Exudative AMD subtypes and eligibility for treatment with ranibizumab

Purpose To ascertain the proportion of patients with neovascular age-related macular degeneration (AMD) eligible for intravitreal treatment with monoclonal antibodies to vascular endothelial growth factor, on the basis of inclusion criteria used in pivotal clinical trials.

Association of VEGF-1499C -> T polymorphism with diabetic nephropathy in type 1 diabetes mellitus

Vascular endothelial growth factor (VEGF) is reported to be implicated in the development of diabetic nephropathy. We performed a case-control study to determine if VEGF-2578C -> A, VEGF-1499C -> T, and VEGF-635G -> C single-nucleotide polymorphisms (SNPs) in the VEGF gene are associated with predisposition to diabetic nephropathy in type I diabetes. Genomic DNA was obtained from Irish type I diabetic individuals with nephropathy (cases, n=242) and those without nephropathy (controls, n=301), in addition to 400 healthy control samples. These samples were genotyped for the three SNPs using TaqMan or Pyrosequencing technology. Chi-squared analyses revealed no significant differences in genotype or allele frequencies in cases versus controls for VEGF-2578C -> A (genotype, P=.58; allele, P=.52) and VEGF-635G -> C (genotype, P=.58; allele, P=.33). However, a positive association with diabetic nephropathy was observed for the VEGF-1499T allele in the Northern Ireland population (P

Targets of genome copy number reduction in primary breast cancers identified by integrative genomics

The identification of specific oncogenes and tumor suppressor genes in regions of recurrent aneuploidy is a major challenge of molecular cancer research. Using both oligonucleotide single-nucleotide polymorphism and mRNA expression arrays, we integrated genomic and transcriptional information to identify and prioritize candidate cancer genes in regions of increased and decreased chromosomal copy number in a cohort of primary breast cancers. Confirming the validity of this approach, several regions of previously-known copy number (CN) alterations in breast cancer could be successfully reidentified. Focusing on regions of decreased CN, we defined a prioritized list of eighteen candidate genes, which included ARPIN, FBNI, and LZTSI, previously shown to be associated with cancers in breast or other tissue types, and novel genes such as P29, MORF4LI, and TBCID5. One such gene, the RUNX3 transcription factor, was selected for further study. We show that RUNX3 is present at reduced CNs in proportion to the rest of the tumor genome and that RUNX3 CN reductions can also be observed in a breast cancer series from a different center. Using tissue microarrays, we demonstrate in an independent cohort of over 120 breast tissues that RUNX3 protein is expressed in normal breast epithelium but not fat and stromal tissue, and widely down-regulated in the majority of breast cancers (> 85%). In vitro, RUNX3 overexpression suppressed the invasive potential of MDA-MB-231 breast cancer cells in a matrigel assay. Our results demonstrate the utility of integrative genomic approaches to identify novel potential cancer-related genes in primary tumors. This article contains Supplementary Material available at http:// www.interscience.wiley.com/jpages/1045-2257/suppmat. (c) 2006 Wiley-Liss, Inc.

Detecting Ca2+ sparks on stationary and varying baselines.

Studies concerning the physiological significance of Ca2+ sparks often depend on the detection and measurement of large populations of events in noisy microscopy images. Automated detection methods have been developed to quickly and objectively distinguish potential sparks from noise artifacts. However, previously described algorithms are not suited to the reliable detection of sparks in images where the local baseline fluorescence and noise properties can vary significantly, and risk introducing additional bias when applied to such data sets. Here, we describe a new, conceptually straightforward approach to spark detection in linescans that addresses this issue by combining variance stabilization with local baseline subtraction. We also show that in addition to greatly increasing the range of images in which sparks can be automatically detected, the use of a more accurate noise model enables our algorithm to achieve similar detection sensitivities with fewer false positives than previous approaches when applied both to synthetic and experimental data sets. We propose, therefore, that it might be a useful tool for improving the reliability and objectivity of spark analysis in general, and describe how it might be further optimized for specific applications.

A puzzling periodicity in the pulsating DA white dwarf G 117-B15A

We present time-resolved optical spectrophotometry of the pulsating hydrogen atmosphere (DA) white dwarf G 117-B15A. We find three periodicities in the pulsation spectrum (215 s, 272 s, and 304 s) all of which have been found in earlier studies. By comparing the fractional wavelength dependence of the pulsation amplitudes ( chromatic amplitudes) with models, we confirm a previous report that the strongest mode, at 215 s, has l = 1. The chromatic amplitude for the 272 s mode is very puzzling, showing an increase in fractional amplitude with wavelength that cannot be reproduced by the models for any ` at optical wavelengths. Based on archival HST data, we show that while the behaviour of the 215 s mode at ultra-violet wavelengths is as expected from models, the weird behaviour of the 272 s periodicity is not restricted to optical wavelengths in that it fails to show the expected increase in fractional amplitude towards shorter wavelengths. We discuss possible causes for the discrepancies found for the 272 s variation, but find that all are lacking, and conclude that the nature of this periodicity remains unclear.

Diphosphine analogues of proton sponge: X-ray crystal structure of [Pd(eta(3)-allyl)(dppn)]BF4 center dot CH2Cl2 (dppn equals 1,8-bis(diphenylphosphino)naphthalene)

The X-ray crystal structure of [Pd(eta(3)-allyl)(dppn)]BF4 . CH2Cl2 (1) where dppn = 1,8-bis(diphenylphosphino)naphthalene is reported. Comparison of the conformation of the ligand in 1 with that in the free state shows that there is a relief of strain on complexation analogous to the relief of strain observed upon protonation of proton sponge.

Translating policy into practice: A case study in the secondary prevention of coronary heart disease

Background: This paper focuses on the relationships between health ‘policy’ as it is embodied in official documentation, and health ‘practice’ as reported and reflected on in the talk of policy makers, health professionals and patients. The specific context for the study involves a comparison of policies relating to the secondary prevention of coronary heart disease (CHD) in the two jurisdictions of Ireland – involving as they do a predominantly state funded (National Health Service) system in the north and a mixed healthcare economy in the south. The key question is to determine how the rhetoric of health policy as contained in policy documents connects to, and gets translated into practice and action.

Methods: The data sources for the study include relevant healthcare policy documents (N=5) and progress reports (N=6) in the two Irish jurisdictions, and semi-structured interviews with a range of policy-makers (N=28), practice nurses (14), general practitioners (12) and patients (13) to explore their awareness of the documents’ contents and how they saw the impact of ‘policy’ on primary care practice.

Results: The findings suggest that although strategic policy documents can be useful for highlighting and channelling attention to health issues that require concerted action, they have little impact on what either professionals or lay people do.

Conclusion: To influence the latter and to encourage a systematic approach to the delivery of health care it seems likely that contractual arrangements – specifying tasks to be undertaken and methods for monitoring and reporting on activity - are required.

Characterisation of polyacetylenes isolated from carrot (Daucus carota) extracts by negative ion tandem mass spectrometry

The potential use of negative electrospray ionisation mass spectrometry (ESI-MS) in the characterisation of the three polyacetylenes common in carrots (Daucus carota) has been assessed. The MS scans have demonstrated that the polyacetylenes undergo a modest degree of in-source decomposition in the negative ionisation mode while the positive ionisation mode has shown predominantly sodiated ions and no [M+H](+) ions. Tandem mass spectrometric (MS/MS) studies have shown that the polyacetylenes follow two distinct fragmentation pathways: one that involves cleavage of the C3-C4 bond and the other with cleavage of the C7-C8 bond. The cleavage of the C7-C8 bond generated product ions m/z 105.0 for falcarinol, m/z 105/107.0 for falcarindiol, m/z 147.0/149.1 for falcarindiol-3-acetate. In addition to these product ions, the transitions m/z 243.2 -> 187.1 (falcarinol), m/z 259.2 -> 203.1 (falcarindiol), m/z 301.2 -> 255.2/203.1 (falcarindiol-3-acetate), mostly from the C3-C4 bond cleavage, can form the basis of multiple reaction monitoring (MRM)-quantitative methods which are poorly represented in the literature. The 'MS3' experimental data confirmed a less pronounced homolytic cleavage site between the C11-C12 bond in the falcarinol-type polacetylenes. The optimised liquid chromatography (LC)/MS conditions have achieved a baseline chromatographic separation of the three polyacetylenes investigated within 40 min total run-time. Copyright (C) 2011 John Wiley & Sons, Ltd.

Manipulating Interaction Strengths and the Consequences for Trivariate Patterns in a Marine Food Web

We are experiencing a global extinction crisis as a result of climate change and human-induced alteration of natural habitats, with large predators at high trophic levels in food webs being particularly vulnerable. Unfortunately, there is a scarcity of food web data that can be used to assess how species extinctions alter the structure and stability of temporally and spatially replicated networks. We established a series of large experimental mesocosms in a shallow subtidal benthic marine system and constructed food webs for each replicate. After 6 months of community assembly, we removed large predators from the core communities of 20 experimental food webs, based on the strength of their trophic interactions, and monitored the changes in the networks' structure and stability over an 8-month period. Our analyses revealed the importance of allometric relationships and size-structuring in natural communities as a means of preserving food web structure and sustainability, despite significant changes in the diversity, stability and productivity of the system.

Animal maiming, intimacy and the politics of shared life: the bestial and the beastly in eighteenth- and early nineteenth-century England

The everyday lives of many farm workers in eighteenth- and early nineteenth-century England were intricately and often intimately bound with the lives of animals, the ebb and flow of human life being inseparable from that of animal life. Farmyards, fields, folds as well as barns and stables were all spaces where animals transcended being the mere instruments of capital to instead being obvious co-constituents of the rhythms of existence. Living and working in such close proximity meant that the ‘species barrier’ was crossed and intimacies developed in everyday agricultural practices. Still, the relationship was based upon, if not reducible to, the workings of capital: the animal enrolled as a form of embodied capital, the labourer engaged by the farmer to act upon the animal. And in such relationships intimacies are mirrored by violences: the keeping captive, slaughter, and – occasionally – abuse. In this formative period in which the discourses and policies that continue to inform animal welfare were first formulated, the declining economic and material fortunes of farm workers when juxtaposed to farm animals’ fortune as increasingly ‘cosseted capital’ gave a particular charge to these abuses. Farm animals, and especially horses and cattle, so it is shown, were subjected to a series of violences. Many cases of animal maiming parodied tenderness in their brutality, whilst other attacks on the sexual organs of animals represented complex statements about the ways in which agrarian capitalism regulated all culture. Analysing the changing relationship between humans and animals therefore also helps us to better understand how capitalism mediates – and is mediated by – the non-human as well as the human, and how it defines cultural relations.