Genetic Discrimination: Overview of the Issue and Proposed Legislation

[Excerpt] A key policy issue before Congress is whether the potential for genetic discrimination by employers and insurers merits protections for genetic information that are more extensive than those already in place for health information. For the stated purpose of prohibiting discrimination on the basis of genetic information with respect to health insurance and employment, the Genetic Information Nondiscrimination Act of 2007 (H.R. 493) was introduced in the House on January 16, 2007. On January 22, 2007, the act was introduced in the Senate (S. 358). The act is identical to the Genetic Information Nondiscrimination Act of 2005, which passed the Senate by a vote of 98-0 (S. 306, 109th). An identical House bill (H.R. 1227, 109th), never came to a vote. S. 306 was very similar to S. 1053 (108th), which the Senate passed in 2003 by a vote of 95-0. A distinct House bill, H.R. 1910 (108th), never came to a vote. This report focuses on the key points in the ongoing debate about genetic discrimination legislation

Rep-tiling for triangles

AbstractIn this paper we prove that one can only tile a triangle with tiles all congruent to each other and similar to the original triangle when k2, l2 + k2, or 3k2 tiles are used. The result is based on the geometry of packing and a result of I. Niven's on rational trigonometric values. In addition we describe how to tile most triangles

Improving Assessment of Drug Safety Through Proteomics: Early Detection and Mechanistic Characterization of the Unforeseen Harmful Effects of Torcetrapib.

BackgroundEarly detection of adverse effects of novel therapies and understanding of their mechanisms could improve the safety and efficiency of drug development. We have retrospectively applied large-scale proteomics to blood samples from ILLUMINATE (Investigation of Lipid Level Management to Understand its Impact in Atherosclerotic Events), a trial of torcetrapib (a cholesterol ester transfer protein inhibitor), that involved 15 067 participants at high cardiovascular risk. ILLUMINATE was terminated at a median of 550 days because of significant absolute increases of 1.2% in cardiovascular events and 0.4% in mortality with torcetrapib. The aims of our analysis were to determine whether a proteomic analysis might reveal biological mechanisms responsible for these harmful effects and whether harmful effects of torcetrapib could have been detected early in the ILLUMINATE trial with proteomics.MethodsA nested case-control analysis of paired plasma samples at baseline and at 3 months was performed in 249 participants assigned to torcetrapib plus atorvastatin and 223 participants assigned to atorvastatin only. Within each treatment arm, cases with events were matched to controls 1:1. Main outcomes were a survey of 1129 proteins for discovery of biological pathways altered by torcetrapib and a 9-protein risk score validated to predict myocardial infarction, stroke, heart failure, or death.ResultsPlasma concentrations of 200 proteins changed significantly with torcetrapib. Their pathway analysis revealed unexpected and widespread changes in immune and inflammatory functions, as well as changes in endocrine systems, including in aldosterone function and glycemic control. At baseline, 9-protein risk scores were similar in the 2 treatment arms and higher in participants with subsequent events. At 3 months, the absolute 9-protein derived risk increased in the torcetrapib plus atorvastatin arm compared with the atorvastatin-only arm by 1.08% (P=0.0004). Thirty-seven proteins changed in the direction of increased risk of 49 proteins previously associated with cardiovascular and mortality risk.ConclusionsHeretofore unknown effects of torcetrapib were revealed in immune and inflammatory functions. A protein-based risk score predicted harm from torcetrapib within just 3 months. A protein-based risk assessment embedded within a large proteomic survey may prove to be useful in the evaluation of therapies to prevent harm to patients.Clinical trial registrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT00134264

Dynamical signatures of freezing: stable fluids, metastable fluids, and crystals

Mean squared displacements and velocity auto correlation functions are calculated using molecular dynamics for hard spheres under a range of conditions (i) for the equilibrium fluid below freezing; (ii) for the metastable fluid above freezing; and (iii) for the hard sphere crystal, both in the metastable region between freezing and melting, and in the stable region above melting. In addition, simulations are carried out for a metastable Lennard-Jones system. The results confirm recent studies that indicated the disappearance of the classical Alder long-time tail, and show that they apply to systems other than the metastable hard sphere fluid. The implications of these results for our understanding of crystallization and the glass transition are discussed

A Soft X-ray Transient in the M31 Bulge

We have examined a probable soft X-ray transient source in the M31 bulge at R.A.=0:42:41.814 +/- 0.08", Dec. = 41:16:35.86 +/- 0.07". On the three occasions we observed the source, its spectrum was soft (kT_{in} ~1 keV). The brightest detection of the source was 2004 July 17 with a 0.3-7 keV luminosity of ~5 X 10^{37} erg/s. The only previous detection of the source was in 1979 by the Einstein observatory. The multiple detections over 25 years suggest the duty cycle of the source is in the range 0.02-0.06. Coordinated HST/ACS imaging before, during, and after the outburst revealed no variable optical source within the position errors of the X-ray source. The optical data place a firm upper limit on the brightness of the counterpart of the X-ray outburst of B>24.7, suggesting the binary has a period <5.2 days. The X-ray spectrum and lack of bright stars at the source location indicate the source was a soft transient event occurring in a low-mass X-ray binary, making this source a good black hole candidate in M31.Comment: 18 pages, 4 tables, 3 figures, accepted for publication in Ap

Monocyte subset recruitment marker profile is inversely associated with blood apoa1 levels

Dyslipidemia promotes development of the atherosclerotic plaques that characterise cardiovascular disease. Plaque progression requires the influx of monocytes into the vessel wall, but whether dyslipidemia is associated with an increased potential of monocytes to extravasate is largely unknown. Here (using flow cytometry) we examined recruitment marker expression on monocytes from generally healthy individuals who differed in lipid profile. Comparisons were made between monocyte subsets, participants and relative to participants’ lipid levels. Monocyte subsets differed significantly in their expression of recruitment markers, with highest expression being on either the classical or non-classical subsets. However, these inter-subset differences were largely overshadowed by considerable inter-participant differences with some participants having higher levels of recruitment markers on all three monocyte subsets. Furthermore, when the expression of one recruitment marker was high, so too was that of most of the other markers, with substantial correlations evident between the markers. The inter-participant differences were explained by lipid levels. Most notably, there was a significant inverse correlation for most markers with ApoA1 levels. Our results indicate that dyslipidemia, in particular low levels of ApoA1, is associated with an increased potential of all monocyte subsets to extravasate, and to do so using a wider repertoire of recruitment markers than currently appreciated

Structures controlling volcanic activity within Masaya caldera, Nicaragua

Geophysical and geological observations collected in 2007-2012 shed light on the mechanisms controlling the style and location of eruptions within the Las Sierras-Masaya Caldera complex, Nicaragua. These results confirm a hypothesised ~3.5 km diameter structure with features compatible with the presence of a ring fracture (50-65°, with inward-dipping bounding walls). A central block is bound by this fracture and defines an incipient nested caldera related to the emptying of the magma chamber following the last Plinian eruption (1.8 ka). The prolongation of the Cofradías fault from the Managua graben represents the most significant structure on the floor of Masaya caldera. Current activity, including a convecting lava lake, largely depends on the interplay between the extensional stress regime associated with the Managua graben and deformation along the inner caldera bounding fault. This high spatial resolution survey uses a novel combination of geophysical methodologies to identify previously overlooked foci for future volcanic activity at Masaya

Monocyte inflammatory profile is specific for individuals and associated with altered blood lipid levels

Background and aims Atherogenesis is dependent upon monocyte influx into the vessel wall. In humans, three monocyte subsets exist, the number and function of which are significantly altered in cardiovascular disease (CVD). Whether such alterations arise in individuals with a perturbed lipid profile remains largely unanswered, but is important to delineate, as adoption of a pro-inflammatory state may promote plaque formation. Here, we compared the inflammatory status of monocyte subsets and determined whether monocyte inflammatory changes are evident in individuals with a perturbed lipid profile. Methods Monocyte subset cytokine production, inflammatory and anti-inflammatory marker expression were determined by whole blood flow cytometry and related to participants' lipid levels. Results The intermediate and non-classical monocytes were more inflammatory than classicals as seen by their higher cytokine production (TNF-α, IL-1β, IL-6) and M1 marker (CD86) expression, but lower levels of M2 markers (CD93, CD163). More importantly, a considerable variation was seen between participants, with all monocytes of one individual being more inflammatory than those of another. Many inter-individual differences were related to participants' lipid levels. IL-1β production correlated negatively with Apo A1 and HDL-C. CD86 and TLR2 correlated positively with Chol:HDL-C but negatively with HDL-C and Apo A1:Apo B. Interestingly, CD163 expression correlated positively with Chol:HDL-C but negatively with Apo A1:Apo B. Conclusions Our data indicates that priming of all monocytes to an inflammatory state occurs in individuals with a perturbed lipid profile, overriding the normal functional distinction attributed to the different monocyte subsets. As such, all monocytes may be important in CVD

Engaging the agricultural community in the development of mental health interventions: a qualitative research study

Background: Farmers and those involved in the wider agricultural industry have a high suicide rate. They are also a ‘hard to reach’ group who make less than average use of mental health services. There is therefore a need to understand how best to develop interventions that meet their needs. The aims of this study were to develop a deeper understanding of the farming context and target population and to engage farmers in the shaping of two potential mental health interventions that could be incorporated in a pilot RCT. Methods: The study was informed throughout by a reference group, who assisted in co-production of the research materials. A snowball approach was used to recruit interested individuals who had an association with farming. Twenty one telephone interviews were undertaken and analysed using the six phases of thematic analysis proposed by Braun and Clarke. Results: Key themes (and sub-themes shown in brackets) related to the study aims were: everyday life (work-life balance; isolation and loneliness); farm management (technology and social media; production, people management, learning and teaching; external pressures; livestock and farm production; financial aspects); demographics (effects of aging); engagement (appropriate wording when talking about mental health; recognising need for help; religion; normalising mental health issues; approaching the conversation); training (mental health training for supporters of the farming community; health &amp; safety and the inclusion of mental health training); and personal stories and experiences, which was an emerging theme. Conclusions: Recruiting farmers into research studies is best done by meeting farmers where they are found, for example, farmers marts. Accessibility of content, tailoring to the farming community, and guided support are key to effective recruitment and retention

X-ray and Radio Variability of M31*, The Andromeda Galaxy Nuclear Supermassive Black Hole

We confirm our earlier tentative detection of M31* in X-rays and measure its light-curve and spectrum. Observations in 2004-2005 find M31* rather quiescent in the X-ray and radio. However, X-ray observations in 2006-2007 and radio observations in 2002 show M31* to be highly variable at times. A separate variable X-ray source is found near P1, the brighter of the two optical nuclei. The apparent angular Bondi radius of M31* is the largest of any black hole, and large enough to be well resolved with Chandra. The diffuse emission within this Bondi radius is found to have an X-ray temperature ~0.3 keV and density 0.1 cm-3, indistinguishable from the hot gas in the surrounding regions of the bulge given the statistics allowed by the current observations. The X-ray source at the location of M31* is consistent with a point source and a power law spectrum with energy slope 0.9+/-0.2. Our identification of this X-ray source with M31* is based solely on positional coincidence.Comment: 25 pages, 8 figures, submitted to Ap