Deletion diagnostics for the generalised linear mixed model with independent random effects.

The Generalised linear mixed model (GLMM) is widely used for modelling environmental data. However, such data are prone to influential observations, which can distort the estimated exposure-response curve particularly in regions of high exposure. Deletion diagnostics for iterative estimation schemes commonly derive the deleted estimates based on a single iteration of the full system holding certain pivotal quantities such as the information matrix to be constant. In this paper, we present an approximate formula for the deleted estimates and Cook's distance for the GLMM, which does not assume that the estimates of variance parameters are unaffected by deletion. The procedure allows the user to calculate standardised DFBETAs for mean as well as variance parameters. In certain cases such as when using the GLMM as a device for smoothing, such residuals for the variance parameters are interesting in their own right. In general, the procedure leads to deleted estimates of mean parameters, which are corrected for the effect of deletion on variance components as estimation of the two sets of parameters is interdependent. The probabilistic behaviour of these residuals is investigated and a simulation based procedure suggested for their standardisation. The method is used to identify influential individuals in an occupational cohort exposed to silica. The results show that failure to conduct post model fitting diagnostics for variance components can lead to erroneous conclusions about the fitted curve and unstable confidence intervals.

A review of multivariate longitudinal data analysis.

Repeated observation of multiple outcomes is common in biomedical and public health research. Such experiments result in multivariate longitudinal data, which are unique in the sense that they allow the researcher to study the joint evolution of these outcomes over time. Special methods are required to analyse such data because repeated observations on any given response are likely to be correlated over time while multiple responses measured at a given time point will also be correlated. We review three approaches for analysing such data in the light of the associated theory, applications and software. The first method consists of the application of univariate longitudinal tools to a single summary outcome. The second method aims at estimating regression coefficients without explicitly modelling the underlying covariance structure of the data. The third method combines all the outcomes into a single joint multivariate model. We also introduce a multivariate longitudinal dataset and use it to illustrate some of the techniques discussed in the article.

Additive models for geo-referenced failure time data.

Asthma researchers have found some evidence that geographical variations in susceptibility to asthma could reflect the effect of community level factors such as exposure to violence. Our methodology was motivated by a study of age at onset of asthma among children of inner-city neighbourhoods in East Boston. Cox's proportional hazards model was not appropriate since there was not enough information about the nature of geographical variations so as to impose a parametric relationship. In addition, some of the known risk factors were believed to have non-linear log-hazard ratios. We extend the geoadditive models of Kamman and Wand to the case where the outcome measure is a possibly censored time to event. We reduce the problem to one of fitting a Poisson mixed model by using Poisson approximations in conjunction with a mixed model formulation of generalized additive modelling. Our method allows for low-rank additive modelling, provides likelihood-based estimation of all parameters including the amount of smoothing and can be implemented using standard software. We illustrate our method on the East Boston data.

Antifungal antibiotics.

The search for new drugs against fungal infections is a major challenge to current research in mycotic diseases. The present article reviews the current types of antifungal infections, the current scenario of antifungal antibiotics, and the need and approaches to search for newer antifungal antibiotics and antifungal drug targets.

Mathemycin B, a new antifungal macrolactone from actinomycete species HIL Y-8620959.

A new macrocyclic lactone antibiotic mathemycin B (1) was isolated from the fermentation broth of an Actinomycete sp. culture Y-8620959. The structure of 1 was elucidated by high-resolution MS and interpretation of 2D NMR results. Mathemycin B is active against a variety of phytopathogenic organisms.

Arthrichitin. A New Cell Wall Active Metabolite from Arthrinium phaeospermum.

Arthrichitin (1), C(33)H(46)N(4)O(9), is a new cell wall active depsipeptide isolated from the fermentation broth of Arthrinium phaeospermum (HIL Y-903022). Its structure was elucidated on the basis of spectroscopic and chemical degradation studies. Arthrichitin consists of serine, beta-keto tryptophan, glutamic acid, and 2,4-dimethyl-3-hydroxydodecanoic acid units.

Balhimycin, a new glycopeptide antibiotic produced by Amycolatopsis sp. Y-86,21022. Taxonomy, production, isolation and biological activity.

A new glycopeptide antibiotic, balhimycin, has been isolated from the fermentation broth of a Amycolatopsis sp. Y-86,21022. Balhimycin belongs to the vancomycin class of glycopeptides and contains a dehydrovancosamine sugar. The biological activity of balhimycin has been compared extensively with that of vancomycin against methicillin resistant staphylococci and also against anaerobes. Balhimycin is marginally superior to vancomycin in its in vitro activity against anaerobes and in its bactericidal properties.

Aranorosinol A and aranorosinol B, two new metabolites from Pseudoarachniotus roseus: production, isolation, structure elucidation and biological properties.

Two new secondary metabolites, aranorosinol A (1) and aranorosinol B (2), were isolated from a strain of Pseudoarachniotus roseus. Their structures were elucidated on the basis of their spectral properties and chemical transformations and were found to be similar to aranorosin (3) isolated from the same strain.

Mersacidin, a new antibiotic from Bacillus. Fermentation, isolation, purification and chemical characterization.

Mersacidin (1) is a new peptide antibiotic containing beta-methyllanthionine. It is classified as a member of the proposed lantibiotic group of antibiotics, and is produced by a species of Bacillus. Mersacidin has a molecular weight of 1,824 (C80H120N20O21S4). The antibiotic is active against Gram-positive organisms including methicillin-resistant Staphylococcus aureus, but has no activity against Gram-negative bacteria or fungi.

Mersacidin, a new antibiotic from Bacillus. In vitro and in vivo antibacterial activity.

Mersacidin is a new peptide antibiotic of the proposed lantibiotic family. It is active in vitro and in vivo against Gram-positive bacteria including the methicillin-resistant Staphylococci. Its in vitro activity is less than those of vancomycin and erythromycin but it shows much higher activity in the in vivo system than can be expected from the in vitro testing results. A water soluble potassium salt has been prepared which has an activity profile similar to that of mersacidin, but has better in vivo activity against Streptococcus pyogenes than the parent compound.

Deoxymulundocandin--a new echinocandin type antifungal antibiotic.

A new echinocandin type antifungal antibiotic, deoxymulundocandin, C48H77N7O15, was isolated from the culture filtrate and mycelia of a fungal culture, Aspergillus sydowii (Bainier and Sartory) Thom and Church var. nov. mulundensis Roy (Culture No. Y-30462). The structure was established by comparative GC-MS analyses of the derivatized acid hydrolysates of deoxymulundocandin and mulundocandin as well as by the high field NMR experiments (COSY, NOESY and DEPT).

Kinetics and mechanism of the collision-activated dissociation of the acetone cation.

For center-of-mass collision energies Ecm = 1-60 eV, the major fragment ions for the collision-activated dissociation (CAD) of the acetone cation are the acetyl cation (m / z 43; absolute branching ratios of 0.96-0.60) and the methyl cation (m/ z 15; absolute branching ratios of 0.02-0.26); the absolute total cross-sections were 24-35) Å(2). The breakdown curves (viz, plots of the absolute branching ratios versus Ecm) show complex, complementary energy dependences for production of MeCO(+) and Me(+), indicating apparent closure of the Me(+) channel for Ecm > 30 eV. Our observations are consistent with a competition between three fast, primary (direct) reactions, each of which opens sequentially at its respective threshold energy (viz, reactions 8, 10, and 8'). [Formula: see text] [Formula: see text] [Formula: see text] That is, the breakdown curves for MeCO(+) and Me(+) (and other CAD fragments) are consistent with the interpretation by other authors that the collisional activation of the acetone cation involves electronic transitions, so that CAD occurs primarily from isolated electronic states (i.e., non-quasi-equilibrium theory (QET) behavior). For acetone we found a correspondence between the photoelectron-photoion-coincidence and CAD breakdown curves. This may indicate that collisional activation in non-QET systems corresponds to scattering angles that emphasize optically allowed transitions accessed by photoionization.