The Early English passion play

This discussion challenges the common understanding that biblical drama in England was dominated by ‘mystery plays’, narrowly understood to be cycles of short pageants, by drawing attention to the evidence for large-scale Passion Plays comparable with those better known from France and Burgundy. In so doing, it makes no apology for standing on the shoulders of Peter Meredith's work on the N-Town manuscript, and with John Tailby on the texts and documents illustrating the variety of staging of religious drama across Europe, as well as Meg Twycross's work on devisor Felsted of London, all of which demonstrate that this material has been available in the public domain for some years. Just as the N-Town Plays were still believed in some quarters to come from Coventry as late as the mid-twentieth century, although Francis Douce knew they did not almost 150 years earlier, so too the domination of modern understandings about English mystery plays has remained wedded to the model of four ‘cycles’ promulgated in the 1970s, despite the accumulation of evidence to the contrary. Peter Meredith's edition of The ‘Passion Play’ from the N. Town Manuscript is now all but unobtainable, and the volumes of Records of Early English Drama are the chosen bedtime reading of few, so here we revisit some texts and records to explore afresh one aspect of an already shifted paradigm

Extension of earth orbits using low-thrust propulsion

The primary motivation for the utilization of space for environmental science, and in-particular Earth Observation, is the unique vantage point which a spacecraft can provide. For example, a spacecraft can provide a global dataset with a much higher temporal resolution than any other platform. Earth Observation spacecraft are increasingly focused on a single primary application, typically conducted from a small set of classical orbits which limits the range of vantage points and hence the type of observations which can be made. The next generation of innovative Earth Observation spacecraft may however only be enabled through new orbit options not considered in the past. The objective of the study was therefore to enlarge the set of potential Earth orbits by considering the use of low-thrust propulsion to extend the conventional Molniya orbit. These new orbits will use existing, or near-term low-thrust propulsion technology to enable new Earth Observation science and offer a radically new set of tools for mission design. Continuous low-thrust propulsion was applied in the radial, transverse and normal directions to vary the critical inclination of the Molniya orbit, while maintaining the zero change in argument of perigee condition. As such the inclination can be freely altered from the expected critical inclination of 63.4 deg, to, for example 90 deg, creating a Polar-Molniya orbit. Analytical expressions were developed which were then validated using a numerical model, to show that not only was the argument of perigee unchanged but all other orbital elements were also unaffected by the applied low-thrust. It was shown that thrusting in the transverse direction allowed the spacecraft to achieve any inclination with the lowest thrust magnitude in any single direction; this value was however found to be further reduced by combining both radial and transverse thrust. Real-time continuous observation of the Arctic Circle is then enabled using current electric propulsion technology, with fewer spacecraft than the traditional Sun-synchronous polar orbit, and at reduced range than a 'pole-sitter'. Applications of such an orbit would include more accurate Arctic weather predictions and severe weather event warnings for this region

Police powers and human rights in the context of terrorism

Purpose – The object of the paper is to analyse the justifications for the modification of police powers in response to terrorist threats, placing this issue in a European context. Design/methodology/approach – The paper consists of a critical examination of provisions relating to terrorism emanating from the European Union and the Council of Europe (European Convention on Human Rights (ECHR)), and the relevant English law on police powers of stop and search, arrest, and detention. Findings – Nothing in European law requires the amendments to police powers contained in English law; European law requires respect for human rights, even in dealing with terrorism; a shoot-to-kill policy is prohibited by the ECHR; and balance is an unsatisfactory method of resolving conflicts in this area. Research limitations/implications – The research was limited in its scope to certain areas of police powers, and to certain fundamental European documents. Future research should consider the issue in relation to wider areas. Originality/value – It challenges the idea of balance between liberty and security, proposing a test based on necessity instead

HFE and transferrin directly compete for transferrin receptor in solution and at the cell surface

Transferrin receptor (TfR) is a dimeric cell surface protein that binds both the serum iron transport protein transferrin (Fe-Tf) and HFE, the protein mutated in patients with the iron overload disorder hereditary hemochromatosis. HFE and Fe-Tf can bind simultaneously to TfR to form a ternary complex, but HFE binding to TfR lowers the apparent affinity of the Fe-Tf/TfR interaction. This apparent affinity reduction could result from direct competition between HFE and Fe-Tf for their overlapping binding sites on each TfR polypeptide chain, from negative cooperativity, or from a combination of both. To explore the mechanism of the affinity reduction, we constructed a heterodimeric TfR that contains mutations such that one TfR chain binds only HFE and the other binds only Fe-Tf. Binding studies using a heterodimeric form of soluble TfR demonstrate that TfR does not exhibit cooperativity in heterotropic ligand binding, suggesting that some or all of the effects of HFE on iron homeostasis result from competition with Fe-Tf for TfR binding. Experiments using transfected cell lines demonstrate a physiological role for this competition in altering HFE trafficking patterns

A small population of hypothalamic neurons govern fertility: the critical role of VAX1 in GnRH neuron development and fertility maintenance.

Fertility depends on the correct maturation and function of approximately 800 gonadotropin-releasing hormone (GnRH) neurons in the brain. GnRH neurons are at the apex of the hypothalamic-pituitary-gonadal axis that regulates fertility. In adulthood, GnRH neurons are scattered throughout the anterior hypothalamic area and project to the median eminence, where GnRH is released into the portal vasculature to stimulate release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the pituitary. LH and FSH then regulate gonadal steroidogenesis and gametogenesis. Absence of GnRH neurons or inappropriate GnRH release leads to infertility. Despite the critical role of GnRH neurons in fertility, we still have a limited understanding of the genes responsible for proper GnRH neuron development and function in adulthood. GnRH neurons originate in the olfactory placode then migrate into the brain. Homeodomain transcription factors expressed within GnRH neurons or along their migratory path are candidate genes for inherited infertility. Using a combined in vitro and in vivo approach, we have identified Ventral Anterior Homeobox 1 (Vax1) as a novel homeodomain transcription factor responsible for GnRH neuron maturation and fertility. GnRH neuron counts in Vax1 knock-out embryos revealed Vax1 to be required for the presence of GnRH-expressing cells at embryonic day 17.5 (E17.5), but not at E13.5. To localize the effects of Vax1 on fertility, we generated Vax1flox mice and crossed them with Gnrhcre mice to specifically delete Vax1 within GnRH neurons. GnRH staining in Vax1flox/flox:GnRHcre mice show a total absence of GnRH expression in the adult. We performed lineage tracing in Vax1flox/flox:GnRHcre:RosaLacZ mice which proved GnRH neurons to be alive, but incapable of expressing GnRH. The absence of GnRH leads to delayed puberty, hypogonadism and complete infertility in both sexes. Finally, using the immortalized model GnRH neuron cell lines, GN11 and GT1-7, we show that VAX1 is a direct regulator of Gnrh1 transcription by binding key ATTA sites within the Gnrh1 promoter. This study identifies VAX1 as a key transcription factor regulating GnRH expression and establishes VAX1 as a novel candidate gene implicated in heritable infertility

Ready, Set, Network! Research Speed Networking for Clinicians, Scientists and Engineers

Objectives: A 2013 Institute of Medicine report urged researchers to “engage in additional substantive and productive collaborations” to address important clinical/translational science questions. To encourage team science among our researchers, Tompkins-McCaw Library for the Health Sciences and Center for Clinical and Translational Research hosted a speed networking event, specifically targeting engineers, clinicians, and basic scientists; an analysis of the event is below. Methods: Invitations were distributed to clinicians, engineers, and basic scientists. To maximize interactions without increasing time spent at the event, researchers were divided into three groups. The event was planned such that each group would meet everyone from the other two groups; researchers were placed into appropriate groups according to their interests. Seated at tables of three, attendees introduced themselves and discussed their research interests for three minutes; then they rotated according to their group’s instructions. Lunch was provided afterwards to give attendees an opportunity to follow up with potential collaborators. Results: Twenty-one faculty researchers attended the speed networking event, which took about 30 minutes, excluding lunch. Using a 5-point Likert scale, all participants selected “strongly agree” or “agree” to respond to questions about whether the event was a valuable use of their time. Also, 53% of attendees “strongly” agreed with the statement “I met a potential collaborator” at the event. Discussion: Subjective evaluations show that researchers see speed networking as an effective way to meet potential collaborators. Objective data including sustained research partnerships and collaborative grant and publication submissions will be tracked

Pathways to Coastal Resiliency: the Adaptive Gradients Framework

Current and future climate-related coastal impacts such as catastrophic and repetitive flooding, hurricane intensity, and sea level rise necessitate a new approach to developing and managing coastal infrastructure. Traditional “hard” or “grey” engineering solutions are proving both expensive and inflexible in the face of a rapidly changing coastal environment. Hybrid solutions that incorporate natural, nature-based, structural, and non-structural features may better achieve a broad set of goals such as ecological enhancement, long-term adaptation, and social benefits, but broad consideration and uptake of these approaches has been slow. One barrier to the widespread implementation of hybrid solutions is the lack of a relatively quick but holistic evaluation framework that places these broader environmental and societal goals on equal footing with the more traditional goal of exposure reduction. To respond to this need, the Adaptive Gradients Framework was developed and pilot-tested as a qualitative, flexible, and collaborative process guide for organizations to understand, evaluate, and potentially select more diverse kinds of infrastructural responses. These responses would ideally include natural, nature-based, and regulatory/cultural approaches, as well as hybrid designs combining multiple approaches. It enables rapid expert review of project designs based on eight metrics called “gradients”, which include exposure reduction, cost efficiency, institutional capacity, ecological enhancement, adaptation over time, greenhouse gas reduction, participatory process, and social benefits. The framework was conceptualized and developed in three phases: relevant factors and barriers were collected from practitioners and experts by survey; these factors were ranked by importance and used to develop the initial framework; several case studies were iteratively evaluated using this technique; and the framework was finalized for implementation. The article presents the framework and a pilot test of its application, along with resources that would enable wider application of the framework by practitioners and theorists

A rapid and convergent synthesis of the integrastatin core

The tetracyclic core of the integrastatin natural products has been prepared in a convergent and rapidmanner. Our strategy relies upon a palladium(II)-catalyzed oxidative cyclization to form the central [3.3.1]-dioxabicycle of the natural product core. Overall, the core has been completed in only 4 linear steps from known compounds

Comparison of a prototype for indications-based prescribing with 2 commercial prescribing systems

Importance: The indication (reason for use) for a medication is rarely included on prescriptions despite repeated recommendations to do so. One barrier has been the way existing electronic prescribing systems have been designed. Objective: To evaluate, in comparison with the prescribing modules of 2 leading electronic health record prescribing systems, the efficiency, error rate, and satisfaction with a new computerized provider order entry prototype for the outpatient setting that allows clinicians to initiate prescribing using the indication. Design, Setting, and Participants: This quality improvement study used usability tests requiring internal medicine physicians, residents, and physician assistants to enter prescriptions electronically, including indication, for 8 clinical scenarios. The tool order assignments were randomized and prescribers were asked to use the prototype for 4 of the scenarios and their usual system for the other 4. Time on task, number of clicks, and order details were captured. User satisfaction was measured using posttask ratings and a validated system usability scale. The study participants practiced in 2 health systems\u27 outpatient practices. Usability tests were conducted between April and October of 2017. Main Outcomes and Measures: Usability (efficiency, error rate, and satisfaction) of indications-based computerized provider order entry prototype vs the electronic prescribing interface of 2 electronic health record vendors. Results: Thirty-two participants (17 attending physicians, 13 residents, and 2 physician assistants) used the prototype to complete 256 usability test scenarios. The mean (SD) time on task was 1.78 (1.17) minutes. For the 20 participants who used vendor 1\u27s system, it took a mean (SD) of 3.37 (1.90) minutes to complete a prescription, and for the 12 participants using vendor 2\u27s system, it took a mean (SD) of 2.93 (1.52) minutes. Across all scenarios, when comparing number of clicks, for those participants using the prototype and vendor 1, there was a statistically significant difference from the mean (SD) number of clicks needed (18.39 [12.62] vs 46.50 [27.29]; difference, 28.11; 95% CI, 21.47-34.75; P \u3c .001). For those using the prototype and vendor 2, there was also a statistically significant difference in number of clicks (20.10 [11.52] vs 38.25 [19.77]; difference, 18.14; 95% CI, 11.59-24.70; P \u3c .001). A blinded review of the order details revealed medication errors (eg, drug-allergy interactions) in 38 of 128 prescribing sessions using a vendor system vs 7 of 128 with the prototype. Conclusions and Relevance: Reengineering prescribing to start with the drug indication allowed indications to be captured in an easy and useful way, which may be associated with saved time and effort, reduced medication errors, and increased clinician satisfaction

Comparison of a prototype for indications-based prescribing with 2 commercial prescribing systems

Importance: The indication (reason for use) for a medication is rarely included on prescriptions despite repeated recommendations to do so. One barrier has been the way existing electronic prescribing systems have been designed. Objective: To evaluate, in comparison with the prescribing modules of 2 leading electronic health record prescribing systems, the efficiency, error rate, and satisfaction with a new computerized provider order entry prototype for the outpatient setting that allows clinicians to initiate prescribing using the indication. Design, Setting, and Participants: This quality improvement study used usability tests requiring internal medicine physicians, residents, and physician assistants to enter prescriptions electronically, including indication, for 8 clinical scenarios. The tool order assignments were randomized and prescribers were asked to use the prototype for 4 of the scenarios and their usual system for the other 4. Time on task, number of clicks, and order details were captured. User satisfaction was measured using posttask ratings and a validated system usability scale. The study participants practiced in 2 health systems\u27 outpatient practices. Usability tests were conducted between April and October of 2017. Main Outcomes and Measures: Usability (efficiency, error rate, and satisfaction) of indications-based computerized provider order entry prototype vs the electronic prescribing interface of 2 electronic health record vendors. Results: Thirty-two participants (17 attending physicians, 13 residents, and 2 physician assistants) used the prototype to complete 256 usability test scenarios. The mean (SD) time on task was 1.78 (1.17) minutes. For the 20 participants who used vendor 1\u27s system, it took a mean (SD) of 3.37 (1.90) minutes to complete a prescription, and for the 12 participants using vendor 2\u27s system, it took a mean (SD) of 2.93 (1.52) minutes. Across all scenarios, when comparing number of clicks, for those participants using the prototype and vendor 1, there was a statistically significant difference from the mean (SD) number of clicks needed (18.39 [12.62] vs 46.50 [27.29]; difference, 28.11; 95% CI, 21.47-34.75; P \u3c .001). For those using the prototype and vendor 2, there was also a statistically significant difference in number of clicks (20.10 [11.52] vs 38.25 [19.77]; difference, 18.14; 95% CI, 11.59-24.70; P \u3c .001). A blinded review of the order details revealed medication errors (eg, drug-allergy interactions) in 38 of 128 prescribing sessions using a vendor system vs 7 of 128 with the prototype. Conclusions and Relevance: Reengineering prescribing to start with the drug indication allowed indications to be captured in an easy and useful way, which may be associated with saved time and effort, reduced medication errors, and increased clinician satisfaction