Chronic Lymphocytic Leukemia (CLL) is defined by a perturbed B-cell receptor-mediated signaling machinery. We aimed to model differential signaling behavior between B cells from CLL and healthy ...individuals to pinpoint modes of dysregulation.
We developed an experimental methodology combining immunophenotyping, multiplexed phosphospecific flow cytometry, and multifactorial statistical modeling. Utilizing patterns of signaling network covariance, we modeled BCR signaling in 67 CLL patients using Partial Least Squares Regression (PLSR). Results from multidimensional modeling were validated using an independent test cohort of 38 patients.
We identified a dynamic and variable imbalance between proximal (pSYK, pBTK) and distal (pPLCγ2, pBLNK, ppERK) phosphoresponses. PLSR identified the relationship between upstream tyrosine kinase SYK and its target, PLCγ2, as maximally predictive and sufficient to distinguish CLL from healthy samples, pointing to this juncture in the signaling pathway as a hallmark of CLL B cells. Specific BCR pathway signaling signatures that correlate with the disease and its degree of aggressiveness were identified. Heterogeneity in the PLSR response variable within the B cell population is both a characteristic mark of healthy samples and predictive of disease aggressiveness.
Single-cell multidimensional analysis of BCR signaling permitted focused analysis of the variability and heterogeneity of signaling behavior from patient-to-patient, and from cell-to-cell. Disruption of the pSYK/pPLCγ2 relationship is uncovered as a robust hallmark of CLL B cell signaling behavior. Together, these observations implicate novel elements of the BCR signal transduction as potential therapeutic targets.
We present measurements of the redshift-space three-point correlation function of galaxies in the Sloan Digital Sky Survey (SDSS). For the first time, we analyze the dependence of this statistic on ...galaxy morphology, color, and luminosity. In order to control systematics due to selection effects, we used
$r$
-band, volume-limited samples of galaxies, constructed from magnitude-limited SDSS data (
$14.5 < r < 17.5$
), and further divided the samples into two morphological types (early and late) or two color populations (red and blue). The three-point correlation function of SDSS galaxies follows the hierarchical relation well, and the reduced three-point amplitudes in redshift-space are almost scale-independent (
$Q_z = 0.5 \sim 1.0$
). In addition, their dependence on the morphology, color, and luminosity is not statistically significant. Given the robust morphological, color, and luminosity dependences of the two-point correlation function, this implies that galaxy biasing is complex on weakly non-linear to non-linear scales. We show that a simple deterministic linear relation with the underlying mass could not explain our measurements on these scales.
This study employs a mixed method, sequential explanatory design strategy, one in which the interpretation of the quantitative data is weighted more heavily than that of the qualitative data, to ...record social media usage among Assyrian Christian Internally Displaced Persons (IDPs) who were held in the Asti 2 IDP camp in Ankawa, Iraq, from 2014 to 2017. Through a quantitative survey instrument and a series of oral interviews, this study explores the social media habits of 315 respondents, paying particular attention to types of social media applications used, attitudes of the IDPs towards the useful of SMA in making the world aware of their plight and resolving their displacement.
Gunderman succeeds Tony Thomas, who has been named president of the real estate investment trust Windstream is creating through the spinoff of certain telecommunications assets.
Screening Prisoners for Intellectual Disabilities in Three English Prisons Murphy, Glynis H.; Gardner, Jeff; Freeman, Mark J.
JARID. Journal of applied research in intellectual disabilities/Journal of applied research in intellectual disabilities,
January 2017, 2017-01-00, 2017-Jan, 20170101, Letnik:
30, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Background
Prisoners with intellectual disabilities are known to be disadvantaged in prisons and to be more susceptible to bullying, segregation, depression and anxiety than other prisoners.
Method
...In this study, nearly 3000 new prisoners entering three English prisons were offered screening for intellectual disabilities, using the LDSQ.
Results
On average, 75% of all new prisoners entering prison were offered screening, and only 14% refused screening. Overall, just less than 7% were screened positive on the LDSQ and prisons made some reasonable adjustments as a result.
Conclusions
It is argued that it is feasible to screen for intellectual disabilities in prisons and, given the inequalities to which prisoners with intellectual disabilities are subject in prison, it is time for such screening to be rolled out to all prisons.
Haloes gone MAD: The Halo-Finder Comparison Project Knebe, Alexander; Knollmann, Steffen R.; Muldrew, Stuart I. ...
Monthly Notices of the Royal Astronomical Society,
08/2011, Letnik:
415, Številka:
3
Journal Article
Recenzirano
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ABSTRACT
We present a detailed comparison of fundamental dark matter halo properties retrieved by a substantial number of different halo finders. These codes span a wide range of techniques including ...friends‐of‐friends, spherical‐overdensity and phase‐space‐based algorithms. We further introduce a robust (and publicly available) suite of test scenarios that allow halo finder developers to compare the performance of their codes against those presented here. This set includes mock haloes containing various levels and distributions of substructure at a range of resolutions as well as a cosmological simulation of the large‐scale structure of the universe.
All the halo‐finding codes tested could successfully recover the spatial location of our mock haloes. They further returned lists of particles (potentially) belonging to the object that led to coinciding values for the maximum of the circular velocity profile and the radius where it is reached. All the finders based in configuration space struggled to recover substructure that was located close to the centre of the host halo, and the radial dependence of the mass recovered varies from finder to finder. Those finders based in phase space could resolve central substructure although they found difficulties in accurately recovering its properties. Through a resolution study we found that most of the finders could not reliably recover substructure containing fewer than 30–40 particles. However, also here the phase‐space finders excelled by resolving substructure down to 10–20 particles. By comparing the halo finders using a high‐resolution cosmological volume, we found that they agree remarkably well on fundamental properties of astrophysical significance (e.g. mass, position, velocity and peak of the rotation curve).
We further suggest to utilize the peak of the rotation curve, vmax, as a proxy for mass, given the arbitrariness in defining a proper halo edge.
This study employs a mixed method, sequential explanatory design strategy, one in which the interpretation of the quantitative data is weighted more heavily than that of the qualitative data, to ...record social media usage among Assyrian Christian Internally Displaced Persons (IDPs) who were held in the Asti 2 IDP camp in Ankawa, Iraq, from 2014 to 2017. Through a quantitative survey instrument and a series of oral interviews, this study explores the social media habits of 315 respondents, paying particular attention to types of social media applications used, attitudes of the IDPs towards the useful of SMA in making the world aware of their plight and resolving their displacement.
Remote ischemic preconditioning is a simple therapy that may reduce cardiac and kidney injury. We undertook a randomized controlled trial to evaluate the effect of this therapy on markers of heart ...and kidney injury after cardiac surgery.
Patients at high risk of death within 30 days after cardiac surgery were randomly assigned to undergo remote ischemic preconditioning or a sham procedure after induction of anesthesia. The preconditioning therapy was three 5-minute cycles of thigh ischemia, with 5 minutes of reperfusion between cycles. The sham procedure was identical except that ischemia was not induced. The primary outcome was peak creatine kinase-myocardial band (CK-MB) within 24 hours after surgery (expressed as multiples of the upper limit of normal, with log transformation). The secondary outcome was change in creatinine level within 4 days after surgery (expressed as log-transformed micromoles per litre). Patient-important outcomes were assessed up to 6 months after randomization.
We randomly assigned 128 patients to remote ischemic preconditioning and 130 to the sham therapy. There were no significant differences in postoperative CK-MB (absolute mean difference 0.15, 95% confidence interval CI -0.07 to 0.36) or creatinine (absolute mean difference 0.06, 95% CI -0.10 to 0.23). Other outcomes did not differ significantly for remote ischemic preconditioning relative to the sham therapy: for myocardial infarction, relative risk (RR) 1.35 (95% CI 0.85 to 2.17); for acute kidney injury, RR 1.10 (95% CI 0.68 to 1.78); for stroke, RR 1.02 (95% CI 0.34 to 3.07); and for death, RR 1.47 (95% CI 0.65 to 3.31).
Remote ischemic precnditioning did not reduce myocardial or kidney injury during cardiac surgery. This type of therapy is unlikely to substantially improve patient-important outcomes in cardiac surgery.
ClinicalTrials.gov, no. NCT01071265.
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