213 research outputs found
Unfractionated heparin inhibits live wild type SARS-CoV-2 cell infectivity at therapeutically relevant concentrations.
BACKGROUND AND PURPOSE: Currently, there are no licensed vaccines and limited antivirals for the treatment of COVID-19. Heparin (delivered systemically) is currently used to treat anticoagulant anomalies in COVID-19 patients. Additionally, in the United Kingdom, Brazil and Australia, nebulised unfractionated heparin (UFH) is being trialled in COVID-19 patients as a potential treatment. A systematic comparison of the potential antiviral effect of various heparin preparations on live wild type SARS-CoV-2, in vitro, is needed. EXPERIMENTAL APPROACH: Seven different heparin preparations including UFH and low MW heparins (LMWH) of porcine or bovine origin were screened for antiviral activity against live SARS-CoV-2 (Australia/VIC01/2020) using a plaque inhibition assay with Vero E6 cells. Interaction of heparin with spike protein RBD was studied using differential scanning fluorimetry and the inhibition of RBD binding to human ACE2 protein using elisa assays was examined. KEY RESULTS: All the UFH preparations had potent antiviral effects, with IC50 values ranging between 25 and 41 Όg·ml-1 , whereas LMWHs were less inhibitory by ~150-fold (IC50 range 3.4-7.8 mg·ml-1 ). Mechanistically, we observed that heparin binds and destabilizes the RBD protein and furthermore, we show heparin directly inhibits the binding of RBD to the human ACE2 protein receptor. CONCLUSION AND IMPLICATIONS: This comparison of clinically relevant heparins shows that UFH has significantly stronger SARS-CoV-2 antiviral activity compared to LMWHs. UFH acts to directly inhibit binding of spike protein to the human ACE2 protein receptor. Overall, the data strongly support further clinical investigation of UFH as a potential treatment for patients with COVID-19
Valid and reliable instruments for arm-hand assessment at ICF activity level in persons with hemiplegia: a systematic review
Contains fulltext :
110141.pdf (publisher's version ) (Open Access)BACKGROUND: Loss of arm-hand performance due to a hemiparesis as a result of stroke or cerebral palsy (CP), leads to large problems in daily life of these patients. Assessment of arm-hand performance is important in both clinical practice and research. To gain more insight in e.g. effectiveness of common therapies for different patient populations with similar clinical characteristics, consensus regarding the choice and use of outcome measures is paramount. To guide this choice, an overview of available instruments is necessary. The aim of this systematic review is to identify, evaluate and categorize instruments, reported to be valid and reliable, assessing arm-hand performance at the ICF activity level in patients with stroke or cerebral palsy. METHODS: A systematic literature search was performed to identify articles containing instruments assessing arm-hand skilled performance in patients with stroke or cerebral palsy. Instruments were identified and divided into the categories capacity, perceived performance and actual performance. A second search was performed to obtain information on their content and psychometrics. RESULTS: Regarding capacity, perceived performance and actual performance, 18, 9 and 3 instruments were included respectively. Only 3 of all included instruments were used and tested in both patient populations. The content of the instruments differed widely regarding the ICF levels measured, assessment of the amount of use versus the quality of use, the inclusion of unimanual and/or bimanual tasks and the inclusion of basic and/or extended tasks. CONCLUSIONS: Although many instruments assess capacity and perceived performance, a dearth exists of instruments assessing actual performance. In addition, instruments appropriate for more than one patient population are sparse. For actual performance, new instruments have to be developed, with specific focus on the usability in different patient populations and the assessment of quality of use as well as amount of use. Also, consensus about the choice and use of instruments within and across populations is needed
Test of lepton universality in decays
The first simultaneous test of muon-electron universality using
and decays is performed, in two ranges of the dilepton
invariant-mass squared, . The analysis uses beauty mesons produced in
proton-proton collisions collected with the LHCb detector between 2011 and
2018, corresponding to an integrated luminosity of 9 . Each
of the four lepton universality measurements reported is either the first in
the given interval or supersedes previous LHCb measurements. The
results are compatible with the predictions of the Standard Model.Comment: All figures and tables, along with any supplementary material and
additional information, are available at
https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-046.html (LHCb
public pages
Observation of Two New Excited Îb0 States Decaying to Îb0 K-Ï+
Two narrow resonant states are observed in the Îb0K-Ï+ mass spectrum using a data sample of proton-proton collisions at a center-of-mass energy of 13 TeV, collected by the LHCb experiment and corresponding to an integrated luminosity of 6 fb-1. The minimal quark content of the Îb0K-Ï+ system indicates that these are excited Îb0 baryons. The masses of the Îb(6327)0 and Îb(6333)0 states are m[Îb(6327)0]=6327.28-0.21+0.23±0.12±0.24 and m[Îb(6333)0]=6332.69-0.18+0.17±0.03±0.22 MeV, respectively, with a mass splitting of Îm=5.41-0.27+0.26±0.12 MeV, where the uncertainties are statistical, systematic, and due to the Îb0 mass measurement. The measured natural widths of these states are consistent with zero, with upper limits of Î[Îb(6327)0]<2.20(2.56) and Î[Îb(6333)0]<1.60(1.92) MeV at a 90% (95%) credibility level. The significance of the two-peak hypothesis is larger than nine (five) Gaussian standard deviations compared to the no-peak (one-peak) hypothesis. The masses, widths, and resonant structure of the new states are in good agreement with the expectations for a doublet of 1D Îb0 resonances
Precision measurement of violation in the penguin-mediated decay
A flavor-tagged time-dependent angular analysis of the decay
is performed using collision data collected
by the LHCb experiment at % at TeV, the center-of-mass energy of
13 TeV, corresponding to an integrated luminosity of 6 fb^{-1}. The
-violating phase and direct -violation parameter are measured
to be rad and
, respectively, assuming the same values
for all polarization states of the system. In these results, the
first uncertainties are statistical and the second systematic. These parameters
are also determined separately for each polarization state, showing no evidence
for polarization dependence. The results are combined with previous LHCb
measurements using collisions at center-of-mass energies of 7 and 8 TeV,
yielding rad and . This is the most precise study of time-dependent violation
in a penguin-dominated meson decay. The results are consistent with
symmetry and with the Standard Model predictions.Comment: All figures and tables, along with any supplementary material and
additional information, are available at
https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2023-001.html (LHCb
public pages
Observation of B(s)0âJ/ÏppÂŻ decays and precision measurements of the B(s)0 masses
The first observation of the decays
B
0
(
s
)
â
J
/
Ï
p
ÂŻ
p
is reported, using proton-proton collision data corresponding to an integrated luminosity of
5.2
â
â
fb
â
1
, collected with the LHCb detector. These decays are suppressed due to limited available phase space, as well as due to Okubo-Zweig-Iizuka or Cabibbo suppression. The measured branching fractions are
B
(
B
0
â
J
/
Ï
p
ÂŻ
p
)
=
[
4.51
±
0.40
(
stat
)
±
0.44
(
syst
)
]
Ă
10
â
7
,
B
(
B
0
s
â
J
/
Ï
p
ÂŻ
p
)
=
[
3.58
±
0.19
(
stat
)
±
0.39
(
syst
)
]
Ă
10
â
6
. For the
B
0
s
meson, the result is much higher than the expected value of
O
(
10
â
9
)
. The small available phase space in these decays also allows for the most precise single measurement of both the
B
0
mass as
5279.74
±
0.30
(
stat
)
±
0.10
(
syst
)
â
â
MeV
and the
B
0
s
mass as
5366.85
±
0.19
(
stat
)
±
0.13
(
syst
)
â
â
MeV
Observation of a resonant structure near the threshold in the decay
An amplitude analysis of the decay is carried out to
study for the first time its intermediate resonant contributions, using
proton-proton collision data collected with the LHCb detector at centre-of-mass
energies of 7, 8 and 13 TeV. A near-threshold peaking structure, referred to as
, is observed in the invariant-mass spectrum with
significance greater than 12 standard deviations. The mass, width and the
quantum numbers of the structure are measured to be MeV,
MeV and , respectively, where the first
uncertainties are statistical and the second systematic. The properties of the
new structure are consistent with recent theoretical predictions for a state
composed of quarks. Evidence for an additional structure is
found around 4140 MeV in the invariant mass, which might be
caused either by a new resonance with the assignment or by a coupled-channel effect.Comment: All figures and tables, along with any supplementary material and
additional information, are available at
https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-018.html (LHCb
public pages
Measurement of the differential branching fraction
The branching fraction of the rare decay is measured for the first time, in the squared dimuon mass
intervals, , excluding the and regions. The data
sample analyzed was collected by the LHCb experiment at center-of-mass energies
of 7, 8, and 13 TeV, corresponding to a total integrated luminosity of $9\
\mathrm{fb}^{-1}q^{2}q^{2} >15.0\
\mathrm{GeV}^2/c^4$, where theoretical predictions have the smallest model
dependence, agrees with the predictions.Comment: All figures and tables, along with any supplementary material and
additional information, are available at
https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-050.html (LHCb
public pages
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