A Bibliometric Study of Authorship and Collaboration Trends Over the Past 30 Years in Four Major Musculoskeletal Science Journals

This study explored changes in bibliometric variables over the last 30 years for four major musculoskeletal science journals (BONE®), Calcified Tissue International® (CTI®), Journal of Bone and Mineral Research® (JBMR®), and Journal of Orthopaedic Research® (JOR®), with a specific focus on author gender. Bibliometric data were collected for all manuscripts in 1985 (BONE®, CTI®, JOR®), 1986 (JBMR®), 1995, 2005, and 2015; 2776 manuscripts met inclusion criteria. Manuscripts from Europe were more often published in BONE® or CTI®, while those from North America in JBMR® or JOR®. All journals demonstrated an increase over time in the number of authors (3.67–7.3), number of countries (1.1–1.4), number of institutions (1.4–3.1), and number of references (25.1–45.4). The number of manuscript pages increased (6.6–8.9) except for JOR® which showed a decline. CTI® had the lowest number of authors (4.9 vs. 5.6–6.8). There was a change in the corresponding author position from first to last for all journals; this change was highest for CTI® (35%) and lowest for BONE® (14.0%). All journals demonstrated an increase over time in female authors; however, CTI® was the highest amongst these four journals. The percentage of female first authors rose from 24.6 to 44.3% (CTI® 29.1–52.3%). The percentage of corresponding female authors rose from 17.5 to 33.6% (CTI® 22.9–40.0%). The proportion of female authors is increasing, likely reflecting the increasing number of women obtaining doctorates in science, medicine, and engineering

Dietary nitrate increases arginine availability and protects mitochondrial complex I and energetics in the hypoxic rat heart

This is the final version. It was first published by Wiley in The Journal of Physiology at http://onlinelibrary.wiley.com/doi/10.1113/jphysiol.2014.275263/abstract.Hypoxic exposure is associated with impaired cardiac energetics in humans and altered mitochondrial function, with suppressed complex I-supported respiration, in rat heart. This response might limit reactive oxygen species (ROS) generation, but at the cost of impaired electron transport chain (ETC) activity. Dietary nitrate supplementation improves mitochondrial efficiency and can promote tissue oxygenation by enhancing blood flow. We therefore hypothesised that ETC dysfunction, impaired energetics and oxidative damage in the hearts of rats exposed to chronic hypoxia could be alleviated by sustained administration of a moderate dose of dietary nitrate. Male Wistar rats (n=40) were given water supplemented with 0.7 mmol/L NaCl (as control) or 0.7 mmol/L NaNO3, elevating plasma nitrate levels by 80%, and were exposed to 13% O2 (hypoxia) or normoxia (n=10 per group) for 14 days. Respiration rates, ETC protein levels, mitochondrial density, ATP content and protein carbonylation were measured in cardiac muscle. Complex I respiration rates and protein levels were 33% lower in hypoxic/NaCl rats compared with normoxic/NaCl controls. Protein carbonylation was 65% higher in hearts of hypoxic rats compared with controls, indicating increased oxidative stress, whilst ATP levels were 62% lower. Respiration rates, complex I protein and activity, protein carbonylation and ATP levels were all fully protected in the hearts of nitrate-supplemented hypoxic rats. Both in normoxia and hypoxia, dietary nitrate suppressed cardiac arginase expression and activity and markedly elevated cardiac L-arginine concentrations, unmasking a novel mechanism of action by which nitrate enhances tissue NO bioavailability. Dietary nitrate therefore alleviates metabolic abnormalities in the hypoxic heart, improving myocardial energetics

Black Diamonds at Brane Junctions

We discuss the properties of black holes in brane-world scenarios where our universe is viewed as a four-dimensional sub-manifold of some higher-dimensional spacetime. We consider in detail such a model where four-dimensional spacetime lies at the junction of several domain walls in a higher dimensional anti-de Sitter spacetime. In this model there may be any number p of infinitely large extra dimensions transverse to the brane-world. We present an exact solution describing a black p-brane which will induce on the brane-world the Schwarzschild solution. This exact solution is unstable to the Gregory-Laflamme instability, whereby long-wavelength perturbations cause the extended horizon to fragment. We therefore argue that at late times a non-rotating uncharged black hole in the brane-world is described by a deformed event horizon in p+4 dimensions which will induce, to good approximation, the Schwarzschild solution in the four-dimensional brane world. When p=2, this deformed horizon resembles a black diamond and more generally for p>2, a polyhedron.Comment: 13 pages, 1 figure, latex, JHEP.cl

The SMC SNR 1E0102.2-7219 as a Calibration Standard for X-ray Astronomy in the 0.3-2.5 keV Bandpass

The flight calibration of the spectral response of CCD instruments below 1.5 keV is difficult in general because of the lack of strong lines in the on-board calibration sources typically available. We have been using 1E 0102.2-7219, the brightest supernova remnant in the Small Magellanic Cloud, to evaluate the response models of the ACIS CCDs on the Chandra X-ray Observatory (CXO), the EPIC CCDs on the XMM-Newton Observatory, the XIS CCDs on the Suzaku Observatory, and the XRT CCD on the Swift Observatory. E0102 has strong lines of O, Ne, and Mg below 1.5 keV and little or no Fe emission to complicate the spectrum. The spectrum of E0102 has been well characterized using high-resolution grating instruments, namely the XMM-Newton RGS and the CXO HETG, through which a consistent spectral model has been developed that can then be used to fit the lower-resolution CCD spectra. We have also used the measured intensities of the lines to investigate the consistency of the effective area models for the various instruments around the bright O (~570 eV and 654 eV) and Ne (~910 eV and 1022 eV) lines. We find that the measured fluxes of the O VII triplet, the O VIII Ly-alpha line, the Ne IX triplet, and the Ne X Ly-alpha line generally agree to within +/-10 % for all instruments, with 28 of our 32 fitted normalizations within +/-10% of the RGS-determined value. The maximum discrepancies, computed as the percentage difference between the lowest and highest normalization for any instrument pair, are 23% for the O VII triplet, 24% for the O VIII Ly-alpha line, 13% for the Ne IX triplet, and 19% for the Ne X Ly-alpha line. If only the CXO and XMM are compared, the maximum discrepancies are 22% for the O VII triplet, 16% for the O VIII Ly-alpha line, 4% for the Ne IX triplet, and 12% for the Ne X Ly-alpha line.Comment: 16 pages, 11 figures, to be published in Proceedings of the SPIE 7011: Space Telescopes and Instrumentation II: Ultraviolet to Gamma Ray 200

Transcriptional Signatures of Tau and Amyloid Neuropathology

Alzheimer's disease (AD) is associated with the intracellular aggregation of hyperphosphorylated tau and the accumulation of β-amyloid in the neocortex. We use transgenic mice harboring human tau (rTg4510) and amyloid precursor protein (J20) mutations to investigate transcriptional changes associated with the progression of tau and amyloid pathology. rTg4510 mice are characterized by widespread transcriptional differences in the entorhinal cortex with changes paralleling neuropathological burden across multiple brain regions. Differentially expressed transcripts overlap with genes identified in genetic studies of familial and sporadic AD. Systems-level analyses identify discrete co-expression networks associated with the progressive accumulation of tau that are enriched for genes and pathways previously implicated in AD pathology and overlap with co-expression networks identified in human AD cortex. Our data provide further evidence for an immune-response component in the accumulation of tau and reveal molecular pathways associated with the progression of AD neuropathology.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.WT_/Wellcome Trust/United Kingdom MR/M008924/1/MRC_/Medical Research Council/United Kingdompublished version, accepted version, submitted versio

Risk Assessment and Comparative Effectiveness of Left Ventricular Assist Device and Medical Management in Ambulatory Heart Failure Patients The ROADMAP Study 2-Year Results

OBJECTIVES The authors sought to provide the pre-specified primary endpoint of the ROADMAP (Risk Assessment and Comparative Effectiveness of Left Ventricular Assist Device and Medical Management in Ambulatory Heart Failure Patients) trial at 2 years. BACKGROUND The ROADMAP trial was a prospective nonrandomized observational study of 200 patients (97 with a left ventricular assist device [LVAD], 103 on optimal medical management [OMM]) that showed that survival with improved functional status at 1 year was better with LVADs compared with OMM in a patient population of ambulatory New York Heart Association functional class IIIb/IV patients. METHODS The primary composite endpoint was survival on original therapy with improvement in 6-min walk distance \u3e= 75 m. RESULTS Patients receiving LVAD versus OMM had lower baseline health-related quality of life, reduced Seattle Heart Failure Model 1-year survival (78% vs. 84%; p = 0.012), and were predominantly INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) profile 4 (65% vs. 34%; p \u3c 0.001) versus profiles 5 to 7. More LVAD patients met the primary endpoint at 2 years: 30% LVAD versus 12% OMM (odds ratio: 3.2 [95% confidence interval: 1.3 to 7.7]; p = 0.012). Survival as treated on original therapy at 2 years was greater for LVAD versus OMM (70 +/- 5% vs. 41 +/- 5%; p \u3c 0.001), but there was no difference in intent-to-treat survival (70 +/- 5% vs. 63 +/- 5%; p = 0.307). In the OMM arm, 23 of 103 (22%) received delayed LVADs (18 within 12 months; 5 from 12 to 24 months). LVAD adverse events declined after year 1 for bleeding (primarily gastrointestinal) and arrhythmias. CONCLUSIONS Survival on original therapy with improvement in 6-min walk distance was superior with LVAD compared with OMM at 2 years. Reduction in key adverse events beyond 1 year was observed in the LVAD group. The ROADMAP trial provides risk-benefit information to guide patient- and physician-shared decision making for elective LVAD therapy as a treatment for heart failure. (Risk Assessment and Comparative Effectiveness of Left Ventricular Assist Device and Medical Management in Ambulatory Heart Failure Patients [ROADMAP]; NCT01452802

N=3 Warped Compactifications

Orientifolds with three-form flux provide some of the simplest string examples of warped compactification. In this paper we show that some models of this type have the unusual feature of D=4, N=3 spacetime supersymmetry. We discuss their construction and low energy physics. Although the local form of the moduli space is fully determined by supersymmetry, to find its global form requires a careful study of the BPS spectrum.Comment: 27 pages, v2: 32pp., RevTeX4, fixed factors, slightly improved sections 3D and 4B, v3: added referenc

Endothelial cell regulation of systemic haemodynamics and metabolism acts through the HIF transcription factors.

BackgroundThe vascular endothelium has important endocrine and paracrine roles, particularly in the regulation of vascular tone and immune function, and it has been implicated in the pathophysiology of a range of cardiovascular and inflammatory conditions. This study uses a series of transgenic murine models to explore for the first time the role of the hypoxia-inducible factors, HIF-1α and HIF-2α in the pulmonary and systemic circulations as potential regulators of systemic vascular function in normoxic or hypoxic conditions and in response to inflammatory stress. We developed a series of transgenic mouse models, the HIF-1α Tie2Cre, deficient in HIF1-α in the systemic and pulmonary vascular endothelium and the L1Cre, a pulmonary endothelium specific knockout of HIF-1α or HIF-2α. In vivo, arterial blood pressure and metabolic activity were monitored continuously in normal atmospheric conditions and following an acute stimulus with hypoxia (10%) or lipopolysaccharide (LPS). Ex vivo, femoral artery reactivity was assessed using wire myography.ResultsUnder normoxia, the HIF-1α Tie2Cre mouse had increased systolic and diastolic arterial pressure compared to litter mate controls over the day-night cycle under normal environmental conditions. VO2 and VCO2 were also increased. Femoral arteries displayed impaired endothelial relaxation in response to acetylcholine mediated by a reduction in the nitric oxide dependent portion of the response. HIF-1α L1Cre mice displayed a similar pattern of increased systemic blood pressure, metabolic rate and impaired vascular relaxation without features of pulmonary hypertension, polycythaemia or renal dysfunction under normal conditions. In response to acute hypoxia, deficiency of HIF-1α was associated with faster resolution of hypoxia-induced haemodynamic and metabolic compromise. In addition, systemic haemodynamics were less compromised by LPS treatment.ConclusionsThese data show that deficiency of HIF-1α in the systemic or pulmonary endothelium is associated with increased systemic blood pressure and metabolic rate, a pattern that persists in both normoxic conditions and in response to acute stress with potential implications for our understanding of the pathophysiology of vascular dysfunction in acute and chronic disease