Age effect on retina and optic disc normal values

Purpose: To investigate retinal thickness and optic disc parameters by the Retinal Thickness Analyzer (RTA) glaucoma program in older normal subjects and to determine any age effect. Methods: Subjects over 40 years of age without any prior history of eye diseases were recruited. Only subjects completely normal on clinical ophthalmologic examination and on visual field testing by Humphrey Field Analyzer (HFA) using the SITA 24-2 program were included. A total of 74 eyes from 74 subjects with even age distribution over the decades were enrolled and underwent topographic measurements of the posterior pole and of the optic disc by RTA. The `glaucoma full' program in software version 4.11B was applied. Results: Mean patient age was 59.9 +/- 10.3 years with a range from 40 to 80 years. The only parameter intraocular pressure (IOP) correlated with was retinal posterior pole asymmetry (r=0.27, p=0.02). IOP itself increased significantly with age (r=0.341, p=0.003). Mean defect and pattern standard deviation of the HFA did not correlate with any of the retinal or optic disc measurements. Increasing age correlated significantly with some of the morphologic measurements of the RTA: decreasing perifoveal minimum thickness (r=-0.258, p=0.026), increased cup-to-disc area ratio (r=0.302, p=0.016) and increased cup area (r=0.338 p=0.007). Conclusions: An age effect exists for some of the retina and optic disc measurements obtained by the RTA. Copyright (C) 2005 S. Karger AG, Basel

Quantitative trait loci conferring grain mineral nutrient concentrations in durum wheat 3 wild emmer wheat RIL population

Mineral nutrient malnutrition, and particularly deficiency in zinc and iron, afflicts over 3 billion people worldwide. Wild emmer wheat, Triticum turgidum ssp. dicoccoides, genepool harbors a rich allelic repertoire for mineral nutrients in the grain. The genetic and physiological basis of grain protein, micronutrients (zinc, iron, copper and manganese) and macronutrients (calcium, magnesium, potassium, phosphorus and sulfur) concentration was studied in tetraploid wheat population of 152 recombinant inbred lines (RILs), derived from a cross between durum wheat (cv. Langdon) and wild emmer (accession G18-16). Wide genetic variation was found among the RILs for all grain minerals, with considerable transgressive effect. A total of 82 QTLs were mapped for 10 minerals with LOD score range of 3.2–16.7. Most QTLs were in favor of the wild allele (50 QTLs). Fourteen pairs of QTLs for the same trait were mapped to seemingly homoeologous positions, reflecting synteny between the A and B genomes. Significant positive correlation was found between grain protein concentration (GPC), Zn, Fe and Cu, which was supported by significant overlap between the respective QTLs, suggesting common physiological and/or genetic factors controlling the concentrations of these mineral nutrients. Few genomic regions (chromosomes 2A, 5A, 6B and 7A) were found to harbor clusters of QTLs for GPC and other nutrients. These identified QTLs may facilitate the use of wild alleles for improving grain nutritional quality of elite wheat cultivars, especially in terms of protein, Zn and Fe

Liver transplantation in cirrhotic patients with diabetes mellitus: Midterm results, survival, and adverse events

Liver cirrhosis is frequently associated with diabetes mellitus (DM), and this metabolic complication is also frequent after orthotopic liver transplantation (OLT). The aim of our study is to investigate which factors are associated with DM before and after OLT and their impact on post-OLT evolution. We evaluated the prevalence of DM among 115 liver transplant candidates with cirrhosis and assessed their evolution after OLT (median follow-up, 41 months). Sixteen candidates had DM requiring pharmacological therapy (group A), 45 candidates had DM controlled with diet (group B), and 54 candidates did not have DM (group C). One-year and 3-year actuarial survival rates were 100% and 100% for group A, 91% and 85% for group B, and 77% and 74% for group C, respectively (P <.03). Post-OLT DM was more frequent in group A. The incidence of other metabolic complications, major infections, rejection, and arterial hypertension; the need for hospitalization; and renal and graft function of patients in groups A, B, and C were similar. The only risk factor for DM 1 year after OLT on multivariate analysis was pre-OLT DM requiring pharmacological treatment. The incidence of complications, need for hospitalization, and renal and graft function 1 year after OLT for patients with post-OLT DM were similar to those of patients without post-OLT DM. In conclusion, patients with cirrhosis who have DM have a greater risk for post-OLT DM, but their midterm survival is not worse than the survival of those without DM

A Comprehensive Analysis of Choroideremia: From Genetic Characterization to Clinical Practice.

Choroideremia (CHM) is a rare X-linked disease leading to progressive retinal degeneration resulting in blindness. The disorder is caused by mutations in the CHM gene encoding REP-1 protein, an essential component of the Rab geranylgeranyltransferase (GGTase) complex. In the present study, we evaluated a multi-technique analysis algorithm to describe the mutational spectrum identified in a large cohort of cases and further correlate CHM variants with phenotypic characteristics and biochemical defects of choroideremia patients. Molecular genetic testing led to the characterization of 36 out of 45 unrelated CHM families (80%), allowing the clinical reclassification of four CHM families. Haplotype reconstruction showed independent origins for the recurrent p.Arg293* and p.Lys178Argfs*5 mutations, suggesting the presence of hotspots in CHM, as well as the identification of two different unrelated events involving exon 9 deletion. No certain genotype-phenotype correlation could be established. Furthermore, all the patients´ fibroblasts analyzed presented significantly increased levels of unprenylated Rabs proteins compared to control cells; however, this was not related to the genotype. This research demonstrates the major potential of the algorithm proposed for diagnosis. Our data enhance the importance of establish a differential diagnosis with other retinal dystrophies, supporting the idea of an underestimated prevalence of choroideremia. Moreover, they suggested that the severity of the disorder cannot be exclusively explained by the genotype

Sinks in the Landscape, Boltzmann Brains, and the Cosmological Constant Problem

This paper extends the recent investigation of the string theory landscape in hep-th/0605266, where it was found that the decay rate of dS vacua to a collapsing space with a negative vacuum energy can be quite large. The parts of space that experience a decay to a collapsing space, or to a Minkowski vacuum, never return back to dS space. The channels of irreversible vacuum decay serve as sinks for the probability flow. The existence of such sinks is a distinguishing feature of the string theory landscape. We describe relations between several different probability measures for eternal inflation taking into account the existence of the sinks. The local (comoving) description of the inflationary multiverse suffers from the so-called Boltzmann brain (BB) problem unless the probability of the decay to the sinks is sufficiently large. We show that some versions of the global (volume-weighted) description do not have this problem even if one ignores the existence of the sinks. We argue that if the number of different vacua in the landscape is large enough, the anthropic solution of the cosmological constant problem in the string landscape scenario should be valid for a broad class of the probability measures which solve the BB problem. If this is correct, the solution of the cosmological constant problem may be essentially measure-independent. Finally, we describe a simplified approach to the calculations of anthropic probabilities in the landscape, which is less ambitious but also less ambiguous than other methods.Comment: 42 pages, 5 figures, the paper is substantially extended, a section on the cosmological constant is addeed; the version published in JCA

Inflation with racetrack superpotential and matter field

Several models of inflation with the racetrack superpotential for the volume modulus coupled to a matter field are investigated. In particular, it is shown that two classes of racetrack inflation models, saddle point and inflection point ones, can be constructed in a fully supersymmetric framework with the matter field F-term as a source of supersymmetry breaking and uplifting. Two models of F-term supersymmetry breaking are considered: the Polonyi model and the quantum corrected O'Raifeartaigh model. In the former case, both classes of racetrack inflation models differ significantly from the corresponding models with non-supersymmetric uplifting. The main difference is a quite strong dominance of the inflaton by the matter field. In addition, fine-tuning of the parameters is relaxed as compared to the original racetrack models. In the case of the racetrack inflation models coupled to the O'Raifeartaigh model, the matter field is approximately decoupled from the inflationary dynamics. In all of the above models the gravitino mass is larger than the Hubble scale during inflation. The possibility of having the gravitino much lighter than the Hubble scale is also investigated. It is very hard to construct models with light gravitino in which the volume modulus dominates inflation. On the other hand, models in which the inflationary dynamics is dominated by the matter field are relatively simple and seem to be more natural.Comment: 40 pages, 13 figures, references added, typos corrected, version to be publishe

A gene-alteration profile of human lung cancer cell lines

ABSTRACT: Aberrant proteins encoded from genes altered in tumors drive cancer development and may also be therapeutic targets. Here we derived a comprehensive gene-alteration profile of lung cancer cell lines. We tested 17 genes in a panel of 88 lung cancer cell lines and found the rates of alteration to be higher than previously thought. Nearly all cells feature inactivation at TP53 and CDKN2A or RB1, whereas BRAF, MET, ERBB2, and NRAS alterations were infrequent. A preferential accumulation of alterations among histopathological types and a mutually exclusive occurrence of alterations of CDKN2A and RB1 as well as of KRAS, epidermal growth factor receptor (EGFR), NRAS, and ERBB2 were seen. Moreover, in nonsmall- cell lung cancer (NSCLC), concomitant activation of signal transduction pathways known to converge in mammalian target of rapamycin (mTOR) was common. Cells with single activation of ERBB2, PTEN, or MET signaling showed greater sensitivity to cell-growth inhibition induced by erlotinib, LY294002, and PHA665752, respectively, than did cells featuring simultaneous activation of these pathways, underlining the need for combined therapeutic strategies in targeted cancer treatments. In conclusion, our gene-alteration landscape of lung cancer cell lines provides insights into how gene alterations accumulate and biological pathways interact in cancer. Hum Mutat 30, 1199–1206, 2009. & 2009Wiley-Liss, Inc

Testing String Theory with CMB

Future detection/non-detection of tensor modes from inflation in CMB observations presents a unique way to test certain features of string theory. Current limit on the ratio of tensor to scalar perturbations, r=T/S, is r < 0.3, future detection may take place for r > 10^{-2}-10^{-3}. At present all known string theory inflation models predict tensor modes well below the level of detection. Therefore a possible experimental discovery of tensor modes may present a challenge to string cosmology. The strongest bound on r in string inflation follows from the observation that in most of the models based on the KKLT construction, the value of the Hubble constant H during inflation must be smaller than the gravitino mass. For the gravitino mass in the usual range, m_{3/2} < O(1) TeV, this leads to an extremely strong bound r < 10^{-24}. A discovery of tensor perturbations with r > 10^{-3} would imply that the gravitinos in this class of models are superheavy, m_{3/2} > 10^{13} GeV. This would have important implications for particle phenomenology based on string theory.Comment: 13 pages, 2 figure

Highlights from the Pierre Auger Observatory

The Pierre Auger Observatory is the world's largest cosmic ray observatory. Our current exposure reaches nearly 40,000 km$^2$ str and provides us with an unprecedented quality data set. The performance and stability of the detectors and their enhancements are described. Data analyses have led to a number of major breakthroughs. Among these we discuss the energy spectrum and the searches for large-scale anisotropies. We present analyses of our X$_{max}$ data and show how it can be interpreted in terms of mass composition. We also describe some new analyses that extract mass sensitive parameters from the 100% duty cycle SD data. A coherent interpretation of all these recent results opens new directions. The consequences regarding the cosmic ray composition and the properties of UHECR sources are briefly discussed.Comment: 9 pages, 12 figures, talk given at the 33rd International Cosmic Ray Conference, Rio de Janeiro 201