Distant X-ray Galaxies: Insights from the Local Population

A full understanding of the origin of the hard X-ray background requires a complete and accurate census of the distant galaxies that produce it. Unfortunately, distant X-ray galaxies tend to be very faint at all wavelengths, which hinders efforts to perform this census. This chapter discusses the insights that can be obtained through comparison of the distant population to local X-ray galaxies, whose properties are well characterized. Such comparisons will ultimately aid investigations into the cosmic evolution of supermassive black holes and their environments.Comment: 19 pages, 10 figures, to appear as Chapter 7 in "Supermassive Black Holes in the Distant Universe" (2004), ed. A. J. Barger, Kluwer Academic Publishers, in pres

The fetal mouse is a sensitive genotoxicity model that exposes lentiviral-associated mutagenesis resulting in liver oncogenesis

This article is available open access through the publisher’s website at the link below. Copyright @ 2013 The American Society of Gene & Cell Therapy.Genotoxicity models are extremely important to assess retroviral vector biosafety before gene therapy. We have developed an in utero model that demonstrates that hepatocellular carcinoma (HCC) development is restricted to mice receiving nonprimate (np) lentiviral vectors (LV) and does not occur when a primate (p) LV is used regardless of woodchuck post-translation regulatory element (WPRE) mutations to prevent truncated X gene expression. Analysis of 839 npLV and 244 pLV integrations in the liver genomes of vector-treated mice revealed clear differences between vector insertions in gene dense regions and highly expressed genes, suggestive of vector preference for insertion or clonal outgrowth. In npLV-associated clonal tumors, 56% of insertions occurred in oncogenes or genes associated with oncogenesis or tumor suppression and surprisingly, most genes examined (11/12) had reduced expression as compared with control livers and tumors. Two examples of vector-inserted genes were the Park 7 oncogene and Uvrag tumor suppressor gene. Both these genes and their known interactive partners had differential expression profiles. Interactive partners were assigned to networks specific to liver disease and HCC via ingenuity pathway analysis. The fetal mouse model not only exposes the genotoxic potential of vectors intended for gene therapy but can also reveal genes associated with liver oncogenesis.Imperial College London, the Wellcome Trust, and Brunel University

Playing God? Synthetic biology as a theological and ethical challenge

In the ethical debate over synthetic biology the formula “playing god” is widely used in order to attack this new branch of biotechnology. The article analyses, contextualizes and criticises this usage with respect to the theological concepts of creation, sin and humans as created in the image of God. Against the background of these theological understandings an ethical corridor of how to responsibly cope with the societal challenges of synthetic biology is presented

Thrombosis Is Reduced by Inhibition of COX-1, but Unaffected by Inhibition of COX-2, in an Acute Model of Platelet Activation in the Mouse

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Relationship between resident workload and self-perceived learning on inpatient medicine wards: a longitudinal study

BACKGROUND: Despite recent residency workload and hour limitations, little research on the relationship between workload and learning has been done. We sought to define residents' perceptions of the optimal patient workload for learning, and to determine how certain variables contribute to those perceptions. Our hypothesis was that the relationship between perceived workload and learning has a maximum point (forming a parabolic curve): that either too many or too few patients results in sub-optimal learning. METHODS: Residents on inpatient services at two academic teaching hospitals reported their team and individual patient censuses, and rated their perception of their learning; the patient acuity; case variety; and how challenged they felt. To estimate maximum learning scores, linear regression models with quadratic terms were fit on learning score. RESULTS: Resident self-perceived learning correlated with higher acuity and greater heterogeneity of case variety. The equation of census versus learning score, adjusted for perception of acuity and case mix scores, showed a parabolic curve in some cases but not in others. CONCLUSION: These data suggest that perceived resident workload is complex, and impacted by additional variables including patient acuity and heterogeneity of case variety. Parabolic curves exist for interns with regard to overall census and for senior residents with regard to new admissions on long call days

The academic backbone: longitudinal continuities in educational achievement from secondary school and medical school to MRCP(UK) and the specialist register in UK medical students and doctors

Background: Selection of medical students in the UK is still largely based on prior academic achievement, although doubts have been expressed as to whether performance in earlier life is predictive of outcomes later in medical school or post-graduate education. This study analyses data from five longitudinal studies of UK medical students and doctors from the early 1970s until the early 2000s. Two of the studies used the AH5, a group test of general intelligence (that is, intellectual aptitude). Sex and ethnic differences were also analyzed in light of the changing demographics of medical students over the past decades. Methods: Data from five cohort studies were available: the Westminster Study (began clinical studies from 1975 to 1982), the 1980, 1985, and 1990 cohort studies (entered medical school in 1981, 1986, and 1991), and the University College London Medical School (UCLMS) Cohort Study (entered clinical studies in 2005 and 2006). Different studies had different outcome measures, but most had performance on basic medical sciences and clinical examinations at medical school, performance in Membership of the Royal Colleges of Physicians (MRCP(UK)) examinations, and being on the General Medical Council Specialist Register. Results: Correlation matrices and path analyses are presented. There were robust correlations across different years at medical school, and medical school performance also predicted MRCP(UK) performance and being on the GMC Specialist Register. A-levels correlated somewhat less with undergraduate and post-graduate performance, but there was restriction of range in entrants. General Certificate of Secondary Education (GCSE)/O-level results also predicted undergraduate and post-graduate outcomes, but less so than did A-level results, but there may be incremental validity for clinical and post-graduate performance. The AH5 had some significant correlations with outcome, but they were inconsistent. Sex and ethnicity also had predictive effects on measures of educational attainment, undergraduate, and post-graduate performance. Women performed better in assessments but were less likely to be on the Specialist Register. Non-white participants generally underperformed in undergraduate and post-graduate assessments, but were equally likely to be on the Specialist Register. There was a suggestion of smaller ethnicity effects in earlier studies. Conclusions: The existence of the Academic Backbone concept is strongly supported, with attainment at secondary school predicting performance in undergraduate and post-graduate medical assessments, and the effects spanning many years. The Academic Backbone is conceptualized in terms of the development of more sophisticated underlying structures of knowledge ('cognitive capital’ and 'medical capital’). The Academic Backbone provides strong support for using measures of educational attainment, particularly A-levels, in student selection

Populations of a Susceptible Amphibian Species Can Grow despite the Presence of a Pathogenic Chytrid Fungus

Disease can be an important driver of host population dynamics and epizootics can cause severe host population declines. Batrachochytrium dendrobatidis (Bd), the pathogen causing amphibian chytridiomycosis, may occur epizootically or enzootically and can harm amphibian populations in many ways. While effects of Bd epizootics are well documented, the effects of enzootic Bd have rarely been described. We used a state-space model that accounts for observation error to test whether population trends of a species highly susceptible to Bd, the midwife toad Alytes obstetricans, are negatively affected by the enzootic presence of the pathogen. Unexpectedly, Bd had no negative effect on population growth rates from 2002–2008. This suggests that negative effects of disease on individuals do not necessarily translate into negative effects at the population level. Populations of amphibian species that are susceptible to the emerging disease chytridiomycosis can persist despite the enzootic presence of the pathogen under current environmental conditions

The effectiveness of public health interventions to reduce the health impact of climate change:a systematic review of systematic reviews

Climate change is likely to be one of the most important threats to public health in the coming years. Yet despite the large number of papers considering the health impact of climate change, few have considered what public health interventions may be of most value in reducing the disease burden. We aimed to evaluate the effectiveness of public health interventions to reduce the disease burden of high priority climate sensitive diseases

Steeper size spectra with decreasing phytoplankton biomass indicate strong trophic amplification and future fish declines

Under climate change, model ensembles suggest that declines in phyto�plankton biomass amplify into greater reductions at higher trophic levels, with serious implications for fisheries and carbon storage. However, the extent and mechanisms of this trophic amplification vary greatly among models, and validation is problematic. In situ size spectra offer a novel alternative, com�paring biomass of small and larger organisms to quantify the net efficiency of energy transfer through natural food webs that are already challenged with multiple climate change stressors. Our global compilation of pelagic size spectrum slopes supports trophic amplification empirically, independently from model simulations. Thus, even a modest (16%) decline in phytoplankton this century would magnify into a 38% decline in supportable biomass of fish within the intensively-fished mid-latitude ocean. We also show that this amplification stems not from thermal controls on consumers, but mainly from temperature or nutrient controls that structure the phytoplankton baseline of the food web. The lack of evidence for direct thermal effects on size structure contrasts with most current thinking, based often on more acute stress experiments or shorter-timescale responses. Our synthesis of size spectra integrates these short-term dynamics, revealing the net efficiency of food webs acclimating and adapting to climatic stressor