The importance of epidemiology in understanding eye disease

Most leading causes of visual impairment are age related, so the health care implications of an increasing prevalence of eye disease in the elderly are significant. Epidemiological research provides the foundation to address immediate and long-term needs associated with visual impairment and eye disease. It contributes to a community's knowledge of the presence, diagnosis, characteristics, and distribution of eye conditions affecting the elderly. Obtaining accurate epidemiological information on the extent of visual impairment and eye disease in the community is essential to determine and estimate the cost of primary and secondary eye health care needs.

Examination compliance and screening for diabetic retinopathy: a 2-year follow-up study

Early detection and timely treatment of diabetic retinopathy can preserve vision, yet many people with diabetes do not have their eyes examined regularly. The purpose of this study was to examine eye care practices of people with diabetes who had not previously accessed eye care services on a regular basis. Screening with non-mydriatic retinal photography for diabetic retinopathy was initiated in 1996, and targeted people with diabetes who did not access eye care services on a regular basis. Each test area was revisited 2 years after the initial screening. Patients that did not attend the biennial screening were followed up by mail survey. Although none of the participants in this study had been previously accessing eye care services on a regular basis, 87% did so after attending the screening. These results indicate that mobile screening with non-mydriatic photography, as an adjunct to current eye care services, has the potential to increase examination compliance for diabetic retinopathy and to achieve sustained behaviour change.

Recruitment methods for community-based screening for diabetic retinopathy

Regular screening of all people with diabetes is the most efficient and cost-effective way to detect early stages of diabetic retinopathy so that laser treatment can be performed at the optimal time. A major aim of the Program for the Early Detection of Diabetic Retinopathy was to increase compliance with guidelines for screening for diabetic retinopathy. This community-based screening program used non-mydriatic retinal photography and was initiated in four areas of Victoria, Australia from 1996-1998. Recruitment strategies included targeted mail-outs, provision of the program brochure in English and the main languages spoken in the areas and media promotion in ethnic newspapers and on ethnic radio stations. In Victoria, only 55% of the population with diabetes currently access eye care services at the recommended intervals. This program was able to increase compliance with guidelines to 70% among people with diabetes that had not had a recent eye examination. A total of 1,197 people with diabetes were screened for diabetic retinopathy. Of the 1,197 people who were screened, 620 (15% of the estimated number of people with diabetes) had not had their eyes examined in the past two years. This pilot study identified strategies to encourage people with diabetes to have their eyes examined at the recommended intervals.

The Hunt for New Physics at the Large Hadron Collider

The Large Hadron Collider presents an unprecedented opportunity to probe the realm of new physics in the TeV region and shed light on some of the core unresolved issues of particle physics. These include the nature of electroweak symmetry breaking, the origin of mass, the possible constituent of cold dark matter, new sources of CP violation needed to explain the baryon excess in the universe, the possible existence of extra gauge groups and extra matter, and importantly the path Nature chooses to resolve the hierarchy problem - is it supersymmetry or extra dimensions. Many models of new physics beyond the standard model contain a hidden sector which can be probed at the LHC. Additionally, the LHC will be a. top factory and accurate measurements of the properties of the top and its rare decays will provide a window to new physics. Further, the LHC could shed light on the origin of neutralino masses if the new physics associated with their generation lies in the TeV region. Finally, the LHC is also a laboratory to test the hypothesis of TeV scale strings and D brane models. An overview of these possibilities is presented in the spirit that it will serve as a companion to the Technical Design Reports (TDRs) by the particle detector groups ATLAS and CMS to facilitate the test of the new theoretical ideas at the LHC. Which of these ideas stands the test of the LHC data will govern the course of particle physics in the subsequent decades.

Fluctuation analysis of lung function as a predictor of long-term response to beta2-agonists

The response to beta(2)-agonists differs between asthmatics and has been linked to subsequent adverse events, even death. Possible determinants include beta(2)-adrenoceptor genotype at position 16, lung function and airway hyperresponsiveness. Fluctuation analysis provides a simple parameter alpha measuring the complex correlation properties of day-to-day peak expiratory flow. The present study investigated whether alpha predicts clinical response to beta(2)-agonist treatment, taking into account other conventional predictors. Analysis was performed on previously published twice-daily peak expiratory flow measurements in 66 asthmatic adults over three 6-month randomised order treatment periods: placebo, salbutamol and salmeterol. Multiple linear regression was used to determine the association between alpha during the placebo period and response to treatment (change in the number of days with symptoms), taking into account other predictors namely beta(2)-adrenoceptor genotype, lung function and its variability, and airway hyperresponsiveness. The current authors found that alpha measured during the placebo period considerably improved the prediction of response to salmeterol treatment, taking into account genotype, lung function or its variability, or airway hyperresponsiveness. The present study provides further evidence that response to beta(2)-agonists is related to the time correlation properties of lung function in asthma. The current authors conclude that fluctuation analysis of lung function offers a novel predictor to identify patients who may respond well or poorly to treatment.

Stringy origin of diboson and dijet excesses at the LHC

Very recently, the ATLAS and CMS Collaborations reported diboson and dijet excesses above standard model expectations in the invariant mass region of 1.8–2.0 TeV. Interpreting the diboson excess of events in a model independent fashion suggests that the vector boson pair production searches are best described by WZ or ZZ topologies, because states decaying into W+W− pairs are strongly constrained by semileptonic searches. Under the assumption of a low string scale, we show that both the diboson and dijet excesses can be steered by an anomalous U(1) field with very small coupling to leptons. The Drell–Yan bounds are then readily avoided because of the leptophobic nature of the massive Z′ gauge boson. The non-negligible decay into ZZ required to accommodate the data is a characteristic footprint of intersecting D-brane models, wherein the Landau–Yang theorem can be evaded by anomaly-induced operators involving a longitudinal Z. The model presented herein can be viewed purely field-theoretically, although it is particularly well motivated from string theory. Should the excesses become statistically significant at the LHC13, the associated Zγ topology would become a signature consistent only with a stringy origin.

Monarch butterflies (Danaus plexippus L.) use a magnetic compass for navigation

Fall migratory monarch butterflies, tested for their directional responses to magnetic cues under three conditions, amagnetic, normal, and reversed magnetic fields, showed three distinct patterns. In the absence of a magnetic field, monarchs lacked directionality as a group. In the normal magnetic field, monarchs oriented to the southwest with a group pattern typical for migrants. When the horizontal component of the magnetic field was reversed, the butterflies oriented to the northeast. In contrast, nonmigratory monarchs lacked directionality in the normal magnetic field. The results are a direct demonstration of magnetic compass orientation in migratory insects.

A p53-dependent S-phase checkpoint helps to protect cells from DNA damage in response to starvation for pyrimidine nucleotides

Normal mammalian cells arrest primarily in G1 in response to N-(phosphonacetyl)-l-aspartate (PALA), which starves them for pyrimidine nucleotides, and do not generate or tolerate amplification of the CAD gene, which confers resistance to PALA. Loss of p53, accompanied by loss of G1 arrest, permits CAD gene amplification and the consequent formation of PALA-resistant colonies. We have found rat and human cell lines that retain wild-type p53 but have lost the ability to arrest in G1 in response to PALA. However, these cells still fail to give PALA-resistant colonies and are protected from DNA damage through the operation of a second checkpoint that arrests them reversibly within S-phase. This S-phase arrest, unmasked in the absence of the G1 checkpoint, is dependent on p53 and independent of p21/waf1.

Isolated cleft palate in mice with a targeted mutation of the LIM homeobox gene Lhx8

Formation of the mammalian secondary palate is a highly regulated and complex process whose impairment often results in cleft palate, a common birth defect in both humans and animals. Loss-of-function analysis has linked a growing number of genes to this process. Here we report that Lhx8, a recently identified LIM homeobox gene, is expressed in the mesenchyme of the mouse palatal structures throughout their development. To test the function of Lhx8 in vivo, we generated a mutant mouse with a targeted deletion of the Lhx8 gene. Our analysis of the mutant animals revealed a crucial role for Lhx8 in palatogenesis. In Lhx8 homozygous mutant embryos, the bilateral primordial palatal shelves formed and elevated normally, but they often failed to make contact and to fuse properly, resulting in a cleft secondary palate. Because development of other craniofacial structures appeared normal, the impaired palatal formation in Lhx8-mutant mice was most likely caused by an intrinsic primary defect in the mesenchyme of the palatal shelves. The cleft palate phenotype observed in Lhx8-mutant mice suggests that Lhx8 is a candidate gene for the isolated nonsyndromic form of cleft palate in humans.

Mechanisms of G2 Arrest in Response to Overexpression of p53

Overexpression of p53 causes G2 arrest, attributable in part to the loss of CDC2 activity. Transcription of cdc2 and cyclin B1, determined using reporter constructs driven by the two promoters, was suppressed in response to the induction of p53. Suppression requires the regions −287 to −123 of the cyclin B1 promoter and −104 to −74 of the cdc2 promoter. p53 did not affect the inhibitory phosphorylations of CDC2 at threonine 14 or tyrosine 15 or the activity of the cyclin-dependent kinase that activates CDC2 by phosphorylating it at threonine 161. Overexpression of p53 may also interfere with the accumulation of CDC2/cyclin B1 in the nucleus, required for cells to enter mitosis. Constitutive expression of cyclin B1, alone or in combination with the constitutively active CDC2 protein T14A Y15F, did not reverse p53-dependent G2 arrest. However, targeting cyclin B1 to the nucleus in cells also expressing CDC2 T14A Y15F did overcome this arrest. It is likely that several distinct pathways contribute to p53-dependent G2 arrest.

p53 controls both the G2/M and the G1 cell cycle checkpoints and mediates reversible growth arrest in human fibroblasts.

Increased expression of wild-type p53 in response to DNA damage arrests cells late in the G1 stage of the cell cycle by stimulating the synthesis of inhibitors of cyclin-dependent kinases, such as p21/WAF1. To study the effects of p53 without the complication of DNA damage, we used tetracycline to regulate its expression in MDAH041 human fibroblasts that lack endogenous p53. When p53 is expressed at a level comparable to that induced by DNA damage in other cells, most MDAH041 cells arrested in G1, but a significant fraction also arrested in G2/M. Cells released from a mimosine block early in S phase stopped predominantly in G2/M in the presence of p53, confirming that p53 can mediate arrest at this stage, as well as in G1. In these cells, there was appreciable induction of p21/WAF1. MDAH041 cells arrested by tetracycline-regulated p53 for as long as 20 days resumed growth when the p53 level was lowered, in striking contrast to the irreversible arrest mediated by DNA damage. Therefore, irreversible arrest must involve processes other than or in addition to the interaction of p53-induced p21/WAF1 with G1 and G2 cyclin-dependent kinases.

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