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One Year Follow-up of a Randomized, Double-Blind, Placebo-Controlled Trial of Percutaneous Peripheral Nerve Stimulation for Chronic Neuropathic Pain Following Amputation
Abstract
INTRODUCTION
Over 85% of patients experience residual limb (RLP) and/or phantom limb (PLP) pain following amputation. Peripheral nerve stimulation (PNS) is a non-opioid approach to relieve postamputation neuropathic pain. A recent multicenter, randomized, double-blind, placebo-controlled study using a novel percutaneous PNS system demonstrated clinically and statistically significant improvements in pain and pain interference with PNS compared to placebo (Gilmore et al, 2019). This work presents prospective 1-yr follow-up to assess durability of pain relief and functional improvements.
METHODS
Over 85% of patients experience residual limb (RLP) and/or phantom limb (PLP) pain following amputation. Peripheral nerve stimulation (PNS) is a non-opioid approach to relieve post-amputation neuropathic pain. A recent multicenter, randomized, double-blind, placebo-controlled study using a novel percutaneous PNS system demonstrated clinically and statistically significant improvements in pain and pain interference with PNS compared to placebo (Gilmore et al, 2019). This work presents prospective one-year follow-up to assess durability of pain relief and functional improvements.
RESULTS
A significantly greater proportion of subjects who completed the 12-mo visit reported = 50% pain relief on the BPI-SF (5/8, 63%; average pain relief = 73% among responders) compared to the placebo group at the time of crossover (0/14, 0%, P = .003; average pain relief = 23%). A majority of subjects also reported = 50% reductions in pain interference at 12 mo (5/8, 63%). Two of 13 (15%) subjects in the placebo group reported sustained improvements in pain interference (P = .06). Average reduction in pain interference among responders in the PNS group was 87%.
CONCLUSION
This work suggests that PNS delivered over 60 d may provide clinically significant and enduring pain relief, enabling improved function and potentially reducing the need for a permanently implanted system
Determinants of Affinity and Activity of the Anti-Sigma Factor AsiA
The AsiA protein is a T4 bacteriophage early gene product that regulates transcription of host and viral genes. Monomeric AsiA binds tightly to the σ70 subunit of Escherichia coli RNA polymerase, thereby inhibiting transcription from bacterial promoters and phage early promoters and co-activating transcription from phage middle promoters. Results of structural studies have identified amino acids at the protomer-protomer interface in dimeric AsiA and at the monomeric AsiA-σ70 interface and demonstrated substantial overlap in the sets of residues that comprise each. Here we evaluate the contributions of individual interfacial amino acid side chains to protomer-protomer affinity in AsiA homodimers, to monomeric AsiA affinity for σ70, and to AsiA function in transcription. Sedimentation equilibrium, dynamic light scattering, electrophoretic mobility shift and transcription activity measurements were used to assess affinity and function of site-specific AsiA mutants. Alanine substitutions for solvent-inaccessible residues positioned centrally in the protomer-protomer interface of the AsiA homodimer – V14, I17, and I40 – resulted in the largest changes in free energy of dimer association, whereas alanine substitutions at other interfacial positions had little effect. These residues also contribute significantly to AsiA-dependent regulation of RNA polymerase activity, as do additional residues positioned at the periphery of the interface (K20 and F21). Notably, the relative contributions of a given amino acid side chain to RNA polymerase inhibition and activation (MotA-independent) by AsiA are very similar in most cases. The mainstay for intermolecular affinity and AsiA function appears to be I17. Our results define the core interfacial residues of AsiA, establish roles for many of the interfacial amino acids, are in agreement with the tenets underlying protein-protein interactions and interfaces, and will be beneficial for a general, comprehensive understanding of the mechanistic underpinnings of bacterial RNA polymerase regulation
Determining Protein Complex Connectivity Using a Probabilistic Deletion Network Derived from Quantitative Proteomics
Protein complexes are key molecular machines executing a variety of essential cellular processes. Despite the availability of genome-wide protein-protein interaction studies, determining the connectivity between proteins within a complex remains a major challenge. Here we demonstrate a method that is able to predict the relationship of proteins within a stable protein complex. We employed a combination of computational approaches and a systematic collection of quantitative proteomics data from wild-type and deletion strain purifications to build a quantitative deletion-interaction network map and subsequently convert the resulting data into an interdependency-interaction model of a complex. We applied this approach to a data set generated from components of the Saccharomyces cerevisiae Rpd3 histone deacetylase complexes, which consists of two distinct small and large complexes that are held together by a module consisting of Rpd3, Sin3 and Ume1. The resulting representation reveals new protein-protein interactions and new submodule relationships, providing novel information for mapping the functional organization of a complex
Combinatorial depletion analysis to assemble the network architecture of the SAGA and ADA chromatin remodeling complexes
A combinatorial depletion strategy is combined with biochemistry, quantitative proteomics and computational approaches to elucidate the structure of the SAGA/ADA complexes. The analysis reveals five connected functional modules capable of independent assembly
Parallel hippocampal-parietal circuits for self- and goal-oriented processing
The hippocampus is critically important for a diverse range of cognitive processes, such as episodic memory, prospective memory, affective processing, and spatial navigation. Using individual-specific precision functional mapping of resting-state functional MRI data, we found the anterior hippocampus (head and body) to be preferentially functionally connected to the default mode network (DMN), as expected. The hippocampal tail, however, was strongly preferentially functionally connected to the parietal memory network (PMN), which supports goal-oriented cognition and stimulus recognition. This anterior-posterior dichotomy of resting-state functional connectivity was well-matched by differences in task deactivations and anatomical segmentations of the hippocampus. Task deactivations were localized to the hippocampal head and body (DMN), relatively sparing the tail (PMN). The functional dichotomization of the hippocampus into anterior DMN-connected and posterior PMN-connected parcels suggests parallel but distinct circuits between the hippocampus and medial parietal cortex for self- versus goal-oriented processing
The Fifth Data Release of the Sloan Digital Sky Survey
This paper describes the Fifth Data Release (DR5) of the Sloan Digital Sky
Survey (SDSS). DR5 includes all survey quality data taken through June 2005 and
represents the completion of the SDSS-I project (whose successor, SDSS-II will
continue through mid-2008). It includes five-band photometric data for 217
million objects selected over 8000 square degrees, and 1,048,960 spectra of
galaxies, quasars, and stars selected from 5713 square degrees of that imaging
data. These numbers represent a roughly 20% increment over those of the Fourth
Data Release; all the data from previous data releases are included in the
present release. In addition to "standard" SDSS observations, DR5 includes
repeat scans of the southern equatorial stripe, imaging scans across M31 and
the core of the Perseus cluster of galaxies, and the first spectroscopic data
from SEGUE, a survey to explore the kinematics and chemical evolution of the
Galaxy. The catalog database incorporates several new features, including
photometric redshifts of galaxies, tables of matched objects in overlap regions
of the imaging survey, and tools that allow precise computations of survey
geometry for statistical investigations.Comment: ApJ Supp, in press, October 2007. This paper describes DR5. The SDSS
Sixth Data Release (DR6) is now public, available from http://www.sdss.or
LSST Science Book, Version 2.0
A survey that can cover the sky in optical bands over wide fields to faint
magnitudes with a fast cadence will enable many of the exciting science
opportunities of the next decade. The Large Synoptic Survey Telescope (LSST)
will have an effective aperture of 6.7 meters and an imaging camera with field
of view of 9.6 deg^2, and will be devoted to a ten-year imaging survey over
20,000 deg^2 south of +15 deg. Each pointing will be imaged 2000 times with
fifteen second exposures in six broad bands from 0.35 to 1.1 microns, to a
total point-source depth of r~27.5. The LSST Science Book describes the basic
parameters of the LSST hardware, software, and observing plans. The book
discusses educational and outreach opportunities, then goes on to describe a
broad range of science that LSST will revolutionize: mapping the inner and
outer Solar System, stellar populations in the Milky Way and nearby galaxies,
the structure of the Milky Way disk and halo and other objects in the Local
Volume, transient and variable objects both at low and high redshift, and the
properties of normal and active galaxies at low and high redshift. It then
turns to far-field cosmological topics, exploring properties of supernovae to
z~1, strong and weak lensing, the large-scale distribution of galaxies and
baryon oscillations, and how these different probes may be combined to
constrain cosmological models and the physics of dark energy.Comment: 596 pages. Also available at full resolution at
http://www.lsst.org/lsst/sciboo
The Seventh Data Release of the Sloan Digital Sky Survey
This paper describes the Seventh Data Release of the Sloan Digital Sky Survey
(SDSS), marking the completion of the original goals of the SDSS and the end of
the phase known as SDSS-II. It includes 11663 deg^2 of imaging data, with most
of the roughly 2000 deg^2 increment over the previous data release lying in
regions of low Galactic latitude. The catalog contains five-band photometry for
357 million distinct objects. The survey also includes repeat photometry over
250 deg^2 along the Celestial Equator in the Southern Galactic Cap. A
coaddition of these data goes roughly two magnitudes fainter than the main
survey. The spectroscopy is now complete over a contiguous area of 7500 deg^2
in the Northern Galactic Cap, closing the gap that was present in previous data
releases. There are over 1.6 million spectra in total, including 930,000
galaxies, 120,000 quasars, and 460,000 stars. The data release includes
improved stellar photometry at low Galactic latitude. The astrometry has all
been recalibrated with the second version of the USNO CCD Astrograph Catalog
(UCAC-2), reducing the rms statistical errors at the bright end to 45
milli-arcseconds per coordinate. A systematic error in bright galaxy photometr
is less severe than previously reported for the majority of galaxies. Finally,
we describe a series of improvements to the spectroscopic reductions, including
better flat-fielding and improved wavelength calibration at the blue end,
better processing of objects with extremely strong narrow emission lines, and
an improved determination of stellar metallicities. (Abridged)Comment: 20 pages, 10 embedded figures. Accepted to ApJS after minor
correction
Fermi Large Area Telescope Constraints on the Gamma-ray Opacity of the Universe
The Extragalactic Background Light (EBL) includes photons with wavelengths
from ultraviolet to infrared, which are effective at attenuating gamma rays
with energy above ~10 GeV during propagation from sources at cosmological
distances. This results in a redshift- and energy-dependent attenuation of the
gamma-ray flux of extragalactic sources such as blazars and Gamma-Ray Bursts
(GRBs). The Large Area Telescope onboard Fermi detects a sample of gamma-ray
blazars with redshift up to z~3, and GRBs with redshift up to z~4.3. Using
photons above 10 GeV collected by Fermi over more than one year of observations
for these sources, we investigate the effect of gamma-ray flux attenuation by
the EBL. We place upper limits on the gamma-ray opacity of the Universe at
various energies and redshifts, and compare this with predictions from
well-known EBL models. We find that an EBL intensity in the optical-ultraviolet
wavelengths as great as predicted by the "baseline" model of Stecker et al.
(2006) can be ruled out with high confidence.Comment: 42 pages, 12 figures, accepted version (24 Aug.2010) for publication
in ApJ; Contact authors: A. Bouvier, A. Chen, S. Raino, S. Razzaque, A.
Reimer, L.C. Reye
LSST: from Science Drivers to Reference Design and Anticipated Data Products
(Abridged) We describe here the most ambitious survey currently planned in
the optical, the Large Synoptic Survey Telescope (LSST). A vast array of
science will be enabled by a single wide-deep-fast sky survey, and LSST will
have unique survey capability in the faint time domain. The LSST design is
driven by four main science themes: probing dark energy and dark matter, taking
an inventory of the Solar System, exploring the transient optical sky, and
mapping the Milky Way. LSST will be a wide-field ground-based system sited at
Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m
effective) primary mirror, a 9.6 deg field of view, and a 3.2 Gigapixel
camera. The standard observing sequence will consist of pairs of 15-second
exposures in a given field, with two such visits in each pointing in a given
night. With these repeats, the LSST system is capable of imaging about 10,000
square degrees of sky in a single filter in three nights. The typical 5
point-source depth in a single visit in will be (AB). The
project is in the construction phase and will begin regular survey operations
by 2022. The survey area will be contained within 30,000 deg with
, and will be imaged multiple times in six bands, ,
covering the wavelength range 320--1050 nm. About 90\% of the observing time
will be devoted to a deep-wide-fast survey mode which will uniformly observe a
18,000 deg region about 800 times (summed over all six bands) during the
anticipated 10 years of operations, and yield a coadded map to . The
remaining 10\% of the observing time will be allocated to projects such as a
Very Deep and Fast time domain survey. The goal is to make LSST data products,
including a relational database of about 32 trillion observations of 40 billion
objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures
available from https://www.lsst.org/overvie
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