Submucosal diclofenac for acute postoperative pain in third molar surgery: A randomized, controlled clinical trial

Diclofenac sodium is a widely used nonsteroidal anti-inflammatory drug (NSAID) for relief of inflammatory pain. A recent formulation combines this drug with hydroxypropyl-β-cyclodextrin (HPβCD) to improve its solubility and to enable subcutaneous administration. Previous studies confirmed the efficacy of this combination. This study’s aim was to evaluate the efficacy, safety, and local tolerability of diclofenac HPβCD administered as a local submucosal injection prior to lower third molar surgery. We conducted a prospective, randomized, double-blind, placebo-controlled, parallel-group phase II single-center study. Seventy-five patients requiring mandibular third molar surgery were randomized into 1 of 5 groups: 5 mg/1 mL diclofenac HPβCD, 12.5 mg/1 mL diclofenac HPβCD, 25 mg/1 mL diclofenac HPβCD, 50 mg/1 mL diclofenac HPβCD, or 1 mL placebo. The respective study drug was injected into the mucosal tissue surrounding the surgical site prior to surgery following achievement of local anesthesia. The primary outcome measure was the area under the curve (AUC) of cumulative pain scores from end of surgery to 6 h postsurgery. This demonstrated a global treatment effect between the active groups and placebo, hence confirming the study drug’s efficacy (P = 0.0126). Secondary outcome measures included the time until onset of pain and the time until patients required rescue medication, both showing statistical significance of the study drug compared to placebo (P < 0.0161 and P < 0.0001, respectively). The time until rescue medication ranged between 7.8 h (for 25 mg/1 mL diclofenac HPβCD) and 16 h (for 50 mg/1 mL diclofenac HPβCD). Interestingly, the 5-mg/1-mL solution appeared superior to the 12.5-mg/1-mL and 25-mg/1-mL solutions (time until rescue medication = 12.44 h). A total of 14% of patients experienced minor adverse drug reactions (ADRs), of which 2 cases demonstrated flap necrosis. These resolved without further intervention. The study results overall indicate efficacy, safety, and relative tolerability of diclofenac HPβCD used locally as a submucosal injection prior to third molar surgery (ClinicalTrials.gov NCT01706588)

Dynamics of a Quantum Phase Transition and Relaxation to a Steady State

We review recent theoretical work on two closely related issues: excitation of an isolated quantum condensed matter system driven adiabatically across a continuous quantum phase transition or a gapless phase, and apparent relaxation of an excited system after a sudden quench of a parameter in its Hamiltonian. Accordingly the review is divided into two parts. The first part revolves around a quantum version of the Kibble-Zurek mechanism including also phenomena that go beyond this simple paradigm. What they have in common is that excitation of a gapless many-body system scales with a power of the driving rate. The second part attempts a systematic presentation of recent results and conjectures on apparent relaxation of a pure state of an isolated quantum many-body system after its excitation by a sudden quench. This research is motivated in part by recent experimental developments in the physics of ultracold atoms with potential applications in the adiabatic quantum state preparation and quantum computation.Comment: 117 pages; review accepted in Advances in Physic

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

The interplay of crack hopping, delamination and interface failure in drying nanoparticle films

Films formed through the drying of nanoparticle suspensions release the build-up of strain through a variety of different mechanisms including shear banding, crack formation and delamination. Here we show that important connections exist between these different phenomena: delamination depends on the dynamics of crack hopping, which in turn is influenced by the presence of shear bands. We also show that delamination does not occur uniformly across the film. As cracks hop they locally initiate the delamination of the film which warps with a timescale much longer than that associated with the hopping of cracks. The motion of a small region of the delamination front, where the shear component of interfacial crack propagation is believed to be enhanced, results in the deposition of a complex zig-zag pattern on the supporting substrate

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

Human cytomegalovirus immediate-early 1 protein rewires upstream STAT3 to downstream STAT1 signaling switching an IL6-type to an IFNγ-like response

MN and CP were supported by the Wellcome Trust (www.wellcome.ac.uk) Institutional Strategic Support Fund and CP was supported by the Deutsche Forschungsgemeinschaft (PA 815/2-1; www.dfg.de).The human cytomegalovirus (hCMV) major immediate-early 1 protein (IE1) is best known for activating transcription to facilitate viral replication. Here we present transcriptome data indicating that IE1 is as significant a repressor as it is an activator of host gene expression. Human cells induced to express IE1 exhibit global repression of IL6- and oncostatin M-responsive STAT3 target genes. This repression is followed by STAT1 phosphorylation and activation of STAT1 target genes normally induced by IFNγ. The observed repression and subsequent activation are both mediated through the same region (amino acids 410 to 445) in the C-terminal domain of IE1, and this region serves as a binding site for STAT3. Depletion of STAT3 phenocopies the STAT1-dependent IFNγ-like response to IE1. In contrast, depletion of the IL6 receptor (IL6ST) or the STAT kinase JAK1 prevents this response. Accordingly, treatment with IL6 leads to prolonged STAT1 instead of STAT3 activation in wild-type IE1 expressing cells, but not in cells expressing a mutant protein (IE1dl410-420) deficient for STAT3 binding. A very similar STAT1-directed response to IL6 is also present in cells infected with a wild-type or revertant hCMV, but not an IE1dl410-420 mutant virus, and this response results in restricted viral replication. We conclude that IE1 is sufficient and necessary to rewire upstream IL6-type to downstream IFNγ-like signaling, two pathways linked to opposing actions, resulting in repressed STAT3- and activated STAT1-responsive genes. These findings relate transcriptional repressor and activator functions of IE1 and suggest unexpected outcomes relevant to viral pathogenesis in response to cytokines or growth factors that signal through the IL6ST-JAK1-STAT3 axis in hCMV-infected cells. Our results also reveal that IE1, a protein considered to be a key activator of the hCMV productive cycle, has an unanticipated role in tempering viral replication.Publisher PDFPeer reviewe

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Visualization of the intracavitary blood flow in systemic ventricles of Fontan patients by contrast echocardiography using particle image velocimetry

<p>Abstract</p> <p>Background</p> <p>Flow patterns in univentricular hearts may have clinical value. Therefore, it is our objective to asses and characterize vortex flow patterns with Fontan circulation in comparison with healthy controls.</p> <p>Methods</p> <p>Twenty-three patients (8 Fontan and 15 normal patients) underwent echocardiography with intravenous contrast agent (Sonovue^®) administration. Dedicated software was used to perform particle image velocimetry (PIV) and to visualize intracavitary flow in the systemic ventricles of the patients. Vortex parameters including vortex depth, length, width, and sphericity index were measured. Vortex pulsatility parameters including relative strength, vortex relative strength, and vortex pulsation correlation were also measured.</p> <p>Results</p> <p>The data from this study show that it is feasible to perform particle velocimetry in Fontan patients. Vortex length (VL) was significantly lower (0.51 ± 0.09 vs 0.65 ± 0.12, <it>P </it>= 0.010) and vortex width (VW) (0.32 ± 0.06 vs 0.27 ± 0.04, <it>p </it>= 0.014), vortex pulsation correlation (VPC) (0.26 ± 0.25 vs -0.22 ± 0.87, <it>p </it>= 0.05) were significantly higher in Fontan patients. Sphericity index (SI) (1.66 ± 0.48 vs 2.42 ± 0.62, <it>p </it>= 0.005), relative strength (RS) (0.77 ± 0.33 vs 1.90 ± 0.47, <it>p </it>= 0.0001), vortex relative strength (VRS) (0.18 ± 0.13 vs 0.43 ± 0.14, <it>p </it>= 0.0001) were significantly lower in the Fontan patients group.</p> <p>Conclusions</p> <p>PIV using contrast echocardiography is feasible in Fontan patients. Fontan patients had aberrant flow patterns as compared to normal hearts in terms of position, shape and sphericity of the main vortices. The vortex from the Fontan group was consistently shorter, wider and rounder than in controls. Whether vortex characteristics are related with clinical outcome is subject to further investigation.</p

Identification and Filtering of Uncharacteristic Noise in the CMS Hadron Calorimeter

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