scholarly journals Translational Block in Stroke: A Constructive and “Out-of-the-Box” Reappraisal

2021 ◽  
Vol 15 ◽  
Author(s):  
Athanasios Lourbopoulos ◽  
Iordanis Mourouzis ◽  
Christodoulos Xinaris ◽  
Nefeli Zerva ◽  
Konstantinos Filippakis ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Conceptual Analysis ◽  
Lessons Learned ◽  
Current Status ◽  
Preclinical Studies ◽  
Prevention Strategies ◽  
Preclinical Research ◽  
Conducting Research ◽  
Translational Block ◽  
Scientific Fields

Why can we still not translate preclinical research to clinical treatments for acute strokes? Despite > 1000 successful preclinical studies, drugs, and concepts for acute stroke, only two have reached clinical translation. This is the translational block. Yet, we continue to routinely model strokes using almost the same concepts we have used for over 30 years. Methodological improvements and criteria from the last decade have shed some light but have not solved the problem. In this conceptual analysis, we review the current status and reappraise it by thinking “out-of-the-box” and over the edges. As such, we query why other scientific fields have also faced the same translational failures, to find common denominators. In parallel, we query how migraine, multiple sclerosis, and hypothermia in hypoxic encephalopathy have achieved significant translation successes. Should we view ischemic stroke as a “chronic, relapsing, vascular” disease, then secondary prevention strategies are also a successful translation. Finally, based on the lessons learned, we propose how stroke should be modeled, and how preclinical and clinical scientists, editors, grant reviewers, and industry should reconsider their routine way of conducting research. Translational success for stroke treatments may eventually require a bold change with solutions that are outside of the box.

scholarly journals Drugs modulating apoptosis: current status

2021 ◽  
Vol 10 (7) ◽  
pp. 870
Author(s):  
Vimala Ananthy ◽  
Raman P. Priyadharsini ◽  
Umamaheswari Subramanian
Keyword(s):  
Multiple Sclerosis ◽  
Combinatorial Chemistry ◽  
Molecular Mechanisms ◽  
Natural Process ◽  
The Body ◽  
Current Status ◽  
Preclinical Studies ◽  
Bcl2 Family ◽  
Novel Approach ◽  
Novel Approaches

Apoptosis (programmed cell death) is a natural process that helps in removing potentially harmful cells from the body and replacing it with normal ones. Like any other process, it is also subjected to lots of deregulations and can lead to diseases like cancer, neurodegenerative conditions, multiple sclerosis, Parkinson’s disease, autoimmune disorders and inappropriate death of cells after liver failure, stroke and myocardial infarction. The knowledge of the molecular mechanisms involved in apoptosis has been progressed tremendously. Thus, therapeutics targeting apoptosis have been emerged as a novel approach for treating various disease conditions. Current approaches induce or inhibit apoptosis by targeting the key regulators of apoptosis such as Bcl2 family of proteins, TRAIL, caspases, MDM2, IAPs and p53. While many apoptotic drugs proved its efficacy in preclinical studies, some are already approved and entered the clinical setting. Numerous novel approaches such as antisense therapy, gene therapy, recombinant biologics and combinatorial chemistry are being employed to target these regulators. This review focused on the pathways of apoptosis, various therapeutic targets in apoptosis and the drugs modulating these targets.

Political Science Research in the Middle East and North Africa

2018 ◽  
Keyword(s):  
Middle East ◽  
Research Methods ◽  
North Africa ◽  
Quantitative Research ◽  
Real Life ◽  
Field Research ◽  
Science Research ◽  
Lessons Learned ◽  
Conducting Research ◽  
Personal Accounts

Based on personal accounts of their experiences conducting qualitative and quantitative research in the countries of the Middle East and North Africa, the contributors to this volume share the real-life obstacles they have encountered in applying research methods in practice and the possible solutions to overcome them. The volume is an important companion book to more standard methods books, which focus on the “how to” of methods but are often devoid of any real discussion of the practicalities, challenges, and common mistakes of fieldwork. The volume is divided into three parts, highlighting the challenges of (1) specific contexts, including conducting research in areas of violence; (2) a range of research methods, including interviewing, process-tracing, ethnography, experimental research, and the use of online media; and (3) the ethics of field research. In sharing their lessons learned, the contributors raise issues of concern to both junior and experienced researchers, particularly those of the Global South but also to those researching the Global North.

Driving with Low Vision

1979 ◽  
Vol 73 (9) ◽  
pp. 345-350
Author(s):  
Dennis K. Kelleher
Keyword(s):  
Preliminary Data ◽  
Visually Impaired ◽  
Low Vision ◽  
Current Status ◽  
Training Sequences ◽  
Conducting Research ◽  
Licensing Standards

Discusses the current status of driving with low vision, both with and without a bioptic telescope. It specifies licensing criteria, training sequences, and identifies problem areas. Preliminary data from a comparison of safety records in three states are presented and recommendations are made for future licensing standards and for conducting research on visually impaired drivers.

scholarly journals The unintended consequences of COVID-19 mitigation measures matter: practical guidance for investigating them

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Anne-Marie Turcotte-Tremblay ◽  
Idriss Ali Gali Gali ◽  
Valéry Ridde
Keyword(s):  
Unintended Consequences ◽  
Lessons Learned ◽  
World Health ◽  
Mitigation Measures ◽  
Extensive Experience ◽  
Systematic Assessment ◽  
Practical Guidance ◽  
Conducting Research ◽  
Health Organization

Abstract Background COVID-19 has led to the adoption of unprecedented mitigation measures which could trigger many unintended consequences. These unintended consequences can be far-reaching and just as important as the intended ones. The World Health Organization identified the assessment of unintended consequences of COVID-19 mitigation measures as a top priority. Thus far, however, their systematic assessment has been neglected due to the inattention of researchers as well as the lack of training and practical tools. Main text Over six years our team has gained extensive experience conducting research on the unintended consequences of complex health interventions. Through a reflexive process, we developed insights that can be useful for researchers in this area. Our analysis is based on key literature and lessons learned reflexively in conducting multi-site and multi-method studies on unintended consequences. Here we present practical guidance for researchers wishing to assess the unintended consequences of COVID-19 mitigation measures. To ensure resource allocation, protocols should include research questions regarding unintended consequences at the outset. Social science theories and frameworks are available to help assess unintended consequences. To determine which changes are unintended, researchers must first understand the intervention theory. To facilitate data collection, researchers can begin by forecasting potential unintended consequences through literature reviews and discussions with stakeholders. Including desirable and neutral unintended consequences in the scope of study can help minimize the negative bias reported in the literature. Exploratory methods can be powerful tools to capture data on the unintended consequences that were unforeseen by researchers. We recommend researchers cast a wide net by inquiring about different aspects of the mitigation measures. Some unintended consequences may only be observable in subsequent years, so longitudinal approaches may be useful. An equity lens is necessary to assess how mitigation measures may unintentionally increase disparities. Finally, stakeholders can help validate the classification of consequences as intended or unintended. Conclusion Studying the unintended consequences of COVID-19 mitigation measures is not only possible but also necessary to assess their overall value. The practical guidance presented will help program planners and evaluators gain a more comprehensive understanding of unintended consequences to refine mitigation measures.

scholarly journals Using magnetic resonance imaging in animal models to guide drug development in multiple sclerosis

2013 ◽  
Vol 20 (1) ◽  
pp. 3-11 ◽  
Author(s):  
Nabeela Nathoo ◽  
V Wee Yong ◽  
Jeff F Dunn
Keyword(s):  
Magnetic Resonance Imaging ◽  
Multiple Sclerosis ◽  
Clinical Trials ◽  
Magnetic Resonance ◽  
Animal Models ◽  
Mr Imaging ◽  
Preclinical Studies ◽  
Resonance Imaging ◽  
Magnetic Resonance Imaging Mri ◽  
Potential Therapeutics

Major advances are taking place in the development of therapeutics for multiple sclerosis (MS), with a move past traditional immunomodulatory/immunosuppressive therapies toward medications aimed at promoting remyelination or neuroprotection. With an increase in diversity of MS therapies comes the need to assess the effectiveness of such therapies. Magnetic resonance imaging (MRI) is one of the main tools used to evaluate the effectiveness of MS therapeutics in clinical trials. As all new therapeutics for MS are tested in animal models first, it is logical that MRI be incorporated into preclinical studies assessing therapeutics. Here, we review key papers showing how MR imaging has been combined with a range of animal models to evaluate potential therapeutics for MS. We also advise on how to maximize the potential for incorporating MRI into preclinical studies evaluating possible therapeutics for MS, which should improve the likelihood of discovering new medications for the condition.

Taking a Byte of Telephony Costs

2010 ◽  
Vol 12 (4) ◽  
pp. 18-34 ◽  
Author(s):  
Bogdan Hoanca ◽  
Richard Whitney
Keyword(s):  
User Satisfaction ◽  
Transition Process ◽  
Lessons Learned ◽  
Decision Makers ◽  
Current Status ◽  
Limited Budget ◽  
Telephone System ◽  
University Of Alaska Anchorage ◽  
Private Branch Exchange ◽  
The University

In 2006, the University of Alaska Anchorage (UAA) upgraded the telephone system at its main campus in Anchorage from a traditional private branch exchange (PBX) architecture to a Voice over Internet Protocol (VoIP) system. This case describes the organizational decisions that led to the change; the scope and the process of upgrading; and the current status of the new VoIP system. The actual migration to VoIP was completed less than a year after the start of the project. The transition process went smoothly. User satisfaction with the performance of the VoIP system is very high. Based on extensive interviews with decision makers and the technical personnel involved, this case also describes financial considerations (including “creative” ways to stretch a limited budget), outsourcing considerations, training related issues, as well as lessons learned.

scholarly journals The Mars Regional Atmospheric Modeling System (MRAMS): Current Status and Future Directions

Atmosphere ◽  
2019 ◽  
Vol 10 (12) ◽  
pp. 747 ◽  
Author(s):  
Scot Rafkin ◽  
Timothy Michaels
Keyword(s):  
Numerical Experiments ◽  
Atmospheric Modeling ◽  
Lessons Learned ◽  
Current Status ◽  
Regional Atmospheric Modeling System ◽  
Future Directions ◽  
Current State ◽  
Development Plans ◽  
Regional Atmospheric Modeling ◽  
Physical Parameterizations

The Mars Regional Atmospheric Modeling System (MRAMS) is closing in on two decades of use as a tool to investigate mesoscale and microscale circulations and dynamics in the atmosphere of Mars. Over this period of time, there have been numerous improvements and additions to the model dynamical core, physical parameterizations, and framework. At the same time, the application of the model to Mars (and related code for other planets) has taught many lessons about limitations and cautions that should be exercised. The current state of MRAMS is described along with a review of prior studies and findings utilizing the model. Where appropriate, lessons learned are provided to help guide future users and aid in the design and interpretation of numerical experiments. The paper concludes with a discussion of future MRAMS development plans.

Theory of advice as an information object targeted at an unmade decision

2019 ◽  
Vol 76 (1) ◽  
pp. 212-230
Author(s):  
Allen J. Flynn
Keyword(s):  
Information And Communication Technology ◽  
Communication Technology ◽  
Design Methodology ◽  
Conceptual Analysis ◽  
Content Type ◽  
Information Object ◽  
Advice Giving ◽  
Information And Communication ◽  
Practical Implications ◽  
Scientific Fields

Purpose The purpose of this paper is to advance an understanding of the concept of advice and its relationship to documents, information and knowledge. Design/methodology/approach A conceptual analysis of a sample of 48 relevant advice studies and two books, directly informed by documentation and information theories, was conducted to find out how researchers have approached advice conceptually since 1940. Further gains in understanding advice came from analyzing its relationship with environmental uncertainty. Findings Researchers have studied advice in the context of human-human, machine-machine and information and communication technology-intermediated interactions. Advice has been conceptualized and categorized in many different ways. Over time, conceptualizations of advice have broadened and become more general. In this light, it is theorized that advice is as an information object targeted at an unmade decision. This conceptualization of advice permits situated and momentary advice documents. A newly developed content-based framework of advice leads to an advice typology with four content-based categories of best possible advice: correct answers, probabilities, possibilities, and acknowledgments of the unknown. Research limitations/implications The refined advice theory, content-based advice framework and related typology of advice contributed here are small steps toward improved clarity about the nature of advice. These findings are limited in their focus to advice theory and advice categorization. Practical implications Scholars, practitioners and information system developers may reconsider advice theory and make use of the content-based framework and related advice typology in their work. These contributions will help advice-givers and the developers of advice-giving information systems and advice networks to provide better advice. Originality/value This paper fills a need for a clear and straightforward overall conceptualization of advice that accounts for advice documents and is informed by how advice has been previously conceptualized in multiple scientific fields.

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