Serum thyroid peroxidase autoantibodies, thyroid volume, and outcome in breast carcinoma

The prevalence of thyroid peroxidase autoantibodies (TPO.Ab) was assessed in patients with either breast carcinoma or benign breast disease, and its association with disease outcome in breast carcinoma was studied. TPO.Ab were detected by direct RIA in serum from 121/356 (34.0%) of patients with breast carcinoma, compared with 36/194 (18.5%) of controls (P < 0.001); and in 31/108 (28.7%) with benign breast disease, compared with 12/88 (13.6%) of controls (P < 0.05). Survival analysis in a group of 142 women with breast carcinoma demonstrated that TPO.Ab titres > or = 0.3 U/mL were associated with a significantly better disease-free [relative risk (RR) = 1.84, P < 0.05] and overall survival (RR = 3.46, P < 0.02), compared with those who were TPO.Ab-negative. Better outcome associated with higher TPO.Ab titres was confined to those who had thyroid volumes within the intermediate range (10.1-18.8 mL) and did not further enhance the good outcome recorded when volumes were < or = 10.0 mL or > 18.8 mL. Multivariate survival analysis showed that both TPO.Ab and thyroid volume were independently associated with prognosis in breast carcinoma and that RRs for disease-free survival were of a similar order of magnitude to well-established prognostic indices such as axillary nodal status or tumor size. These findings supply evidence that manifestations of thyroid autoimmunity are associated with a beneficial effect on disease outcome in breast carcinoma and provide the strongest evidence to date of a biological link between breast carcinoma and thyroid disease.     

Parametric methods in the analysis of survival data

Parametric methods have been used extensively to analyze survival data. The parametric distribution that has been most widely used in fitting survival data is the exponential. However, the exponential survival distribution does not generally provide a satisfactory fit to survival data. One reason is that the hazard rate in survival studies is not usually constant with respect to time. In roughly the last decade, other survival distributions have been used to fit to survival data. They include the Weibull, gamma, lognormal and extreme value distributions. These distributions allow more flexibility than the exponential because their associated hazard rates are not constant with respect to time.Methods are presented for estimating the parameters of the survival distributions mentioned above in the cases for which the data are uncensored and censored. Furthermore, survival may be correlated with some other variable or variables such as age, weight, or a diagnostic characteristic such as white blood count. To account for the relationship between survival and the variables related to survival, survival models have been developed which take into consideration these concomitant variables. Methodology is also presented for estimating parameters of survival models that include concomitant variables.Finally, methods are discussed concerning growth in survival. For example, a clinical trial may be conducted in stages; each stage representing a treatment regimen that is an improvement over previous stage treatments. Reliability growth models are discussed in order to assess survival at all stages of the clinical trial that have been conducted and predict survival probabilities at future stages.     

Reliability Efforts in Large European Programs for Military and Commercial Aircraft Development

Many large complex aerospace programs in Europe are carried out on an international basis, i.e., by multinational industrial consortia and based on multinational governmental support. The sophisticated program structures established for this reason create a new type of problem area which influences project performance and also extends on the reliability area. Whereas, generally, reliability is primarily directed towards overcoming technical risks by well-known engineering methods and control procedures, in multinational projects the aspect of overall risk management is becoming increasingly important and has to be adequately considered in the organizational structure. The above considerations are reflected in the reliability cooperation models of the Panavia 200 (MRCA) and the European Airbus A 300 Programs, which represent two of the largest current European multinational development programs. The experience gained through these programs can be applied to any other type of complex international development task. International cooperation in the reliability area can strongly increase the resources of technical information and know-how useable for the project. Although compromises between conflicting opinions and philosophies are unavoidable, reliability work may become more efficient overall because of more practical approaches.     

An Approach to the Minimization of Misclassification in the Repair of Equipment

A problem which can be quite costly to an agency involved with repairable equipment on a large scale is the misclassification which can arise when repair work is initiated. Often, a piece of equipment finds its way to the repair shop even though it has not experienced a failure. On the other hand, a failed component may not be repaired properly because the cause of failure is not properly diagnosed; thus a delay will occur in returning the component to service. A mathematical model is developed which accounts for the two misclassification possibilities and a procedure is given which minimizes the misclassification probabilities, contingent on a fixed amount of available capital for this purpose. The model is of the Markov type with the simplifying assumption of constant transition rates (over time) among the various states.     

Bayesian assessment of uncertainty in aerosol size distributions and index of refraction retrieved from multiwavelength lidar measurements

We investigate the assessment of uncertainty in the inference of aerosol size distributions from backscatter and extinction measurements that can be obtained from a modern elastic/Raman lidar system with a Nd:YAG laser transmitter. To calculate the uncertainty, an analytic formula for the correlated probability density function (PDF) describing the error for an optical coefficient ratio is derived based on a normally distributed fractional error in the optical coefficients. Assuming a monomodal lognormal particle size distribution of spherical, homogeneous particles with a known index of refraction, we compare the assessment of uncertainty using a more conventional forward Monte Carlo method with that obtained from a Bayesian posterior PDF assuming a uniform prior PDF and show that substantial differences between the two methods exist. In addition, we use the posterior PDF formalism, which was extended to include an unknown refractive index, to find credible sets for a variety of optical measurement scenarios. We find the uncertainty is greatly reduced with the addition of suitable extinction measurements in contrast to the inclusion of extra backscatter coefficients, which we show to have a minimal effect and strengthens similar observations based on numerical regularization methods.     

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometric analysis of cellular glycerophospholipids enabled by multiplexed solvent dependent analyte-matrix interactions

A matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) based approach was developed for the rapid analyses of cellular glycerophospholipids. Through multiplexed solvent-enabled optimization of analyte-matrix interactions during the crystallization process, over a 30-fold increase in S/N was achieved using 9-aminoacridine as the matrix. The linearity of response (r(2) = 0.99) and dynamic range of this method (over 2 orders of magnitude) were excellent. Moreover, through multiplexing ionization conditions by generating suites of different analyte-matrix interactions in the absence or presence of different alkali metal cations in the matrix, discrete lipid classes were highly and selectively ionized under different conditions resulting in the de facto resolution of lipid classes without chromatography. The resultant decreases in spectral complexity facilitated tandem mass spectrometric analysis through high energy fragmentation of lithiated molecular ions that typically resulted in informative fragment ions. Anionic phospholipids were also detected as singly negatively charged species that could be fragmented using MALDI tandem mass spectrometry leading to structural assignments. Collectively, these results identify a rapid, sensitive, and highly informative MALDI-TOF MS approach for analysis of cellular glycerophospholipids directly from extracts of mammalian tissues without the need for prior chromatographic separation.     

Chemical Defense in <Emphasis Type="Italic">Elodea nuttallii</Emphasis> Reduces Feeding and Growth of Aquatic Herbivorous Lepidoptera

The submersed macrophyte Elodea nuttallii (Hydrocharitaceae) is invasive in Europe and frequently found in aquatic plant communities. Many invertebrate herbivores, such as larvae of the generalist aquatic moth, Acentria ephemerella (Lepidoptera, Pyralidae), avoid feeding on E. nuttallii and preferably consume native species. First instar larvae exhibited a high mortality on E. nuttallii compared to the native macrophyte Potamogeton perfoliatus. Mortality of older larvae was also high when fed E. nuttallii exposed to high light intensities. Growth of older larvae was strongly reduced on E. nuttallii compared to pondweeds (Potamogeton lucens). Neither differences in nitrogen nor phosphorus content explained the different performance on these submerged macrophytes, but plants differed in their flavonoid content. To investigate whether plant-derived allelochemicals from E. nuttallii affect larval performance in the same way as live plants, we developed a functional bioassay, in which Acentria larvae were reared on artificial diets. We offered larvae Potamogeton leaf disks coated with crude Elodea extracts and partially purified flavonoids. Elodea extracts deterred larvae from feeding on otherwise preferred Potamogeton leaves, and yet, unknown compounds in the extracts reduced growth and survival of Acentria. The flavonoid fraction containing luteolin-7-O-diglucuronide, apigenin-7-O-diglucuronide, and chrysoeriol-7-O-diglucuronide strongly reduced feeding of larvae, but did not increase mortality. The concentrations of these compounds in our assays were 0.01–0.09% of plant dry mass, which is in the lower range of concentrations found in the field (0.02–1.2%). Chemical defense in E. nuttallii thus plays an ecologically relevant role in this aquatic plant–herbivore system.     

Spatiotemporal heterodyne detection

We describe a scheme in which a camera is turned into an efficient tunable frequency filter of a few-Hertz bandwidth in an off-axis, heterodyne optical mixing configuration, enabling one to perform parallel, high-resolution coherent spectral imaging. This approach is made possible through the combination of a spatial and temporal modulation of the signal to reject noise contributions. Experimental data obtained with dynamically scattered light by a suspension of particles in Brownian motion is interpreted.