Regulation of P-Glycoprotein in the Brain

Maintenance of the tightly regulated homeostatic environment of the brain is facilitated by the blood–brain barrier (BBB). P-glycoprotein (P-gp), an ATP-binding cassette transporter, is expressed on the luminal surface of the endothelial cells in the BBB, and actively exports a wide variety of substrates to limit exposure of the vulnerable brain environment to waste buildup and neurotoxic compounds. Downregulation of P-gp expression and activity at the BBB have been reported with ageing and in neurodegenerative diseases. Upregulation of P-gp at the BBB contributes to poor therapeutic outcomes due to altered pharmacokinetics of CNS-acting drugs. The regulation of P-gp is highly complex, but unravelling the mechanisms involved may help the development of novel and nuanced strategies to modulate P-gp expression for therapeutic benefit. This review summarises the current understanding of P-gp regulation in the brain, encompassing the transcriptional, post-transcriptional and post-translational mechanisms that have been identified to affect P-gp expression and transport activity

Alumina-on-Polyethylene Bearing Surfaces in Total Hip Arthroplasty

The long-term durability of polyethylene lining total hip arthroplasty (THA) mainly depends on periprosthetic osteolysis due to wear particles, especially in young active patients. In hip simulator study, reports revealed significant wear reduction of the alumina ceramic-on-polyethylene articulation of THA compared with metal-on-polyethylene bearing surfaces. However, medium to long-term clinical studies of THA using the alumina ceramic-on-polyethylene are few and the reported wear rate of this articulation is variable. We reviewed the advantages and disadvantages of ceramicon- polyethylene articulation in THA, hip simulator study and retrieval study for polyethylene wear, in vivo clinical results of THA using alumina ceramic-on-polyethylene bearing surfaces in the literature, and new trial alumina ceramic-onhighly cross linked polyethylene bearing surfaces

Model-based cross-correlation search for gravitational waves from the low-mass X-ray binary Scorpius X-1 in LIGO O3 data

We present the results of a model-based search for continuous gravitational waves from the low-mass X-ray binary Scorpius X-1 using LIGO detector data from the third observing run of Advanced LIGO, Advanced Virgo and KAGRA. This is a semicoherent search which uses details of the signal model to coherently combine data separated by less than a specified coherence time, which can be adjusted to balance sensitivity with computing cost. The search covered a range of gravitational-wave frequencies from 25Hz to 1600Hz, as well as ranges in orbital speed, frequency and phase determined from observational constraints. No significant detection candidates were found, and upper limits were set as a function of frequency. The most stringent limits, between 100Hz and 200Hz, correspond to an amplitude h0 of about 1e-25 when marginalized isotropically over the unknown inclination angle of the neutron star's rotation axis, or less than 4e-26 assuming the optimal orientation. The sensitivity of this search is now probing amplitudes predicted by models of torque balance equilibrium. For the usual conservative model assuming accretion at the surface of the neutron star, our isotropically-marginalized upper limits are close to the predicted amplitude from about 70Hz to 100Hz; the limits assuming the neutron star spin is aligned with the most likely orbital angular momentum are below the conservative torque balance predictions from 40Hz to 200Hz. Assuming a broader range of accretion models, our direct limits on gravitational-wave amplitude delve into the relevant parameter space over a wide range of frequencies, to 500Hz or more

All-sky search for long-duration gravitational-wave bursts in the third Advanced LIGO and Advanced Virgo run

After the detection of gravitational waves from compact binary coalescences, the search for transient gravitational-wave signals with less well-defined waveforms for which matched filtering is not well suited is one of the frontiers for gravitational-wave astronomy. Broadly classified into “short” ≲1  s and “long” ≳1  s duration signals, these signals are expected from a variety of astrophysical processes, including non-axisymmetric deformations in magnetars or eccentric binary black hole coalescences. In this work, we present a search for long-duration gravitational-wave transients from Advanced LIGO and Advanced Virgo’s third observing run from April 2019 to March 2020. For this search, we use minimal assumptions for the sky location, event time, waveform morphology, and duration of the source. The search covers the range of 2–500 s in duration and a frequency band of 24–2048 Hz. We find no significant triggers within this parameter space; we report sensitivity limits on the signal strength of gravitational waves characterized by the root-sum-square amplitude hrss as a function of waveform morphology. These hrss limits improve upon the results from the second observing run by an average factor of 1.8

Diving below the spin-down limit:constraints on gravitational waves from the energetic young pulsar PSR J0537-6910

We present a search for continuous gravitational-wave signals from the young, energetic X-ray pulsar PSR J0537-6910 using data from the second and third observing runs of LIGO and Virgo. The search is enabled by a contemporaneous timing ephemeris obtained using NICER data. The NICER ephemeris has also been extended through 2020 October and includes three new glitches. PSR J0537-6910 has the largest spin-down luminosity of any pulsar and is highly active with regards to glitches. Analyses of its long-term and inter-glitch braking indices provided intriguing evidence that its spin-down energy budget may include gravitational-wave emission from a time-varying mass quadrupole moment. Its 62 Hz rotation frequency also puts its possible gravitational-wave emission in the most sensitive band of LIGO/Virgo detectors. Motivated by these considerations, we search for gravitational-wave emission at both once and twice the rotation frequency. We find no signal, however, and report our upper limits. Assuming a rigidly rotating triaxial star, our constraints reach below the gravitational-wave spin-down limit for this star for the first time by more than a factor of two and limit gravitational waves from the l = m = 2 mode to account for less than 14% of the spin-down energy budget. The fiducial equatorial ellipticity is limited to less than about 3 x 10⁻⁵, which is the third best constraint for any young pulsar

Search for continuous gravitational wave emission from the Milky Way center in O3 LIGO--Virgo data

We present a directed search for continuous gravitational wave (CW) signals emitted by spinning neutron stars located in the inner parsecs of the Galactic Center (GC). Compelling evidence for the presence of a numerous population of neutron stars has been reported in the literature, turning this region into a very interesting place to look for CWs. In this search, data from the full O3 LIGO--Virgo run in the detector frequency band $[10,2000]\rm~Hz$ have been used. No significant detection was found and 95$\%$ confidence level upper limits on the signal strain amplitude were computed, over the full search band, with the deepest limit of about $7.6\times 10^{-26}$ at $\simeq 142\rm~Hz$. These results are significantly more constraining than those reported in previous searches. We use these limits to put constraints on the fiducial neutron star ellipticity and r-mode amplitude. These limits can be also translated into constraints in the black hole mass -- boson mass plane for a hypothetical population of boson clouds around spinning black holes located in the GC.Comment: 25 pages, 5 figure

A systematic review of randomised controlled trials assessing effectiveness of prosthetic and orthotic interventions.

BACKGROUND: Assistive products are items which allow older people and people with disabilities to be able to live a healthy, productive and dignified life. It has been estimated that approximately 1.5% of the world's population need a prosthesis or orthosis. OBJECTIVE: The objective of this study was to systematically identify and review the evidence from randomized controlled trials assessing effectiveness and cost-effectiveness of prosthetic and orthotic interventions. METHODS: Literature searches, completed in September 2015, were carried out in fourteen databases between years 1995 and 2015. The search results were independently screened by two reviewers. For the purpose of this manuscript, only randomized controlled trials which examined interventions using orthotic or prosthetic devices were selected for data extraction and synthesis. RESULTS: A total of 342 randomised controlled trials were identified (319 English language and 23 non-English language). Only 4 of these randomised controlled trials examined prosthetic interventions and the rest examined orthotic interventions. These orthotic interventions were categorised based on the medical conditions/injuries of the participants. From these studies, this review focused on the medical condition/injuries with the highest number of randomised controlled trials (osteoarthritis, fracture, stroke, carpal tunnel syndrome, plantar fasciitis, anterior cruciate ligament, diabetic foot, rheumatoid and juvenile idiopathic arthritis, ankle sprain, cerebral palsy, lateral epicondylitis and low back pain). The included articles were assessed for risk of bias using the Cochrane Risk of Bias tool. Details of the clinical population examined, the type of orthotic/prosthetic intervention, the comparator/s and the outcome measures were extracted. Effect sizes and odds ratios were calculated for all outcome measures, where possible. CONCLUSIONS: At present, for prosthetic and orthotic interventions, the scientific literature does not provide sufficient high quality research to allow strong conclusions on their effectiveness and cost-effectiveness

Search for Gravitational Waves Associated with Gamma-Ray Bursts Detected by Fermi and Swift during the LIGO-Virgo Run O3a

We search for gravitational-wave transients associated with gamma-ray bursts detected by the Fermi and Swift satellites during the first part of the third observing run of Advanced LIGO and Advanced Virgo (1 April 2019 15:00 UTC - 1 October 2019 15:00 UTC). 105 gamma-ray bursts were analyzed using a search for generic gravitational-wave transients; 32 gamma-ray bursts were analyzed with a search that specifically targets neutron star binary mergers as short gamma-ray burst progenitors. We describe a method to calculate the probability that triggers from the binary merger targeted search are astrophysical and apply that method to the most significant gamma-ray bursts in that search. We find no significant evidence for gravitational-wave signals associated with the gamma-ray bursts that we followed up, nor for a population of unidentified subthreshold signals. We consider several source types and signal morphologies, and report for these lower bounds on the distance to each gamma-ray burst

All-sky search for gravitational wave emission from scalar boson clouds around spinning black holes in LIGO O3 data

This paper describes the first all-sky search for long-duration, quasimonochromatic gravitational-wave signals emitted by ultralight scalar boson clouds around spinning black holes using data from the third observing run of Advanced LIGO. We analyze the frequency range from 20 to 610 Hz, over a small frequency derivative range around zero, and use multiple frequency resolutions to be robust towards possible signal frequency wanderings. Outliers from this search are followed up using two different methods, one more suitable for nearly monochromatic signals, and the other more robust towards frequency fluctuations. We do not find any evidence for such signals and set upper limits on the signal strain amplitude, the most stringent being ≈10−25 at around 130 Hz. We interpret these upper limits as both an “exclusion region” in the boson mass/black hole mass plane and the maximum detectable distance for a given boson mass, based on an assumption of the age of the black hole/boson cloud system