362 research outputs found
Clinical Leadership in Athletic Training
Purpose: Clinical leadership behaviors demonstrated by nurses delivering patient care are associated with improved patient outcomes and increased job satisfaction. Clinical leadership behaviors have not been studied in athletic training; therefore, the purpose of this study was to investigate athletic trainersâ frequency of demonstrating these behaviors. Method: Participates completed an electronically distributed survey consisting of demographic variables, the Clinical Leadership Survey (CLS), and the Global Rating of Clinical Leadership Scale (GRCLS). Results: We found statistically significant differences between the CLS score of those in a supervisory role (M = 65.3 ± 5.4) and those who are not (M = 63.5 ± 5.5, mean difference = 1.8 ± 0.8, t (212) = 2.27, p = 0.02). A moderate positive correlation (r = 0.51, p \u3c 0.001) exists between an individualâs CLS score and perceiving themselves as a clinical leader. A moderate positive correlation (r = 0.59, p \u3c 0.001) exists between an individualâs CLS score and believing they demonstrate leadership behaviors in clinical practice. Conclusion: Athletic trainers in supervisory roles report demonstrating clinical leadership behaviors more often than those who are not. A discrepancy exists between athletic trainersâ reported frequency of demonstrating individual clinical leadership behaviors, their belief they are leaders, and their demonstration of leadership behaviors. The data suggest athletic trainers who are not in supervisory roles may believe, because they hold no positional authority, they are not clinical leaders. Organizations can implement strategies to promote clinical leadership in staff and improve patient outcomes
The water cycle and regolith-atmosphere interaction at Gale crater, Mars
We perform mesoscale simulations of the water cycle in a region around Gale crater, including the diffusion of water vapour in and out of the regolith, and compare our results with measurements from the REMS instrument on board the Curiosity rover. Simulations are performed at three times of year, and show that diffusion in and out of the regolith and adsorption/desorption needs to be taken into account in order to match the diurnal variation of relative humidity measured by REMS. During the evening and night, local downslope flows transport water vapour down the walls of Gale crater. When including regolith-atmosphere interaction, the amount of vapour reaching the crater floor is reduced (by factors of 2â3 depending on season) due to vapour diffusing into the regolith along the crater walls. The transport of vapour into Gale crater is also affected by the regional katabatic flow over the dichotomy boundary, with the largest flux of vapour into the regolith initially occurring on the northern crater wall, and moving to the southern wall by early morning. Upslope winds during the day transport vapour desorbing and mixing out of the regolith up crater walls, where it can then be transported a few hundred metres into the atmosphere at convergence boundaries. Regolith-atmosphere interaction limits the formation of surface ice by reducing water vapour abundances in the lower atmosphere, though in some seasons ice can still form in the early morning on eastern crater walls. Subsurface ice amounts are small in all seasons, with ice only existing in the upper few millimetres of regolith during the night. The results at Gale crater are representative of the behaviour at other craters in the mesoscale domain
PHF6 regulates phenotypic plasticity through chromatin organization within lineage-specific genes
Developmental and lineage plasticity have been observed in numerous malignancies and have been correlated with tumor progression and drug resistance. However, little is known about the molecular mechanisms that enable such plasticity to occur. Here, we describe the function of the plant homeodomain finger protein 6 (PHF6) in leukemia and define its role in regulating chromatin accessibility to lineage-specific transcription factors. We show that loss of Phf6 in B-cell leukemia results in systematic changes in gene expression via alteration of the chromatin landscape at the transcriptional start sites of B-cell- and T-cell-specific factors. Additionally, Phf6KO cells show significant down-regulation of genes involved in the development and function of normal B cells, show up-regulation of genes involved in T-cell signaling, and give rise to mixed-lineage lymphoma in vivo. Engagement of divergent transcriptional programs results in phenotypic plasticity that leads to altered disease presentation in vivo, tolerance of aberrant oncogenic signaling, and differential sensitivity to frontline and targeted therapies. These findings suggest that active maintenance of a precise chromatin landscape is essential for sustaining proper leukemia cell identity and that loss of a single factor (PHF6) can cause focal changes in chromatin accessibility and nucleosome positioning that render cells susceptible to lineage transition.National Cancer Institute ; F31-CA183405 - National Institutes of Health ; 1122374 - National Science Foundation ; Ludwig Center for Molecular Oncology at Massachusetts Institute of Technology ; Koch Institute ; Dana-Farber/Harvard Cancer Center ; P30-CA14051 - Koch Institute ; NCI ; NIH ; National Science Foundatio
Targeting Cytokine Signaling and Lymphocyte Traffic via Small Molecules in Inflammatory Bowel Disease: JAK Inhibitors and S1PR Agonists
The inflammatory Bowel diseases (IBDs) are a chronic, relapsing inflammatory diseases of the gastrointestinal tract with heterogeneous behavior and prognosis. The introduction of biological therapies including anti-TNF, anti-IL-12/23, and anti-integrins, has revolutionized the treatment of IBD, but these drugs are not universally effective. Due to the complex molecular structures of biologics, they are uniformly immunogenic. New discoveries concerning the underlying mechanisms involved in the pathogenesis of IBD have allowed for progress in the development of new treatment options. The advantage of small molecules (SMs) over biological therapies includes their lack of immunogenicity, short half-life, oral administration, and low manufacturing cost. Among these, the Janus Kinases (JAKs) inhibition has emerged as a novel strategy to modulate downstream cytokine signaling during immune-mediated diseases. These drugs target various cytokine signaling pathways that participate in the pathogenesis of IBD. Tofacitinib, a JAK inhibitor targeting predominantly JAK1 and JAK3, has been approved for the treatment of ulcerative colitis (UC), and there are other specific JAK inhibitors under development that may be effective in Crohnâs. Similarly, the traffic of lymphocytes can now be targeted by another SM. Sphingosine-1-phosphate receptor (S1PR) agonism is a novel strategy that acts, in part, by interfering with lymphocyte recirculation, through blockade of lymphocyte egress from lymph nodes. S1PR agonists are being studied in IBD and other immune-mediated disorders. This review will focus on SM drugs approved and under development, including JAK inhibitors (tofacitinib, filgotinib, upadacitinib, peficitinib) and S1PR agonists (KRP-203, fingolimod, ozanimod, etrasimod, amiselimod), and their mechanism of action
Quantitative proteomics identify Tenascin-C as a promoter of lung cancer progression and contributor to a signature prognostic of patient survival
The extracellular microenvironment is an integral component of normal and diseased tissues that is poorly understood owing to its complexity. To investigate the contribution of the microenvironment to lung fibrosis and adenocarcinoma progression, two pathologies characterized by excessive stromal expansion, we used mouse models to characterize the extracellular matrix (ECM) composition of normal lung, fibrotic lung, lung tumors, and metastases. Using quantitative proteomics, we identified and assayed the abundance of 113 ECM proteins, which revealed robust ECM protein signatures unique to fibrosis, primary tumors, or metastases. These analyses indicated significantly increased abundance of several S100 proteins, including Fibronectin and Tenascin-C (Tnc), in primary lung tumors and associated lymph node metastases compared with normal tissue. We further showed that Tnc expression is repressed by the transcription factor Nkx2-1, a well-established suppressor of metastatic progression. We found that increasing the levels of Tnc, via CRISPR-mediated transcriptional activation of the endogenous gene, enhanced the metastatic dissemination of lung adenocarcinoma cells. Interrogation of human cancer gene expression data revealed that high TNC expression correlates with worse prognosis for lung adenocarcinoma, and that a three-gene expression signature comprising TNC, S100A10, and S100A11 is a robust predictor of patient survival independent of age, sex, smoking history, and mutational load. Our findings suggest that the poorly understood ECM composition of the fibrotic and tumor microenvironment is an underexplored source of diagnostic markers and potential therapeutic targets for cancer patients
Search for Gravitational Wave Bursts from Soft Gamma Repeaters
We present the results of a LIGO search for short-duration gravitational
waves (GWs) associated with Soft Gamma Repeater (SGR) bursts. This is the first
search sensitive to neutron star f-modes, usually considered the most efficient
GW emitting modes. We find no evidence of GWs associated with any SGR burst in
a sample consisting of the 27 Dec. 2004 giant flare from SGR 1806-20 and 190
lesser events from SGR 1806-20 and SGR 1900+14 which occurred during the first
year of LIGO's fifth science run. GW strain upper limits and model-dependent GW
emission energy upper limits are estimated for individual bursts using a
variety of simulated waveforms. The unprecedented sensitivity of the detectors
allows us to set the most stringent limits on transient GW amplitudes published
to date. We find upper limit estimates on the model-dependent isotropic GW
emission energies (at a nominal distance of 10 kpc) between 3x10^45 and 9x10^52
erg depending on waveform type, detector antenna factors and noise
characteristics at the time of the burst. These upper limits are within the
theoretically predicted range of some SGR models.Comment: 6 pages, 1 Postscript figur
Search for gravitational waves from binary inspirals in S3 and S4 LIGO data
We report on a search for gravitational waves from the coalescence of compact
binaries during the third and fourth LIGO science runs. The search focused on
gravitational waves generated during the inspiral phase of the binary
evolution. In our analysis, we considered three categories of compact binary
systems, ordered by mass: (i) primordial black hole binaries with masses in the
range 0.35 M(sun) < m1, m2 < 1.0 M(sun), (ii) binary neutron stars with masses
in the range 1.0 M(sun) < m1, m2 < 3.0 M(sun), and (iii) binary black holes
with masses in the range 3.0 M(sun)< m1, m2 < m_(max) with the additional
constraint m1+ m2 < m_(max), where m_(max) was set to 40.0 M(sun) and 80.0
M(sun) in the third and fourth science runs, respectively. Although the
detectors could probe to distances as far as tens of Mpc, no gravitational-wave
signals were identified in the 1364 hours of data we analyzed. Assuming a
binary population with a Gaussian distribution around 0.75-0.75 M(sun), 1.4-1.4
M(sun), and 5.0-5.0 M(sun), we derived 90%-confidence upper limit rates of 4.9
yr^(-1) L10^(-1) for primordial black hole binaries, 1.2 yr^(-1) L10^(-1) for
binary neutron stars, and 0.5 yr^(-1) L10^(-1) for stellar mass binary black
holes, where L10 is 10^(10) times the blue light luminosity of the Sun.Comment: 12 pages, 11 figure
All-sky search for periodic gravitational waves in LIGO S4 data
We report on an all-sky search with the LIGO detectors for periodic
gravitational waves in the frequency range 50-1000 Hz and with the frequency's
time derivative in the range -1.0E-8 Hz/s to zero. Data from the fourth LIGO
science run (S4) have been used in this search. Three different semi-coherent
methods of transforming and summing strain power from Short Fourier Transforms
(SFTs) of the calibrated data have been used. The first, known as "StackSlide",
averages normalized power from each SFT. A "weighted Hough" scheme is also
developed and used, and which also allows for a multi-interferometer search.
The third method, known as "PowerFlux", is a variant of the StackSlide method
in which the power is weighted before summing. In both the weighted Hough and
PowerFlux methods, the weights are chosen according to the noise and detector
antenna-pattern to maximize the signal-to-noise ratio. The respective
advantages and disadvantages of these methods are discussed. Observing no
evidence of periodic gravitational radiation, we report upper limits; we
interpret these as limits on this radiation from isolated rotating neutron
stars. The best population-based upper limit with 95% confidence on the
gravitational-wave strain amplitude, found for simulated sources distributed
isotropically across the sky and with isotropically distributed spin-axes, is
4.28E-24 (near 140 Hz). Strict upper limits are also obtained for small patches
on the sky for best-case and worst-case inclinations of the spin axes.Comment: 39 pages, 41 figures An error was found in the computation of the C
parameter defined in equation 44 which led to its overestimate by 2^(1/4).
The correct values for the multi-interferometer, H1 and L1 analyses are 9.2,
9.7, and 9.3, respectively. Figure 32 has been updated accordingly. None of
the upper limits presented in the paper were affecte
Search for Gravitational Waves Associated with 39 Gamma-Ray Bursts Using Data from the Second, Third, and Fourth LIGO Runs
We present the results of a search for short-duration gravitational-wave
bursts associated with 39 gamma-ray bursts (GRBs) detected by gamma-ray
satellite experiments during LIGO's S2, S3, and S4 science runs. The search
involves calculating the crosscorrelation between two interferometer data
streams surrounding the GRB trigger time. We search for associated
gravitational radiation from single GRBs, and also apply statistical tests to
search for a gravitational-wave signature associated with the whole sample. For
the sample examined, we find no evidence for the association of gravitational
radiation with GRBs, either on a single-GRB basis or on a statistical basis.
Simulating gravitational-wave bursts with sine-gaussian waveforms, we set upper
limits on the root-sum-square of the gravitational-wave strain amplitude of
such waveforms at the times of the GRB triggers. We also demonstrate how a
sample of several GRBs can be used collectively to set constraints on
population models. The small number of GRBs and the significant change in
sensitivity of the detectors over the three runs, however, limits the
usefulness of a population study for the S2, S3, and S4 runs. Finally, we
discuss prospects for the search sensitivity for the ongoing S5 run, and beyond
for the next generation of detectors.Comment: 24 pages, 10 figures, 14 tables; minor changes to text and Fig. 2;
accepted by Phys. Rev.
A Joint Search for Gravitational Wave Bursts with AURIGA and LIGO
The first simultaneous operation of the AURIGA detector and the LIGO
observatory was an opportunity to explore real data, joint analysis methods
between two very different types of gravitational wave detectors: resonant bars
and interferometers. This paper describes a coincident gravitational wave burst
search, where data from the LIGO interferometers are cross-correlated at the
time of AURIGA candidate events to identify coherent transients. The analysis
pipeline is tuned with two thresholds, on the signal-to-noise ratio of AURIGA
candidate events and on the significance of the cross-correlation test in LIGO.
The false alarm rate is estimated by introducing time shifts between data sets
and the network detection efficiency is measured with simulated signals with
power in the narrower AURIGA band. In the absence of a detection, we discuss
how to set an upper limit on the rate of gravitational waves and to interpret
it according to different source models. Due to the short amount of analyzed
data and to the high rate of non-Gaussian transients in the detectors noise at
the time, the relevance of this study is methodological: this was the first
joint search for gravitational wave bursts among detectors with such different
spectral sensitivity and the first opportunity for the resonant and
interferometric communities to unify languages and techniques in the pursuit of
their common goal.Comment: 18 pages, IOP, 12 EPS figure
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