Planetary Imaging in Powers of Ten: A Multiscale, Multipurpose Astrobiological Imager

Contextual, multiscale astrobiological imaging is necessary to discover, map, and image patchy microbial colonization in extreme environments on planetary surfaces. The large difference in scale—several orders of magnitude—between search environment and microorganisms or microbial communities represents a challenge, which to date no single imaging instrument is able to overcome. In support of future planetary reconnaissance missions, we introduce an adapter-based imager, built from an off-the-shelf consumer digital camera, that offers scalable imaging ranging from macroscopic (meters per pixel) to microscopic (micrometers per pixel) imaging, that is, spanning at least 6 orders of magnitude. Magnification in digital cameras is governed by the native resolution of the CCD/CMOS chip of the camera, the distance between camera and object to be imaged (focal length), and the built-in optical and digital zoom. Both telezoom and macro mode alone are usually insufficient for microscopic imaging. Therefore, the focal distance has to be shortened, and the native CCD resolution of the camera has to be increased to attain a microscopic imaging capability. Our adapter-based imager bridges the gap between macroscopic and microscopic imaging, thereby enabling for the first time contextual astrobiological imaging with the same instrument. Real-world applications for astrobiology and planetary geology are discussed, and proof-of-concept imagery taken with our prototype is presented

A randomized phase II study of lapatinib + pazopanib versus lapatinib in patients with HER2+ inflammatory breast cancer

This multi-center Phase II study evaluated lapatinib, pazopanib, and the combination in patients with relapsed HER2+ inflammatory breast cancer. In Cohort 1, 76 patients were randomized 1:1 to receive lapatinib 1,500 mg + placebo or lapatinib 1,500 mg + pazopanib 800 mg (double-blind) once daily until disease progression, unacceptable toxicity, or death. Due to high-grade diarrhea observed with this dose combination in another study (VEG20007), Cohort 1 was closed. The protocol was amended such that an additional 88 patients (Cohort 2) were randomized in a 5:5:2 ratio to receive daily monotherapy lapatinib 1,500 mg, lapatinib 1,000 mg + pazopanib 400 mg, or monotherapy pazopanib 800 mg, respectively. The primary endpoint was overall response rate (ORR). Secondary endpoints included duration of response, progression-free survival (PFS), overall survival, and safety. In Cohort 1, ORR for the lapatinib (n = 38) and combination (n = 38) arms was 29 and 45 %, respectively; median PFS was 16.1 and 14.3 weeks, respectively. Grade ≥3 adverse events (AEs) were more frequent in the combination arm (71 %) than in the lapatinib arm (24 %). Dose reductions and interruptions due to AEs were also more frequent in the combination arm (45 and 53 %, respectively) than in the lapatinib monotherapy arm (0 and 11 %, respectively). In Cohort 2, ORR for patients treated with lapatinib (n = 36), lapatinib + pazopanib (n = 38), and pazopanib (n = 13) was 47, 58, and 31 %, respectively; median PFS was 16.0, 16.0, and 11.4 weeks, respectively. In the lapatinib, combination, and pazopanib therapy arms, grade ≥3 AEs were reported for 17, 50, and 46 % of patients, respectively, and the incidence of discontinuations due to AEs was 0, 24, and 23 %, respectively. The lapatinib–pazopanib combination was associated with a numerically higher ORR but no increase in PFS compared to lapatinib alone. The combination also had increased toxicity resulting in more dose reductions, modifications, and treatment delays. Activity with single-agent lapatinib was confirmed in this population

Alcohol use after liver transplantation in alcoholics: A clinical cohort follow-up study

The purposes of this study were to determine among a cohort of long-term alcoholic survivors after liver transplantation (1) the incidence of alcohol use, (2) its effect on allograft integrity and extrahepatic health, and (3) the validity of the pretransplant alcohol prognosis screening process. Retrospective clinical cohort study of all alcoholic patients undergoing orthotopic liver transplantation at a single center from February 1987 until January 1991 with follow-up through December 1994, giving a median duration of follow-up of 63 months (range, 6-89 months). Multidisciplinary liver transplantation program at a tertiary-care academic medical center. Fifty alcoholic, long-term liver transplant recipients. The frequency of alcohol relapse, defined as any alcohol use in the period after transplantation, was determined by two questionnaire studies and by clinical follow-up. Allograft integrity was assessed by coded review of serial percutaneous allograft biopsies. Potential systemic effects of alcohol relapse were assessed by chart review. The alcohol prognosis screening process was evaluated by retrospectively comparing pretransplant estimates of putative indicators of alcoholism prognosis in posttransplant alcohol users and abstainers. Thirty-three recipients (66%) consistently denied any alcohol use throughout the duration of posttransplant follow-up, whereas 17 (34%) were identified as having consumed alcohol at least once since the transplant. There were no significant differences at the time of evaluation between abstainers and alcohol users in age, sex distribution, severity of liver dysfunction, median duration of abstinence, or University of Michigan alcoholism prognosis score. The median interval from transplantation to alcohol relapse was 17 months, with a range of 3 to 45 months. Recurrent alcohol use was associated with significant medical complications sufficient to require admission to the hospital in 6 patients. One patient died of graft dysfunction, noncompliance with immunosuppressant medications, and presumed graft rejection while drinking. Mild or progressive hepatitis, which was the most common abnormality in posttransplant liver biopsy findings, was equally distributed between both alcohol users and abstainers and sometimes occurred in the absence of antibody to hepatitis C virus antibodies. There was a similar frequency of biopsy-proven acute cellular rejection in alcohol users and abstainers. Typical histological features of alcoholic liver injury were present in posttransplant biopsies from 1 alcohol user only. Alcohol use by alcoholics is uncommon in the first 5 years after liver transplantation, and alcohol-associated liver injury is unusual. Mild nonspecific hepatitis is common in both alcohol users and nonusers alike. Among a small subset of alcoholic transplant recipients, drinking behavior after liver transplantation is associated with considerable morbidity, requiring hospital admissions and occasionally leading to graft loss and death.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34767/1/510250526_ftp.pd

Prospecting in ultracool dwarfs : Measuring the metallicities of mid- and late-m dwarfs

© 2014. The American Astronomical Society. All rights reserved.Metallicity is a fundamental parameter that contributes to the physical characteristics of a star. The low temperatures and complex molecules present in M dwarf atmospheres make it difficult to measure their metallicities using techniques that have been commonly used for Sun-like stars. Although there has been significant progress in developing empirical methods to measure M dwarf metallicities over the last few years, these techniques have been developed primarily for early- to mid-M dwarfs. We present a method to measure the metallicity of mid- to late-M dwarfs from moderate resolution (R ∼ 2000) K-band (≃ 2.2 μm) spectra. We calibrate our formula using 44 wide binaries containing an F, G, K, or early-M primary of known metallicity and a mid- to late-M dwarf companion. We show that similar features and techniques used for early-M dwarfs are still effective for late-M dwarfs. Our revised calibration is accurate to ∼0.07 dex for M4.5-M9.5 dwarfs with -0.58 <[Fe/H] <+0.56 and shows no systematic trends with spectral type, metallicity, or the method used to determine the primary star metallicity. We show that our method gives consistent metallicities for the components of M+M wide binaries. We verify that our new formula works for unresolved binaries by combining spectra of single stars. Lastly, we show that our calibration gives consistent metallicities with the Mann et al. study for overlapping (M4-M5) stars, establishing that the two calibrations can be used in combination to determine metallicities across the entire M dwarf sequence.Peer reviewe