Why anthropic reasoning cannot predict Lambda.

We revisit anthropic arguments purporting to explain the measured value of the cosmological constant. We argue that different ways of assigning probabilities to candidate universes lead to totally different anthropic predictions. As an explicit example, we show that weighting different universes by the total number of possible observations leads to an extremely small probability for observing a value of Lambda equal to or greater than what we now measure. We conclude that anthropic reasoning within the framework of probability as frequency is ill-defined and that in the absence of a fundamental motivation for selecting one weighting scheme over another the anthropic principle cannot be used to explain the value of Lambda, nor, likely, any other physical parameters.

Indication for primordial anisotropies in the neutrino background from the Wilkinson microwave anisotropy probe and the Sloan digital sky survey.

We demonstrate that combining cosmic microwave background anisotropy measurements from the 1st year Wilkinson Microwave Anisotropy Probe observations with clustering data from the Sloan galaxy redshift survey yields an indication for primordial anisotropies in the cosmological neutrino background.

Trends in pharmacogenomics of drugs acting on hypertension.

With the recent rapid increase in scientific understanding of the human genome it is becoming possible to identify the extent to which genetic variations influence drug response. The emergence of pharmacogenetics heralds a new era in which drug therapies will be selected on the basis of differences in individuals' genotypes, enhancing drug safety and efficacy. The major focus of this review is pharmacogenetics of antihypertensive drugs. Genetics can influence the pharmacokinetics and pharmacodynamics of such drugs at different levels. The presently available applications of genetic concepts to some drugs commonly used in the treatment of hypertension (ACE-inhibitors, diuretics, beta-blockers...) will be summarized. Also sensitivity to salt intake will be considered as an example of pharmacogenetics. The identification of genetic markers of drug response will help to achieve a better control of blood pressure in the population, by allowing a better tailor of antihypertensive therapy to individual patients.

Interleukin-1 gene cluster polymorphisms and risk of coronary artery disease.

BACKGROUND AND OBJECTIVES: The pro-inflammatory cytokine interleukin (IL)-1 has been suggested to play a role in atherosclerosis. Several genetic polymorphisms have been described in the genes of the IL-1 cluster and associations with coronary artery disease (CAD) have been reported, although with contrasting results. DESIGN AND METHODS: The associations of a variable number tandem repeat (86 bp) polymorphism in intron 2 of interleukin-1 receptor antagonist (IL1-RA) and of the 511 C/T polymorphism of IL-1b with the risk of CAD were studied. Three hundred and thirty-five case (CAD+) patients with angiographically documented CAD (stenosis >50% in at least one major coronary artery) were compared with 205 unrelated individuals free of CAD signs at angiogram (CAD- controls). One hundred and two (30.5%) CAD+ patients had single-vessel disease (SVD) and 233 (69.5%) multiple-vessel disease (MVD). RESULTS: There was no statistically significant difference in either genotype distribution or allele frequency of both IL-1 RA and IL-1b 511 C/T polymorphisms between CAD+ cases and CAD- controls. Moreover in multivariate analysis, adjusting for multiple comparisons and confounding factors, no difference was found in IL-1 RA genotype distribution between patients with SVD or MVD. INTERPRETATION AND CONCLUSIONS: Our study does not support the association between IL-1 RA intron 2 VNTR and IL-1b 511 C/T polymorphisms and the risk of CAD in individuals undergoing coronary angiography.