2,583 research outputs found
Tiludronate and clodronate do not affect bone structure or remodeling kinetics over a 60 day randomized trial
Background
Tiludronate and clodronate are FDA-approved bisphosphonate drug therapies for navicular disease in horses. Although clinical studies have determined their ability to reduce lameness associated with skeletal disorders in horses, data regarding the effect on bone structure and remodeling is lacking. Additionally, due to off-label use of these drugs in young performance horses, effects on bone in young horses need to be investigated. Therefore, the purpose of this randomized, experimental pilot study was to determine the effect of tiludronate and clodronate on normal bone cells, structure and remodeling after 60 days in clinically normal, young horses. Additionally, the effect of clodronate on bone healing 60 days after an induced defect was investigated.
Results
All horses tolerated surgery well, with no post-surgery lameness and all acquired biopsies being adequate for analyses. Overall, tiludronate and clodronate did not significantly alter any bone structure or remodeling parameters, as evaluated by microCT and dynamic histomorphometry. Tiludronate did not extensively impact bone formation or resorption parameters as evaluated by static histomorphometry. Similarly, clodronate did not affect bone formation or resorption after 60 days. Sixty days post-defect, healing was minimally affected by clodronate.
Conclusions
Tiludronate and clodronate do not appear to significantly impact bone tissue on a structural or cellular level using standard dose and administration schedules
A Random Matrix Model of Adiabatic Quantum Computing
We present an analysis of the quantum adiabatic algorithm for solving hard
instances of 3-SAT (an NP-complete problem) in terms of Random Matrix Theory
(RMT). We determine the global regularity of the spectral fluctuations of the
instantaneous Hamiltonians encountered during the interpolation between the
starting Hamiltonians and the ones whose ground states encode the solutions to
the computational problems of interest. At each interpolation point, we
quantify the degree of regularity of the average spectral distribution via its
Brody parameter, a measure that distinguishes regular (i.e., Poissonian) from
chaotic (i.e., Wigner-type) distributions of normalized nearest-neighbor
spacings. We find that for hard problem instances, i.e., those having a
critical ratio of clauses to variables, the spectral fluctuations typically
become irregular across a contiguous region of the interpolation parameter,
while the spectrum is regular for easy instances. Within the hard region, RMT
may be applied to obtain a mathematical model of the probability of avoided
level crossings and concomitant failure rate of the adiabatic algorithm due to
non-adiabatic Landau-Zener type transitions. Our model predicts that if the
interpolation is performed at a uniform rate, the average failure rate of the
quantum adiabatic algorithm, when averaged over hard problem instances, scales
exponentially with increasing problem size.Comment: 9 pages, 7 figure
Simon\u27s fundamental rich-get-richer model entails a dominant first-mover advantage
Herbert Simon\u27s classic rich-get-richer model is one of the simplest empirically supported mechanisms capable of generating heavy-tail size distributions for complex systems. Simon argued analytically that a population of flavored elements growing by either adding a novel element or randomly replicating an existing one would afford a distribution of group sizes with a power-law tail. Here, we show that, in fact, Simon\u27s model does not produce a simple power-law size distribution as the initial element has a dominant first-mover advantage, and will be overrepresented by a factor proportional to the inverse of the innovation probability. The first group\u27s size discrepancy cannot be explained away as a transient of the model, and may therefore be many orders of magnitude greater than expected. We demonstrate how Simon\u27s analysis was correct but incomplete, and expand our alternate analysis to quantify the variability of long term rankings for all groups. We find that the expected time for a first replication is infinite, and show how an incipient group must break the mechanism to improve their odds of success. We present an example of citation counts for a specific field that demonstrates a first-mover advantage consistent with our revised view of the rich-get-richer mechanism. Our findings call for a reexamination of preceding work invoking Simon\u27s model and provide an expanded understanding going forward
Personality Is Reflected in the Brain's Intrinsic Functional Architecture
Personality describes persistent human behavioral responses to broad classes of environmental stimuli. Investigating how personality traits are reflected in the brain's functional architecture is challenging, in part due to the difficulty of designing appropriate task probes. Resting-state functional connectivity (RSFC) can detect intrinsic activation patterns without relying on any specific task. Here we use RSFC to investigate the neural correlates of the five-factor personality domains. Based on seed regions placed within two cognitive and affective ‘hubs’ in the brain—the anterior cingulate and precuneus—each domain of personality predicted RSFC with a unique pattern of brain regions. These patterns corresponded with functional subdivisions responsible for cognitive and affective processing such as motivation, empathy and future-oriented thinking. Neuroticism and Extraversion, the two most widely studied of the five constructs, predicted connectivity between seed regions and the dorsomedial prefrontal cortex and lateral paralimbic regions, respectively. These areas are associated with emotional regulation, self-evaluation and reward, consistent with the trait qualities. Personality traits were mostly associated with functional connections that were inconsistently present across participants. This suggests that although a fundamental, core functional architecture is preserved across individuals, variable connections outside of that core encompass the inter-individual differences in personality that motivate diverse responses
Diarrhea in young children from low-income countries leads to large-scale alterations in intestinal microbiota composition
Acknowledgments This work was funded in part by the William and Melinda Gates Foundation, award 42917 to JPN and OCS; US National Institutes of Health grants 5R01HG005220 to HCB, 5R01HG004885 to MP; US National Science Foundation Graduate Research Fellowship award DGE0750616 to JNP; AWW and JP are funded by The Wellcome Trust (Grant No. WT098051).Peer reviewedPublisher PD
Sex differences in procedural and clinical outcomes following rotational atherectomy
Aim:
Evaluate sex differences in procedural net adverse clinical events and long‐term outcomes following rotational atherectomy (RA).
Methods and Results:
From August 2010 to 2016, 765 consecutive patients undergoing RA PCI were followed up for a median of 4.7 years. 285 (37%) of subjects were female. Women were older (mean 76 years vs. 72 years; p < .001) and had more urgent procedures (64.6 vs. 47.3%; p < .001). Females received fewer radial procedures (75.1 vs. 85.1%; p < .001) and less intravascular imaging guidance (16.8 vs. 25.0%; p = .008). After propensity score adjustment, the primary endpoint of net adverse cardiac events (net adverse clinical events: all‐cause death, myocardial infarction, stroke, target vessel revascularization plus any procedural complication) occurred more often in female patients (15.1 vs. 9.0%; adjusted OR 1.81 95% CI 1.04–3.13; p = .037). This was driven by an increased risk of procedural complications rather than procedural major adverse cardiac events (MACE). Specifically, women were more likely to experience coronary dissection (4.6 vs. 1.3%; p = .008), cardiac tamponade (2.1 vs. 0.4%; p = .046) and significant bleeding (BARC ≥2: 5.3 vs. 2.3). Despite this, overall MACE‐free survival was similar between males and females (adjusted HR 1.03; 95% CI 0.80–1.34; p = .81). Procedural complications during RA were associated with almost double the incidence of MACE at long‐term follow‐up (HR 1.92; 95% CI 1.34–2.77; p < .001).
Conclusion:
Women may be at greater risk of procedural complications following rotational atherectomy. These include periprocedural bleeding episodes and coronary perforation leading to cardiac tamponade. Despite this, the adjusted overall long‐term survival free of major adverse cardiac events was similar between males and females
The Murchison Widefield Array: Design Overview
The Murchison Widefield Array (MWA) is a dipole-based aperture array
synthesis telescope designed to operate in the 80-300 MHz frequency range. It
is capable of a wide range of science investigations, but is initially focused
on three key science projects. These are detection and characterization of
3-dimensional brightness temperature fluctuations in the 21cm line of neutral
hydrogen during the Epoch of Reionization (EoR) at redshifts from 6 to 10,
solar imaging and remote sensing of the inner heliosphere via propagation
effects on signals from distant background sources,and high-sensitivity
exploration of the variable radio sky. The array design features 8192
dual-polarization broad-band active dipoles, arranged into 512 tiles comprising
16 dipoles each. The tiles are quasi-randomly distributed over an aperture
1.5km in diameter, with a small number of outliers extending to 3km. All
tile-tile baselines are correlated in custom FPGA-based hardware, yielding a
Nyquist-sampled instantaneous monochromatic uv coverage and unprecedented point
spread function (PSF) quality. The correlated data are calibrated in real time
using novel position-dependent self-calibration algorithms. The array is
located in the Murchison region of outback Western Australia. This region is
characterized by extremely low population density and a superbly radio-quiet
environment,allowing full exploitation of the instrumental capabilities.Comment: 9 pages, 5 figures, 1 table. Accepted for publication in Proceedings
of the IEE
Randomized controlled trial comparing three different modalities of lithotrites for intracorporeal lithotripsy in pcnl
Purpose: To compare the efficiency (stone fragmentation and removal time) and complications of three models of intracorporeal lithotripters in percutaneous nephrolithotomy (PCNL). Materials and Methods: Prospective, randomized controlled trial at nine centers in the North America from 2009 to 2016. Patients were randomized to one of three lithotripter devices: the Cyberwand, a dual probe ultrasonic device; the Swiss Lithoclast Select, a combination pneumatic and ultrasonic device; and the StoneBreaker, a portable pneumatic device powered by CO2 cartridges. Since the StoneBreaker lacks an ultrasonic component, it was used with the LUS‐II ultrasonic lithotripter to allow fair comparison with combination devices. Results: 270 patients were enrolled, 69 were excluded after randomization. 201 patients completed the study: 71 in the Cyberwand group, 66 in the Lithoclast Select, and 64 in the StoneBreaker group. The baseline patient characteristics of the three groups were similar. Mean stone surface area was smaller in the StoneBreaker group at 407.8mm2 vs 577.5mm2 (Lithoclast Select) and 627.9mm2 (Cyberwand). The stone clearance rate was slowest in the StoneBreaker group at 24.0 mm2/min vs 28.9 mm2/min and 32.3 mm2/min in the Lithoclast Select and Cyberwand groups respectively. After statistically adjusting for the smaller mean stone size in the StoneBreaker group, there was no difference in the stone clearance rate among the three groups (p=0.249). Secondary outcomes, including complications and stone free rates, were similar between the groups. Conclusions: The Cyberwand, Lithoclast Select, and the StoneBreaker lithotripters have similar adjusted stone clearance rates in PCNL for stones > 2cm. The safety and efficacy of these devices are comparable
A clinical genetic method to identify mechanisms by which pain causes depression and anxiety
BACKGROUND: Pain patients are often depressed and anxious, and benefit less from psychotropic drugs than pain-free patients. We hypothesize that this partial resistance is due to the unique neurochemical contribution to mood by afferent pain projections through the spino-parabrachial-hypothalamic-amygdalar systems and their projections to other mood-mediating systems. New psychotropic drugs for pain patients might target molecules in such brain systems. We propose a method to prioritize molecular targets by studying polymorphic genes in cohorts of patients undergoing surgical procedures associated with a variable pain relief response. We seek molecules that show a significant statistical interaction between (1) the amount of surgical pain relief, and (2) the alleles of the gene, on depression and anxiety during the first postoperative year. RESULTS: We collected DNA from 280 patients with sciatica due to a lumbar disc herniation, 162 treated surgically and 118 non-surgically, who had been followed for 10 years in the Maine Lumbar Spine Study, a large, prospective, observational study. In patients whose pain was reduced >25% by surgery, symptoms of depression and anxiety, assessed with the SF-36 Mental Health Scale, improved briskly at the first postoperative measurement. In patients with little or no surgical pain reduction, mood scores stayed about the same on average. There was large inter-individual variability at each level of residual pain. Polymorphisms in three pre-specified pain-mood candidate genes, catechol-O-methyl transferase (COMT), serotonin transporter, and brain-derived neurotrophic factor (BDNF) were not associated with late postoperative mood or with a pain-gene interaction on mood. Although the sample size did not provide enough power to persuasively search through a larger number of genes, an exploratory survey of 25 other genes provides illustrations of pain-gene interactions on postoperative mood – the mu opioid receptor for short-term effects of acute sciatica on mood, and the galanin-2 receptor for effects of unrelieved post-discectomy pain on mood one year after surgery. CONCLUSION: Genomic analysis of longitudinal studies of pain, depression, and anxiety in patients undergoing pain-relieving surgery may help to identify molecules through which pain alters mood. Detection of alleles with modest-sized effects will require larger cohorts
Author Correction: Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases.
Emmanuelle Souzeau, who contributed to analysis of data, was inadvertently omitted from the author list in the originally published version of this Article. This has now been corrected in both the PDF and HTML versions of the Article
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