Harry L. Hurd

Blood transfusion is an independent predictor of increased mortality in nonoperatively managed blunt hepatic and splenic injuries.

BACKGROUND Management strategies for blunt solid viscus injuries often include blood transfusion. However, transfusion has previously been identified as an independent predictor of mortality in unselected trauma admissions. We hypothesized that transfusion would adversely affect mortality and outcome in patients presenting with blunt hepatic and splenic injuries after controlling for injury severity and degree of shock. METHODS We retrospectively reviewed records from all adults with blunt hepatic and/or splenic injuries admitted to a Level I trauma center over a 4-year period. Demographics, physiologic variables, injury severity, and amount of blood transfused were analyzed. Univariate and multivariate analysis with logistic and linear regression were used to identify predictors of mortality and outcome. RESULTS One hundred forty-three (45%) of 316 patients presenting with blunt hepatic and/or splenic injuries received blood transfusion within the first 24 hours. Two hundred thirty patients (72.8%) were selected for nonoperative management, of whom 75 (33%) required transfusion in the first 24 hours. Transfusion was an independent predictor of mortality in all patients (odds ratio [OR], 4.75; 95% confidence interval [CI], 1.37-16.4; p = 0.014) and in those managed nonoperatively (OR, 8.45; 95% CI, 1.95-36.53; p = 0.0043) after controlling for indices of shock and injury severity. The risk of death increased with each unit of packed red blood cells transfused (OR per unit, 1.16; 95% CI, 1.10-1.24; p < 0.0001). Blood transfusion was also an independent predictor of increased hospital length of stay (coefficient, 5.45; 95% CI, 1.64-9.25; p = 0.005). CONCLUSION Blood transfusion is a strong independent predictor of mortality and hospital length of stay in patients with blunt liver and spleen injuries after controlling for indices of shock and injury severity. Transfusion-associated mortality risk was highest in the subset of patients managed nonoperatively. Prospective examination of transfusion practices in treatment algorithms of blunt hepatic and splenic injuries is warranted.

Nonparametric time series analysis for periodically correlated processes

Correlation functions of continuous-time periodically correlated processes can be represented by a Fourier series with coefficient functions. It is shown that the usual estimator for stationary covariances, formed from a single sample path of the process, can be simply modified to provide a consistent (in quadratic mean) estimator for any of the coefficient functions resulting from the aforementioned representation. It is shown that, if the process is Gaussian and B/sub k/( tau ) is a Fourier integral with respect to a density function g/sub k/( lambda ), a two-dimensional periodogram, formed from a single sample function, can be smoothed along a line of constant difference frequency to provide a consistent estimator for g/sub k/( lambda ). This natural extension of the well-known procedure for stationary processes provides a method for nonparametric spectral analysis of periodically correlated processes. >

Correlation theory of almost periodically correlated processes

A second-order stochastic process X is called almost periodically correlated (PC) in the sense of Gladyshev if its mean function m(t) and covariance R(t + [tau], t) are uniformly continuous with respect to t, [tau] and are almosst periodic functions of t for every [tau]. We show that the mean uniformly almost periodic processes discussed by Kawata are also almost PC in the sense of Gladyshev. If X is almost PC, then for each fixed [tau] the function R(t + [tau], t) has the Fourier series and exists for every [lambda] and [tau], independently of the constant c. Assuming only that a([lambda], [tau]) exists in this sense for every [lambda] and [tau], we show a([lambda], [tau]) is a Fourier transform a([lambda] [tau]) = [integral operator]Rexp(iy[tau]) rlambda;(dy) if and only if a(0, [tau]) is continuous at [tau] = 0; under this same condition, the set [Lambda] = {[lambda]: a([lambda], [tau]) [not equal to] 0 for some [tau]} is countable. We show that a strongly harmonizable process is almost PC if and only if its spectral measure is concentrated on a countable set of diagonal lines S[lambda] = {([gamma]1, [gamma]2): [gamma]2 = [gamma]1 - [lambda]}; further, one may identify the spectral measure on the k th line with the measure r[lambda]k appearing in (iii). Finally we observe that almost PC processes are asymptotically stationary and give conditions under which strongly harmonizable almost PC processes may be made stationary by an independent random time shift.

Azithromycin treatment alters gene expression in inflammatory, lipid metabolism, and cell cycle pathways in well-differentiated human airway epithelia.

Prolonged macrolide antibiotic therapy at low doses improves clinical outcome in patients affected with diffuse panbronchiolitis and cystic fibrosis. Consensus is building that the therapeutic effects are due to anti-inflammatory, rather than anti-microbial activities, but the mode of action is likely complex. To gain insights into how the macrolide azithromycin (AZT) modulates inflammatory responses in airways, well-differentiated primary cultures of human airway epithelia were exposed to AZT alone, an inflammatory stimulus consisting of soluble factors from cystic fibrosis airways, or AZT followed by the inflammatory stimulus. RNA microarrays were conducted to identify global and specific gene expression changes. Analysis of gene expression changes revealed that the AZT treatment alone altered the gene profile of the cells, primarily by significantly increasing the expression of lipid/cholesterol genes and decreasing the expression of cell cycle/mitosis genes. The increase in cholesterol biosynthetic genes was confirmed by increased filipin staining, an index of free cholesterol, after AZT treatment. AZT also affected genes with inflammatory annotations, but the effect was variable (both up- and down-regulation) and gene specific. AZT pretreatment prevented the up-regulation of some genes, such as MUC5AC and MMP9, triggered by the inflammatory stimulus, but the up-regulation of other inflammatory genes, e.g., cytokines and chemokines, such as interleukin-8, was not affected. On the other hand, HLA genes were increased by AZT. Notably, secreted IL-8 protein levels did not reflect mRNA levels, and were, in fact, higher after AZT pretreatment in cultures exposed to the inflammatory stimulus, suggesting that AZT can affect inflammatory pathways other than by altering gene expression. These findings suggest that the specific effects of AZT on inflamed and non-inflamed airway epithelia are likely relevant to its clinical activity, and their apparent complexity may help explain the diverse immunomodulatory roles of macrolides.

Climatological Time Series with Periodic Correlation

Abstract Many climatological time series display a periodic correlation structure. This paper examines three issues encountered when analyzing such time series: detection of periodic correlation, modeling periodic correlation, and trend estimation under periodic correlation. Time series containing monthly observations of stratospheric ozone concentrations, average temperatures, and carbon dioxide concentrations are tested for periodic correlation and analyzed further in the paper. A frequency domain test to detect periodic correlation is first reviewed. This test shows that the ozone and temperature series analyzed have a periodic autocorrelation structure; the carbon dioxide series shows periodicities only through its seasonal mean. Next, PARMA models (autoregressive moving average models with periodically varying parameters) are introduced as models for periodically correlated series. Algorithms for fitting a parsimonious PARMA model to a periodically correlated series are presented. Finally, trend esti...

Representation of strongly harmonizable periodically correlated processes and their covariances

This paper addresses the representation of continuous-time strongly harmonizable periodically correlated processes and their covariance functions. We show that the support of the 2-dimensional spectral measure is constrained to a set of equally spaced lines parallel to the diagonal. Our main result is that any harmonizable periodically correlated process may be represented in quadratic mean as a Fourier series whose coefficients are a family of unique jointly wide sense stationary processes; the corresponding family of cross spectral distribution functions may be simply identified from the two-dimensional spectral measure resulting from the assumption of strong harmonizability.

Effect of ventilatory rate on airway cytokine levels and lung injury

BACKGROUND Controversy exists regarding the effect of large-volume mechanical ventilation (MV), as a sole stimulus, on the pulmonary cytokine milieu. We used a well described experimental model of ventilator-induced lung injury (VILI) to examine the impact of large volume ventilation on pulmonary cytokines in vivo and to study the effect of respiratory rate (RR) variation on these levels. MATERIALS AND METHODS Sixty rats (410 +/- 47 g) were randomized to: 1) non ventilated control; 2) V(t) = 40 ml/kg, RR = 40 bpm; 3) V(t) = 40 ml/kg, RR = 20 bpm; 4) V(t) = 7 ml/kg, RR = 40 bpm; or 5) V(t) = 7 ml/kg, RR = 20 bpm. After 1 h of MV, bronchoalveolar lavage (BAL) and serum were collected. BAL was analyzed for urea, protein, lactate dehydrogenase (LDH), tumor necrosis factor (TNF)alpha and interleukin (IL)-6. Epithelial lining fluid volume (ELF) was calculated. RESULTS Regardless of RR, animals ventilated at 7 ml/kg did not differ from control in any outcome. In contrast, MV at 40 ml/kg V(t) with 40 bpm produced lung injury characterized by significant elevations of BAL TNFalpha, IL-6, protein, ELF, and LDH. At 40 ml/kg V(t), RR reduction (20 bpm) significantly reduced all injury measures. CONCLUSION This study confirms that large-volume MV, as a sole stimulus, produces lung injury and cytokine release. Whereas increasing RR at low V(t) has little impact on injury parameters, RR reduction under VILI-promoting conditions significantly limits lung injury.

Stationarizing Properties of Random Shifts

Let

Estimation of the Fourier coefficient functions and their spectral densities for \gf-mixing almost periodically correlated processes

\{ X(t,\omega ), - \infty < t < \infty \}

On AR(1) models with periodic and almost periodic coefficients

be a real jointly measurable stochastic process and