Radial Velocities as an Exoplanet Discovery Method

The precise radial velocity technique is a cornerstone of exoplanetary astronomy. Astronomers measure Doppler shifts in the star's spectral features, which track the line-of/sight gravitational accelerations of a star caused by the planets orbiting it. The method has its roots in binary star astronomy, and exoplanet detection represents the low-companion-mass limit of that application. This limit requires control of several effects of much greater magnitude than the signal sought: the motion of the telescope must be subtracted, the instrument must be calibrated, and spurious Doppler shifts "jitter" must be mitigated or corrected. Two primary forms of instrumental calibration are the stable spectrograph and absorption cell methods, the former being the path taken for the next generation of spectrographs. Spurious, apparent Doppler shifts due to non-center-of-mass motion (jitter) can be the result of stellar magnetic activity or photospheric motions and granulation. Several avoidance, mitigation, and correction strategies exist, including careful analysis of line shapes and radial velocity wavelength dependence.Comment: Invited review chapter. 13pp. v2 includes corrections to Eqs 3-6, updated references, and minor edit

Long-Term Results of Conservative Surgery and Radiotherapy for Ductal Carcinoma In Situ Using Lung Density Correction: The University of Michigan Experience

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72520/1/j.1524-4741.2007.00447.x.pd

Adherence to self-administered tuberculosis treatment in a high HIV-prevalence setting: a cross-sectional survey in Homa Bay, Kenya.

Good adherence to treatment is crucial to control tuberculosis (TB). Efficiency and feasibility of directly observed therapy (DOT) under routine program conditions have been questioned. As an alternative, Médecins sans Frontières introduced self-administered therapy (SAT) in several TB programs. We aimed to measure adherence to TB treatment among patients receiving TB chemotherapy with fixed dose combination (FDC) under SAT at the Homa Bay district hospital (Kenya). A second objective was to compare the adherence agreement between different assessment tools

ATAD5 promotes replication restart by regulating RAD51 and PCNA in response to replication stress

Maintaining stability of replication forks is important for genomic integrity. However, it is not clear how replisome proteins contribute to fork stability under replication stress. Here, we report that ATAD5, a PCNA unloader, plays multiple functions at stalled forks including promoting its restart. ATAD5 depletion increases genomic instability upon hydroxyurea treatment in cultured cells and mice. ATAD5 recruits RAD51 to stalled forks in an ATR kinase-dependent manner by hydroxyurea-enhanced protein-protein interactions and timely removes PCNA from stalled forks for RAD51 recruitment. Consistent with the role of RAD51 in fork regression, ATAD5 depletion inhibits slowdown of fork progression and native 5-bromo-2??-deoxyuridine signal induced by hydroxyurea. Single-molecule FRET showed that PCNA itself acts as a mechanical barrier to fork regression. Consequently, DNA breaks required for fork restart are reduced by ATAD5 depletion. Collectively, our results suggest an important role of ATAD5 in maintaining genome integrity during replication stress

A phase II study of biweekly oxaliplatin plus infusional 5-fluorouracil and folinic acid (FOLFOX-4) as first-line treatment of advanced gastric cancer patients

The aim of the study was to assess the toxicity and the clinical activity of biweekly oxaliplatin in combination with infusional 5-fluorouracil (5-FU) and folinic acid (FA) administered every 2 weeks (FOLFOX-4 regimen) in patients with advanced gastric cancer (AGC). A total of 61 previously untreated AGC patients were treated with oxaliplatin 85 mg m−2 on day 1, FA 200 mg m−2 as a 2 h infusion followed by bolus 5-FU 400 mg m−2 and a 22 h infusion of 5-FU 600 mg m−2, repeated for 2 consecutive days every 2 weeks. All patients were assessable for toxicity and response to treatment. Four (7%) complete responses and 19 partial responses were observed (overall response rate, 38%). Stable disease was observed in 22 (36%) patients, with progressive disease in the other six (10%) patients. Median time to progression (TTP) and median overall survival (OS) were 7.1 and 11.2 months, respectively. National Cancer Institute Common Toxicity Criteria grade 3 and 4 haematologic toxicities were neutropenia, anaemia and thrombocytopenia in 36, 10 and 5% of the patients, respectively. Grade 3 peripheral neuropathy was recorded in three (5%) patients. FOLFOX-4 is an active and well-tolerated chemotherapy. Response rate (RR), TTP and OS were comparable with those of other oxaliplatin-based regimens, suggesting a role for this combination in gastric cancer

Methodological Deficits in Diagnostic Research Using ‘-Omics’ Technologies: Evaluation of the QUADOMICS Tool and Quality of Recently Published Studies

Background: QUADOMICS is an adaptation of QUADAS (a quality assessment tool for use in systematic reviews of diagnostic accuracy studies), which takes into account the particular challenges presented by '-omics' based technologies. Our primary objective was to evaluate the applicability and consistency of QUADOMICS. Subsequently we evaluated and describe the methodological quality of a sample of recently published studies using the tool. Methodology/Principal Findings: 45'-omics'- based diagnostic studies were identified by systematic search of Pubmed using suitable MeSH terms (>Genomics>, >Sensitivity and specificity>, >Diagnosis>). Three investigators independently assessed the quality of the articles using QUADOMICS and met to compare observations and generate a consensus. Consistency and applicability was assessed by comparing each reviewer's original rating with the consensus. Methodological quality was described using the consensus rating. Agreement was above 80% for all three reviewers. Four items presented difficulties with application, mostly due to the lack of a clearly defined gold standard. Methodological quality of our sample was poor; studies met roughly half of the applied criteria (mean ± sd, 54.7±18.4°%). Few studies were carried out in a population that mirrored the clinical situation in which the test would be used in practice, (6, 13.3%);none described patient recruitment sufficiently; and less than half described clinical and physiological factors that might influence the biomarker profile (20, 44.4%). Conclusions: The QUADOMICS tool can consistently be applied to diagnostic '-omics' studies presently published in biomedical journals. A substantial proportion of reports in this research field fail to address design issues that are fundamental to make inferences relevant for patient care. © 2010 Parker et al.This work was supported by the Spanish Agency for Health Technology Assessment, Exp PI06/90311, Instituto de Salud Carlos III and CIBER en Epidemiología y Salud Pública (CIBERESP) in SpainPeer Reviewe

TESS Hunt for Young and Maturing Exoplanets (THYME). III. A Two-planet System in the 400 Myr Ursa Major Group

Exoplanets can evolve significantly between birth and maturity as their atmospheres, orbits, and structures are shaped by their environment. Young planets ($<$1 Gyr) offer the opportunity to probe these sculpting processes. However, most of the known young planets orbit prohibitively faint stars. We present the discovery of two planets transiting HD 63433 (TOI 1726, TIC 130181866), a young Sun-like ($M_*=0.99\pm0.03$) star. Through kinematics, lithium abundance, and rotation, we confirm that HD 63433 is a member of the Ursa Major moving group ($\tau=414\pm23$ Myr). Based on the TESS light curve and updated stellar parameters, the planet radii are $2.15\pm0.10R_\oplus$ and $2.67\pm0.12R_\oplus$, the orbital periods are 7.11 and 20.55 days, and the orbital eccentricities are lower than abut 0.2. Using HARPS-N velocities, we measure the Rossiter-McLaughlin signal of the inner planet, demonstrating the orbit is prograde. Since the host star is bright (V=6.9), both planets are amenable to transmission spectroscopy, radial velocity measurements of their masses, and more precise determination of the stellar obliquity. This system is therefore poised to play an important role in our understanding of planetary system evolution in the first billion years after formation