The Destined Duke

The idea for what would become this fiction piece, The Destined Duke, occurred to me during my first graduate writing class at Hollins University with Professor Amanda Cockrell. I remember the first question she asked of us, her students, was in regard to what genre we loved to read and what we may be interested in writing. As I sat at the large class table about two-thirds around, I awaited my turn, listening to my fellow classmates and trying to determine if I was brave enough in a graduate writing class to admit that I love to read romance novels and historical fiction – both genres that some of my “literary” friends grimaced at and proclaimed to be “chick lit” – and, certainly not worthy to be considered literature. However, the more I sat and listened to my classmates and considered what I may like to write, I knew that I was going to be in trouble if I tried to say anything other than the truth – for working during the day as a technical writer for an engineering company and free-lance writing and editing pharmaceutical monographs pretty much left me spent and I knew in my heart that I just didn’t have it in me to spend any more time writing something that I couldn’t completely enjoy. So, when it was my turn to share my favorite genre, I trepidatiously found my voice and admitted that I loved romance novels and historical fiction. To my amazement, Professor Cockrell didn’t grimace or reject either as literature and even shared that she too enjoyed the genre. I knew that very moment that I was at the correct university, in the right class, and with the best professor for me. From that instant, I have never turned back, although I will say my characters and plot have evolved dramatically from where I started to where I now conclude my graduate project for submission. And while, my MALS essay is concluding, my efforts to improve my writing, as well as complete my novel, will continue – all thanks to Professor Cockrell, who has taught me that writing is a craft that takes a lifetime to develop and hopefully perfect. So, without further ado, I present the first chapters of The Destined Duke, a fiction piece that centers on the life of Nicholas Pierce, The Duke of Hastings, and Isabella Marie Wells

A systematic review and meta-analysis of thiazide-induced hyponatraemia: time to reconsider electrolyte monitoring regimens after thiazide initiation?

Aims: Hyponatraemia is one of the major adverse effects of thiazide and thiazide-like diuretics and the leading cause of drug-induced hyponatraemia requiring hospital admission. We sought to review and analyze all published cases of this important condition. Methods: Ovid Medline, Embase, Web of Science and PubMed electronic databases were searched to identify all relevant articles published before October 2013. A proportions meta-analysis was undertaken. Results: One hundred and two articles were identified of which 49 were single patient case reports. Meta-analysis showed that mean age was 75 (95% CI 73, 77) years, 79% were women (95% CI 74, 82) and mean body mass index was 25 (95% CI 20, 30) kg m−2. Presentation with thiazide-induced hyponatraemia occurred a mean of 19 (95% CI 8, 30) days after starting treatment, with mean trough serum sodium concentration of 116 (95% CI 113, 120) mm and serum potassium of 3.3 (95% CI 3.0, 3.5) mm. Mean urinary sodium concentration was 64 mm (95% CI 47, 81). The most frequently reported drugs were hydrochlorothiazide, indapamide and bendroflumethiazide. Conclusions: Patients with thiazide-induced hyponatraemia were characterized by advanced age, female gender, inappropriate saliuresis and mild hypokalaemia. Low BMI was not found to be a significant risk factor, despite previous suggestions. The time from thiazide initiation to presentation with hyponatraemia suggests that the recommended practice of performing a single investigation of serum biochemistry 7–14 days after thiazide initiation may be insufficient or suboptimal. Further larger and more systematic studies of thiazide-induced hyponatraemia are required

A systematic review and meta-analysis of thiazide-induced hyponatraemia: time to reconsider electrolyte monitoring regimens after thiazide initiation?

Aims: Hyponatraemia is one of the major adverse effects of thiazide and thiazide-like diuretics and the leading cause of drug-induced hyponatraemia requiring hospital admission. We sought to review and analyze all published cases of this important condition. Methods: Ovid Medline, Embase, Web of Science and PubMed electronic databases were searched to identify all relevant articles published before October 2013. A proportions meta-analysis was undertaken. Results: One hundred and two articles were identified of which 49 were single patient case reports. Meta-analysis showed that mean age was 75 (95% CI 73, 77) years, 79% were women (95% CI 74, 82) and mean body mass index was 25 (95% CI 20, 30) kg m−2. Presentation with thiazide-induced hyponatraemia occurred a mean of 19 (95% CI 8, 30) days after starting treatment, with mean trough serum sodium concentration of 116 (95% CI 113, 120) mm and serum potassium of 3.3 (95% CI 3.0, 3.5) mm. Mean urinary sodium concentration was 64 mm (95% CI 47, 81). The most frequently reported drugs were hydrochlorothiazide, indapamide and bendroflumethiazide. Conclusions: Patients with thiazide-induced hyponatraemia were characterized by advanced age, female gender, inappropriate saliuresis and mild hypokalaemia. Low BMI was not found to be a significant risk factor, despite previous suggestions. The time from thiazide initiation to presentation with hyponatraemia suggests that the recommended practice of performing a single investigation of serum biochemistry 7–14 days after thiazide initiation may be insufficient or suboptimal. Further larger and more systematic studies of thiazide-induced hyponatraemia are required

Europe, listen and respond. Enhancing the European Commission´s online public consultation tool.

Fac. de Ciencias de la InformaciónFALSEpu

FKBP5 Modulates Attention Bias for Threat: Associations with Hippocampal Function and Morphology

Context: The FKBP5 gene product regulates glucocorticoid receptor (GR) sensitivity and hypothalamicpituitary‐adrenal axis functioning, and has been associated with a number of stress‐related psychiatric disorders. The study of intermediate phenotypes, such as emotion‐processing biases and their neural substrates, provides a way to clarify the mechanisms by which FKBP5 dysregulation mediates psychopathology risk. Objective: To examine whether allelic variations for a putatively functional SNP associated with FKBP5 gene regulation (rs1360780) would relate differentially to attentional bias for threat; this was measured through behavioral response on a dot probe task and hippocampal activation during task performance. Morphological substrates of differential hippocampal response were also measured. Design: Cross-sectional study examining associations between genotype, behavioral response and neural response (using fMRI) on the dot probe; Voxel-based morphometry (VBM), global and local shape analyses were used to measure structural differences in hippocampi between genotype groups

Meta-Analysis of Differentiating Mouse Embryonic Stem Cell Gene Expression Kinetics Reveals Early Change of a Small Gene Set

Stem cell differentiation involves critical changes in gene expression. Identification of these should provide endpoints useful for optimizing stem cell propagation as well as potential clues about mechanisms governing stem cell maintenance. Here we describe the results of a new meta-analysis methodology applied to multiple gene expression datasets from three mouse embryonic stem cell (ESC) lines obtained at specific time points during the course of their differentiation into various lineages. We developed methods to identify genes with expression changes that correlated with the altered frequency of functionally defined, undifferentiated ESC in culture. In each dataset, we computed a novel statistical confidence measure for every gene which captured the certainty that a particular gene exhibited an expression pattern of interest within that dataset. This permitted a joint analysis of the datasets, despite the different experimental designs. Using a ranking scheme that favored genes exhibiting patterns of interest, we focused on the top 88 genes whose expression was consistently changed when ESC were induced to differentiate. Seven of these (103728_at, 8430410A17Rik, Klf2, Nr0b1, Sox2, Tcl1, and Zfp42) showed a rapid decrease in expression concurrent with a decrease in frequency of undifferentiated cells and remained predictive when evaluated in additional maintenance and differentiating protocols. Through a novel meta-analysis, this study identifies a small set of genes whose expression is useful for identifying changes in stem cell frequencies in cultures of mouse ESC. The methods and findings have broader applicability to understanding the regulation of self-renewal of other stem cell types

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy