197 research outputs found
Musculoskeletal foot problems in primary care: what influences older people to consult?
Objective. To estimate the incidence of, and factors associated with, consultation for musculoskeletal foot problems in primary care
Tunable control of CAR T cell activity through tetracycline mediated disruption of protein-protein interaction
Chimeric antigen receptor (CAR) T cells are a promising form of cancer immunotherapy, although they are often associated with severe toxicities. Here, we present a split-CAR design incorporating separate antigen recognition and intracellular signaling domains. These exploit the binding between the tetracycline repressor protein and a small peptide sequence (TIP) to spontaneously assemble as a functional CAR. Addition of the FDA-approved, small molecule antibiotic minocycline, acts as an "off-switch" by displacing the signaling domain and down-tuning CAR T activity. Here we describe the optimization of this split-CAR approach to generate a CAR in which cytotoxicity, cytokine secretion and proliferation can be inhibited in a dose-dependent and reversible manner. Inhibition is effective during on-going CAR T cell activation and inhibits activation and tumor control in vivo. This work shows how optimization of split-CAR structure affects function and adds a novel design allowing easy CAR inhibition through an FDA-approved small molecule
A rasch analysis of the Manchester foot pain and disability index
© 2009 Muller and Roddy; licensee BioMed Central Ltd
The Use of a Mobile Laboratory Unit in Support of Patient Management and Epidemiological Surveillance during the 2005 Marburg Outbreak in Angola
A mobile laboratory unit (MLU) was deployed to Uige, Angola as part of the World Health Organization response to an outbreak of viral hemorrhagic fever caused by Marburg virus (MARV). Utilizing mainly quantitative real-time PCR assays, this laboratory provided specific MARV diagnostics in the field. The MLU operated for 88 consecutive days allowing MARV-specific diagnostic response in <4 hours from sample receiving. Most cases were found among females in the child-bearing age and in children less than five years of age including a high number of paediatric cases implicating breastfeeding as potential transmission route. Oral swabs were identified as a useful alternative specimen source to the standard whole blood/serum specimens for patients refusing blood draw. There was a high concordance in test results between the MLU and the reference laboratory in Luanda operated by the US Centers for Disease Control and Prevention. The MLU was an important outbreak response asset providing valuable support in patient management and epidemiological surveillance. Field laboratory capacity should be expanded and made an essential part of any future outbreak investigation
Evaluation of the measurement properties of the Manchester foot pain and disability index
BACKGROUND: The Manchester Foot Pain and Disability Index (MFPDI, 19 items) was developed to measure functional limitations, pain and appearance for patients with foot pain and is frequently used in both observational studies and randomised controlled trials. A Dutch version of the MFPDI was developed. The aims of this study were to evaluate all the measurement properties for the Dutch version of the MFPDI and to evaluate comparability to the original version. METHOD: The MFPDI was translated into Dutch using a forward/backward translation process. The dimensionality was evaluated using exploratory and confirmatory factor analysis. Measurement properties were evaluated per subscale according to the COSMIN taxonomy consisting of: reliability (internal consistency, test-retest reliability and measurement error), validity (structural validity, content validity and cross-cultural validity comparing the Dutch version to the English version) responsiveness and interpretation. RESULTS: The questionnaire consists of three scales, measuring foot function, foot pain and perception. The reliability of the foot function scale is acceptable (Cronbach’s α > 0.7, ICC = 0.7, SEM = 2.2 on 0-18 scale). The construct validity of the function and pain scale was confirmed and only the pain scale contains one item with differential item functioning (DIF). The responsiveness of the function and pain scale is moderate when compared to anchor questions. CONCLUSION: Results using the Dutch MFPDI version can be compared to results using the original version. The foot function sub-scale (items 1-9) is a reliable and valid sub-scale. This study indicates that the use of the MFPDI as a longitudinal instrument might be problematic for measuring change in musculoskeletal foot pain due to moderate responsiveness
Implications For The Origin Of GRB 051103 From LIGO Observations
We present the results of a LIGO search for gravitational waves (GWs)
associated with GRB 051103, a short-duration hard-spectrum gamma-ray burst
(GRB) whose electromagnetically determined sky position is coincident with the
spiral galaxy M81, which is 3.6 Mpc from Earth. Possible progenitors for
short-hard GRBs include compact object mergers and soft gamma repeater (SGR)
giant flares. A merger progenitor would produce a characteristic GW signal that
should be detectable at the distance of M81, while GW emission from an SGR is
not expected to be detectable at that distance. We found no evidence of a GW
signal associated with GRB 051103. Assuming weakly beamed gamma-ray emission
with a jet semi-angle of 30 deg we exclude a binary neutron star merger in M81
as the progenitor with a confidence of 98%. Neutron star-black hole mergers are
excluded with > 99% confidence. If the event occurred in M81 our findings
support the the hypothesis that GRB 051103 was due to an SGR giant flare,
making it the most distant extragalactic magnetar observed to date.Comment: 8 pages, 3 figures. For a repository of data used in the publication,
go to: https://dcc.ligo.org/cgi-bin/DocDB/ShowDocument?docid=15166 . Also see
the announcement for this paper on ligo.org at:
http://www.ligo.org/science/Publication-GRB051103/index.ph
Upper limits on the strength of periodic gravitational waves from PSR J1939+2134
The first science run of the LIGO and GEO gravitational wave detectors
presented the opportunity to test methods of searching for gravitational waves
from known pulsars. Here we present new direct upper limits on the strength of
waves from the pulsar PSR J1939+2134 using two independent analysis methods,
one in the frequency domain using frequentist statistics and one in the time
domain using Bayesian inference. Both methods show that the strain amplitude at
Earth from this pulsar is less than a few times .Comment: 7 pages, 1 figure, to appear in the Proceedings of the 5th Edoardo
Amaldi Conference on Gravitational Waves, Tirrenia, Pisa, Italy, 6-11 July
200
Sensitivity to Gravitational Waves from Compact Binary Coalescences Achieved during LIGO's Fifth and Virgo's First Science Run
We summarize the sensitivity achieved by the LIGO and Virgo gravitational
wave detectors for compact binary coalescence (CBC) searches during LIGO's
fifth science run and Virgo's first science run. We present noise spectral
density curves for each of the four detectors that operated during these
science runs which are representative of the typical performance achieved by
the detectors for CBC searches. These spectra are intended for release to the
public as a summary of detector performance for CBC searches during these
science runs.Comment: 12 pages, 5 figure
Improving the sensitivity to gravitational-wave sources by modifying the input-output optics of advanced interferometers
We study frequency dependent (FD) input-output schemes for signal-recycling
interferometers, the baseline design of Advanced LIGO and the current
configuration of GEO 600. Complementary to a recent proposal by Harms et al. to
use FD input squeezing and ordinary homodyne detection, we explore a scheme
which uses ordinary squeezed vacuum, but FD readout. Both schemes, which are
sub-optimal among all possible input-output schemes, provide a global noise
suppression by the power squeeze factor, while being realizable by using
detuned Fabry-Perot cavities as input/output filters. At high frequencies, the
two schemes are shown to be equivalent, while at low frequencies our scheme
gives better performance than that of Harms et al., and is nearly fully
optimal. We then study the sensitivity improvement achievable by these schemes
in Advanced LIGO era (with 30-m filter cavities and current estimates of
filter-mirror losses and thermal noise), for neutron star binary inspirals, and
for narrowband GW sources such as low-mass X-ray binaries and known radio
pulsars. Optical losses are shown to be a major obstacle for the actual
implementation of these techniques in Advanced LIGO. On time scales of
third-generation interferometers, like EURO/LIGO-III (~2012), with
kilometer-scale filter cavities, a signal-recycling interferometer with the FD
readout scheme explored in this paper can have performances comparable to
existing proposals. [abridged]Comment: Figs. 9 and 12 corrected; Appendix added for narrowband data analysi
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