592 research outputs found
MRI T2 and T1ρ relaxation in patients at risk for knee osteoarthritis: A systematic review and meta-analysis
© 2019 The Author(s). Background: Magnetic resonance imaging (MRI) T2 and T1ρ relaxation are increasingly being proposed as imaging biomarkers potentially capable of detecting biochemical changes in articular cartilage before structural changes are evident. We aimed to: 1) summarize MRI methods of published studies investigating T2 and T1ρ relaxation time in participants at risk for but without radiographic knee OA; and 2) compare T2 and T1ρ relaxation between participants at-risk for knee OA and healthy controls. Methods: We conducted a systematic review of studies reporting T2 and T1ρ relaxation data that included both participants at risk for knee OA and healthy controls. Participant characteristics, MRI methodology, and T1ρ and T2 relaxation data were extracted. Standardized mean differences (SMDs) were calculated within each study. Pooled effect sizes were then calculated for six commonly segmented knee compartments. Results: 55 articles met eligibility criteria. There was considerable variability between scanners, coils, software, scanning protocols, pulse sequences, and post-processing. Moderate risk of bias due to lack of blinding was common. Pooled effect sizes indicated participants at risk for knee OA had lengthened T2 relaxation time in all compartments (SMDs from 0.33 to 0.74; p \u3c 0.01) and lengthened T1ρ relaxation time in the femoral compartments (SMD from 0.35 to 0.40; p \u3c 0.001). Conclusions: T2 and T1ρ relaxation distinguish participants at risk for knee OA from healthy controls. Greater standardization of MRI methods is both warranted and required for progress towards biomarker validation
Decay of isolated surface features driven by the Gibbs-Thomson effect in analytic model and simulation
A theory based on the thermodynamic Gibbs-Thomson relation is presented which
provides the framework for understanding the time evolution of isolated
nanoscale features (i.e., islands and pits) on surfaces. Two limiting cases are
predicted, in which either diffusion or interface transfer is the limiting
process. These cases correspond to similar regimes considered in previous works
addressing the Ostwald ripening of ensembles of features. A third possible
limiting case is noted for the special geometry of "stacked" islands. In these
limiting cases, isolated features are predicted to decay in size with a power
law scaling in time: A is proportional to (t0-t)^n, where A is the area of the
feature, t0 is the time at which the feature disappears, and n=2/3 or 1. The
constant of proportionality is related to parameters describing both the
kinetic and equilibrium properties of the surface. A continuous time Monte
Carlo simulation is used to test the application of this theory to generic
surfaces with atomic scale features. A new method is described to obtain
macroscopic kinetic parameters describing interfaces in such simulations.
Simulation and analytic theory are compared directly, using measurements of the
simulation to determine the constants of the analytic theory. Agreement between
the two is very good over a range of surface parameters, suggesting that the
analytic theory properly captures the necessary physics. It is anticipated that
the simulation will be useful in modeling complex surface geometries often seen
in experiments on physical surfaces, for which application of the analytic
model is not straightforward.Comment: RevTeX (with .bbl file), 25 pages, 7 figures from 9 Postscript files
embedded using epsf. Submitted to Phys. Rev. B A few minor changes made on
9/24/9
The MITRE trial protocol: a study to evaluate the microbiome as a biomarker of efficacy and toxicity in cancer patients receiving immune checkpoint inhibitor therapy.
BACKGROUND: The gut microbiome is implicated as a marker of response to immune checkpoint inhibitors (ICI) based on preclinical mouse models and preliminary observations in limited patient series. Furthermore, early studies suggest faecal microbial transfer may have therapeutic potential, converting ICI non-responders into responders. So far, identification of specific responsible bacterial taxa has been inconsistent, which limits future application. The MITRE study will explore and validate a microbiome signature in a larger scale prospective study across several different cancer types. METHODS: Melanoma, renal cancer and non-small cell lung cancer patients who are planned to receive standard immune checkpoint inhibitors are being recruited to the MITRE study. Longitudinal stool samples are collected prior to treatment, then at 6 weeks, 3, 6 and 12 months during treatment, or at disease progression/recurrence (whichever is sooner), as well as after a severe (≥grade 3 CTCAE v5.0) immune-related adverse event. Additionally, whole blood, plasma, buffy coat, RNA and peripheral blood mononuclear cells (PBMCs) is collected at similar time points and will be used for exploratory analyses. Archival tumour tissue, tumour biopsies at progression/relapse, as well as any biopsies from body organs collected after a severe toxicity are collected. The primary outcome measure is the ability of the microbiome signature to predict 1 year progression-free survival (PFS) in patients with advanced disease. Secondary outcomes include microbiome correlations with toxicity and other efficacy end-points. Biosamples will be used to explore immunological and genomic correlates. A sub-study will evaluate both COVID-19 antigen and antibody associations with the microbiome. DISCUSSION: There is an urgent need to identify biomarkers that are predictive of treatment response, resistance and toxicity to immunotherapy. The data generated from this study will both help inform patient selection for these drugs and provide information that may allow therapeutic manipulation of the microbiome to improve future patient outcomes. TRIAL REGISTRATION: NCT04107168 , ClinicalTrials.gov, registered 09/27/2019. Protocol V3.2 (16/04/2021)
Dreaming of drams: Authenticity in Scottish whisky tourism as an expression of unresolved Habermasian rationalities
In this paper, the production of whisky tourism at both independently owned and corporately owned distilleries in Scotland is explored by focusing on four examples (Arran, Glengoyne, Glenturret and Bruichladdich). In particular, claims of authenticity and Scottishness of Scottish whiskies through commercial materials, case studies, website-forum discussions and 'independent' writing about such whisky are analysed. It is argued that the globalisation and commodification of whisky and whisky tourism, and the communicative backlash to these trends typified by the search for authenticity, is representative of a Habermasian struggle between two irreconcilable rationalities. This paper will demonstrate that the meaning and purpose of leisure can be understood through such explorations of the tension between the instrumentality of commodification and the freedom of individuals to locate their own leisure lives in the lifeworld that remains. © 2011 Taylor & Francis
First observations of separated atmospheric nu_mu and bar{nu-mu} events in the MINOS detector
The complete 5.4 kton MINOS far detector has been taking data since the beginning of August 2003 at a depth of 2070 meters water-equivalent in the Soudan mine, Minnesota. This paper presents the first MINOS observations of nuµ and [overline nu ]µ charged-current atmospheric neutrino interactions based on an exposure of 418 days. The ratio of upward- to downward-going events in the data is compared to the Monte Carlo expectation in the absence of neutrino oscillations, giving Rup/downdata/Rup/downMC=0.62-0.14+0.19(stat.)±0.02(sys.). An extended maximum likelihood analysis of the observed L/E distributions excludes the null hypothesis of no neutrino oscillations at the 98% confidence level. Using the curvature of the observed muons in the 1.3 T MINOS magnetic field nuµ and [overline nu ]µ interactions are separated. The ratio of [overline nu ]µ to nuµ events in the data is compared to the Monte Carlo expectation assuming neutrinos and antineutrinos oscillate in the same manner, giving R[overline nu ][sub mu]/nu[sub mu]data/R[overline nu ][sub mu]/nu[sub mu]MC=0.96-0.27+0.38(stat.)±0.15(sys.), where the errors are the statistical and systematic uncertainties. Although the statistics are limited, this is the first direct observation of atmospheric neutrino interactions separately for nuµ and [overline nu ]µ
Global circulation patterns of seasonal influenza viruses vary with antigenic drift.
Understanding the spatiotemporal patterns of emergence and circulation of new human seasonal influenza virus variants is a key scientific and public health challenge. The global circulation patterns of influenza A/H3N2 viruses are well characterized, but the patterns of A/H1N1 and B viruses have remained largely unexplored. Here we show that the global circulation patterns of A/H1N1 (up to 2009), B/Victoria, and B/Yamagata viruses differ substantially from those of A/H3N2 viruses, on the basis of analyses of 9,604 haemagglutinin sequences of human seasonal influenza viruses from 2000 to 2012. Whereas genetic variants of A/H3N2 viruses did not persist locally between epidemics and were reseeded from East and Southeast Asia, genetic variants of A/H1N1 and B viruses persisted across several seasons and exhibited complex global dynamics with East and Southeast Asia playing a limited role in disseminating new variants. The less frequent global movement of influenza A/H1N1 and B viruses coincided with slower rates of antigenic evolution, lower ages of infection, and smaller, less frequent epidemics compared to A/H3N2 viruses. Detailed epidemic models support differences in age of infection, combined with the less frequent travel of children, as probable drivers of the differences in the patterns of global circulation, suggesting a complex interaction between virus evolution, epidemiology, and human behaviour.T.B.
was
supported
by
a
Newton
International
Fellowship
from
the
Royal
Society
and
through
NIH
U54
GM111274.
S.R.
was
supported
by
MRC
(UK,
Project
MR/J008761/1),
Wellcome
Trust
(UK,
Project
093488/Z/10/Z),
Fogarty
International
Centre
(USA,
R01
TW008246‐01),
DHS
(USA,
RAPIDD
program),
NIGMS
(USA,
MIDAS
U01
GM110721‐01)
and
NIHR
(UK,
Health
Protection
Research
Unit
funding).
The
Melbourne
WHO
Collaborating
Centre
for
Reference
and
Research
on
Influenza
was
supported
by
the
Australian
Government
Department
of
Health
and
thanks
N.
Komadina
and
Y.‐M.
Deng.
The
Atlanta
WHO
Collaborating
Center
for
Surveillance,
Epidemiology
and
Control
of
Influenza
was
supported
by
the
U.S.
Department
of
13
Health
and
Human
Services.
NIV
thanks
A.C.
Mishra,
M.
Chawla‐Sarkar,
A.M.
Abraham,
D.
Biswas,
S.
Shrikhande,
AnuKumar
B,
and
A.
Jain.
Influenza
surveillance
in
India
was
expanded,
in
part,
through
US
Cooperative
Agreements
(5U50C1024407
and
U51IP000333)
and
by
the
Indian
Council
of
Medical
Research.
M.A.S.
was
supported
through
NSF
DMS
1264153
and
NIH
R01
AI
107034.
Work
of
the
WHO
Collaborating
Centre
for
Reference
and
Research
on
Influenza
at
the
MRC
National
Institute
for
Medical
Research
was
supported
by
U117512723.
P.L.,
A.R.
&
M.A.S
were
supported
by
EU
Seventh
Framework
Programme
[FP7/2007‐2013]
under
Grant
Agreement
no.
278433-‐PREDEMICS
and
ERC
Grant
agreement
no.
260864.
C.A.R.
was
supported
by
a
University
Research
Fellowship
from
the
Royal
Society.This is the author accepted manuscript. It is currently under infinite embargo pending publication of the final version
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