On the role of specific drug binding in modelling arterial eluting stents

In this paper we consider drug binding in the arterial wall following delivery by a drug-eluting stent. Whilst it is now generally accepted that a non-linear saturable reversible binding model is required to properly describe the binding process, the precise form of the binding model varies between authors. Our particular interest in this manuscript is in assessing to what extent modelling specific and non-specific binding in the arterial wall as separate phases is important. We study this issue by extending a recently developed coupled model of drug release and arterial tissue distribution, and comparing simulated profiles of drug concentration and drug mass in each phase within the arterial tissue

Simulating Drug-Eluting Stents: Progress Made and the Way Forward

Drug-eluting stents have significantly improved the treatment of coronary artery disease. Compared with their bare metal predecessors, they offer reduced rates of restenosis and thus represent the current gold standard in percutaneous coronary interventions. Drug-eluting stents have been around for over a decade, and while progress is continually being made, they are not suitable in all patients and lesion types. Furthermore there are still real concerns over incomplete healing and late stent thrombosis. In this paper, some modelling approaches are reviewed and the future of modelling and simulation in this field is discussed

Global Health Leadership Pathway: A Novel Approach to Global Radiology Curriculum Integration for Residents

Purpose: Our radiology residency programs are at an academic medical center in the southeastern United States and are accredited by the Accreditation Council for Graduate Medical Education (ACGME). During the initial eight years of our department’s global health program, 22 residents participated in our global health collaborations with a related $31,000 in extradepartmental travel awards. Increasingly, residents applying to our program convey interest in the integration of global health into their careers as radiologists. To that end, our administration, global health faculty, and residency program directors created and approved a Global Health Leadership Pathway (GHLP). The Pathway spans all years of radiology training to provide curriculum support with the aim of ensuring that our residents have the knowledge and skills necessary to become future leaders in global health. Description: The GHLP is a residency track that residents apply to join with a related radiology clinical education, global health specific curriculum throughout all training years, integration of the RAD-AID Certificate of Proficiency in Global Health Radiology, individual mentorship, and participation with an international elective. Structured education on global radiology, epidemiology, access implications, and related methodologies give our residents the opportunity to learn best practices for sustainability in global health. Conclusion: Because of increasing interest and due to the past successful involvement of our radiology residents in global health, our department created this Global Health Leadership Pathway to give our trainees the educational resources to support their future leadership and involvement in the academic field of global health

Modelling bispecific monoclonal antibody interaction with two cell membrane targets indicates the importance of surface diffusion

We have developed a mathematical framework for describing a bispecific monoclonal antibody interaction with two independent membrane-bound targets that are expressed on the same cell surface. The bispecific antibody in solution binds either of the two targets first, and then cross-links with the second one whilst on the cell surface, subject to rate-limiting lateral diffusion step within the lifetime of the monovalently engaged antibody-antigen complex. At experimental densities, only a small fraction of the free targets is expected to lie within the reach of the antibody binding sites at any time. Using ordinary differential equation and Monte Carlo simulation-based models, we validated this approach against an independently published anti-CD4/CD70 DuetMab experimental data set. As a result of dimensional reduction, the cell surface reaction is expected to be so rapid that, in agreement with the experimental data, no monovalently bound bispecific antibody binary complexes accumulate until cross-linking is complete. The dissociation of the bispecific antibody from the ternary cross-linked complex is expected to be significantly slower than that from either of the monovalently bound variants. We estimate that the effective affinity of the bivalently bound bispecific antibody is enhanced for about four orders of magnitude over that of the monovalently bound species. This avidity enhancement allows for the highly specific binding of anti-CD4/CD70 DuetMab to the cells that are positive for both target antigens over those that express only one or the other We suggest that the lateral diffusion of target antigens in the cell membrane also plays a key role in the avidity effect of natural antibodies and other bivalent ligands in their interactions with their respective cell surface receptors

Use of physical activity measures in rehabilitation interventions following lower extremity amputation

Purpose of review: This systematic review aims to evaluate physical performance outcome tools that are used most frequently to assess rehabilitation interventions. The scope of this paper focused on outcomes used with established lower limb amputees when assessing interventions such as exercise programs or changes in prescription published in the last five years. Recent Findings: The most recorded outcome measures used across all the papers were timed walk tests and the Activity Balance Confidence Scale. Many outcomes did not produce statistically significant results with established amputee cohorts. Understanding the minimal important clinical difference is key. Summary: The use of outcome measures is essential. Training and education are likely to increase the use of outcome measures. Quality of life measures are important in conjunction with physical outcomes. Simple timed walk tests are commonly used. These are in general easy to administer requiring a small space, limited equipment, and a short time frame

Cod response to past and current warm phases in the Seas of Iceland, a time series analysis

Climate change, and in particular global warming, is already affecting the Arctic and is expected to continue in the near future. A sustainable use the Arctic resources requires an increased understanding of its functioning that helps us anticipate change and adapt to it. Cod time series in Iceland cover a period of more than 50 years. Three distinct phases can be identified over this span of time: (1) the current warm phase characterised by relatively high cod biomasses, (2) an earlier phase (around the 1950s) with similar conditions separated by (3) some 20 years of cold temperatures and low biomasses. The aim of this study is to identify possible regime-dependent dynamics associated to these warm and cold phases that can help us identify key drivers in the current and future warm regime. To do this we compiled a database of fishing pressure, hydrographical and biological (copepods and euphausiids) variables as well as three cod population descriptors: (i) total spawning stock biomass, (ii) the population growth rate derived from matrix population models and (iii) disaggregated number at age time series. These three cod indices were subsequently regressed (GAM and threshold GAM) against the environmental and anthropogenic variables. Our results point out a probable regime-dependent mechanism where plankton effects would only be important for cod under warm conditions. No threshold-like responses were found in the population growth rate nor in the number at age for the various age classes

Recommendations for Child Play Areas

Design guide for the planning, programming and design of children\u27s outdoor play environments. Includes 75 patterns for a range of children\u27s play areas imbedded in a tiered park system and in conjunction with recreation, community and educational facilities. Based on current research information. Received an Award for Applied Research in 1980 from Progressive Architecture. Reprinted 1983, with new photographs in 1985, 1988, and in 1991. Highly illustrated.https://dc.uwm.edu/caupr_mono/1033/thumbnail.jp

Development and resilience in three Arctic ecosystems: Baltic, Barents and Iceland Seas

In this GreenMAR project we look into the historical development of the marine ecosystems that surround the Nordic countries in an effort to forecast their future evolution. We pay particular attention to the way their food webs responded to similar stressors (warming) and fishing regimes in the past. We have compiled historical information on environmental and biological components, from plankton to fish, over the last 25 to 45 years, depending on the system. On these four ecosystems we have: (i) carried out multivariate analyses to describe their main trends and (ii) constructed stability landscapes to quantify their resilience. We will show these results and discuss their implications

Descriptive Analysis of a Baseline Concussion Battery Among U.S. Service Academy Members: Results from the Concussion Assessment, Research, and Education (CARE) Consortium

Introduction The prevalence and possible long-term consequences of concussion remain an increasing concern to the U.S. military, particularly as it pertains to maintaining a medically ready force. Baseline testing is being used both in the civilian and military domains to assess concussion injury and recovery. Accurate interpretation of these baseline assessments requires one to consider other influencing factors not related to concussion. To date, there is limited understanding, especially within the military, of what factors influence normative test performance. Given the significant physical and mental demands placed on service academy members (SAM), and their relatively high risk for concussion, it is important to describe demographics and normative profile of SAMs. Furthermore, the absence of available baseline normative data on female and non-varsity SAMs makes interpretation of post-injury assessments challenging. Understanding how individuals perform at baseline, given their unique individual characteristics (e.g., concussion history, sex, competition level), will inform post-concussion assessment and management. Thus, the primary aim of this manuscript is to characterize the SAM population and determine normative values on a concussion baseline testing battery. Materials and Methods All data were collected as part of the Concussion Assessment, Research and Education (CARE) Consortium. The baseline test battery included a post-concussion symptom checklist (Sport Concussion Assessment Tool (SCAT), psychological health screening inventory (Brief Symptom Inventory (BSI-18) and neurocognitive evaluation (ImPACT), Balance Error Scoring System (BESS), and Standardized Assessment of Concussion (SAC). Linear regression models were used to examine differences across sexes, competition levels, and varsity contact levels while controlling for academy, freshman status, race, and previous concussion. Zero inflated negative binomial models estimated symptom scores due to the high frequency of zero scores. Results Significant, but small, sex effects were observed on the ImPACT visual memory task. While, females performed worse than males (p < 0.0001, pη2 = 0.01), these differences were small and not larger than the effects of the covariates. A similar pattern was observed for competition level on the SAC. There was a small, but significant difference across competition level. SAMs participating in varsity athletics did significantly worse on the SAC compared to SAMs participating in club or intramural athletics (all p’s < 0.001, η2 = 0.01). When examining symptom reporting, males were more than two times as likely to report zero symptoms on the SCAT or BSI-18. Intramural SAMs had the highest number of symptoms and severity compared to varsity SAMs (p < 0.0001, Cohen’s d < 0.2). Contact level was not associated with SCAT or BSI-18 symptoms among varsity SAMs. Notably, the significant differences across competition level on SCAT and BSI-18 were sub-clinical and had small effect sizes. Conclusion The current analyses provide the first baseline concussion battery normative data among SAMs. While statistically significant differences may be observed on baseline tests, the effect sizes for competition and contact levels are very small, indicating that differences are likely not clinically meaningful at baseline. Identifying baseline differences and significant covariates is important for future concussion-related analyses to inform concussion evaluations for all athlete levels