28 research outputs found
Determinants of mortality for adults with cystic fibrosis admitted in Intensive Care Unit: a multicenter study
BACKGROUND: Intensive care unit (ICU) admission of adults with cystic fibrosis (CF) is controversial because of poor outcome. This appraisal needs re-evaluation following recent changes in both CF management and ICU daily practice. Objectives were to determine long-term outcome of adults with CF admitted in ICU and to identify prognostic factors. METHODS: Retrospective multicenter study of 60 ICU hospitalizations for 42 adult CF patients admitted between 2000 and 2003. Reason for ICU admission, ventilatory support provided and one-year survival were recorded. Multiple logistic analysis was used to determine predictors of mortality. RESULTS: Prior to ICU admission, all patients (mean age 28.1 ± 8 yr) had a severe lung disease (mean FEV(1 )28 ± 12% predicted; mean PaCO(2 )47 ± 9 mmHg). Main reason for ICU hospitalization was pulmonary infective exacerbation (40/60). At admission, noninvasive ventilation was used in 57% of cases and was successful in 67% of patients. Endotracheal intubation was implemented in 19 episodes. Overall ICU mortality rate was 14%. One year after ICU discharge, 10 of the 28 survivors have been lung transplanted. Among recognized markers of CF disease severity, only the annual FEV(1 )loss was associated with a poor outcome (HR = 1.47 [1.18–1.85], p = 0.001). SAPSII (HR = 1.08 [1.03–1.12], p < 0.001) and endotracheal intubation (HR = 16.60 [4.35–63.34], p < 0.001) were identified as strong independent predictors of mortality. CONCLUSION: Despite advanced lung disease, adult patients with CF admitted in ICU have high survival rate. Endotracheal intubation is associated with a poor prognosis and should be used as the last alternative. Although efforts have to be made in selecting patients with CF likely to benefit from ICU resources, ICU admission of these patients should be considered
The quest for the solar g modes
Solar gravity modes (or g modes) -- oscillations of the solar interior for
which buoyancy acts as the restoring force -- have the potential to provide
unprecedented inference on the structure and dynamics of the solar core,
inference that is not possible with the well observed acoustic modes (or p
modes). The high amplitude of the g-mode eigenfunctions in the core and the
evanesence of the modes in the convection zone make the modes particularly
sensitive to the physical and dynamical conditions in the core. Owing to the
existence of the convection zone, the g modes have very low amplitudes at
photospheric levels, which makes the modes extremely hard to detect. In this
paper, we review the current state of play regarding attempts to detect g
modes. We review the theory of g modes, including theoretical estimation of the
g-mode frequencies, amplitudes and damping rates. Then we go on to discuss the
techniques that have been used to try to detect g modes. We review results in
the literature, and finish by looking to the future, and the potential advances
that can be made -- from both data and data-analysis perspectives -- to give
unambiguous detections of individual g modes. The review ends by concluding
that, at the time of writing, there is indeed a consensus amongst the authors
that there is currently no undisputed detection of solar g modes.Comment: 71 pages, 18 figures, accepted by Astronomy and Astrophysics Revie
Encoding optical control in LCK kinase to quantitatively investigate its activity in live cells.
LCK is a tyrosine kinase that is essential for initiating T-cell antigen receptor (TCR) signaling. A complete understanding of LCK function is constrained by a paucity of methods to quantitatively study its function within live cells. To address this limitation, we generated LCK*, in which a key active-site lysine is replaced by a photocaged equivalent, using genetic code expansion. This strategy enabled fine temporal and spatial control over kinase activity, thus allowing us to quantify phosphorylation kinetics in situ using biochemical and imaging approaches. We find that autophosphorylation of the LCK active-site loop is indispensable for its catalytic activity and that LCK can stimulate its own activation by adopting a more open conformation, which can be modulated by point mutations. We then show that CD4 and CD8, T-cell coreceptors, can enhance LCK activity, thereby helping to explain their effect in physiological TCR signaling. Our approach also provides general insights into SRC-family kinase dynamics
Determinants of Leukocyte Margination in Rectangular Microchannels
Microfabrication of polydimethylsiloxane (PDMS) devices has provided a new set of tools for studying fluid dynamics of blood at the scale of real microvessels. However, we are only starting to understand the power and limitations of this technology. To determine the applicability of PDMS microchannels for blood flow analysis, we studied white blood cell (WBC) margination in channels of various geometries and blood compositions. We found that WBCs prefer to marginate downstream of sudden expansions, and that red blood cell (RBC) aggregation facilitates the process. In contrast to tubes, WBC margination was restricted to the sidewalls in our low aspect ratio, pseudo-2D rectangular channels and consequently, margination efficiencies of more than 95% were achieved in a variety of channel geometries. In these pseudo-2D channels blood rheology and cell integrity were preserved over a range of flow rates, with the upper range limited by the shear in the vertical direction. We conclude that, with certain limitations, rectangular PDMS microfluidic channels are useful tools for quantitative studies of blood rheology
Dynamism in the solar core
Recent results of a mixed shell model heated asymmetrically by transient
increases in nuclear burning indicate the transient generation of small hot
spots inside the Sun somewhere between 0.1 and 0.2 solar radii. These hot
bubbles are followed by a nonlinear differential equation system with finite
amplitude non-homologous perturbations which is solved in a solar model. Our
results show the possibility of a direct connection between the dynamic
phenomena of the solar core and the atmospheric activity. Namely, an initial
heating about DQ_0 ~ 10^{31}-10^{37} ergs can be enough for a bubble to reach
the outer convective zone. Our calculations show that a hot bubble can arrive
into subphotospheric regions with DQ_final ~ 10^{28} - 10^{34} ergs with a high
speed, up to 10 km s-1, approaching the local sound speed. We point out that
the developing sonic boom transforms the shock front into accelerated particle
beam injected upwards into the top of loop carried out by the hot bubble above
its forefront traveling from the solar interior. As a result, a new perspective
arises to explain flare energetics. We show that the particle beams generated
by energetic deep-origin hot bubbles in the subphotospheric layers have masses,
energies, and chemical compositions in the observed range of solar
chromospheric and coronal flares. It is shown how the emergence of a hot bubble
into subphotospheric regions offers a natural mechanism that can generate both
the eruption leading to the flare and the observed coronal magnetic topology
for reconnection. We show a list of long-standing problems of solar physics
that our model explains. We present some predictions for observations, some of
which are planned to be realized in the near future.Comment: 44 pages, 20 figure