Evolutionary Divergence of Duplicate Copies of the Growth Hormone Gene in Suckers (Actinopterygii: Catostomidae)

Catostomid fishes (suckers) have duplicate copies of the growth hormone gene and other nuclear genes, due to a genome duplication event early in the group’s history. Yet, paralogs of GH in suckers are more than 90% conserved in nucleotide (nt) and amino acid (aa) sequence. Within paralogs across species, variation in nt and aa sequence averages 3.33% and 4.46% for GHI, and 3.22% and 2.43% for GHII, respectively. Selection tests suggest that the two GH paralogs are under strong purifying selection. Consensus trees from phylogenetic analysis of GH coding region data for 23 species of suckers, other cypriniform fishes and outgroups resolved cypriniform relationships and relationships among GHI sequences of suckers more or less consistently with analyses based on other molecular data. However, the analysis failed to resolve all sucker GHI and GHII sequences as monophyletic sister groups. This unexpected topology did not differ significantly from topologies constrained to make all GH sequences monophyletic. We attribute this result either to limitations in our GHII data set or convergent adaptive changes in GHII of tribe Catostomini

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

Case–Control Study of an Acute Aflatoxicosis Outbreak, Kenya, 2004

Objectives: During January–June 2004, an aflatoxicosis outbreak in eastern Kenya resulted in 317 cases and 125 deaths. We conducted a case–control study to identify risk factors for contamination of implicated maize and, for the first time, quantitated biomarkers associated with acute aflatoxicosis. Design: We administered questionnaires regarding maize storage and consumption and obtained maize and blood samples from participants. Participants: We recruited 40 case-patients with aflatoxicosis and 80 randomly selected controls to participate in this study. Evaluations/Measurements: We analyzed maize for total aflatoxins and serum for aflatoxin B(1)–lysine albumin adducts and hepatitis B surface antigen. We used regression and survival analyses to explore the relationship between aflatoxins, maize consumption, hepatitis B surface antigen, and case status. Results: Homegrown (not commercial) maize kernels from case households had higher concentrations of aflatoxins than did kernels from control households [geometric mean (GM) = 354.53 ppb vs. 44.14 ppb; p = 0.04]. Serum adduct concentrations were associated with time from jaundice to death [adjusted hazard ratio = 1.3; 95% confidence interval (CI), 1.04–1.6]. Case patients had positive hepatitis B titers [odds ratio (OR) = 9.8; 95% CI, 1.5–63.1] more often than controls. Case patients stored wet maize (OR = 3.5; 95% CI, 1.2–10.3) inside their homes (OR = 12.0; 95% CI, 1.5–95.7) rather than in granaries more often than did controls. Conclusion: Aflatoxin concentrations in maize, serum aflatoxin B(1)–lysine adduct concentrations, and positive hepatitis B surface antigen titers were all associated with case status. Relevance: The novel methods and risk factors described may help health officials prevent future outbreaks of aflatoxicosis

An Introduction to Gas Accretion onto Galaxies

Evidence for gas accretion onto galaxies can be found throughout the universe. In this chapter, I summarize the direct and indirect signatures of this process and discuss the primary sources. The evidence for gas accretion includes the star formation rates and metallicities of galaxies, the evolution of the cold gas content of the universe with time, numerous indirect indicators for individual galaxies, and a few direct detections of inflow. The primary sources of gas accretion are the intergalactic medium, satellite gas and feedback material. There is support for each of these sources from observations and simulations, but the methods with which the fuel ultimately settles in to form stars remain murky.Comment: 14 pages, 5 figures, Invited review to appear in Gas Accretion onto Galaxies, Astrophysics and Space Science Library, eds. A. J. Fox & R. Dav\'e, to be published by Springe

Construct-level predictive validity of educational attainment and intellectual aptitude tests in medical student selection: meta-regression of six UK longitudinal studies

Background: Measures used for medical student selection should predict future performance during training. A problem for any selection study is that predictor-outcome correlations are known only in those who have been selected, whereas selectors need to know how measures would predict in the entire pool of applicants. That problem of interpretation can be solved by calculating construct-level predictive validity, an estimate of true predictor-outcome correlation across the range of applicant abilities. Methods: Construct-level predictive validities were calculated in six cohort studies of medical student selection and training (student entry, 1972 to 2009) for a range of predictors, including A-levels, General Certificates of Secondary Education (GCSEs)/O-levels, and aptitude tests (AH5 and UK Clinical Aptitude Test (UKCAT)). Outcomes included undergraduate basic medical science and finals assessments, as well as postgraduate measures of Membership of the Royal Colleges of Physicians of the United Kingdom (MRCP(UK)) performance and entry in the Specialist Register. Construct-level predictive validity was calculated with the method of Hunter, Schmidt and Le (2006), adapted to correct for right-censorship of examination results due to grade inflation. Results: Meta-regression analyzed 57 separate predictor-outcome correlations (POCs) and construct-level predictive validities (CLPVs). Mean CLPVs are substantially higher (.450) than mean POCs (.171). Mean CLPVs for first-year examinations, were high for A-levels (.809; CI: .501 to .935), and lower for GCSEs/O-levels (.332; CI: .024 to .583) and UKCAT (mean = .245; CI: .207 to .276). A-levels had higher CLPVs for all undergraduate and postgraduate assessments than did GCSEs/O-levels and intellectual aptitude tests. CLPVs of educational attainment measures decline somewhat during training, but continue to predict postgraduate performance. Intellectual aptitude tests have lower CLPVs than A-levels or GCSEs/O-levels. Conclusions: Educational attainment has strong CLPVs for undergraduate and postgraduate performance, accounting for perhaps 65% of true variance in first year performance. Such CLPVs justify the use of educational attainment measure in selection, but also raise a key theoretical question concerning the remaining 35% of variance (and measurement error, range restriction and right-censorship have been taken into account). Just as in astrophysics, ‘dark matter’ and ‘dark energy’ are posited to balance various theoretical equations, so medical student selection must also have its ‘dark variance’, whose nature is not yet properly characterized, but explains a third of the variation in performance during training. Some variance probably relates to factors which are unpredictable at selection, such as illness or other life events, but some is probably also associated with factors such as personality, motivation or study skills

A Census of Oxygen in Star-Forming Galaxies: An Empirical Model Linking Metallicities, Star Formation Rates and Outflows

In this contribution we present the first census of oxygen in star-forming galaxies in the local universe. We examine three samples of galaxies with metallicities and star formation rates at z = 0.07, 0.8 and 2.26, including the SDSS and DEEP2 surveys. We infer the total mass of oxygen produced and mass of oxygen found in the gas-phase from our local SDSS sample. The star formation history is determined by requiring that galaxies evolve along the relation between stellar mass and star formation rate observed in our three samples. We show that the observed relation between stellar mass and star formation rate for our three samples is consistent with other samples in the literature. The mass-metallicity relation is well established for our three samples and from this we empirically determine the chemical evolution of star-forming galaxies. Thus, we are able to simultaneously constrain the star formation rates and metallicities of galaxies over cosmic time allowing us to estimate the mass of oxygen locked up in stars. Combining this work with independent measurements reported in the literature we conclude that the loss of oxygen from the interstellar medium of local star-forming galaxies is likely to be a ubiquitous process with the oxygen mass loss scaling (almost) linearly with stellar mass. We estimate the total baryonic mass loss and argue that only a small fraction of the baryons inferred from cosmological observations accrete onto galaxies.Comment: 24 pages, 18 figures. Accepted for publication in Ap

Anomalous Heat Conduction and Anomalous Diffusion in Low Dimensional Nanoscale Systems

Thermal transport is an important energy transfer process in nature. Phonon is the major energy carrier for heat in semiconductor and dielectric materials. In analogy to Ohm's law for electrical conductivity, Fourier's law is a fundamental rule of heat transfer in solids. It states that the thermal conductivity is independent of sample scale and geometry. Although Fourier's law has received great success in describing macroscopic thermal transport in the past two hundreds years, its validity in low dimensional systems is still an open question. Here we give a brief review of the recent developments in experimental, theoretical and numerical studies of heat transport in low dimensional systems, include lattice models, nanowires, nanotubes and graphenes. We will demonstrate that the phonon transports in low dimensional systems super-diffusively, which leads to a size dependent thermal conductivity. In other words, Fourier's law is breakdown in low dimensional structures

Type Ia Supernova host galaxies as seen with IFU spectroscopy

(abridged) We used the wide-field IFU spectrograph PMAS/PPAK at the 3.5m telescope of Calar Alto Observatory to observe six nearby spiral galaxies that hosted SNe Ia. Spatially resolved 2D maps of the properties of the ionized gas and the stellar populations were derived. Five of the observed galaxies have an ongoing star formation rate of 1-5 M_sun/yr and mean stellar population ages ~5 Gyr. The sixth galaxy shows no star formation and has an about 12 Gyr old stellar population. All galaxies have stellar masses larger than 2E+10 M_sun and metallicities above solar. Four galaxies show negative radial metallicity gradients of the ionized gas up to -0.058 dex/kpc and one has nearly uniform metallicity with a possible shallow positive slope. The stellar components show shallower negative metallicity gradients up to -0.03 dex/kpc. We find no clear correlation between the properties of the galaxy and those of the supernovae, which may be because of the small ranges spanned by the galaxy parameters. However, we note that the Hubble residuals are on average positive while negative Hubble residuals are expected for SNe Ia in massive hosts such as the galaxies in our sample. In conclusion, IFU spectroscopy on 4-m telescopes is a viable technique for studying host galaxies of nearby SNe Ia. It allows one to correlate the supernova properties with the properties of their host galaxies at the projected positions of the supernovae. Our current sample of six galaxies is too small to draw conclusions about the SN Ia progenitors or correlations with the galaxy properties, but the ongoing CALIFA IFU survey will provide a solid basis to exploit this technique more and improve our understanding of SNe Ia as cosmological standard candles.Comment: accepted by A&A, final language-edited version, layout change

Cirrhosis: Morphologic dynamics for the nonmorphologist

Cirrhosis is an irreversible end-stage liver disease characterized by septate scars dividing a distorted liver into nodules. It generates through a sequence of dynamic changes and once it develops, it may alter its appearance through variations in secondary factors, such as injury and nutrition. The different classification schemes have, unfortunately, only served to make cirrhosis static in our thinking. Stationary morphologic characteristics are of value only if they can be correlated with etiology.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44380/1/10620_2005_Article_BF02231300.pd