Predicting in-hospital mortality of patients receiving cardiopulmonary resuscitation: unit-weighted MultiODA for binary data

Widely used, linear classification functions may be derived on the basis of several different statistical paradigms. Since, regardless of choice, analysis generally yields an equation with unwieldy intercept and attribute coefficients, researchers often construct simpler scoring schemes based on unit weights. Accordingly, for applications involving entirely binary data, we discuss a simple procedure for obtaining unit-weighted (that is, we restrict attribute coefficients to the values of 0, 1 or -1) MultiODA functions that explicitly maximize classification accuracy in the training sample. We illustrate this with an application involving prediction of in-hospital mortality of patients receiving cardiopulmonary resuscitation. In training analysis of 88 patients, unit-weighted MultiODA outperformed prior scoring schemes and logistic regression analysis. Unit-weighted MultiODA also yielded superior hold-out (cross-generalizability) validity for an independent sample of 26 patients.     

Fluorescence activated cell sorting: a reliable method in tissue engineering of a bioprosthetic heart valve

BACKGROUND: Techniques of tissue engineering are used to seed human autologous cells in vitro on degradable mesh to create new functional tissue like a bioprosthetic heart valve. A precondition is subsequent seeding of native-valve-analogous pure endothelial and myofibroblast cell lines. The aim of this study is to find a safe method of isolating viable cell lines out of tissues from the operating room. METHODS: Mixed cells from ascending aorta obtained from the operating room were incubated with an endothelial-specific fluorescent marker. The labeled cells were activated and sorted by flow cytometry. Isolated cell lines were cultured and thereafter square sheets of polymeric scaffold were seeded with myofibroblasts, followed by endothelial cells. The created tissue was stained with hematoxylin and eosin, van Gieson stain, and stains for factor VIII and CD34. RESULTS: Control culture samples (n = 25) revealed vital uncontaminated endothelial and myofibroblast cell lines. Microscopy of the seeded meshes (n = 16) demonstrated a tissue-like structure. Van Gieson stain showed production of collagen. Endothelial cells formed a superficial monolayer, demonstrated by factor VIII and CD34; no invasive formation of capillaries was detectable. CONCLUSIONS: These results demonstrate that fluorescence activated cell sorting is a reliable and safe method to gain pure vital autologous cell lines out of human mixed cells for subsequent seeding on degradable mesh and that those cells are active to form new tissue.     

60K gelatinase involved in mammary gland involution is regulated by beta-oestradiol

Imperfect reference standards (alloyed standards) often hinder evaluation of new diagnostic tests. Discrepant analysis, a two-stage modification of the standard evaluation of diagnostic tests, has been used to circumvent this problem. In discrepant analysis, additional testing is performed to resolve discrepant results of the new diagnostic test and the alloyed standard. This article demonstrates algebraically that sensitivity and specificity will be overestimated by discrepant analysis, even when a perfect gold standard is used to resolve the discrepant results. The magnitude of the bias depends on the true sensitivity and specificity of the new test and initial alloyed standard, the prevalence of disease in the study population, and the proportion of concordant errors between the two tests. The article also demonstrates substantial bias associated with the use of alloyed standard tests in both stages of discrepant analysis. This procedure should not be used routinely for evaluation of diagnostic tests.     

Linkage of chromosome 5q and 11q gene markers to asthma-associated quantitative traits in Australian children

Asthma is a genetically complex disease, and the investigation of putative linkages to candidate loci in independent populations is an important part of the gene discovery process. This study investigated the linkage of microsatellite markers in the 5q and 11q regions to asthma-associated quantitative traits in 121 Australian Caucasian nuclear families. The families were recruited on the basis of a child proband: a cohort of 95 randomly recruited families of unselected probands (n = 442 subjects) and a cohort of 26 families of probands selected on the basis of severe symptomatic asthma (n = 134 subjects). The quantitative traits assessed included serum levels of total IgE and specific IgE to house dust mite and mixed grass, blood eosinophil counts, and the dose-response slope (DRS) of FEV1 to histamine provocation. Multipoint linkage analysis using Haseman-Elston sib-pair methods provided evidence of significant linkage between the chromosome 5q markers and loge total serum IgE levels, specific serum IgE levels, and loge blood eosinophil counts. The chromosome 11q markers showed evidence of significant linkage to specific serum IgE levels. Neither region demonstrated significant linkage to the loge DRS to histamine. Phenotypes were residualized for age and sex. These data are consistent with the existence of loci regulating asthma-associated quantitative traits in both the 5q31-33 and 11q13 chromosomal regions.     

A 12-month prospective study of the relationship between stress fractures and bone turnover in athletes

Studies on 33 anesthetized white mice were used to determine the motor representation of facial muscles and limb muscles by an intracortical microstimulation method. Microstimulation produced predominantly ipsilateral movement responses of facial muscles and contralateral responses in fore- and hindlimb muscles. Low-threshold stimulation in the left and right hemispheres showed a clear asymmetry of the motor representation of the facial muscles. Movement responses of the hindlimbs were obtained on microstimulation of the frontal regions of the neocortex, demonstrating the existence of multiple motor representations of muscles in the neocortex.     

Selection dynamics in autocatalytic systems: templates replicating through binary ligation

The theory of autocatalytic binary ligation is reviewed within the context of a consistently applied Michaelis-Menten quasi-steady-state approximation to obtain explicit analytical results describing time-course data from experiments. A detailed protocol for the step-wise elucidation of a minimal set of experimental parameters is outlined. The kinetic equations are then generalized to cases of self- and cross-catalysis among an arbitrary number of different templates and applied to experiments involving just two templates. Depending on the values of various kinetic parameters such systems can display exclusionary Darwinian selection corresponding to an exponential growth law, selective coexistence or coexistence of all species characteristic of a parabolic growth law; the intermediate behaviour arises as a property of the full mechanism analysed here. Our results are applicable to the classical case of self-replicating nucleic acids and their analogues as well as to newly discovered self-replicating peptides.     

Isolated lung perfusion with melphalan and tumor necrosis factor for metastatic pulmonary adenocarcinoma

BACKGROUND: Isolated left lung perfusion with melphalan and human tumor necrosis factor-alpha for pulmonary metastatic adenocarcinoma in the WAG/Rij rat was studied. METHODS: Survival was determined for melphalan, human tumor necrosis-alpha. Lung, pulmonary effluent, and serum melphalan were analyzed by chromatography after isolated lung perfusion or intravenous injection. On day 0, rats were injected with 2.0 x 10(6) CC531S cells intravenously. On day 7, rats underwent sham thoracotomy, received melphalan intravenously, or underwent isolated left lung perfusion with saline, melphalan, tumor necrosis factor, and a combination of the latter two. On day 14, tumor nodules were counted. RESULTS: For the doses of 400 microg tumor necrosis factor, 1,000 microg tumor necrosis factor, or both melphalan and tumor necrosis factor (2 mg + 200 microg), survival rates after contralateral pneumonectomy were 33%, 17%, and 80%, respectively. Survival in all other groups was 100%. Left lung melphalan level was significantly higher after isolated lung perfusion compared to intravenous administration. Significantly fewer left lung nodules were found for 0.5 mg isolated lung perfusion with melphalan (28+/-17) compared to isolated administration (200+/-0) (p = 0.001), and for 1.0 mg intravenous lung perfusion with melphalan (16+/-10) compared to controls (171+/-65) (p = 0.00047). Tumor necrosis factor showed no significant effect. CONCLUSIONS: Isolated lung perfusion with melphalan is an effective treatment for pulmonary metastases from adenocarcinoma in the rat.     

Numerical calculation of energy deposition by high-energy electron beams: III-B. Improvements to the 6D phase space evolution model

The phase space evolution model of Huizenga and Storchi, Morawska-Kaczyńska and Huizenga and Janssen et al has been modified to (i) allow application on currently available computer equipment with limited memory (128 Megabytes) and (ii) allow 3D dose calculations based on 3D computer tomographic patient data. This is a further development aimed at the use of the phase space evolution model in radiotherapy electrons beam treatment planning. The first modification regards the application of depth evolution of the phase space state combined with an alternative method to transport back-scattered electrons. This depth evolution method requires of the order of 15 times less computer memory than the energy evolution method. Results of previous and new electron transport methods are compared and show that the new electron transport method for back-scattered electrons hardly affects the accuracy of the calculated dose distributions. The second modification regards the simulation of electron transport through tissues with varying densities by applying distributed electron transport through similarly composed media with a limited number of fixed densities. Results of non-distributed and distributed electron transport are compared and show that the distributed electron transport method hardly affects the accuracy of the calculated dose distributions. It is also shown that the results of the new dose distribution calculations are still in good agreement with and require significantly less computation time than results obtained with the EGS4 Monte Carlo method.     

Hypomagnesemia inhibits nitric oxide release from coronary endothelium: protective role of magnesium infusion after cardiac operations

BACKGROUND: Postoperative hypomagnesemia is common in patients who have undergone cardiac operations and is associated with clinically significant morbidity resulting from atrial and ventricular dysrhythmias. Magnesium supplementation may increase the cardiac index in the early postoperative period. METHODS: The action of the magnesium cation on coronary vascular reactivity was studied. Segments of canine epicardial coronary artery were suspended in organ chambers to measure isometric force (95% O2/5% CO2, 37 degrees C). RESULTS: In coronary segments constricted with prostaglandin F2alpha (2 x 10[-6] mol/L), acetylcholine and adenosine diphosphate (10[-9] to 10[-4] mol/L) induced vasodilation in arteries with endothelium (n=10, each group; p < 0.05). Acetylcholine-mediated vasodilation was blocked by NG-monomethyl-L-arginine (10[-4] mol/L) and NG-nitro-L-arginine (10[-4] mol/L), two inhibitors of nitric oxide synthesis from L-arginine (n=10, p < 0.05). The removal of magnesium from the organ chamber solution impaired vasodilation in response to acetylcholine and adenosine diphosphate. However, normal endothelium-dependent vasodilation could be restored by return of magnesium to the bathing solution. Vascular relaxation in response to bradykinin (10[-9] to 10[-6] mol/L), which was found to induce endothelium-dependent vasodilation independent of nitric oxide production, was unaffected by magnesium removal (n=10). CONCLUSIONS: Hypomagnesemia selectively impaired the release of nitric oxide from the coronary endothelium. Because nitric oxide is a potent endogenous nitro-vasodilator and inhibitor of platelet aggregation and adhesion, hypomagnesemia could promote vasoconstriction and coronary thrombosis in the early postoperative period.