The Spanish Constitution of 1978: Legislative Competence of the Autonomous Communities in Civil Law Matters

The Spanish Constitution of 1978 had to deal with the issues that emerged with the advent of a democratic regime following the death of General Francisco Franco in 1975. Political pluralism, the relationship between church and state, and the official language of the Spanish state were among the dilemmas facing the Constitutional Commission. Yet the historically sensitive issue of the autonomy of the Spanish regions proved to be the most troublesome. Title VIII of the Constitution provides a political compromise in resolution of this issue although scholars and politicians, including some constitutional draftsmen, have criticized the ambiguity of this title. This study focuses on article 149, paragraph 1, section 8 of the Spanish Constitution and the legislative powers granted therein to the autonomous regions in matters of civil law. Not only should it provide some insight into one of the most perplexing clauses of the founding document of post-Franco Spain, but, moreover, it should prove to be an enlightening case study of the interaction between politics and law in the uneasy relationship between Madrid and the present and aspiring autonomous regions of Spain

The Transit Light Curve Project. VI. Three Transits of the Exoplanet TrES-2

Of the nearby transiting exoplanets that are amenable to detailed study, TrES-2 is both the most massive and has the largest impact parameter. We present z-band photometry of three transits of TrES-2. We improve upon the estimates of the planetary, stellar, and orbital parameters, in conjunction with the spectroscopic analysis of the host star by Sozzetti and co-workers. We find the planetary radius to be 1.222 +/- 0.038 R_Jup and the stellar radius to be 1.003 +/- 0.027 R_Sun. The quoted uncertainties include the systematic error due to the uncertainty in the stellar mass (0.980 +/- 0.062 M_Sun). The timings of the transits have an accuracy of 25s and are consistent with a uniform period, thus providing a baseline for future observations with the NASA Kepler satellite, whose field of view will include TrES-2.Comment: 15 pages, including 2 figures, accepted Ap

Financing drug discovery for orphan diseases

Recently proposed ‘megafund’ financing methods for funding translational medicine and drug development require billions of dollars in capital per megafund to de-risk the drug discovery process enough to issue long-term bonds. Here, we demonstrate that the same financing methods can be applied to orphan drug development but, because of the unique nature of orphan diseases and therapeutics (lower development costs, faster FDA approval times, lower failure rates and lower correlation of failures among disease targets) the amount of capital needed to de-risk such portfolios is much lower in this field. Numerical simulations suggest that an orphan disease megafund of only US$575 million can yield double-digit expected rates of return with only 10–20 projects in the portfolio.MIT Laboratory for Financial Engineerin

Mass and radius determinations for five transiting M-dwarf stars

We have derived masses and radii for both components in five short-period single-lined eclipsing binary stars discovered by the TrES wide-angle photometric survey for transiting planets. All these systems consist of a visible F-star primary and an unseen M-star secondary (M_A > 0.8 M_sun, M_B < 0.45 M_sun). The spectroscopic orbital solution combined with a high precision transit light curve for each system gives sufficient information to calculate the density of the primary star and the surface gravity of the secondary. The masses of the primary stars were obtained using stellar evolution models. The solutions were compared with results obtained by calculating the radius of the primary stars under the assumption of rotational synchronization with the orbital period and alignment between their spin axis and the axis of the orbit. Four systems show an acceptable match between the two sets of results, but one system shows a clear mismatch between the two solutions, which may indicate the absence of synchronization or a misalignment between the rotational and orbital axis. When compared to low-mass stellar evolution models, the derived masses and radii of the unseen M dwarfs are inconsistent (three only marginally) with the predicted values, with all of the radii being larger than expected for their masses. These results confirm the discrepancy shown in previous work between the predicted and observed radii on low-mass binary stars. This work also shows that reliance on the assumption of synchronization to derive the mass and radius of stars in eclipsing single--lined F+M binaries is a useful tool, but may not always be warranted and should be carefully tested against stellar evolution models.Comment: 36 pages: 20 pages of text, 13 tables, 7 figures. Accepted for publication in Ap

Commercializing Biomedical Research Through Securitization Techniques

Biomedical innovation has become riskier, more expensive and more difficult to finance with traditional sources such as private and public equity. Here we propose a financial structure in which a large number of biomedical programs at various stages of development are funded by a single entity to substantially reduce the portfolio's risk. The portfolio entity can finance its activities by issuing debt, a critical advantage because a much larger pool of capital is available for investment in debt versus equity. By employing financial engineering techniques such as securitization, it can raise even greater amounts of more-patient capital. In a simulation using historical data for new molecular entities in oncology from 1990 to 2011, we find that megafunds of $5–15 billion may yield average investment returns of 8.9–11.4% for equity holders and 5–8% for 'research-backed obligation' holders, which are lower than typical venture-capital hurdle rates but attractive to pension funds, insurance companies and other large institutional investors

CAMKII as a therapeutic target for growth factor-induced retinal and choroidal neovascularisation

This study was supported by grants from the British Heart Foundation (PG/11/99/29207 and PG/11/94/29169), Fight for Sight, UK (1387/88), Health & Social Care R&D Division, Northern Ireland (STL/4748/13) and the Medical Research Council (MC_PC_15026). We would like to thank Gordon Revolta for excellent assistance with colony management and genotyping.Peer reviewedPublisher PD

Using Cluster Analysis of Cytokines to Identify Patterns of Inflammation in Hospitalized Patients with Community-acquired Pneumonia:A Pilot Study

Purpose: Patients with severe community-acquired pneumonia (CAP) are believed to have an exaggerated inflammatory response to bacterial infection. Therapies aiming to modulate the inflammatory response have been largely unsuccessful, perhaps reflecting that CAP is a heterogeneous disorder that cannot be modulated by a single anti-inflammatory approach. We hypothesize that the host inflammatory response to pneumonia may be characterized by distinct cytokine patterns, which can be harnessed for personalized therapies. Methods: Here, we use hierarchical cluster analysis of cytokines to examine if patterns of inflammatory response in 13 hospitalized patients with CAP can be defined. This was a secondary data analysis of the Community-Acquired Pneumonia Inflammatory Study Group (CAPISG) database. The following cytokines were measured in plasma and sputum on the day of admission: interleukin (IL)-1β, IL-1 receptor antagonist (IL-1ra), IL-6, CXCL8 (IL-8), IL-10, IL-12p40, IL-17, interferon (IFN)γ, tumor necrosis factor (TNF)α, and CXCL10 (IP-10). Hierarchical agglomerative clustering algorithms were used to evaluate clusters of patients within plasma and sputum cytokine determinations. Results: A total of thirteen patients were included in this pilot study. Cluster analysis identified distinct inflammatory response patterns of cytokines in the plasma, sputum, and the ratio of plasma to sputum. Conclusions: Inflammatory response patterns in plasma and sputum can be identified in hospitalized patients with CAP. Characterization of the local and systemic inflammatory response may help to better discriminate patients for enrollment into clinical trials of immunomodulatory therapies