John Knox: reformation rhetoric and the traditions of Scots prose

Knox has seldom been taken seriously as a literary figure; in fact it is often assumed that he was hostile to `art' of any kind. Most British literary critics who have examined his work have done so superficially and have concluded that his prose was plain or unadorned and that its most important feature was a drift towards anglicisation. In the introductory section, `The Myths, the Writer and the Canon', it is argued that, on the contrary, the latter assessment cannot be made definitively for textual reasons and is, in any case, irrelevant to literary criticism. Moreover, the study suggests that Knox was one of the most highly rhetorical of all the sixteenth-century prose writers, although his rhetoric was never decorative. Chapter one traces the beginnings of Scottish literary prose from 1490 onwards, examining such texts as John Ireland's The Meroure of Wyssdome, John Gau's The Richt Vay to the Kingdom of Hevin, The Complaynt of Scotland and so forth, and establishes that works before Knox reflect religious belief even at the levels of lexis and syntactic structure, but generally speaking, do not consistently and convincingly reveal the personalities of their authors (with the possible exception of the Complayner). Chapter two illustrates that Knox's prose is always double-edged; its rhetorical aims are both offensive and defensive, it is often psychologically self-expressive and simultaneously revealing of his fundamental religious beliefs. The remaining chapters attempt to identify the range of rhetorical devices through which Knox manifests his own character and his religion, to assess how they may have affected his audience, to establish his sources, and whenever possible, to set them within pre-existing literary traditions, Scottish or otherwise. Chapters one and five are concentrated especially on the historiographical milieu in mid-sixteenth century Scotland and beyond, in order to set The Historie of the Reformatioun, the first great work of Scots prose, in its proper context. Chapter five itself consists of a number of generic divisions which are isolated to facilitate detailed analysis of disparate literary strands in Knox's magnum opus. Thus, according to the author, as far as prose is concerned, Knox's rhetoric and literary works represent the culmination of homiletic and historiographical traditions, the maturation of incipient religious forces in the sixteenth century, and the earliest establishment in Scotland of a fully-rounded literary personality

Protein Catalyzed Capture Agents with Tailored Performance for In Vitro and In Vivo Applications

We report on peptide-based ligands matured through the protein catalyzed capture (PCC) agent method to tailor molecular binders for in vitro sensing/diagnostics and in vivo pharmacokinetics parameters. A vascular endothelial growth factor (VEGF) binding peptide and a peptide against the protective antigen (PA) protein of Bacillus anthracis discovered through phage and bacterial display panning technologies, respectively, were modified with click handles and subjected to iterative in situ click chemistry screens using synthetic peptide libraries. Each azide-alkyne cycloaddition iteration, promoted by the respective target proteins, yielded improvements in metrics for the application of interest. The anti-VEGF PCC was explored as a stable in vivo imaging probe. It exhibited excellent stability against proteases and a mean elimination in vivo half-life (T_(1/2)) of 36 min. Intraperitoneal injection of the reagent results in slow clearance from the peritoneal cavity and kidney retention at extended times, while intravenous injection translates to rapid renal clearance. The ligand competed with the commercial antibody for binding to VEGF in vivo. The anti-PA ligand was developed for detection assays that perform in demanding physical environments. The matured anti-PA PCC exhibited no solution aggregation, no fragmentation when heated to 100°C, and  > 81% binding activity for PA after heating at 90°C for 1 h. We discuss the potential of the PCC agent screening process for the discovery and enrichment of next generation antibody alternatives

Circulating αKlotho influences phosphate handling by controlling FGF23 production

The FGF23 coreceptor αKlotho (αKL) is expressed as a membrane-bound protein (mKL) that forms heteromeric complexes with FGF receptors (FGFRs) to initiate intracellular signaling. It also circulates as an endoproteolytic cleavage product of mKL (cKL). Previously, a patient with increased plasma cKL as the result of a translocation [t(9;13)] in the αKLOTHO (KL) gene presented with rickets and a complex endocrine profile, including paradoxically elevated plasma FGF23, despite hypophosphatemia. The goal of this study was to test whether cKL regulates phosphate handling through control of FGF23 expression. To increase cKL levels, mice were treated with an adeno-associated virus producing cKL. The treated groups exhibited dose-dependent hypophosphatemia and hypocalcemia, with markedly elevated FGF23 (38 to 456 fold). The animals also manifested fractures, reduced bone mineral content, expanded growth plates, and severe osteomalacia, with highly increased bone Fgf23 mRNA (>150 fold). cKL activity in vitro was specific for interactions with FGF23 and was FGFR dependent. These results demonstrate that cKL potently stimulates FGF23 production in vivo, which phenocopies the KL translocation patient and metabolic bone syndromes associated with elevated FGF23. These findings have important implications for the regulation of αKL and FGF23 in disorders of phosphate handling and biomineralization

Protein Catalyzed Capture Agents with Tailored Performance for In Vitro and In Vivo Applications

We report on peptide-based ligands matured through the protein catalyzed capture (PCC) agent method to tailor molecular binders for in vitro sensing/diagnostics and in vivo pharmacokinetics parameters. A vascular endothelial growth factor (VEGF) binding peptide and a peptide against the protective antigen (PA) protein of Bacillus anthracis discovered through phage and bacterial display panning technologies, respectively, were modified with click handles and subjected to iterative in situ click chemistry screens using synthetic peptide libraries. Each azide-alkyne cycloaddition iteration, promoted by the respective target proteins, yielded improvements in metrics for the application of interest. The anti-VEGF PCC was explored as a stable in vivo imaging probe. It exhibited excellent stability against proteases and a mean elimination in vivo half-life (T_(1/2)) of 36 min. Intraperitoneal injection of the reagent results in slow clearance from the peritoneal cavity and kidney retention at extended times, while intravenous injection translates to rapid renal clearance. The ligand competed with the commercial antibody for binding to VEGF in vivo. The anti-PA ligand was developed for detection assays that perform in demanding physical environments. The matured anti-PA PCC exhibited no solution aggregation, no fragmentation when heated to 100°C, and  > 81% binding activity for PA after heating at 90°C for 1 h. We discuss the potential of the PCC agent screening process for the discovery and enrichment of next generation antibody alternatives

Race Yourselves: A Longitudinal Exploration of Self-Competition Between Past, Present, and Future Performances in a VR Exergame

Participating in competitive races can be a thrilling experience for athletes, involving a rush of excitement and sensations of flow, achievement, and self-fulfilment. However, for non-athletes, the prospect of competition is often a scary one which affects intrinsic motivation negatively, especially for less fit, less competitive individuals. We propose a novel method making the positive racing experience accessible to non-athletes using a high-intensity cycling VR exergame: by recording and replaying all their previous gameplay sessions simultaneously, including a projected future performance, players can race against a crowd of "ghost" avatars representing their individual fitness journey. The experience stays relevant and exciting as every race adds a new competitor. A longitudinal study over four weeks and a cross-sectional study found that the new method improves physical performance, intrinsic motivation, and flow compared to a non-competitive exergame. Additionally, the longitudinal study provides insights into the longer-term effects of VR exergames

Patient Preferences for Receiving Education on Venous Thromboembolism Prevention – A Survey of Stakeholder Organizations

<div><p>Importance</p><p>Venous thromboembolism (VTE) is a major cause of morbidity and mortality among hospitalized patients and is largely preventable. Strategies to decrease the burden of VTE have focused on improving clinicians’ prescribing of prophylaxis with relatively less emphasis on patient education.</p><p>Objective</p><p>To develop a patient-centered approach to education of patients and their families on VTE: including importance, risk factors, and benefit/harm of VTE prophylaxis in hospital settings.</p><p>Design, Setting and Participants</p><p>The objective of this study was to develop a patient-centered approach to education of patients and their families on VTE: including importance, risk factors, and benefit/harm of VTE prophylaxis in hospital settings. We implemented a three-phase, web-based survey (SurveyMonkey) between March 2014 and September 2014 and analyzed survey data using descriptive statistics. Four hundred twenty one members of several national stakeholder organizations and a single local patient and family advisory board were invited to participate via email. We assessed participants’ preferences for VTE education topics and methods of delivery.</p><p>Participants wanted to learn about VTE symptoms, risk factors, prevention, and complications in a context that emphasized harm. Although participants were willing to learn using a variety of methods, most preferred to receive education in the context of a doctor-patient encounter. The next most common preferences were for video and paper educational materials.</p><p>Conclusions</p><p>Patients want to learn about the harm associated with VTE through a variety of methods. Efforts to improve VTE prophylaxis and decrease preventable harm from VTE should target the entire continuum of care and a variety of stakeholders including patients and their families.</p></div

Preferred route of administration of Pharmacologic VTE prophylaxis.

<p>Preferred route of administration of Pharmacologic VTE prophylaxis.</p

Respondents’ preferences for receiving VTE education (methods).

<p>A bar graph showing stakeholders’ preferred methods for receiving VTE education. Respondents were asked to rank methods of receiving VTE education in order of preference. Preference categories, 1^st, 2^nd and 3^rd were assigned weights of 3, 2 and 1 respectively and a category that is not ranked was assigned a weight of 0. Borda Counts were derived as the sum of weights allocated to the respective preference ranks by participants.</p

Respondents’ preferences for the length of educational material (video).

<p>A pie chart showing stakeholders’ preferences in regards to the length of educational material (video). Patients were asked whether or not they would be willing to watch a video that is 5, 10, 15 or 20 minutes long.</p