Phase equilibrium studies in the "MnO"-Al2O3-SiO2 system

Phase relations and the liquidus surface in the system "MnO"-Al2O3-SiO2 at manganese-rich alloy saturation have been investigated in the temperature range from 1373 to 1773 K. This system contains the primary-phase fields of tridymite and cristobalite (SiO2); mullite (3Al(2)O(3).2SiO(2)); corundum (Al2O3); galaxite (MnO.Al2O3); manganosite (MnO); tephroite (2MnO.SiO2); rhodonite (MnO.SiO2); spessartine (3MnO.Al2O3.SiO2); and the compound MnO.Al2O3.2SiO(2).

What is the best size descriptor to use for pharmacokinetic studies in the obese?

The prevalence of obesity in the western world is dramatically rising, with many of these individuals requiring therapeutic intervention for a variety of disease states. Despite the growing prevalence of obesity there is a paucity of information describing how doses should be adjusted, or indeed whether they need to be adjusted, in the clinical setting. This review is aimed at identifying which descriptors of body size provide the most information about the relationship between dose and concentration in the obese. The size descriptors, weight, lean body weight, ideal body weight, body surface area, body mass index, fat-free mass, percent ideal body weight, adjusted body weight and predicted normal body weight were considered as potential size descriptors. We conducted an extensive review of the literature to identify studies that have assessed the quantitative relationship between the parameters clearance (CL) and volume of distribution (V) and these descriptors of body size. Surprisingly few studies have addressed the relationship between obesity and CL or V in a quantitative manner. Despite the lack of studies there were consistent findings: (i) most studies found total body weight to be the best descriptor of V. A further analysis of the studies that have addressed V found that total body weight or another descriptor that incorporated fat mass was the preferred descriptor for drugs that have high lipophilicity; (ii) in contrast, CL was best described by lean body mass and no apparent relationship between lipophilicity or clearance mechanism and preference for body size descriptor was found. In conclusion, no single descriptor described the influence of body size on both CL and V equally well. For drugs that are dosed chronically, and therefore CL is of primary concern, dosing for obese patients should not be based on their total weight. If a weight-based dose individualization is required then we would suggest that chronic drug dosing in the obese subject should be based on lean body weight, at least until a more robust size descriptor becomes available.

Changes in estimated coronary risk in the 1980s: data from 38 populations in the WHO MONICA Project

The World Health Organization (WHO) MONICA Project is a 10-year study monitoring trends and determinants of cardiovascular disease in geographically defined populations. Data were collected from over 100 000 randomly selected participants in two risk factor surveys conducted approximately 5 years apart in 38 populations using standardized protocols. The net effects of changes in the risk factor levels were estimated using risk scores derived from longitudinal studies in the Nordic countries. The prevalence of cigarette smoking decreased among men in most populations, but the trends for women varied. The prevalence of hypertension declined in two-thirds of the populations. Changes in the prevalence of raised total cholesterol were small but highly correlated between the genders (r = 0.8). The prevalence of obesity increased in three-quarters of the populations for men and in more than half of the populations for women. In almost half of the populations there were statistically significant declines in the estimated coronary risk for both men and women, although for Beijing the risk score increased significantly for both genders. The net effect of the changes in the risk factor levels in the 1980s in most of the study populations of the WHO MONICA Project is that the rates of coronary disease are predicted to decline in the 1990s.

Search for time variation of the fine structure constant

An order of magnitude sensitivity gain is described for using quasar spectra to investigate possible time or space variation in the fine structure constant alpha. Applied to a sample of 30 absorption systems, spanning redshifts 0.5 < z < 1.6, we derive limits on variations in alpha over a wide range of epochs. For the whole sample, Delta alpha/alpha = (-1.1 +/- 0.4) x 10(-5). This deviation is dominated by measurements at z > 1, where Delta alpha/alpha = (-1.9 +/- 0.5) x 10(-5). For z < 1, Delta alpha/alpha = (-0.2 +/- 0.4) x 10(-5). While this is consistent with a time-varying alpha, further work is required to explore possible systematic errors in the data, although careful searches have so far revealed none.

X-linked myoclonic epilepsy with spasticity and intellectual disability - Mutation in the homeobox gene ARX

Objective: To describe a new syndrome of X-linked myoclonic epilepsy with generalized spasticity and intellectual disability (XMESID) and identify the gene defect underlying this disorder. Methods: The authors studied a family in which six boys over two generations had intractable seizures using a validated seizure questionnaire, clinical examination, and EEG studies. Previous records and investigations were obtained. Information on seizure disorders was obtained on 271 members of the extended family. Molecular genetic analysis included linkage studies and mutational analysis using a positional candidate gene approach. Results: All six affected boys had myoclonic seizures and TCS; two had infantile spasms, but only one had hypsarrhythmia. EEG studies show diffuse background slowing with slow generalized spike wave activity. All affected boys had moderate to profound intellectual disability. Hyperreflexia was observed in obligate carrier women. A late-onset progressive spastic ataxia in the matriarch raises the possibility of late clinical manifestations in obligate carriers. The disorder was mapped to Xp11.2-22.2 with a maximum lod score of 1.8. As recently reported, a missense mutation (1058C>T/P353L) was identified within the homeodomain of the novel human Aristaless related homeobox gene (ARX). Conclusions: XMESID is a rare X-linked recessive myoclonic epilepsy with spasticity and intellectual disability in boys. Hyperreflexia is found in carrier women. XMESID is associated with a missense mutation in ARX. This disorder is allelic with X-linked infantile spasms (ISSX; MIM 308350) where polyalanine tract expansions are the commonly observed molecular defect. Mutations of ARX are associated with a wide range of phenotypes; functional studies in the future may lend insights to the neurobiology of myoclonic seizures and infantile spasms.