1,710 research outputs found
Bench-to-bedside review: Latest results in hemorrhagic shock
Hemorrhagic shock is a leading cause of death in trauma patients worldwide. Bleeding control, maintenance of tissue oxygenation with fluid resuscitation, coagulation support, and maintenance of normothermia remain mainstays of therapy for patients with hemorrhagic shock. Although now widely practised as standard in the USA and Europe, shock resuscitation strategies involving blood replacement and fluid volume loading to regain tissue perfusion and oxygenation vary between trauma centers; the primary cause of this is the scarcity of published evidence and lack of randomized controlled clinical trials. Despite enormous efforts to improve outcomes after severe hemorrhage, novel strategies based on experimental data have not resulted in profound changes in treatment philosophy. Recent clinical and experimental studies indicated the important influences of sex and genetics on pathophysiological mechanisms after hemorrhage. Those findings might provide one explanation why several promising experimental approaches have failed in the clinical arena. In this respect, more clinically relevant animal models should be used to investigate pathophysiology and novel treatment approaches. This review points out new therapeutic strategies, namely immunomodulation, cardiovascular maintenance, small volume resuscitation, and so on, that have been introduced in clinics or are in the process of being transferred from bench to bedside. Control of hemorrhage in the earliest phases of care, recognition and monitoring of individual risk factors, and therapeutic modulation of the inflammatory immune response will probably constitute the next generation of therapy in hemorrhagic shock. Further randomized controlled multicenter clinical trials are needed that utilize standardized criteria for enrolling patients, but existing ethical requirements must be maintained
Activated partial thromboplastin time waveform analysis as specific sepsis marker in cardiopulmonary bypass surgery
Throughout the last years, several new diagnostic biomarkers have been introduced into clinical routine to identify a systemic inflammatory response syndrome (SIRS) or a septic state and to discriminate between these two entities. According to studies in selected patients, measurement of these biomarkers may be advantageous under certain clinical conditions. On an individual basis, however, these sepsis markers usually lack an adequate negative or positive predictive power. Therefore, physicians in charge still have to rely on a combination of personal experience and results from clinical or laboratory tests when deciding on a patient's therapy. For surgical patients, a key problem consists of the time delay which is associated with the diagnosis of serious postoperative infections and which may negatively affect outcome. It is in this context where the activated partial thromboplastin time waveform analysis may represent a promising new method to discriminate between SIRS and sepsis, thereby shortening the time to therapy. Nevertheless, studies involving large patient populations will be necessary to prove the efficacy of this new diagnostic concept either as a single tool or in combination with the measurement of other biomarkers
Non-contrast renal magnetic resonance imaging to assess perfusion and corticomedullary differentiation in health and chronic kidney disease
AIMS
Arterial spin labelling (ASL) MRI measures perfusion without administration of contrast agent. While ASL has been validated in animals and healthy volunteers (HVs), application to chronic kidney disease (CKD) has been limited. We investigated the utility of ASL MRI in patients with CKD.
METHODS
We studied renal perfusion in 24 HVs and 17 patients with CKD (age 22-77 years, 40% male) using ASL MRI at 3.0T. Kidney function was determined using estimated glomerular filtration rate (eGFR). T1 relaxation time was measured using modified look-locker inversion and xFB02;ow-sensitive alternating inversion recovery true-fast imaging and steady precession was performed to measure cortical and whole kidney perfusion.
RESULTS
T1 was higher in CKD within cortex and whole kidney, and there was association between T1 time and eGFR. No association was seen between kidney size and volume and either T1, or ASL perfusion. Perfusion was lower in CKD in cortex (136 ± 37 vs. 279 ± 69 ml/min/100 g; p < 0.001) and whole kidney (146 ± 24 vs. 221 ± 38 ml/min/100 g; p < 0.001). There was significant, negative, association between T1 longitudinal relaxation time and ASL perfusion in both the cortex (r = -0.75, p < 0.001) and whole kidney (r = -0.50, p < 0.001). There was correlation between eGFR and both cortical (r = 0.73, p < 0.01) and whole kidney (r = 0.69, p < 0.01) perfusion.
CONCLUSIONS
Significant differences in renal structure and function were demonstrated using ASL MRI. T1 may be representative of structural changes associated with CKD; however, further investigation is required into the pathological correlates of reduced ASL perfusion and increased T1 time in CKD
The potential role of T-cells and their interaction with antigen-presenting cells in mediating immunosuppression following trauma-hemorrhage
Objective: Trauma-hemorrhage results in depressed immune responses of antigen-presenting cells (APCs) and T-cells. Recent studies suggest a key role of depressed T-cell derived interferon (IFN)-g in this complex immune cell interaction. The aim of this study was to elucidate further the underlying mechanisms responsible for dysfunctional T-cells and their interaction with APCs following trauma-hemorrhage.
Design: Adult C3H/HeN male mice were subjected to trauma-hemorrhage (3-cm midline laparotomy) followed by hemorrhage (blood pressure of 35�5mmHg for 90 min and resuscitation) or sham operation. At 24 h thereafter, spleens were harvested and T-cells (by Microbeads) and APCs (via adherence) were Isolated. Co-cultures of T-cells and APCs were established for 48 h and stimulated with concanavalin A and lipopolysaccharide. T-Cell specific cytokines known to affect APC function (i.e. interleukin(IL)-2, IL-4 and granulocyte-macrophage colony-stimulating factor (GM-CSF)) were measured in culture supernatants by Multiplex assay. The expression of MHC class II as well as co-stimulatory surface molecules on T-cells and APCs was determined by flow cytometry.
Results: The release of IL-4 and GM-CSF by T-cells was suppressed following trauma-hemorrhage, irrespective of whether sham or trauma-hemorrhage APCs were present. Antigen-presenting cells from animals subjected to trauma-hemorrhage did not affect T-cell derived cytokine release by sham T-cells. In contrast, T-cells from traumahemorrhage animals depressed MHC class II expression of CD11c(þ) cells, irrespective of whether APCs underwent sham or trauma-hemorrhage procedure. Surprisingly, co-stimulatory molecules on APCs (CD80, CD86) were not affected by trauma-hemorrhage.
Conclusions: These results suggest that beside IFN-g other T-cell derived cytokines contribute to immunosuppression following trauma-hemorrhage causing diminished MHC II expression on APCs. Thus, T-cells appear to play an important role in this interaction at the time-point examined. Therapeutic approaches should aim at maintenance of T-cell function and their interaction with APCs to prevent extended immunosuppression following trauma-hemorrhage
Loops under Strategies ... Continued
While there are many approaches for automatically proving termination of term
rewrite systems, up to now there exist only few techniques to disprove their
termination automatically. Almost all of these techniques try to find loops,
where the existence of a loop implies non-termination of the rewrite system.
However, most programming languages use specific evaluation strategies, whereas
loop detection techniques usually do not take strategies into account. So even
if a rewrite system has a loop, it may still be terminating under certain
strategies.
Therefore, our goal is to develop decision procedures which can determine
whether a given loop is also a loop under the respective evaluation strategy.
In earlier work, such procedures were presented for the strategies of
innermost, outermost, and context-sensitive evaluation. In the current paper,
we build upon this work and develop such decision procedures for important
strategies like leftmost-innermost, leftmost-outermost,
(max-)parallel-innermost, (max-)parallel-outermost, and forbidden patterns
(which generalize innermost, outermost, and context-sensitive strategies). In
this way, we obtain the first approach to disprove termination under these
strategies automatically.Comment: In Proceedings IWS 2010, arXiv:1012.533
From 3D hydrodynamic simulations of common-envelope interaction to gravitational-wave mergers
Modeling the evolution of progenitors of gravitational-wave merger events in
binary stars faces two major uncertainties: the common-envelope phase and
supernova kicks. These two processes are critical for the final orbital
configuration of double compact-object systems with neutron stars and black
holes. Predictive one-dimensional models of common-envelope interaction are
lacking and multidimensional simulations are challenged by the vast range of
relevant spatial and temporal scales. Here, we present three-dimensional
hydrodynamic simulations of the common-envelope interaction of an initially
red supergiant primary star with a black-hole and a
neutron-star companion. We show that the high-mass regime is accessible to full
ab-initio simulations. Nearly complete envelope ejection is reached assuming
that all recombination energy still available at the end of our simulation
continues to help unbinding the envelope. In contrast to previous assumptions,
we find that the dynamical plunge-in of both companions terminates at orbital
separations too wide for gravitational waves to merge the systems in a Hubble
time. We discuss the further evolution of the system based on analytical
estimates. A subsequent mass-transfer episode from the remaining
core of the supergiant to the compact companion does not shrink the orbit
sufficiently either. A neutron-star--neutron-star and neutron-star--black-hole
merger is still expected for a fraction of the systems if the supernova kick
aligns favorably with the orbital motion. For double neutron star
(neutron-star--black-hole) systems we estimate mergers in about ()
of cases while about () of binaries are disrupted, i.e.,
supernova kicks actually enable gravitational-wave mergers in our cases;
however, we expect a reduction in predicted gravitational-wave merger events.
(abbr.)Comment: 16 pages, 11 figures, accepted by A&
Higher Daily Air Temperature Is Associated with Shorter Leukocyte Telomere Length
[Image: see text] Higher air temperature is associated with increased age-related morbidity and mortality. To date, short-term effects of air temperature on leukocyte telomere length have not been investigated in an adult population. We aimed to examine the short-term associations between air temperature and leukocyte telomere length in an adult population-based setting, including two independent cohorts. This population-based study involved 5864 participants from the KORA F3 (2004–2005) and F4 (2006–2008) cohort studies conducted in Augsburg, Germany. Leukocyte telomere length was assessed by a quantitative PCR-based method. We estimated air temperature at each participant′s residential address through a highly resolved spatiotemporal model. We conducted cohort-specific generalized additive models to explore the short-term effects of air temperature on leukocyte telomere length at lags 0–1, 2–6, 0–6, and 0–13 days separately and pooled the estimates by fixed-effects meta-analysis. Our study found that between individuals, an interquartile range (IQR) increase in daily air temperature was associated with shorter leukocyte telomere length at lags 0–1, 2–6, 0–6, and 0–13 days (%change: −2.96 [−4.46; −1.43], −2.79 [−4.49; −1.07], −4.18 [−6.08; −2.25], and −6.69 [−9.04; −4.27], respectively). This meta-analysis of two cohort studies showed that between individuals, higher daily air temperature was associated with shorter leukocyte telomere length
Field-free deterministic ultra fast creation of skyrmions by spin orbit torques
Magnetic skyrmions are currently the most promising option to realize
current-driven magnetic shift registers. A variety of concepts to create
skyrmions were proposed and demonstrated. However, none of the reported
experiments show controlled creation of single skyrmions using integrated
designs. Here, we demonstrate that skyrmions can be generated deterministically
on subnanosecond timescales in magnetic racetracks at artificial or natural
defects using spin orbit torque (SOT) pulses. The mechanism is largely similar
to SOT-induced switching of uniformly magnetized elements, but due to the
effect of the Dzyaloshinskii-Moriya interaction (DMI), external fields are not
required. Our observations provide a simple and reliable means for skyrmion
writing that can be readily integrated into racetrack devices
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