Radiative properties of visible and subvisible Cirrus: Scattering on hexagonal ice crystals

One of the main objectives of the First International Satellite Cloud Climatology Project (ISCCP) Regional Experiment (FIRE) is to provide a better understanding of the physics of upper level clouds. The focus is on just one specific aspect of cirrus physics, namely on characterizing the radiative properties of single, nonspherical ice particles. The basis for further more extensive studies of the radiative transfer through upper level clouds is provided. Radiation provides a potential mechanism for strong feedback between the divergence of in-cloud radiative flux and the cloud microphysics and ultimately on the dynamics of the cloud. Some aspects of ice cloud microphysics that are relevant to the radiation calculations are described. Next, the Discrete Dipole Approximation (DDA) is introduced and some new results of scattering by irregular crystals are presented. The Anomalous Diffraction Theory (ADT) was adopted to investigate the scattering properties of even larger crystals. In this way the scattering properties of nonspherical particles were determined over a range of particle sizes

An investigation of polymorphisms in the 17q11.2-12 CC chemokine gene cluster for association with multiple sclerosis in Australians

BACKGROUND: Multiple sclerosis (MS) is a disorder of the central nervous system (CNS) characterised by inflammation and neuronal degeneration. It is believed to result from the complex interaction of a number of genes, each with modest effect. Chemokines are vital to the migration of cells to sites of inflammation, including the CNS, and many are implicated in MS pathogenesis. Most of the CC chemokine genes are encoded in a cluster on chromosome 17q11.2-12, which has been identified in a number of genome wide screens as being potentially associated with MS. METHODS: We conducted a two-stage analysis to investigate the chemokine gene cluster for association with MS. After sequencing the chemokine genes in several DNA pools to identify common polymorphisms, 12 candidate single-nucleotide polymorphisms (SNPs) were genotyped in a cohort of Australian MS trio families. RESULTS: Marginally significant (uncorrected) transmission distortion was identified for four of the SNPs after stratification for several factors. We also identified marginally significant (uncorrected) transmission distortion for haplotypes encompassing the CCL2 and CCL11 genes, using two independent cohorts, which was consistent with recent reports from another group. CONCLUSION: Our results implicate several chemokines as possibly being associated with MS susceptibility, and given that chemokines and their receptors are suitable targets for therapeutic agents, further investigation is warranted in this region

NGX-4010, a capsaicin 8% patch, for the treatment of painful HIV-associated distal sensory polyneuropathy: integrated analysis of two phase III, randomized, controlled trials

BACKGROUND HIV-associated distal sensory polyneuropathy (HIV-DSP) is the most frequently reported neurologic complication associated with HIV infection. NGX-4010 is a capsaicin 8% dermal patch with demonstrated efficacy in the treatment of HIV-DSP. Data from two phase III, double-blind studies were integrated to further analyze the efficacy and safety of NGX-4010 and explore the effect of demographic and baseline factors on NGX-4010 treatment in HIV-DSP. METHODS Data from two similarly designed studies in which patients with HIV-DSP received NGX-4010 or a low-concentration control patch (capsaicin 0.04% w/w) for 30 or 60 minutes were integrated. Efficacy assessments included the mean percent change from baseline in Numeric Pain Rating Scale (NPRS) scores to Weeks 2-12. Safety and tolerability assessments included adverse events (AEs) and pain during and after treatment. RESULTS Patients (n = 239) treated with NGX-4010 for 30 minutes demonstrated significantly (p = 0.0026) greater pain relief compared with controls (n = 100); the mean percent change in NPRS scores from baseline to Weeks 2-12 was -27.0% versus -15.7%, respectively. Patients who received a 60-minute application of NGX-4010 (n = 243) showed comparable pain reductions (-27.5%) to patients treated for 30 minutes, but this was not statistically superior to controls (n = 115). NGX-4010 was effective regardless of gender, baseline pain score, duration of HIV-DSP, or use of concomitant neuropathic pain medication, although NGX-4010 efficacy was greater in patients not receiving concomitant neuropathic pain medications. NGX-4010 was well tolerated; the most common AEs were application-site pain and erythema, and most AEs were mild to moderate. The transient increase in pain associated with NGX-4010 treatment decreased the day after treatment and returned to baseline by Day 2. CONCLUSIONS A single 30-minute application of NGX-4010 provides significant pain relief for at least 12 weeks in patients with HIV-DSP and is well tolerated. TRIAL REGISTRATION C107 = NCT00064623; C119 = NCT00321672

Multiple Isoforms of ANRIL in Melanoma Cells: Structural Complexity Suggests Variations in Processing

The long non-coding RNA ANRIL, antisense to the CDKN2B locus, is transcribed from a gene that encompasses multiple disease-associated polymorphisms. Despite the identification of multiple isoforms of ANRIL, expression of certain transcripts has been found to be tissue-specific and the characterisation of ANRIL transcripts remains incomplete. Several functions have been associated with ANRIL. In our judgement, studies on ANRIL functionality are premature pending a more complete appreciation of the profusion of isoforms. We found differential expression of ANRIL exons, which indicates that multiple isoforms exist in melanoma cells. In addition to linear isoforms, we identified circular forms of ANRIL (circANRIL). Further characterisation of circANRIL in two patient-derived metastatic melanoma cell lines (NZM7 and NZM37) revealed the existence of a rich assortment of circular isoforms. Moreover, in the two melanoma cell lines investigated, the complements of circANRIL isoforms were almost completely different. Novel exons were also discovered. We also found the family of linear ANRIL was enriched in the nucleus, whilst the circular isoforms were enriched in the cytoplasm and they differed markedly in stability. With respect to the variable processing of circANRIL species, bioinformatic analysis indicated that intronic Arthrobacter luteus (Alu) restriction endonuclease inverted repeats and exon skipping were not involved in selection of back-spliced exon junctions. Based on our findings, we hypothesise that “ANRIL” has wholly distinct dual sets of functions in melanoma. This reveals the dynamic nature of the locus and constitutes a basis for investigating the functions of ANRIL in melanoma.Peer reviewe

Little evidence for association between the TGFBR1*6A variant and colorectal cancer: a family-based association study on non-syndromic family members from Australia and Spain

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Genome-wide linkage studies have identified the 9q22 chromosomal region as linked with colorectal cancer (CRC) predisposition. A candidate gene in this region is transforming growth factor β receptor 1 (TGFBR1). Investigation of TGFBR1 has focused on the common genetic variant rs11466445, a short exonic deletion of nine base pairs which results in truncation of a stretch of nine alanine residues to six alanine residues in the gene product. While the six alanine (*6A) allele has been reported to be associated with increased risk of CRC in some population based study groups this association remains the subject of robust debate. To date, reports have been limited to population-based case–control association studies, or case–control studies of CRC families selecting one affected individual per family. No study has yet taken advantage of all the genetic information provided by multiplex CRC families

An Integrated Approach for Characterizing Aerosol Climate Impacts and Environmental Interactions

Aerosols exert myriad influences on the earth's environment and climate, and on human health. The complexity of aerosol-related processes requires that information gathered to improve our understanding of climate change must originate from multiple sources, and that effective strategies for data integration need to be established. While a vast array of observed and modeled data are becoming available, the aerosol research community currently lacks the necessary tools and infrastructure to reap maximum scientific benefit from these data. Spatial and temporal sampling differences among a diverse set of sensors, nonuniform data qualities, aerosol mesoscale variabilities, and difficulties in separating cloud effects are some of the challenges that need to be addressed. Maximizing the long-term benefit from these data also requires maintaining consistently well-understood accuracies as measurement approaches evolve and improve. Achieving a comprehensive understanding of how aerosol physical, chemical, and radiative processes impact the earth system can be achieved only through a multidisciplinary, inter-agency, and international initiative capable of dealing with these issues. A systematic approach, capitalizing on modern measurement and modeling techniques, geospatial statistics methodologies, and high-performance information technologies, can provide the necessary machinery to support this objective. We outline a framework for integrating and interpreting observations and models, and establishing an accurate, consistent, and cohesive long-term record, following a strategy whereby information and tools of progressively greater sophistication are incorporated as problems of increasing complexity are tackled. This concept is named the Progressive Aerosol Retrieval and Assimilation Global Observing Network (PARAGON). To encompass the breadth of the effort required, we present a set of recommendations dealing with data interoperability; measurement and model integration; multisensor synergy; data summarization and mining; model evaluation; calibration and validation; augmentation of surface and in situ measurements; advances in passive and active remote sensing; and design of satellite missions. Without an initiative of this nature, the scientific and policy communities will continue to struggle with understanding the quantitative impact of complex aerosol processes on regional and global climate change and air quality

Little evidence for association between the TGFBR1*6A variant and colorectal cancer: a family-based association study on non-syndromic family members from Australia and Spain.

Genome-wide linkage studies have identified the 9q22 chromosomal region as linked with colorectal cancer (CRC) predisposition. A candidate gene in this region is transforming growth factor beta receptor 1 (TGFBR1). Investigation of TGFBR1 has focused on the common genetic variant rs11466445, a short exonic deletion of nine base pairs which results in truncation of a stretch of nine alanine residues to six alanine residues in the gene product. While the six alanine (*6A) allele has been reported to be associated with increased risk of CRC in some population based study groups this association remains the subject of robust debate. To date, reports have been limited to population-based case-control association studies, or case-control studies of CRC families selecting one affected individual per family. No study has yet taken advantage of all the genetic information provided by multiplex CRC families. Methods: We have tested for an association between rs11466445 and risk of CRC using several family-based statistical tests in a new study group comprising members of non-syndromic high risk CRC families sourced from three familial cancer centres, two in Australia and one in Spain. Results: We report a finding of a nominally significant result using the pedigree-based association test approach (PBAT; p = 0.028), while other family-based tests were non-significant, but with a p-value < 0.10 in each instance. These other tests included the Generalised Disequilibrium Test (GDT; p = 0.085), parent of origin GDT Generalised Disequilibrium Test (GDT-PO; p = 0.081) and empirical Family-Based Association Test (FBAT; p = 0.096, additive model). Related-person case-control testing using the 'More Powerful' Quasi-Likelihood Score Test did not provide any evidence for association (M-QL5; p = 0.41). Conclusions: After conservatively taking into account considerations for multiple hypothesis testing, we find little evidence for an association between the TGFBR1*6A allele and CRC risk in these families. The weak support for an increase in risk in CRC predisposed families is in agreement with recent meta-analyses of case-control studies, which estimate only a modest increase in sporadic CRC risk among 6*A allele carriers

The Atacama Cosmology Telescope: Cross Correlation with Planck maps

We present the temperature power spectrum of the Cosmic Microwave Background obtained by cross-correlating maps from the Atacama Cosmology Telescope (ACT) at 148 and 218 GHz with maps from the Planck satellite at 143 and 217 GHz, in two overlapping regions covering 592 square degrees. We find excellent agreement between the two datasets at both frequencies, quantified using the variance of the residuals between the ACT power spectra and the ACTxPlanck cross-spectra. We use these cross-correlations to calibrate the ACT data at 148 and 218 GHz, to 0.7% and 2% precision respectively. We find no evidence for anisotropy in the calibration parameter. We compare the Planck 353 GHz power spectrum with the measured amplitudes of dust and cosmic infrared background (CIB) of ACT data at 148 and 218 GHz. We also compare planet and point source measurements from the two experiments.Comment: 9 pages, 8 figure

3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors reduce the risk of perioperative stroke and mortality after carotid endarterectomy

ObjectiveThere is increasing evidence that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) reduce cardiovascular and cerebrovascular events through anti-inflammatory, plaque stabilization, and neuroprotective effects independent of lipid lowering. This study was designed to investigate whether statin use reduces the incidence of perioperative stroke and mortality among patients undergoing carotid endarterectomy (CEA).MethodsAll patients undergoing CEA from 1994 to 2004 at a large academic medical center were retrospectively reviewed. The independent association of statin use and perioperative morbidity was assessed via multivariate logistic regression analysis.ResultsCEA was performed by 13 surgeons on 1566 patients (987 men and 579 women; mean age, 72 ± 10 years), including 1440 (92%) isolated and 126 (8%) combined CEA/coronary artery bypass grafting procedures. The indication for CEA was symptomatic disease in 660 (42%) cases. Six hundred fifty-seven (42%) patients received a statin medication for at least 1 week before surgery. Statin use was associated with a reduction in perioperative strokes (1.2% vs 4.5%; P < .01), transient ischemic attacks (1.5% vs 3.6%; P < .01), all-cause mortality (0.3% vs 2.1%; P < .01), and median (interquartile range) length of hospitalization (2 days [2-5 days] vs 3 days [2-7 days]; P < .05). Adjusting for all demographics and comorbidities in multivariate analysis, statin use independently reduced the odds of stroke threefold (odds ratio [95% confidence interval], 0.35 [0.15-0.85]; P < .05) and death fivefold (odds ratio [95% confidence interval], 0.20 [0.04-0.99]; P < .05).ConclusionsThese data suggest that perioperative statin use may reduce the incidence of cerebrovascular events and mortality among patients undergoing CEA