Bayesian Methods for Exoplanet Science

Exoplanet research is carried out at the limits of the capabilities of current telescopes and instruments. The studied signals are weak, and often embedded in complex systematics from instrumental, telluric, and astrophysical sources. Combining repeated observations of periodic events, simultaneous observations with multiple telescopes, different observation techniques, and existing information from theory and prior research can help to disentangle the systematics from the planetary signals, and offers synergistic advantages over analysing observations separately. Bayesian inference provides a self-consistent statistical framework that addresses both the necessity for complex systematics models, and the need to combine prior information and heterogeneous observations. This chapter offers a brief introduction to Bayesian inference in the context of exoplanet research, with focus on time series analysis, and finishes with an overview of a set of freely available programming libraries.Comment: Invited revie

Exoplanet Atmosphere Measurements from Transmission Spectroscopy and other Planet-Star Combined Light Observations

It is possible to learn a great deal about exoplanet atmospheres even when we cannot spatially resolve the planets from their host stars. In this chapter, we overview the basic techniques used to characterize transiting exoplanets - transmission spectroscopy, emission and reflection spectroscopy, and full-orbit phase curve observations. We discuss practical considerations, including current and future observing facilities and best practices for measuring precise spectra. We also highlight major observational results on the chemistry, climate, and cloud properties of exoplanets.Comment: Accepted review chapter; Handbook of Exoplanets, eds. Hans J. Deeg and Juan Antonio Belmonte (Springer-Verlag). 22 pages, 6 figure

Detection of Pneumocystis DNA in samples from patients suspected of bacterial pneumonia- a case-control study

BACKGROUND: Pneumocystis jiroveci (formerly known as P. carinii f.sp. hominis) is an opportunistic fungus that causes Pneumocystis pneumonia (PCP) in immunocompromised individuals. Pneumocystis jiroveci can be detected by polymerase chain reaction (PCR). To investigate the clinical importance of a positive Pneumocystis-PCR among HIV-uninfected patients suspected of bacterial pneumonia, a retrospective matched case-control study was conducted. METHODS: Respiratory samples from 367 patients suspected of bacterial pneumonia were analysed by PCR amplification of Pneumocystis jiroveci. To compare clinical factors associated with carriage of P. jiroveci, a case-control study was done. For each PCR-positive case, four PCR-negative controls, randomly chosen from the PCR-negative patients, were matched on sex and date of birth. RESULTS: Pneumocystis-DNA was detected in 16 (4.4%) of patients. The median age for PCR-positive patients was higher than PCR-negative patients (74 vs. 62 years, p = 0.011). PCR-positive cases had a higher rate of chronic or severe concomitant illness (15 (94%)) than controls (32 (50%)) (p = 0.004). Twelve (75%) of the 16 PCR positive patients had received corticosteroids, compared to 8 (13%) of the 64 PCR-negative controls (p < 0.001). Detection of Pneumocystis-DNA was associated with a worse prognosis: seven (44%) of patients with positive PCR died within one month compared to nine (14%) of the controls (p = 0.01). None of the nine PCR-positive patients who survived had developed PCP at one year of follow-up. CONCLUSIONS: Our data suggest that carriage of Pneumocystis jiroveci is associated with old age, concurrent disease and steroid treatment. PCR detection of P. jiroveci has low specificity for diagnosing PCP among patients without established immunodeficiency. Whether overt infection is involved in the poorer prognosis or merely reflects sub-clinical carriage is not clear. Further studies of P. jiroveci in patients receiving systemic treatment with corticosteroids are warranted

V3 Loop Sequence Space Analysis Suggests Different Evolutionary Patterns of CCR5- and CXCR4-Tropic HIV

The V3 loop of human immunodeficiency virus type 1 (HIV-1) is critical for coreceptor binding and is the main determinant of which of the cellular coreceptors, CCR5 or CXCR4, the virus uses for cell entry. The aim of this study is to provide a large-scale data driven analysis of HIV-1 coreceptor usage with respect to the V3 loop evolution and to characterize CCR5- and CXCR4-tropic viral phenotypes previously studied in small- and medium-scale settings. We use different sequence similarity measures, phylogenetic and clustering methods in order to analyze the distribution in sequence space of roughly 1000 V3 loop sequences and their tropism phenotypes. This analysis affords a means of characterizing those sequences that are misclassified by several sequence-based coreceptor prediction methods, as well as predicting the coreceptor using the location of the sequence in sequence space and of relating this location to the CD4+ T-cell count of the patient. We support previous findings that the usage of CCR5 is correlated with relatively high sequence conservation whereas CXCR4-tropic viruses spread over larger regions in sequence space. The incorrectly predicted sequences are mostly located in regions in which their phenotype represents the minority or in close vicinity of regions dominated by the opposite phenotype. Nevertheless, the location of the sequence in sequence space can be used to improve the accuracy of the prediction of the coreceptor usage. Sequences from patients with high CD4+ T-cell counts are relatively highly conserved as compared to those of immunosuppressed patients. Our study thus supports hypotheses of an association of immune system depletion with an increase in V3 loop sequence variability and with the escape of the viral sequence to distant parts of the sequence space

High tide or riptide on the cosmic shoreline? A water-rich atmosphere or stellar contamination for the warm super-Earth GJ 486b from JWST observations

Planets orbiting M-dwarf stars are prime targets in the search for rocky exoplanet atmospheres. The small size of M dwarfs renders their planets exceptional targets for transmission spectroscopy, facilitating atmospheric characterization. However, it remains unknown whether their host stars' highly variable extreme-UV radiation environments allow atmospheres to persist. With JWST, we have begun to determine whether or not the most favorable rocky worlds orbiting M dwarfs have detectable atmospheres. Here, we present a 2.8–5.2 μm JWST NIRSpec/G395H transmission spectrum of the warm (700 K, 40.3× Earth's insolation) super-Earth GJ 486b (1.3 R⊕ and 3.0 M⊕). The measured spectrum from our two transits of GJ 486b deviates from a flat line at 2.2σ − 3.3σ, based on three independent reductions. Through a combination of forward and retrieval models, we determine that GJ 486b either has a water-rich atmosphere (with the most stringent constraint on the retrieved water abundance of H2O > 10% to 2σ) or the transmission spectrum is contaminated by water present in cool unocculted starspots. We also find that the measured stellar spectrum is best fit by a stellar model with cool starspots and hot faculae. While both retrieval scenarios provide equal quality fits (${\chi }_{\nu }^{2}=1.0$) to our NIRSpec/G395H observations, shorter wavelength observations can break this degeneracy and reveal if GJ 486b sustains a water-rich atmosphere

Qualitative assessment of innovations in healthcare provision

<p>Abstract</p> <p>Background</p> <p>The triad of quality, innovation and economic restraint is as important in health care as it is in the business world. There are many proposals for the assessment of quality and of economic restraints in health care but only a few address assessment of innovations. We propose a strategy and new structures to standardize the description of health care innovations and to quantify them.</p> <p>Discussion</p> <p>Strategy and structure are based on the assumption that in the early phase of an innovation only data on the feasibility and possibly on the efficacy or effectiveness of an innovation can be expected. From the patient's perspective, benefit resulting from an innovation can be confirmed only in a later phase of development. Early indicators of patient's benefit will be surrogate parameters which correlate only weakly with the desired endpoints. After the innovation has been in use, there will be more evidence on correlations between surrogate parameters and the desired endpoints to provide evidence of the patient benefit. From an administrative perspective, this evidence can be considered in decisions about public financing. Different criteria are proposed for the assessment of innovations in prevention, diagnosis and therapy. For decisions on public financing a public fund for innovations may be helpful. Depending on the phase of innovation risk sharing models are proposed between manufacturers, private insurers and public funding.</p> <p>Summary</p> <p>Potential for patient benefit is always uncertain during early stages of innovations. This uncertainty decreases with increasing information on the effects of the innovation. Information about an innovation can be quantified, categorized and integrated into rational economic decisions.</p

Knockout mice: Is it just genetics? Effect of enriched housing on fibulin-4+/- mice

Background. Fibulin-4 is an extracellular matrix protein expressed by vascular smooth muscle cells that is essential for maintaining arterial integrity. Fibulin-4-/- mice die just before birth due to arterial hemorrhage, but fibulin-4+/- mice appear to be outwardly normal. Experiments were therefore performed to determine whether fibulin-4+/- mice display arterial pathologies on a microscopic scale. After preliminary experiments were performed, a second purpose developed, which was to test the hypothesis that any observed pathologies would be ameliorated by housing the animals in enriched cages. Methodology. Fibulin-4+/- and wild-type mice were housed either four/cage in standard cages or two per cage in larger cages, each cage containing a tunnel and a wheel. After three weeks the mice were sacrificed, and the aortas perfusion-fixed and excised for light and electron microscopy. Principle Findings. When the mice were in standard cages, localized regions of disorganized extracellular matrix and collagen fibers consistently appeared between some of the medial smooth muscle cells in the fibulin-4+/- mice. In the wild-type mice, the smooth muscle cells were closely connected to each other and the media was more compact. The number of disorganized regions per square mm was significantly greater for fibulin-4+/- mice (172±43 (SEM)) than for wild-type mice (15±8) (p<0.01, n = 8). When the mice were in enriched cages, the fibulin-4+/- mice showed significantly fewer disorganized regions than those in standard cages (35±12) (p<0.05, n = 8). The wild type mice also showed fewer disorganized regions (3±2), but this difference was not significant. Conclusions. These results indicate that arterial pathologies manifested in fibulin-4+/- mice can be reduced by enriching the housing conditions, and imply that appropriate environments may counteract the effects of some genetic deficiencies

Circumstellar disks and planets. Science cases for next-generation optical/infrared long-baseline interferometers

We present a review of the interplay between the evolution of circumstellar disks and the formation of planets, both from the perspective of theoretical models and dedicated observations. Based on this, we identify and discuss fundamental questions concerning the formation and evolution of circumstellar disks and planets which can be addressed in the near future with optical and infrared long-baseline interferometers. Furthermore, the importance of complementary observations with long-baseline (sub)millimeter interferometers and high-sensitivity infrared observatories is outlined.Comment: 83 pages; Accepted for publication in "Astronomy and Astrophysics Review"; The final publication is available at http://www.springerlink.co