Evaluation of health effects of air pollution in the Chestnut Ridge area : preliminary analysis

This project involves several tasks designed to take advantage of (1) a very extensive air pollution monitoring system that is operating ..n the Chestnut Ridge.region of Western Pennsylvania and (2) -the very well developed analytic dispersion models that have been previously fine-tuned to this particular area.. The major task in this project is to establish, through several distinct epidemiolopic approaches, health data to be used to test hypotheses about relations of air pollution exposures to morbidity and mortality rates in this region. Because the air quality monitoring network involves no expense to this contract this project affords a very cost-effective 6pportunity-for state-of-the-art techniques to be used in both costly areas of air pollution and health -effects data col1 ection. . The closely spaced network of monitors, plus the dispersion modeling capabilities,.allow for the investigation- of health impacts of. various pollutant gradients in neighboring geographic areas, thus minimizing -the confounding effects of social, ethnic, and economic factors. The pollutants that are monitored in this network include total gaseous sulfur, sulfates, total suspended particulates, NOx, NO, ozone/oxidants, and coefficient of haze. In addition to enabling the simulation of exposure profiles between monitors, the air quality2 modeling, along with extensive source and background inventories, will allow for upgrading the quality of the monitored data. as well as simulating the exposure levels for about 25 additional air pollutants. Another important goal of this project is to collect and test the many available models for associating.health effects with air pollution, to determine their predictive validity and their usefulness in the choice and siting of future energy facilities

Mutation analysis of HIF prolyl hydroxylases (PHD/EGLN) in individuals with features of phaeochromocytoma and renal cell carcinoma susceptibility

Germline mutations in the von Hippel–Lindau disease (VHL) and succinate dehydrogenase subunit B (SDHB) genes can cause inherited phaeochromocytoma and/or renal cell carcinoma(RCC). Dysregulation of the hypoxia-inducible factor (HIF) transcription factors has been linked to VHL and SDHB-related RCC; both HIF dysregulation and disordered function of a prolyl hydroxylase domain isoform 3 (PHD3/EGLN3)-related pathway of neuronal apoptosis have been linked to the development of phaeochromocytoma. The 2-oxoglutarate-dependent prolyl hydroxylase enzymes PHD1 (EGLN2), PHD2 (EGLN1) and PHD3 (EGLN3) have a key role in regulating the stability of HIF-a subunits (and hence expression of the HIF-a transcription factors). A germline PHD2 mutation has been reported in association with congenital erythrocytosis and recurrent extra-adrenal phaeochromocytoma. We undertook mutation analysis of PHD1, PHD2 and PHD3 in two cohorts of patients with features of inherited phaeochromocytoma (nZ82) and inherited RCC (nZ64) and no evidence of germline mutations in known susceptibility genes. No confirmed pathogenic mutations were detected suggesting that mutations in these genes are not a frequent cause of inherited phaeochromocytoma or RCC

Perturbations of a Universe Filled with Dust and Radiation

A first-order perturbation approach to $k=0$ Friedmann cosmologies filled with dust and radiation is developed. Adopting the coordinate gauge comoving with the perturbed matter, and neglecting the vorticity of the radiation, a pair of coupled equations is obtained for the trace $h$ of the metric perturbations and for the velocity potential $v$. A power series solution with upwards cutoff exists such that the leading terms for large values of the dimensionless time $\xi$ agree with the relatively growing terms of the dust solution of Sachs and Wolfe.Comment: 9 pp, typeset in late

Methylation profiling and evaluation of demethylating therapy in renal cell carcinoma.

BACKGROUND: Despite therapeutic advances in targeted therapy, metastatic renal cell carcinoma (RCC) remains incurable for the vast majority of patients. Key molecular events in the pathogenesis of RCC include inactivation of the VHL tumour suppressor gene (TSG), inactivation of chromosome 3p TSGs implicated in chromatin modification and remodelling and de novo tumour-specific promoter methylation of renal TSGs. In the light of these observations it can be proposed that, as in some haematological malignancies, demethylating agents such as azacitidine might be beneficial for the treatment of advanced RCC. RESULTS: Here we report that the treatment of RCC cell lines with azacitidine suppressed cell proliferation in all 15 lines tested. A marked response to azacitidine therapy (>50% reduction in colony formation assay) was detected in the three cell lines with VHL promoter methylation but some RCC cell lines without VHL TSG methylation also demonstrated a similar response suggesting that multiple methylated TSGs might determine the response to demethylating therapies. To identify novel candidate methylated TSGs implicated in RCC we undertook a combined analysis of copy number and CpG methylation array data. Candidate novel epigenetically inactivated TSGs were further prioritised by expression analysis of RCC cell lines pre and post-azacitidine therapy and comparative expression analysis of tumour/normal pairs. Thus, with subsequent investigation two candidate genes were found to be methylated in more than 25% of our series and in the TCGA methylation dataset for 199 RCC samples: RGS7 (25.6% and 35.2% of tumours respectively) and NEFM in (25.6% and 30.2%). In addition three candidate genes were methylated in >10% of both datasets (TMEM74 (15.4% and 14.6%), GCM2 (41.0% and 14.6%) and AEBP1 (30.8% and 13.1%)). Methylation of GCM2 (P = 0.0324), NEFM (P = 0.0024) and RGS7 (P = 0.0067) was associated with prognosis. CONCLUSIONS: These findings provide preclinical evidence that treatment with demethylating agents such as azacitidine might be useful for the treatment of advanced RCC and further insights into the role of epigenetic changes in the pathogenesis of RCC

Conjunctions of Among Constraints

Many existing global constraints can be encoded as a conjunction of among constraints. An among constraint holds if the number of the variables in its scope whose value belongs to a prespecified set, which we call its range, is within some given bounds. It is known that domain filtering algorithms can benefit from reasoning about the interaction of among constraints so that values can be filtered out taking into consideration several among constraints simultaneously. The present pa- per embarks into a systematic investigation on the circumstances under which it is possible to obtain efficient and complete domain filtering algorithms for conjunctions of among constraints. We start by observing that restrictions on both the scope and the range of the among constraints are necessary to obtain meaningful results. Then, we derive a domain flow-based filtering algorithm and present several applications. In particular, it is shown that the algorithm unifies and generalizes several previous existing results.Comment: 15 pages plus appendi

The Counterpart Principle of Analogical Support by Structural Similarity

We propose and investigate an Analogy Principle in the context of Unary Inductive Logic based on a notion of support by structural similarity which is often employed to motivate scientific conjectures

Manipulative therapy and/or NSAIDs for acute low back pain: design of a randomized controlled trial [ACTRN012605000036617]

BACKGROUND: Acute low back pain is a common condition resulting in pain and disability. Current national and international guidelines advocate general practitioner care including advice and paracetamol (4 g daily in otherwise well adults) as the first line of care for people with acute low back pain. Non-steroidal anti-inflammatory drugs (NSAIDs) and spinal manipulative therapy (SMT) are advocated in many guidelines as second line management options for patients with acute low back pain who are not recovering. No studies have explored the role of NSAIDs and/or SMT in addition to first line management for acute low back pain. The primary aim of this study is to investigate if NSAIDs and/or SMT in addition to general practitioner advice and paracetamol results in shorter recovery times for patients with acute low back pain. The secondary aims of the study are to evaluate whether the addition of SMT and/or NSAIDs influences pain, disability and global perceived effect at 1, 2, 4 and 12 weeks after onset of therapy for patients with significant acute low back pain. METHODS/DESIGN: This paper presents the rationale and design of a randomised controlled trial examining the addition of NSAIDs and/or SMT in 240 people who present to their general practitioner with significant acute low back pain

The effects of different arsenic species in relation to straighthead disease in rice

The effects of inorganic arsenic on plants, the mechanisms involved in the uptake and transport of arsenic and how inorganic arsenic enters food chains are well documented. Regulatory limits have been established to control the inorganic arsenic concentrations in certain foods including rice. There is, however, a knowledge gap with respect to dimethylarsenic concentrations. In this study rice was grown hydroponically and exposed to varying DMA concentrations. High levels of DMA were detrimental to rice plants whereby plants showed symptoms consistent with Straighthead disease, a disease that results in dramatic yield losses.Australian Government ResearchTraining Program ANU OCG Travel Scholarshi

Heavy-Higgs Lifetime at Two Loops

The Standard-Model Higgs boson with mass $M_H >> 2M_Z$ decays almost exclusively to pairs of $W$ and $Z$ bosons. We calculate the dominant two-loop corrections of $O( G_F^2 M_H^4 )$ to the partial widths of these decays. In the on-mass-shell renormalization scheme, the correction factor is found to be $1 + 14.6$, where the second term is the one-loop correction. We give full analytic results for all divergent two-loop Feynman diagrams. A subset of finite two-loop vertex diagrams is computed to high precision using numerical techniques. We find agreement with a previous numerical analysis. The above correction factor is also in line with a recent lattice calculation.Comment: 26 pages, 6 postscript figures. The complete paper including figures is also available via WWW at http://www.physik.tu-muenchen.de/tumphy/d/T30d/PAPERS/TUM-HEP-247-96.ps.g