletal muscle growth and bone formation by enhancing autophagy and bone morphogenetic protein signalling in aged rats. Therefore, downhill running exercise might be a practical intervention to improve skeletal muscle and bone protection in the elderly.

Recent evidence suggests that autophagy and the bone morphogenetic protein (BMP) signalling pathway regulate skeletal muscle growth and bone formation in aged rats. However, the effect of downhill running on muscle growth and bone formation is not well understood. Thus, we investigated the effect of downhill and uphill running on age‐related muscle and bone weakness. Young and late middle‐aged rats were randomly assigned to control groups (young, YC; and late middle‐aged, LMC) and two types of running training groups (late middle‐aged downhill, LMD; and late middle‐aged uphill, LMU). Training was progressively carried out on a treadmill at a speed of 21 m min−1 with a slope of +10 deg for uphill training versus 16 m min−1 with a slope of −16 deg for downhill training, both for 60 min day−1, 5 days week−1 for 8 weeks. Downhill and uphill training increased autophagy‐related protein 5, microtubule‐associated protein light chain, Beclin‐1 and p62 proteins in aged rats. In addition, superoxide dismutase, haem oxygenase‐1 and the BMP signalling pathway were elevated. Phosphorylation of mammalian target of rapamycin and myogenic differentiation were increased significantly in the LMD and LMU groups. Consequently, in the femur, BMP‐2, BMP‐7 and autophagy molecules were highly expressed in the LMD and LMU groups. These results suggest that both downhill and uphill training appear to have a positive effect on expression of autophagy molecules and BMPs. In particular, these physiological adaptations from gradual downhill exercise have an effect on bone morphological changes and muscle quality similar to gradual uphill training interventions in ageing.
Na+/H+ exchange via the Drosophila vesicular glutamate transporter mediates activity‐induced acid efflux from presynaptic terminals
Authors: Rossano Adam J. , Kato Akira , Minard Karyl I. , Romero Michael F. , Macleod Gregory T. 
Published: September 2016

Key points
Intracellular pH regulation is vital to neurons as nerve activity produces large and rapid acid loads in presynaptic terminals.
Rapid clearance of acid loads is necessary to maintain control of neurotransmission, but neuronal acid clearance mechanisms remain poorly understood.
Glutamate is loaded into synaptic vesicles via the vesicular glutamate transporter (VGLUT), a mechanism conserved across phyla, and this study reports a previously unknown role for VGLUT as an acid‐extruding protein when deposited in the plasmamembrane during exocytosis.
The finding was made in Drosophila (fruit fly) larval motor neurons through a combined pharamacological and genetic dissection of presynaptic pH homeostatic mechanisms.
A dual role for VGLUT serves to integrate neuronal activity and pH regulation in presynaptic nerve terminals.
AbstractNeuronal activity can result in transient acidification of presynaptic terminals, and such shifts in cytosolic pH (pHcyto) probably influence mechanisms underlying forms of synaptic plasticity with a presynaptic locus. As neuronal activity drives acid loading in presynaptic terminals, we hypothesized that the same activity might drive acid efflux mechanisms to maintain pHcyto homeostasis. To better understand the integration of neuronal activity and pHcyto regulation we investigated the acid extrusion mechanisms at Drosophila glutamatergic motorneuron terminals. Expression of a fluorescent genetically encoded pH indicator, named ‘pHerry’, in the presynaptic cytosol revealed acid efflux following nerve activity to be greater than that predicted from measurements of the intrinsic rate of acid efflux. Analysis of activity‐induced acid transients in terminals deficient in either endocytosis or exocytosis revealed an acid efflux mechanism reliant upon synaptic vesicle exocytosis. Pharmacological and genetic dissection in situ and in a heterologous expression system indicate that this acid efflux is mediated by conventional plasmamembrane acid transporters, and also by previously unrecognized intrinsic H+/Na+ exchange via the Drosophila vesicular glutamate transporter (DVGLUT). DVGLUT functions not only as a vesicular glutamate transporter but also serves as an acid‐extruding protein when deposited on the plasmamembrane.
Current and future perspectives on lumbar degenerative disc disease: a UK survey exploring specialist multidisciplinary clinical opinion
Authors: Deane Janet A , McGregor Alison H 
Published: September 2016

ObjectivesDespite lumbar degenerative disc disease (LDDD) being significantly associated with non-specific low back pain and effective treatment remaining elusive, specialist multidisciplinary clinical stakeholder opinion remains unexplored. The present study examines the views of such experts.DesignA reliable and valid electronic survey was designed to establish trends using theoretical constructs relating to current assessment and management practices. Clinicians from the Society of Back Pain Research (SBPR) UK were invited to take part. Quantitative data were collated and coded using Bristol Online Surveys (BOS) software, and content analysis was used to systematically code and categorise qualitative data.SettingSpecialist multidisciplinary spinal interest group in the UK.Participants38/141 clinically active, multidisciplinary SBPR members with specialist spinal interest participated. Among them, 84% had >9 years postgraduate clinical experience.InterventionsNone.Outcome measuresFrequency distributions were used to establish general trends in quantitative data. Qualitative responses were coded and categorised in relation to each theme and percentage responses were calculated.ResultsLDDD symptom recurrence, in the absence of psychosocial influence, was associated with physical signs of joint stiffness (26%), weakness (17%) and joint hypermobility (6%), while physical factors (21%) and the ability to adapt (11%) were postulated as reasons why some experience pain and others do not. No one management strategy was supported exclusively or with consensus. Regarding effective modalities, there was no significant difference between allied health professional and medic responses (p=0.1–0.8). The future of LDDD care was expressed in terms of improvements in patient communication (35%), patient education (38%) and treatment stratification (24%).ConclusionsResults suggest that multidisciplinary expert spinal clinicians appear to follow UK-based assessment guidelines with regard to recurrent LDDD; there are, however, inconsistencies in the management approaches supported. This reflects the current literature and the lack of specific, formalised guidance. LDDD treatment stratification and further research are explicitly supported.
Primary care physicians’ willingness to disclose oncology errors involving multiple providers to patients
Authors: Mazor Kathleen , Roblin Douglas W , Greene Sarah M , Fouayzi Hassan , Gallagher Thomas H 
Published: September 2016

BackgroundFull disclosure of harmful errors to patients, including a statement of regret, an explanation, acceptance of responsibility and commitment to prevent recurrences is the current standard for physicians in the USA.ObjectiveTo examine the extent to which primary care physicians’ perceptions of event-level, physician-level and organisation-level factors influence intent to disclose a medical error in challenging situations.DesignCross-sectional survey containing two hypothetical vignettes: (1) delayed diagnosis of breast cancer, and (2) care coordination breakdown causing a delayed response to patient symptoms. In both cases, multiple physicians shared responsibility for the error, and both involved oncology diagnoses.SettingThe study was conducted in the context of the HMO Cancer Research Network Cancer Communication Research Center.ParticipantsPrimary care physicians from three integrated healthcare delivery systems located in Washington, Massachusetts and Georgia; responses from 297 participants were included in these analyses.Main measuresThe dependent variable intent to disclose included intent to provide an apology, an explanation, information about the cause and plans for preventing recurrences. Independent variables included event-level factors (responsibility for the event, perceived seriousness of the event, predictions about a lawsuit); physician-level factors (value of patient-centred communication, communication self-efficacy and feelings about practice); organisation-level factors included perceived support for communication and time constraints.Key resultsA majority of respondents would not fully disclose in either situation. The strongest predictors of disclosure were perceived personal responsibility, perceived seriousness of the event and perceived value of patient-centred communication. These variables were consistently associated with intent to disclose.ConclusionTo make meaningful progress towards improving disclosure; physicians, risk managers, organisational leaders, professional organisations and accreditation bodies need to understand the factors which influence disclosure. Such an understanding is required to inform institutional policies and provider training.
Yet Another Compressed Cache
Authors: Sardashti Somayeh , Seznec Andre , Wood David A. 
Published: September 2016

Cache memories play a critical role in bridging the latency, bandwidth, and energy gaps between cores and off-chip memory. However, caches frequently consume a significant fraction of a multicore chip's area and thus account for a significant fraction of its cost. Compression has the potential to improve the effective capacity of a cache, providing the performance and energy benefits of a larger cache while using less area. The design of a compressed cache must address two important issues: (i) a low-latency, low-overhead compression algorithm that can represent a fixed-size cache block using fewer bits and (ii) a cache organization that can efficiently store the resulting variable-size compressed blocks. This article focuses on the latter issue.
Here, we propose Yet Another Compressed Cache (YACC), a new compressed cache design that targets improving effective cache capacity with a simple design. YACC uses super-blocks to reduce tag overheads while packing variable-size compressed blocks to reduce internal fragmentation. YACC achieves the benefits of two state-of-the art compressed caches—Decoupled Compressed Cache (DCC) [Sardashti and Wood 2013a, 2013b] and Skewed Compressed Cache (SCC) [Sardashti et al. 2014]—with a more practical and simpler design. YACC's cache layout is similar to conventional caches, with a largely unmodified tag array and unmodified data array. Compared to DCC and SCC, YACC requires neither the significant extra metadata (i.e., back pointers) needed by DCC to track blocks nor the complexity and overhead of skewed associativity (i.e., indexing ways differently) needed by SCC. An additional advantage over previous work is that YACC enables modern replacement mechanisms, such as RRIP.
For our benchmark set, compared to a conventional uncompressed 8MB LLC, YACC improves performance by 8% on average and up to 26%, and reduces total energy by 6% on average and up to 20%. An 8MB YACC achieves approximately the same performance and energy improvements as a 16MB conventional cache at a much smaller silicon footprint, with only 1.6% greater area than an 8MB conventional cache. YACC performs comparably to DCC and SCC but is much simpler to implement.
The Challenge of Developing Autophagy Inhibition as a Therapeutic Strategy
Authors: Gewirtz David A. 
Published: September 2016

Abstract
The finding that cancer chemotherapeutic drugs and ionizing radiation often promote autophagy has provided the foundation for clinical trials combining autophagy-blocking agents with antitumor drugs and radiation. The premise driving these trials is that therapy-induced autophagy is cytoprotective; consequently, inhibition of autophagy is anticipated to sensitize malignancies to therapy. However, it is well-established that autophagy may also mediate the toxicity of antitumor drugs while evidence also exists for a nonprotective function of autophagy. Consequently, given that it cannot be predicted what form autophagy will take upon treatment with chemotherapy or radiation, the current ongoing clinical trials are likely to generate contradictory or inconsistent results, with the potential consequence that autophagy inhibition could be dismissed as therapeutic strategy based on what are essentially false-negative outcomes. Appropriate interpretation of the outcomes of these trials would require knowledge as to whether the drugs or radiation used promote the cytoprotective form of autophagy in the tumor cells as well as whether the chloroquine or hydroxychloroquine actually inhibit the autophagy. Ultimately, it will be necessary to identify those patients for whom the strategy of autophagy inhibition would be anticipated to improve the response to therapy. However, this is currently not feasible in the absence of appropriate bioassays or predictive markers for characterization of the autophagy or the effectiveness of pharmacologic approaches for autophagy inhibition in the clinic. Cancer Res; 76(19); 5610–4. ©2016 AACR.
Transgender, Culture, and Social Class in Early Twentieth Century’s Mecca
Authors: El-Zein Amira 
Published: September 2016

This paper examines the theme of androgyny in the novelKhatamby the Saudi writer Raja Alem. It applies the theories of post-feminists such as Judith Butler and Kate Bornstein and Jungian writers such as June Singer and Erich Neumann. It also draws on theories of gendered space using the works of Foucault.The paper elucidates how the author used the theme of androgyny to unveil the biased patriarchal power in Meccan society at the turn of the twentieth century. Furthermore, it argues that through exploring the complex character of her androgynous heroine, Khatam, Alem intended to reach beyond gender proper in order to reclaim Khatam’s humanity. The paper also investigates the question of social classes in early twentieth century Mecca, with particular focus on slavery andashrâf(nobles).