Prudence even beyond other women : the rhetorical maneuvers of Elizabeth I

Elizabeth Tudor (1533-1603) did not set out to better the status of women; as queen, she wanted to neither overturn nor disrupt the very system that authorized her position. Though later generations have anachronistically read her as a type of protofeminist, she saw herself as trying, within necessary constraints, to fulfill simultaneously her roles as both woman and ruler, which meant fitting into the expectations of her society in order to rule and function. However, her society found the very nature of female rule problematic and contradictory to its vision of the natural order. To accomplish this task, Elizabeth used her extensive Humanist training in rhetoric to turn the stations of woman into a series of socially acceptable metaphors. I argue that rather than wishing to step outside of her gender Elizabeth actually immersed herself in the language of gender the better to subvert expectations and create space for her to rule

The effect of institutional distance on cross-border merger and acquisition time to completion: an empirical analysis of European Union deals

Cross-border merger and acquisitions (CBM&As) have extensively been used as a favorite entry mode in foreign markets, rapidly providing resources, competencies and local intelligence without risk of facing the liability of foreignness, or the burden of starting a greenfield investment. Studies indicate that greater institutional distance increases the costs of doing business in a foreign country, because it is associated with greater uncertainty and non-familiarity with the local environment. Besides that, prolonged duration of the M&A process has negative consequences for target and acquirer firms and bear significant costs for both parties. However, until so far, the studies regarding the effect of institutional distances on time to completion of a CBM&A deal are scarce. My theoretical model speculates on the effect of institutional distances (Political, Economic, Administrative and Cultural) in CBM&As time to completion. I further propose that European Union membership, of both target and acquirer countries, moderates the effect of institutional distances on CBM&As time to completion. The hypotheses are tested using a sample of 2,110 CBM&A deals that occurred during 2011 in European Union. On one hand, the results suggest that Political and Cultural distance have a positive effect on the time hiatus between announcement and completion of a CBM&A deal. On the other hand, the results suggest that European Union membership does moderate the effect of Economic and Administrative distance in CBM&A time to completion

Individual, occupational, and workplace correlates of occupational health and safety vulnerability in a sample of Canadian workers

Objective: To describe OH&amp;S vulnerability across a diverse sample of Canadian workers.Methods: A survey was administered to 1,835 workers employed more than 15 hrs/week in workplaces with at least five employees. Adjusted logistic models were fitted for three specific and one overall measure of workplace vulnerability developed based on hazard exposure and access to protective OH&amp;S policies and procedures, awareness of employment rights and responsibilities, and workplace empowerment.Results: More than one third of the sample experienced some OH&amp;S vulnerability. The type and magnitude of vulnerability varied by labor market sub-group. Younger workers and those in smaller workplaces experienced signficantly higher odds of multiple types of vulnerability. Temporary workers reported elevated odds of overall, awareness- and empowerment-related vulnerability, while respondents born outside of Canada had significantly higher odds of awareness vulnerability.Conclusion: Knowing how labor market sub-groups experience different types of vulnerability can inform better-tailored primary prevention interventions.<br /

Functional profiling of the gut microbiome in disease-associated inflammation

The microbial residents of the human gut are a major factor in the development and lifelong maintenance of health. The gut microbiota differs to a large degree from person to person and has an important influence on health and disease due to its interaction with the human immune system. Its overall composition and microbial ecology have been implicated in many autoimmune diseases, and it represents a particularly important area for translational research as a new target for diagnostics and therapeutics in complex inflammatory conditions. Determining the biomolecular mechanisms by which altered microbial communities contribute to human disease will be an important outcome of current functional studies of the human microbiome. In this review, we discuss functional profiling of the human microbiome using metagenomic and metatranscriptomic approaches, focusing on the implications for inflammatory conditions such as inflammatory bowel disease and rheumatoid arthritis. Common themes in gut microbial ecology have emerged among these diverse diseases, but they have not yet been linked to targetable mechanisms such as microbial gene and genome composition, pathway and transcript activity, and metabolism. Combining these microbial activities with host gene, transcript and metabolic information will be necessary to understand how and why these complex interacting systems are altered in disease-associated inflammation

Relating the metatranscriptome and metagenome of the human gut

Although the composition of the human microbiome is now wellstudied, the microbiota’s \u3e8 million genes and their regulation remain largely uncharacterized. This knowledge gap is in part because of the difficulty of acquiring large numbers of samples amenable to functional studies of the microbiota. We conducted what is, to our knowledge, one of the first human microbiome studies in a well-phenotyped prospective cohort incorporating taxonomic, metagenomic, and metatranscriptomic profiling at multiple body sites using self-collected samples. Stool and saliva were provided by eight healthy subjects, with the former preserved by three different methods (freezing, ethanol, and RNAlater) to validate self-collection. Within-subject microbial species, gene, and transcript abundances were highly concordant across sampling methods, with only a small fraction of transcripts (\u3c5%) displaying between-method variation. Next, we investigated relationships between the oral and gut microbial communities, identifying a subset of abundant oral microbes that routinely survive transit to the gut, but with minimal transcriptional activity there. Finally, systematic comparison of the gut metagenome and metatranscriptome revealed that a substantial fraction (41%) of microbial transcripts were not differentially regulated relative to their genomic abundances. Of the remainder, consistently underexpressed pathways included sporulation and amino acid biosynthesis, whereas up-regulated pathways included ribosome biogenesis and methanogenesis. Across subjects, metatranscriptional profiles were significantly more individualized than DNA-level functional profiles, but less variable than microbial composition, indicative of subject-specific whole-community regulation. The results thus detail relationships between community genomic potential and gene expression in the gut, and establish the feasibility of metatranscriptomic investigations in subject-collected and shipped samples

Creating New β-Globin-Expressing Lentiviral Vectors by High-Resolution Mapping of Locus Control Region Enhancer Sequences.

Hematopoietic stem cell gene therapy is a promising approach for treating disorders of the hematopoietic system. Identifying combinations of cis-regulatory elements that do not impede packaging or transduction efficiency when included in lentiviral vectors has proven challenging. In this study, we deploy LV-MPRA (lentiviral vector-based, massively parallel reporter assay), an approach that simultaneously analyzes thousands of synthetic DNA fragments in parallel to identify sequence-intrinsic and lineage-specific enhancer function at near-base-pair resolution. We demonstrate the power of LV-MPRA in elucidating the boundaries of previously unknown intrinsic enhancer sequences of the human β-globin locus control region. Our approach facilitated the rapid assembly of novel therapeutic βAS3-globin lentiviral vectors harboring strong lineage-specific recombinant control elements capable of correcting a mouse model of sickle cell disease. LV-MPRA can be used to map any genomic locus for enhancer activity and facilitates the rapid development of therapeutic vectors for treating disorders of the hematopoietic system or other specific tissues and cell types

Observations of SN 2017ein Reveal Shock Breakout Emission and A Massive Progenitor Star for a Type Ic Supernova

We present optical and ultraviolet observations of nearby type Ic supernova SN 2017ein as well as detailed analysis of its progenitor properties from both the early-time observations and the prediscovery Hubble Space Telescope (HST) images. The optical light curves started from within one day to $\sim$275 days after explosion, and optical spectra range from $\sim$2 days to $\sim$90 days after explosion. Compared to other normal SNe Ic like SN 2007gr and SN 2013ge, \mbox{SN 2017ein} seems to have more prominent C{\footnotesize II} absorption and higher expansion velocities in early phases, suggestive of relatively lower ejecta mass. The earliest photometry obtained for \mbox{SN 2017ein} show indications of shock cooling. The best-fit obtained by including a shock cooling component gives an estimate of the envelope mass as $\sim$0.02 M$_{\odot}$ and stellar radius as 8$\pm$4 R$_{\odot}$. Examining the pre-explosion images taken with the HST WFPC2, we find that the SN position coincides with a luminous and blue point-like source, with an extinction-corrected absolute magnitude of M$_V$$\sim$$-$8.2 mag and M$_I$$\sim$$-$7.7 mag.Comparisons of the observations to the theoretical models indicate that the counterpart source was either a single WR star or a binary with whose members had high initial masses, or a young compact star cluster. To further distinguish between different scenarios requires revisiting the site of the progenitor with HST after the SN fades away.Comment: 28 pages, 19 figures; accepted for publication in The Astrophysical Journa

The direct medical costs of epilepsy in children and young people: a population-based study of health resource utilisation

We described the health resource utilisation (HRU) and associated direct medical costs of managing epilepsy in children and young people (CYP) using population-level data from the United Kingdom. The study cohort were CYP born between 1988 and 2004 who were newly diagnosed with epilepsy and identified using a nationally representative primary care database from the United Kingdom. Reference unit costs were applied to each element of HRU to calculate annual direct medical costs per child. We assessed whether HRU and costs differed by time from diagnosis, age, sex and socioeconomic deprivation. Of 798 CYP newly diagnosed with epilepsy, 56% were male and the mean age at diagnosis was 5.6 years. The highest burden of HRU was in the first year following diagnosis with a mean annual cost of £930 (95% confidence interval (CI) £839–1022) per child in this first year. This decreased to £461 (95%CI 368–551) in the second year which remained fairly constant each subsequent year (£413 (95% CI 282–540) in the 8th year). The highest contribution to the annual medical costs was from inpatient hospital admissions followed by the costs of AEDs. Mean annual medical costs were significantly higher in children under 6 years of age compared with older children (p &lt; 0.01), but were similar across socioeconomic groups (p = 0.62). The direct medical costs of HRU in CYP with epilepsy are higher in the first year after diagnosis compared to subsequent years, reflecting HRU related to the diagnostic process in the first year. Medical costs did not vary substantially by sex or socioeconomic deprivation indicating a similar level of consultation and care across these groups

Restoration of normal blood flow in atherosclerotic arteries promotes plaque stabilization

Blood flow is a key regulator of atherosclerosis. Disturbed blood flow promotes atherosclerotic plaque development, whereas normal blood flow protects against plaque development. We hypothesized that normal blood flow is also therapeutic, if it were able to be restored within atherosclerotic arteries. Apolipoprotein E-deficient (ApoE-/-) mice were initially instrumented with a blood flow-modifying cuff to induce plaque development and then five weeks later the cuffwas removed to allowrestoration of normal blood flow. Plaques in decuffed mice exhibited compositional changes that indicated increased stability compared to plaques in mice with the cuff maintained. The therapeutic benefit of decuffingwas comparable to atorvastatin and the combination had an additive effect. In addition, decuffing allowed restoration of lumen area, blood velocity, and wall shear stress to near baseline values, indicating restoration of normal blood flow. Our findings demonstrate that the mechanical effects of normal blood flow on atherosclerotic plaques promote stabilization

Smooth muscle cells affect differential nanoparticle accumulation in disturbed blood flow-induced murine atherosclerosis

Atherosclerosis is a lipid-driven chronic inflammatory disease that leads to the formation of plaques in the inner lining of arteries. Plaques form over a range of phenotypes, the most severe of which is vulnerable to rupture and causes most of the clinically significant events. In this study, we evaluated the efficacy of nanoparticles (NPs) to differentiate between two plaque phenotypes based on accumulation kinetics in a mouse model of atherosclerosis. This model uses a perivascular cuff to induce two regions of disturbed wall shear stress (WSS) on the inner lining of the instrumented artery, low (upstream) and multidirectional (downstream), which, in turn, cause the development of an unstable and stable plaque phenotype, respectively. To evaluate the influence of each WSS condition, in addition to the final plaque phenotype, in determining NP uptake, mice were injected with NPs at intermediate and fully developed stages of plaque growth. The kinetics of artery wall uptake were assessed in vivo using dynamic contrast-enhanced magnetic resonance imaging. At the intermediate stage, there was no difference in NP uptake between the two WSS conditions, although both were different from the control arteries. At the fully-developed stage, however, NP uptake was reduced in plaques induced by low WSS, but not multidirectional WSS. Histological evaluation of plaques induced by low WSS revealed a significant inverse correlation between the presence of smooth muscle cells and NP accumulation, particularly at the plaque-lumen interface, which did not exist with other constituents (lipid and collagen) and was not present in plaques induced by multidirectional WSS. These findings demonstrate that NP accumulation can be used to differentiate between unstable and stable murine atherosclerosis, but accumulation kinetics are not directly influenced by the WSS condition. This tool could be used as a diagnostic to evaluate the efficacy of experimental therapeutics for atherosclerosis