Dynamic lactate indices as predictors of outcome in critically ill patients

INTRODUCTION: Dynamic changes in lactate concentrations in the critically ill may predict patient outcome more accurately than static indices. We aimed to compare the predictive value of dynamic indices of lactatemia in the first 24 hours of intensive care unit (ICU) admission with the value of more commonly used static indices. METHODS: This was a retrospective observational study of a prospectively obtained intensive care database of 5,041 consecutive critically ill patients from four Australian university hospitals. We assessed the relationship between dynamic lactate values collected in the first 24 hours of ICU admission and both ICU and hospital mortality. RESULTS: We obtained 36,673 lactate measurements in 5,041 patients in the first 24 hours of ICU admission. Both the time weighted average lactate (LACTW₂₄) and the change in lactate (LACΔ₂₄) over the first 24 hours were independently predictive of hospital mortality with both relationships appearing to be linear in nature. For every one unit increase in LACTW₂₄ and LACΔ₂₄ the risk of hospital death increased by 37% (OR 1.37, 1.29 to 1.45; P < 0.0001) and by 15% (OR 1.15, 1.10 to 1.20; P < 0.0001) respectively. Such dynamic indices, when combined with Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, improved overall outcome prediction (P < 0.0001) achieving almost 90% accuracy. When all lactate measures in the first 24 hours were considered, the combination of LACTW₂₄ and LACΔ₂₄ significantly outperformed (P < 0.0001) static indices of lactate concentration, such as admission lactate, maximum lactate and minimum lactate. CONCLUSIONS: In the first 24 hours following ICU admission, dynamic indices of hyperlactatemia have significant independent predictive value, improve the performance of illness severity score-based outcome predictions and are superior to simple static indices of lactate concentration

Relative hyperlactatemia and hospital mortality in critically ill patients: a retrospective multi-centre study

INTRODUCTION: Higher lactate concentrations within the normal reference range (relative hyperlactatemia) are not considered clinically significant. We tested the hypothesis that relative hyperlactatemia is independently associated with an increased risk of hospital death. METHODS: This observational study examined a prospectively obtained intensive care database of 7,155 consecutive critically ill patients admitted to the Intensive Care Units (ICUs) of four Australian university hospitals. We assessed the relationship between ICU admission lactate, maximal lactate and time-weighted lactate levels and hospital outcome in all patients and also in those patients whose lactate concentrations (admission n = 3,964, maximal n = 2,511, and time-weighted n = 4,584) were under 2 mmol.L-1 (i.e. relative hyperlactatemia). RESULTS: We obtained 172,723 lactate measurements. Higher admission and time-weightedlactate concentration within the reference range was independently associated with increased hospital mortality (admission odds ratio (OR) 2.1, 95% confidence interval (CI) 1.3 to 3.5, P = 0.01; time-weighted OR 3.7, 95% CI 1.9 to 7.00, P 0.75 mmol.L-1. Furthermore, in patients whose lactate ever exceeded 2 mmol.L-1, higher time-weighted lactate remained strongly associated with higher hospital mortality (OR 4.8, 95% CI 1.8 to 12.4, P 0.75 mmol.L-1 can be used by clinicians to identify patients at higher risk of death. The current reference range for lactate in the critically ill may need to be re-assessed

Network queueing systems

System sieciowy jest to system złożony z kilku jednocześnie działających stacji obsługi. Oprócz normalnych założeń przyjmujemy, że jednostka po zakończeniu obsługi w jednej stacji móże z pewnym prawdopodobieństwem przejść do innej stacji lub opuścić system; jednostka jak gdyby odbywa losowy spacer po stacjach. W niniejszej pracy przedstawione zostały systemy sieciowe z wejściem poissonowskim, o parametrze zależnym od aktualnego stanu systemu. Zdefiniowano proces opisujący pracę systemu, podano twierdzenie ergodyczne (konstrukcja procesu i idea twierdzenia oparte zostały na pracy I. Kowalenki (1964), dotyczącej procesów przedziałami liniowych) oraz wyprowadzono wzory na rozkłady stanu równowagi dla pewnej szerokiej klasy systemów.From the introduction: "We represent network systems with a Poisson arrival stream whose parameter depends on the actual state of the system. We define a process which describes the operation of a system and present an ergodic theorem (the construction of the process and the concept of the theorem are based on a paper by I. N. Kovalenko [Izv. Akad. Nauk SSSR Tekhn. Kibernet. 1964, no. 6, 3–9; ibid. 1965, no. 1, 14–20; ibid. 1965, no. 3, 3–11; MR0204195] concerning piecewise-linear processes). We give examples of distribution of an equilibrium state for a broad class of systems.'' MR070781

SAXS studies of X-ray induced disulfide bond damage: Engineering high-resolution insight from a low-resolution technique.

A significant problem in biological X-ray crystallography is the radiation chemistry caused by the incident X-ray beam. This produces both global and site-specific damage. Site specific damage can misdirect the biological interpretation of the structural models produced. Cryo-cooling crystals has been successful in mitigating damage but not eliminating it altogether; however, cryo-cooling can be difficult in some cases and has also been shown to limit functionally relevant protein conformations. The doses used for X-ray crystallography are typically in the kilo-gray to mega-gray range. While disulfide bonds are among the most significantly affected species in proteins in the crystalline state at both cryogenic and higher temperatures, there is limited information on their response to low X-ray doses in solution, the details of which might inform biomedical applications of X-rays. In this work we engineered a protein that dimerizes through a susceptible disulfide bond to relate the radiation damage processes seen in cryo-cooled crystals to those closer to physiologic conditions. This approach enables a low-resolution technique, small angle X-ray scattering (SAXS), to detect and monitor a residue specific process. A dose dependent fragmentation of the engineered protein was seen that can be explained by a dimer to monomer transition through disulfide bond cleavage. This supports the crystallographically derived mechanism and demonstrates that results obtained crystallographically can be usefully extrapolated to physiologic conditions. Fragmentation was influenced by pH and the conformation of the dimer, providing information on mechanism and pointing to future routes for investigation and potential mitigation. The novel engineered protein approach to generate a large-scale change through a site-specific interaction represents a promising tool for advancing radiation damage studies under solution conditions

Amplitude and frequency variability of the pulsating DB white dwarf stars KUV 05134+2605 and PG 1654+160 observed with the Whole Earth Telescope

We have acquired new time series photometry of the two pulsating DB white dwarf stars KUV 05134+2605 and PG 1654+160 with the Whole Earth Telescope. Additional single-site photometry is also presented. We use all these data plus all available archival measurements to study the temporal behaviour of the pulsational amplitudes and frequencies of these stars for the first time. We demonstrate that both KUV 05134+2605 and PG 1654+160 pulsate in many modes, the amplitudes of which are variable in time; some frequency variability of PG 1654+160 is also indicated. Beating of multiple pulsation modes cannot explain our observations; the amplitude variability must therefore be intrinsic. We cannot find stable modes to be used for determinations of the evolutionary period changes of the stars. Some of the modes of PG 1654+160 appear at the same periods whenever detected. The mean spacing of these periods (≈40 s) suggests that they are probably caused by non-radial gravity-mode pulsations of spherical degree l = 1. If so, PG 1654+160 has a mass around 0.6Mʘ. The time-scales of the amplitude variability of both stars (down to two weeks) are consistent with theoretical predictions of resonant mode coupling, a conclusion which might however be affected by the temporal distribution of our data