Litigation Versus Legislation: The Emerging Role of State Attorneys General as National Policymakers

In the Margaret Chase Smith Essay, Andrew Ketterer, who served three terms as Maine‘s Attorney General, discusses the increasingly important role of state attorneys general in influencing policy. This has come about to an extent because of multi-state lawsuits, such as the landmark national suit against tobacco companies

Design of the iLocater Acquisition Camera Demonstration System

Existing planet-finding spectrometers are limited by systematic errors that result from their seeing-limited design. Of particular concern is the use of multi-mode fibers (MMFs), which introduce modal noise and accept significant amounts of background radiation from the sky. We present the design of a single-mode fiber-based acquisition camera for a diffraction-limited spectrometer named "iLocater." By using the "extreme" adaptive optics (AO) system of the Large Binocular Telescope (LBT), iLocater will overcome the limitations that prevent Doppler instruments from reaching their full potential, allowing precise radial velocity (RV) measurements of terrestrial planets around nearby bright stars. The instrument presented in this paper, which we refer to as the acquisition camera "demonstration system," will measure on-sky single-mode fiber (SMF) coupling efficiency using one of the 8.4m primaries of the LBT in fall 2015

On-sky single-mode fiber coupling measurements at the Large Binocular Telescope

The demonstration of efficient single-mode fiber (SMF) coupling is a key requirement for the development of a compact, ultra-precise radial velocity (RV) spectrograph. iLocater is a next generation instrument for the Large Binocular Telescope (LBT) that uses adaptive optics (AO) to inject starlight into a SMF. In preparation for commissioning iLocater, a prototype SMF injection system was installed and tested at the LBT in the Y-band (0.970-1.065 $\mu$m). This system was designed to verify the capability of the LBT AO system as well as characterize on-sky SMF coupling efficiencies. SMF coupling was measured on stars with variable airmasses, apparent magnitudes, and seeing conditions for six half-nights using the Large Binocular Telescope Interferometer. We present the overall optical and mechanical performance of the SMF injection system, including details of the installation and alignment procedure. A particular emphasis is placed on analyzing the instrument's performance as a function of telescope elevation to inform the final design of the fiber injection system for iLocater.Comment: 11 pages, 7 figure

Final Design and On-Sky Testing of the iLocater SX Acquisition Camera: Broadband Single-Mode Fiber Coupling

Enabling efficient injection of light into single-mode fibers (SMFs) is a key requirement in realizing diffraction-limited astronomical spectroscopy on ground-based telescopes. SMF-fed spectrographs, facilitated by the use of adaptive optics (AO), offer distinct advantages over comparable seeing-limited designs, including higher spectral resolution within a compact and stable instrument volume, and a telescope independent spectrograph design. iLocater is an extremely precise radial velocity (EPRV) spectrograph being built for the Large Binocular Telescope (LBT). We have designed and built the front-end fiber injection system, or acquisition camera, for the SX (left) primary mirror of the LBT. The instrument was installed in 2019 and underwent on-sky commissioning and performance assessment. In this paper, we present the instrument requirements, acquisition camera design, as well as results from first-light measurements. Broadband single-mode fiber coupling in excess of 35% (absolute) in the near-infrared (0.97-1.31{\mu}m) was achieved across a range of target magnitudes, spectral types, and observing conditions. Successful demonstration of on-sky performance represents both a major milestone in the development of iLocater and in making efficient ground-based SMF-fed astronomical instruments a reality.Comment: 18 pages, 17 figures. Accepted for publication in MNRA

A genome-wide association study identifies protein quantitative trait loci (pQTLs)

There is considerable evidence that human genetic variation influences gene expression. Genome-wide studies have revealed that mRNA levels are associated with genetic variation in or close to the gene coding for those mRNA transcripts - cis effects, and elsewhere in the genome - trans effects. The role of genetic variation in determining protein levels has not been systematically assessed. Using a genome-wide association approach we show that common genetic variation influences levels of clinically relevant proteins in human serum and plasma. We evaluated the role of 496,032 polymorphisms on levels of 42 proteins measured in 1200 fasting individuals from the population based InCHIANTI study. Proteins included insulin, several interleukins, adipokines, chemokines, and liver function markers that are implicated in many common diseases including metabolic, inflammatory, and infectious conditions. We identified eight Cis effects, including variants in or near the IL6R (p = 1.8×10 -57), CCL4L1 (p = 3.9×10-21), IL18 (p = 6.8×10-13), LPA (p = 4.4×10-10), GGT1 (p = 1.5×10-7), SHBG (p = 3.1×10-7), CRP (p = 6.4×10-6) and IL1RN (p = 7.3×10-6) genes, all associated with their respective protein products with effect sizes ranging from 0.19 to 0.69 standard deviations per allele. Mechanisms implicated include altered rates of cleavage of bound to unbound soluble receptor (IL6R), altered secretion rates of different sized proteins (LPA), variation in gene copy number (CCL4L1) and altered transcription (GGT1). We identified one novel trans effect that was an association between ABO blood group and tumour necrosis factor alpha (TNF-alpha) levels (p = 6.8×10-40), but this finding was not present when TNF-alpha was measured using a different assay , or in a second study, suggesting an assay-specific association. Our results show that protein levels share some of the features of the genetics of gene expression. These include the presence of strong genetic effects in cis locations. The identification of protein quantitative trait loci (pQTLs) may be a powerful complementary method of improving our understanding of disease pathways. © 2008 Melzer et al

Persistent Gastric Colonization with Burkholderia pseudomallei and Dissemination from the Gastrointestinal Tract following Mucosal Inoculation of Mice

Melioidosis is a disease of humans caused by opportunistic infection with the soil and water bacterium Burkholderia pseudomallei. Melioidosis can manifest as an acute, overwhelming infection or as a chronic, recurrent infection. At present, it is not clear where B. pseudomallei resides in the mammalian host during the chronic, recurrent phase of infection. To address this question, we developed a mouse low-dose mucosal challenge model of chronic B. pseudomallei infection and investigated sites of bacterial persistence over 60 days. Sensitive culture techniques and selective media were used to quantitate bacterial burden in major organs, including the gastrointestinal (GI) tract. We found that the GI tract was the primary site of bacterial persistence during the chronic infection phase, and was the only site from which the organism could be consistently cultured during a 60-day infection period. The organism could be repeatedly recovered from all levels of the GI tract, and chronic infection was accompanied by sustained low-level fecal shedding. The stomach was identified as the primary site of GI colonization as determined by fluorescent in situ hybridization. Organisms in the stomach were associated with the gastric mucosal surface, and the propensity to colonize the gastric mucosa was observed with 4 different B. pseudomallei isolates. In contrast, B. pseudomallei organisms were present at low numbers within luminal contents in the small and large intestine and cecum relative to the stomach. Notably, inflammatory lesions were not detected in any GI tissue examined in chronically-infected mice. Only low-dose oral or intranasal inoculation led to GI colonization and development of chronic infection of the spleen and liver. Thus, we concluded that in a mouse model of melioidosis B. pseudomallei preferentially colonizes the stomach following oral inoculation, and that the chronically colonized GI tract likely serves as a reservoir for dissemination of infection to extra-intestinal sites

Rare Complications of Acute Appendicitis: A Case Report

Introduction: Appendicitis is a common disease, and as we have improved in early diagnosis and management of this disease process, late stage complications have become extremely rare, but can have indolent presentations.Case Report: A 37-year-old male with no past medical history presented to the emergency department (ED) with vague abdominal pain as well as 12 days of cyclical fever. He had no significant findings on laboratory workup with the exception of a mild aspartate transaminase and alanine transaminase and relative neutrophilia between outpatient, urgent care, and ultimate ED visit. His ED workup included cross-sectional imaging of his abdomen revealing multiple liver abscesses and septic thrombophlebitis secondary to ruptured appendicitis.Conclusion: Liver abscesses and septic thrombophlebitis are an extremely rare complication of appendicitis that has only been documented twice previously