Operation Restoration: How Can Patent Holders Protect Themselves From Medimmune?

The Supreme Court’s recent decision in MedImmune v. Genentech shifts the balance of power in license agreements from patent holders to their licensees. This iBrief outlines the potential implications of the new rules on all stages of patent prosecution and protection. Further, it evaluates remedial contract provisions patent holders may include in future license agreements and how these provisions may mitigate the decision’s effects on preexisting commercial relationships

Expanding the Known DNA-binding Specificity of Homeodomains for Utility in Customizable Sequence-specific Nucleases: A Dissertation

Homeodomains (HDs) are a large family of DNA-binding domains contained in transcription factors that are most notable for regulating body development and patterning in metazoans. HDs consist of three alpha helices preceded by an N- terminal arm, where the third helix (the recognition helix) and the N-terminal arm are responsible for defining DNA-binding specificity. Here we attempted to engineer the HDs by fully randomizing positions in the recognition helix to specify each of the 64 possible 3’ triplet sites (i.e. TAANNN). We recovered HD variants that preferentially recognize or are compatible with 44 of the possible sites, a dramatic increase from the previously observed range of specificities. Many of these HD variants contain combinations of novel specificity determinants that are uncommon or absent in extant HDs, where these determinants can be grafted into alternate HD backbones with an accompanying alteration in their specificity. The identified determinates expand our understanding of HD recognition, allowing for the creation of more explicit recognition models for this family. Additionally, we demonstrate that HDs can recognize a broader range of DNA sequences than anticipated, thus raising questions about the fitness barrier that restricts the evolution HD-DNA recognition in nature. Finally, these new HD variants have utility as DNA-binding domains to direct targeting of customizable sequence-specific nuclease as demonstrated by site-specific lesions created in zebrafish. Thus HDs can guide sequence-specific enzymatic function precisely and predictably within a complex genome when used in engineered artificial enzymes

Stick index of knots and links in the cubic lattice

The cubic lattice stick index of a knot type is the least number of sticks necessary to construct the knot type in the 3-dimensional cubic lattice. We present the cubic lattice stick index of various knots and links, including all (p,p+1)-torus knots, and show how composing and taking satellites can be used to obtain the cubic lattice stick index for a relatively large infinite class of knots. Additionally, we present several bounds relating cubic lattice stick index to other known invariants.Comment: 16 pages, 12 figure

Reduced expression in preterm birth of sFLT-1 and PlGF with a high sFLT-1/PlGF ratio in extracellular vesicles suggests a potential biomarker

Preterm birth may have a pathological impact on intrauterine development of the fetal brain, resulting in developmental disabilities. In this study, we examine the expression of soluble Fms-like tyrosine kinase 1 (sFLT-1) and placental growth factor (PlGF), which is one of the vascular endothelial growth factors (VEGFs), as these play a key role in angiogenesis; in particular, we examine their effect on the sFLT-1/PlGF ratio in cases of preterm birth as compared to typical pregnancies. Enzyme-linked immunosorbent assay was performed on samples of maternal-derived plasma and extracellular vesicles-exosomes (EVs-EXs) isolated at the third trimester, consisting of 17 samples from cases of preterm birth and 38 control cases. Our results showed that both sFLT-1 (P=0.0014) and PlGF (P=0.0032) were significantly downregulated in cases of preterm birth compared to controls, while the sFLT-1/PIGF ratio was significantly (P=0.0008) increased in EVs-EXs, but not in maternal plasma. Our results suggest that this reduced expression of sFLT-1 and PlGF with an elevated sFLT-1/PlGF ratio in EVs-EXs may represent a potential biomarker for prediction of PTB

Design of MARQUIS2: study protocol for a mentored implementation study of an evidence-based toolkit to improve patient safety through medication reconciliation.

BackgroundThe first Multi-center Medication Reconciliation Quality Improvement Study (MARQUIS1) demonstrated that implementation of a medication reconciliation best practices toolkit decreased total unintentional medication discrepancies in five hospitals. We sought to implement the MARQUIS toolkit in more diverse hospitals, incorporating lessons learned from MARQUIS1.MethodsMARQUIS2 is a pragmatic, mentored implementation QI study which collected clinical and implementation outcomes. Sites implemented a revised toolkit, which included interventions from these domains: 1) best possible medication history (BPMH)-taking; 2) discharge medication reconciliation and patient/caregiver counseling; 3) identifying and defining clinician roles and responsibilities; 4) risk stratification; 5) health information technology improvements; 6) improved access to medication sources; 7) identification and correction of real-time discrepancies; and, 8) stakeholder engagement. Eight hospitalists mentored the sites via one site visit and monthly phone calls over the 18-month intervention period. Each site's local QI team assessed opportunities to improve, implemented at least one of the 17 toolkit components, and accessed a variety of resources (e.g. implementation manual, webinars, and workshops). Outcomes to be assessed will include unintentional medication discrepancies per patient.DiscussionA mentored multi-center medication reconciliation QI initiative using a best practices toolkit was successfully implemented across 18 medical centers. The 18 participating sites varied in size, teaching status, location, and electronic health record (EHR) platform. We introduce barriers to implementation and lessons learned from MARQUIS1, such as the importance of utilizing dedicated, trained medication history takers, simple EHR solutions, clarifying roles and responsibilities, and the input of patients and families when improving medication reconciliation

Independent Review of the 2021 CDP submission based on SCATTER by Newcastle City Council

The path to Net-Zero is always a complex one. Newcastle City Council has long been a leader on green city and climate policy, recently has developed the Net Zero Newcastle: 2030 Action Plan and currently is a CDT tier-A city (based on its 2020 submission). In 2020 Newcastle City Council (NCC) made a Carbon Disclosure Project (CDP) submission for the first time. NCC deems this as a successful submission, which scored highly (A score) as a city. NCC therefore set the bar high and need to maintain that standard going forwards, especially with COP looming. To this end, one of the areas where NCC can improve its 2021 submission is to have an independent evaluation of our emissions inventory for the city, which by and large is based on national data which is extrapolated to local level and is largely based on the attached analysis through a tool called SCATTER which has been developed by Anthesis and made available to UK Local Authorities through a time-limited grant support from BEIS central government. This exercise was undertaken jointly by Northumbria and Newcastle universities, in a pro-bono activity in their guise as civic universities supporting the implementation of the UN{\textquoteright}s Sustainable Development Goals, including as members of the COP26 Universities Network1 which both Northumbria and Newcastle University are part of. The independent evaluation took its cue from initial suggestions from NCC to verify – as far as possible within the time frame and the resources at hand - its 2021 SCATTER-based CDP submission (data, questionnaire, and local proxy data suggestions for the future) and to provide some general advice on how NCC (alongside its partners across the city and region) could potentially improve its disclosure and data strategy (including and especially with a more bottom-up one) in the future. A series of (online) meetings took place between NCC colleagues and the independent evaluations over June and July 2021, including an audit-style one where NCC colleagues demonstrated how they access and use the SCATTER tool, and obtain the data from there. Live questions were asked by the independent evaluators in the meeting, in addition to a list of questions that was shared with the NCC team only some hours before this audit-style meeting. NCC colleagues made a series of documents and data files available during the course of the exercise, including some reference examples after the audit-style meeting. The cross-universities independent evaluation team considers that Newcastle city Council is engaging well with the process and procedure of the SCATTER-based CDP disclosure activity, is committed to understand better inventory and the data pre-populated by the Anthesis Group for its submission, is clearly on the way to consider potential improvements for the future which may also rest (partly) on a more bottom-up (locally generated and verified data). The evaluators have made some comments on the SCATTER tool and methodological approach in this report, and furthermore discuss in general terms some of the current limitations. The report also provides some general pointers as to how a more bottom-up data strategy could be built in the future for both CDP-compliant disclosure, but also to consider the links between data recording and interventions/policy impacts on the journey towards Net Zero (or carbon neutrality) via meeting the city{\textquoteright}s 2030 carbon emission reductions target

Argument-Driven Engineering in Middle School Science: An Exploratory Study of Changes in Engineering Identity Over an Academic Year

The goal of this study was to examine how the use of a new instructional model is related to changes in middle school students’ engineering identity. The intent of this instructional model, which is called argument-driven engineering (ADE), is to give students opportunities to design and critique solutions to meaningful problems using the core ideas and practices of science and engineering. The model also reflects current recommendations found in the literature for supporting the development or maintenance of engineering identity. This study took place in the context of an eighth-grade science classroom in order to explore how middle school students’ engineering identities change over time as they become more familiar with engineering core ideas and practices. One hundred students participated in this study. These students completed three design tasks during the school year that were created using the ADE instructional model. These students also completed a survey that was designed to measure two important aspects of an engineering identity (recognition and interest) at three different time points. The results of a hierarchical linear modeling analysis suggest that students’ ideas about how they view themselves and others view them in terms of engineering did not change over time and their reported interest decreased from one survey to the next. The difficulty of the design tasks and the ways teachers enacted the instructional model are proposed as potential explanations for this counterintuitive finding

Assessing the accuracy of a large observational registry of neovascular age-related macular degeneration

PURPOSE To evaluate the accuracy of an observational database that tracks real-world treatment outcomes for neovascular age-related macular degeneration. METHODS We audited 245 randomly sampled eyes from 189 patients with 3,356 visits from 11 doctors in the Fight Retinal Blindness! DATABASE Sex, birth year, previous treatments received, treatment, and visual acuity were validated against the clinical notes. Error rates, the proportion of missed visits (the number of visits present in the patient record but not entered into Fight Retinal Blindness!), the level of agreement using Cohen's kappa (κ) and intraclass correlation coefficients, and positive and negative predictive values were calculated. A visual acuity error was defined as an absolute difference of ≥5 letters. RESULTS The overall error rate was 3.5% (95% confidence interval: 3.1-3.9). The error rate for visual acuity was 5.1% (95% confidence interval: 4.2-5.9) and <5% for the remaining fields. The level of agreement for each field ranged from good to excellent (κ or intraclass correlation ≥ 0.75). The positive predictive value and negative predictive value for visits were 99% and 89%, respectively. The proportion of missed visits was 10.2%. CONCLUSION Accuracy of the Fight Retinal Blindness! database was good (>95%). The rate of missed visits was high, possibly due to the high burden of retrospective data entry or patients switching practitioners during treatment