The algebraic equality of two asymptotic tests for the hypothesis that a normal distribution has a specified correlation matrix

It is proved the algebraic equality between Jennrich's (1970) asymptotic$X^2$ test for equality of correlation matrices, and a Wald test statisticderived from Neudecker and Wesselman's (1990) expression of theasymptoticvariance matrix of the sample correlation matrix.

Variable Kernel estimates: On the impossibility of tuning the parameters

For the standard kernel density estimate, it is known that one can tune the bandwidth such that the expected L1 error is within a constant factor of the optimal L1 error (obtained when one is allowed to choose the bandwidth with knowledge of the density). In this paper, we pose the same problem for variable bandwidth kernel estimates where the bandwidths are allowed to depend upon the location. We show in particular that for positive kernels on the real line, for any data-based bandwidth, there exists a densityfor which the ratio of expected L1 error over optimal L1 error tends to infinity. Thus, the problem of tuning the variable bandwidth in an optimal manner is ``too hard''. Moreover, from the class of counterexamples exhibited in the paper, it appears thatplacing conditions on the densities (monotonicity, convexity, smoothness) does not help.

Sitobion graminis Takahashi, 1950 (Hemiptera, Aphididae): first record in Brazil, biological and morphometric parameters

The species Sitobion graminis Takahashi, 1950 (Hemiptera, Aphididae) was first detected in Brazil in 1998, in Curitiba, Paraná state, associated with the grass species Erianthus sp., Calamagrotis sp. and Paspalum urvilei. Both the field-collected and laboratory-reared specimens presented a noticeable intrapopulational variation in body and appendix length and in dorso-abdominal sclerotization. This species has been recorded in Malaysia, New Guinea, India, Philippines and Africa, where it colonizes several species of Poaceae. S. graminis differs from other Sitobion species from Brazil associated with grasses, as it presents black cauda and siphunculi and exhibits a constriction in the base of the last rostral segment. Biological data were obtained in the laboratory by rearing newborn nymphs on the inflorescence of the host plants. They passed through four nymphal instars. The mean duration of the nymphal stage was of 11.4 days, with a mortality ratio of 36.5%. The mean pre-larviposition period was of 1.8 days; mean longevity of the females was 25.2 days; and mean fecundity was 18.7 nymphs/female, ranging from 2 to 41 nymphs/female.

Functional avidity of tumor antigen-specific CTL recognition directly correlates with the stability of MHC/peptide multimer binding to TCR.

Avidity of Ag recognition by tumor-specific T cells is one of the main parameters that determines the potency of a tumor rejection Ag. In this study we show that the relative efficiency of staining of tumor Ag-specific T lymphocytes with the corresponding fluorescent MHC class I/peptide multimeric complexes can considerably vary with staining conditions and does not necessarily correlate with avidity of Ag recognition. Instead, we found a clear correlation between avidity of Ag recognition and the stability of MHC class I/peptide multimeric complexes interaction with TCR as measured in dissociation kinetic experiments. These findings are relevant for both identification and isolation of tumor-reactive CTL.

Illusory correlation in the remuneration of chief executive officers: It pays to play golf, and well

Illusory correlation refers to the use of information in decisions that is uncorrelated with the relevantcriterion. We document illusory correlation in CEO compensation decisions by demonstrating thatinformation, that is uncorrelated with corporate performance, is related to CEO compensation. We usepublicly available data from the USA for the years 1998, 2000, 2002, and 2004 to examine the relationsbetween golf handicaps of CEOs and corporate performance, on the one hand, and CEO compensationand golf handicaps, on the other hand. Although we find no relation between handicap and corporateperformance, we do find a relation between handicap and CEO compensation. In short, golfers earnmore than non-golfers and pay increases with golfing ability. We relate these findings to the difficultiesof judging compensation for CEOs. To overcome this and possibly other illusory correlations inthese kinds of decisions, we recommend the use of explicit, mechanical decision rules.

Physical considerations on discrepancies in target volume delineation.

BACKGROUND AND PURPOSE: To compare the delineations and interpretations of target volumes by physicians in different radio-oncology centers. MATERIALS AND METHODS: Eleven Swiss radio-oncology centers delineated volumes according to ICRU 50 recommendations for one prostate and one head and neck case. In order to evaluate the consistency of the volume delineations, the following parameters were determined: 1) the target volumes (GTV, CTV and manually expanded PTV) and their extensions in the three main axes and 2) the correlation of the volume delineated by each pair of centers using the ratio of the intersection to the union (called proximity index). RESULTS: The delineated prostate volume was 105+/-55cm(3) for the CTV and 218+/-44cm(3) for the PTV. The delineated head and neck volume was 46+/-15cm(3) for the GTV, 327+/-154cm(3) for the CTV and 528+/-106cm(3) for the PTV. The mean proximity index for the prostate case was 0.50+/-0.13 for the CTV and 0.57+/-0.11 for the PTV. The proximity index for the head and neck case was 0.45+/-0.09 for the GTV, 0.42+/-0.13 for the CTV and 0.59+/-0.06 for the PTV. CONCLUSIONS: Large discrepancies between all the delineated target volumes were observed. There was an inverse relationship between the CTV volume and the margin between CTV and PTV, leading to less discrepancies in the PTV than is the CTV delineations. There was more spread in the sagittal and frontal planes due to CT pixel anisotropy, which suggests that radiation oncologists should delineate the target volumes not only in the transverse plane, but also in the sagittal and frontal planes to improve the delineation by allowing a consistency check.

Value of sTREM-1, procalcitonin and CRP as laboratory parameters for postmortem diagnosis of sepsis.

OBJECTIVES: Triggering receptor expressed on myeloid cells-1 (TREM-1) was reported to be up-regulated in various inflammatory diseases as well as in bacterial sepsis. Increased cell-surface TREM-1 expression was also shown to result in marked plasma elevation of the soluble form of this molecule (sTREM-1) in patients with bacterial infections. In this study, we investigated sTREM-1, procalcitonin and C-reactive protein in postmortem serum in a series of sepsis-related fatalities and control individuals who underwent medico-legal investigations. sTREM-1 was also measured in pericardial fluid and urine. METHODS: Two study groups were prospectively formed, a sepsis-related fatalities group and a control group. The sepsis-related fatalities group consisted of sixteen forensic autopsy cases. Eight of these had a documented clinical diagnosis of sepsis in vivo. The control group consisted of sixteen forensic autopsy cases with various causes of death. RESULTS: Postmortem serum sTREM-1 concentrations were higher in the sepsis group with a mean value of 173.6 pg/ml in septic cases and 79.2 pg/ml in control individuals. The cutoff value of 90 pg/ml provided the best sensitivity and specificity. Pericardial fluid sTREM-1 values were higher in the septic group, with a mean value of 296.7 pg/ml in septic cases and 100.9 pg/ml in control individuals. The cutoff value of 135 pg/ml provided the best sensitivity and specificity. Mean urine sTREM-1 concentration was 102.9 pg/ml in septic cases and 89.3 pg/ml in control individuals. CONCLUSIONS: Postmortem serum sTREM-1, individually considered, did not provide better sensitivity and specificity than procalcitonin in detecting sepsis. However, simultaneous assessment of procalcitonin and sTREM-1 in postmortem serum can be of help in clarifying contradictory postmortem findings. sTREM-1 determination in pericardial fluid can be an alternative to postmortem serum in those situations in which biochemical analyses are required and blood collected during autopsy proves insufficient.

Femoroacetabular impingement: normal values of the quantitative morphometric parameters in asymptomatic hips.

OBJECTIVE: To determine the means and the reference intervals of the quantitative morphometric parameters of femoroacetabular impingement (FAI) in normal hips with high-resolution computed tomography (CT). METHODS: We prospectively included 94 adult individuals who underwent CT for thoracic, abdominal or urologic pathologies. Patients with a clinical history of hip pathology and/or with osteoarthritis on CT were excluded. We calculated means and 95 % reference intervals for imaging signs of cam-type (alpha angle at 90° and 45° and femoral head-neck offset) and pincer-type impingement (acetabular version angle, lateral centre-edge angle and acetabular index). RESULTS: The 95 % reference interval limits were all far beyond the abnormal thresholds found in the literature for cam-type and to a lesser extent for pincer-type FAI. The upper limits of the reference intervals for the alpha angles (at 90°/45°) were 68°/83° (men) and 69°/84° (women), compared to thresholds from the literature (50°, 55° or 60°). Reference intervals were similar between genders for cam-type parameters, and slightly differed for pincer-type. CONCLUSION: The 95 % reference intervals of morphometric measurements of FAI in asymptomatic hips were beyond the abnormal thresholds, which was especially true for cam-type FAI. Our results suggest the need for redefining the current morphometric parameters used in the diagnosis of FAI. KEY POINTS: ? 95 % reference intervals limits of FAI morphotype were beyond currently defined thresholds. ? Reference intervals of pincer-type morphotype measurements were close to current definitions. ? Reference intervals of cam-type morphotype measurements were far beyond the current definitions. ? Current morphometric definitions of cam-type morphotype should be used with care.

On the performance of small-area estimators: Fixed vs. random area parameters

Most methods for small-area estimation are based on composite estimators derived from design- or model-based methods. A composite estimator is a linear combination of a direct and an indirect estimator with weights that usually depend on unknown parameters which need to be estimated. Although model-based small-area estimators are usually based on random-effects models, the assumption of fixed effects is at face value more appropriate.Model-based estimators are justified by the assumption of random (interchangeable) area effects; in practice, however, areas are not interchangeable. In the present paper we empirically assess the quality of several small-area estimators in the setting in which the area effects are treated as fixed. We consider two settings: one that draws samples from a theoretical population, and another that draws samples from an empirical population of a labor force register maintained by the National Institute of Social Security (NISS) of Catalonia. We distinguish two types of composite estimators: a) those that use weights that involve area specific estimates of bias and variance; and, b) those that use weights that involve a common variance and a common squared bias estimate for all the areas. We assess their precision and discuss alternatives to optimizing composite estimation in applications.

Generalized canonical correlation analysis of matrices with different row and column orders

A Method is offered that makes it possible to apply generalized canonicalcorrelations analysis (CANCOR) to two or more matrices of different row and column order. The new method optimizes the generalized canonical correlationanalysis objective by considering only the observed values. This is achieved byemploying selection matrices. We present and discuss fit measures to assessthe quality of the solutions. In a simulation study we assess the performance of our new method and compare it to an existing procedure called GENCOM,proposed by Green and Carroll. We find that our new method outperforms the GENCOM algorithm both with respect to model fit and recovery of the truestructure. Moreover, as our new method does not require any type of iteration itis easier to implement and requires less computation. We illustrate the methodby means of an example concerning the relative positions of the political parties inthe Netherlands based on provincial data.

Exact tests for correlation and for the slope in simple linear regressions without making assumptions

We present an exact test for whether two random variables that have known bounds on their support are negatively correlated. The alternative hypothesis is that they are not negatively correlated. No assumptions are made on the underlying distributions. We show by example that the Spearman rank correlation test as the competing exact test of correlation in nonparametric settings rests on an additional assumption on the data generating process without which it is not valid as a test for correlation.We then show how to test for the significance of the slope in a linear regression analysis that invovles a single independent variable and where outcomes of the dependent variable belong to a known bounded set.

Biological characteristics and parasitism capacity of Trichogramma pretiosum Riley (Hymenoptera, Trichogrammatidae) on eggs of Spodoptera frugiperda (J. E. Smith) (Lepidoptera, Noctuidae)

This study aimed at evaluating the biological characteristics and the capacity of parasitism of a Trichogramma pretiosum Riley, 1869 (Hymenoptera, Trichogrammatidae) strain (T. pretiosum RV) collected in Rio Verde County, State of Goiás, Brazil. The study was carried out on eggs of Spodoptera frugiperda (J. E. Smith, 1797) (Lepidoptera, Noctuidae) and conducted under controlled environmental conditions at different constant temperatures. The biological parameters determined were: developmental time (egg-adult; days); emergence (%); sex ratio; number of progeny/egg; number of generation/year; thermal constant (K); temperature threshold (Tb); daily number of parasitized eggs; cumulative parasitism (%); total number of eggs parasitized by T. pretiosum; and female longevity. To study the T. pretiosum parasitism capacity, 20 S. frugiperda eggs (< 24 h old) were placed into 8.0 cm x 2.0 cm glass vials containing one female (< 24 h old) each. Trials were carried out in a completely randomized experimental design, with 20 replications at each temperature. The environmental chambers (BOD type) were set at 18ºC, 20ºC, 22ºC, 25ºC, 28ºC and 32ºC ± 1ºC, 70 ±10% relative humidity, and 14/10 h (L:D) photoperiod. The eggs of S. frugiperda were replaced daily until parasitoid death. Results have shown an inverse correlation between developmental time and temperature, with statistically significant differences among means, except at 25ºC and 28ºC (10 days). Parasitoid emergence (%) was also influenced by temperature. The lowest percent emergence was observed at 32ºC, and the highest ones at 18ºC and 20ºC temperatures. The temperature did not affect T. pretiosum sex ratio and number of parasitoids per egg, thus allowing changes in the temperature to control insect mass production in the laboratory to meet the needs for field releases.

SwissParam: a fast force field generation tool for small organic molecules.

The drug discovery process has been deeply transformed recently by the use of computational ligand-based or structure-based methods, helping the lead compounds identification and optimization, and finally the delivery of new drug candidates more quickly and at lower cost. Structure-based computational methods for drug discovery mainly involve ligand-protein docking and rapid binding free energy estimation, both of which require force field parameterization for many drug candidates. Here, we present a fast force field generation tool, called SwissParam, able to generate, for arbitrary small organic molecule, topologies, and parameters based on the Merck molecular force field, but in a functional form that is compatible with the CHARMM force field. Output files can be used with CHARMM or GROMACS. The topologies and parameters generated by SwissParam are used by the docking software EADock2 and EADock DSS to describe the small molecules to be docked, whereas the protein is described by the CHARMM force field, and allow them to reach success rates ranging from 56 to 78%. We have also developed a rapid binding free energy estimation approach, using SwissParam for ligands and CHARMM22/27 for proteins, which requires only a short minimization to reproduce the experimental binding free energy of 214 ligand-protein complexes involving 62 different proteins, with a standard error of 2.0 kcal mol(-1), and a correlation coefficient of 0.74. Together, these results demonstrate the relevance of using SwissParam topologies and parameters to describe small organic molecules in computer-aided drug design applications, together with a CHARMM22/27 description of the target protein. SwissParam is available free of charge for academic users at www.swissparam.ch.

Expanding molecular modeling and design tools to non-natural sidechains.

Protein-protein interactions encode the wiring diagram of cellular signaling pathways and their deregulations underlie a variety of diseases, such as cancer. Inhibiting protein-protein interactions with peptide derivatives is a promising way to develop new biological and therapeutic tools. Here, we develop a general framework to computationally handle hundreds of non-natural amino acid sidechains and predict the effect of inserting them into peptides or proteins. We first generate all structural files (pdb and mol2), as well as parameters and topologies for standard molecular mechanics software (CHARMM and Gromacs). Accurate predictions of rotamer probabilities are provided using a novel combined knowledge and physics based strategy. Non-natural sidechains are useful to increase peptide ligand binding affinity. Our results obtained on non-natural mutants of a BCL9 peptide targeting beta-catenin show very good correlation between predicted and experimental binding free-energies, indicating that such predictions can be used to design new inhibitors. Data generated in this work, as well as PyMOL and UCSF Chimera plug-ins for user-friendly visualization of non-natural sidechains, are all available at http://www.swisssidechain.ch. Our results enable researchers to rapidly and efficiently work with hundreds of non-natural sidechains.

iLOGP: A Simple, Robust, and Efficient Description of n-Octanol/Water Partition Coefficient for Drug Design Using the GB/SA Approach.

The n-octanol/water partition coefficient (log Po/w) is a key physicochemical parameter for drug discovery, design, and development. Here, we present a physics-based approach that shows a strong linear correlation between the computed solvation free energy in implicit solvents and the experimental log Po/w on a cleansed data set of more than 17,500 molecules. After internal validation by five-fold cross-validation and data randomization, the predictive power of the most interesting multiple linear model, based on two GB/SA parameters solely, was tested on two different external sets of molecules. On the Martel druglike test set, the predictive power of the best model (N = 706, r = 0.64, MAE = 1.18, and RMSE = 1.40) is similar to six well-established empirical methods. On the 17-drug test set, our model outperformed all compared empirical methodologies (N = 17, r = 0.94, MAE = 0.38, and RMSE = 0.52). The physical basis of our original GB/SA approach together with its predictive capacity, computational efficiency (1 to 2 s per molecule), and tridimensional molecular graphics capability lay the foundations for a promising predictor, the implicit log P method (iLOGP), to complement the portfolio of drug design tools developed and provided by the SIB Swiss Institute of Bioinformatics.