Are preclinical research findings replicable: An empirical analysis based on EpoR studies in cancer.

This study attempts to explore the tourists' satisfaction within a tourism context, specifically with reference to the destination-based attributes. The study was conducted in India with a sample of Chinese tourists. Gathering data was analyzed by using t-tests. The research findings indicated that the dimension of accommodation services was the strongest predictor of the Chinese tourists' satisfaction, followed by incoming travel agency services and facilities in India. The dimension of accommodation services also was the strongest predictor of the female tourists' overall holiday satisfaction, followed by destination facilities and incoming travel agency services. Moreover, the mean scores of all the items within the main dimensions were above the neutral point. These results revealed that both male and female tourists were generally satisfied with their holiday in India.

Download Full-text

How can non-elected representatives secure democratic representation?

Policy & Politics ◽

10.1332/030557321x16371011677734 ◽

2022 ◽

Author(s):

Karin Fossheim

Keyword(s):

Decision Making ◽

Empirical Analysis ◽

Democratic Legitimacy ◽

Democratic Representation ◽

Governance Networks ◽

Research Findings ◽

Electoral Representation ◽

Elected Representatives

Research on the democratic legitimacy of non-elected actors influencing policy while acting as representatives is often lacking in governance literature, despite being increasingly relevant worldwide. Recent theories of representation argue that there are non-electoral mechanisms to appoint such non-elected representatives and hold them responsible for their actions. Consequently, democratic non-electoral representation can be achieved. Through empirical analysis, this article explores democratic non-electoral representation in governance networks by comparing how non-elected representatives, their constituents and the decision-making audience understand the outcome of representation to benefit the constituency, authorisation and accountability. The research findings conclude that all three groups mostly share the understanding of democratic non-electoral representation as ongoing interactions between representatives and constituents, multiple (if any) organisational and discursive sources of authorisation and deliberative aspects of accountability. All of these are non-electoral mechanisms that secure democratic representation. These findings make an important contribution to the literature on non-electoral representation in policymaking.

Download Full-text

Lost in Translation - Bridging the preclinical and clinical worlds concepts, Examples, Successes, and Failures in Translational Medicine

10.31219/osf.io/ujzwe ◽

2019 ◽

Author(s):

Attila A Seyhan

Keyword(s):

Drug Development ◽

Biomedical Research ◽

Development Process ◽

Public Funding ◽

Human Studies ◽

Attrition Rate ◽

Drug Development Process ◽

Preclinical Research ◽

Attrition Rates ◽

Research Findings

The biopharmaceutical companies involved in developing drugs for human diseases are facing considerable challenges, both politically and fiscally. There is growing pressure from the general public, funding agencies, and the policymakers for scientists and industry to improve drug development process, better bridge basic and translational human studies, and ultimately improve the process of the development of more effective, safer, and less costly drugs.The crisis involving the scale of the reproducibility and translatability of preclinical research to human studies and high attrition rate of drug development process is widely recognized both in academia and industry. Despite all this, the high attrition rates of drug development and the magnitude of the reproducibility and translatability problems with the preclinical research findings to human studies remain a fact.Recent reports in literature also suggest that many published research findings in preclinical research are misleading, not as robust as they claim, or cannot be reproduced and hence cannot be translated to human studies. The reasons are complex and challenging. Potential culprits range from the complexity of modern biomedical research to the limitations of tools, the trivial methodological differences, to poor experimental designs, inappropriate data analysis, misuse of statistics, the poor predictability of animal results in humans, as well as training and perverse incentives in academia.There are many reports suggesting solutions to overcome these roadblocks in biomedical research. However, how scientists, researchers, and the biopharmaceutical industry deal with this problem depends on the understanding of the root causes of the problem and the strategies and approaches to solving this problem to improve biomedical research.The purpose of this article is to conduct a thorough literature review to evaluate the nature of some of the problems leading to high attrition rates of drug development and to provide some suggestion to overcome the obstacles that impede the drug development process.

Download Full-text

Antisense oligonucleotides targeting angiotensinogen: insights from animal studies

Bioscience Reports ◽

10.1042/bsr20180201 ◽

2019 ◽

Vol 39 (1) ◽

Cited By ~ 3

Author(s):

Chia-Hua Wu ◽

Ya Wang ◽

Murong Ma ◽

Adam E. Mullick ◽

Rosanne M. Crooke ◽

...

Keyword(s):

Antisense Oligonucleotides ◽

Therapeutic Approach ◽

Animal Studies ◽

Preclinical Research ◽

Angiotensin Peptides ◽

Research Findings

Abstract Angiotensinogen (AGT) is the unique substrate of all angiotensin peptides. We review the recent preclinical research of AGT antisense oligonucleotides (ASOs), a rapidly evolving therapeutic approach. The scope of the research findings not only opens doors for potentially new therapeutics of hypertension and many other diseases, but also provides insights into understanding critical physiological and pathophysiological roles mediated by AGT.

Download Full-text

Enhancing Interrogation of Skeletal Muscle Samples for Informative Quantitative Data

Journal of Neuromuscular Diseases ◽

10.3233/jnd-210736 ◽

2021 ◽

pp. 1-13

Author(s):

Terence A. Partridge

Keyword(s):

Skeletal Muscle ◽

Homo Sapiens ◽

Practical Importance ◽

Analytical Techniques ◽

Sampling Bias ◽

Preclinical Research ◽

Muscle Sample ◽

Accurate Picture ◽

Research Findings ◽

Accurate Comparison

Careful quantitative analysis of histological preparations of muscle samples is crucial to accurate investigation of myopathies in man and of interpretation of data from animals subjected to experimental or potentially therapeutic treatments. Protocols for measuring cell numbers are subject to problems arising from biases associated with preparative and analytical techniques. Prominent among these is the effect of polarized structure of skeletal muscle on sampling bias. It is also common in this tissue to collect data as ratios to convenient reference dominators, the fundamental bases of which are ill-defined, or unrecognized or not accurately assessable. Use of such ‘floating’ denominators raises a barrier to estimation of the absolute values that assume practical importance in medical research, where accurate comparison between different scenarios in different species is essential to the aim of translating preclinical research findings in animal models to clinical utility in Homo sapiens. This review identifies some of the underappreciated problems with current morphometric practice, some of which are exacerbated in skeletal muscle, and evaluates the extent of their intrusiveness into the of building an objective, accurate, picture of the structure of the muscle sample. It also contains recommendations for eliminating or at least minimizing these problems. Principal among these, would be the use of stereological procedures to avoid the substantial counting biases arising from inter-procedure differences in object size and section thickness. Attention is also drawn to the distortions of interpretation arising from use of undefined or inappropriate denominators.

Download Full-text

An Empirical Analysis of Perceived Importance Attached to Destination Attributes of Chinese Tourists' Visiting in India

Destination Management and Marketing ◽

10.4018/978-1-7998-2469-5.ch023 ◽

2020 ◽

pp. 410-426

Author(s):

Mohinder Chand Dhiman ◽

Sunil Kumar

Keyword(s):

Empirical Analysis ◽

Neutral Point ◽

Travel Agency ◽

Male And Female ◽

Perceived Importance ◽

Research Findings ◽

Chinese Tourists ◽

The Mean ◽

Gathering Data

This study attempts to explore the tourists' satisfaction within a tourism context, specifically with reference to the destination-based attributes. The study was conducted in India with a sample of Chinese tourists. Gathering data was analyzed by using t-tests. The research findings indicated that the dimension of accommodation services was the strongest predictor of the Chinese tourists' satisfaction, followed by incoming travel agency services and facilities in India. The dimension of accommodation services also was the strongest predictor of the female tourists' overall holiday satisfaction, followed by destination facilities and incoming travel agency services. Moreover, the mean scores of all the items within the main dimensions were above the neutral point. These results revealed that both male and female tourists were generally satisfied with their holiday in India.

Download Full-text

Reproducibility2020: Progress and Priorities

10.1101/109017 ◽

2017 ◽

Author(s):

Leonard P. Freedman ◽

Gautham Venugopalan ◽

Rosann Wisman

Keyword(s):

Open Access ◽

Publication Bias ◽

Biomedical Research ◽

Idea Generation ◽

Research Process ◽

Research Community ◽

Preclinical Studies ◽

Preclinical Research ◽

Research Findings ◽

Standards And Guidelines

ABSTRACTThe preclinical research process is a cycle of idea generation, experimentation, and reporting of results. The biomedical research community relies on the reproducibility of published discoveries to create new lines of research and to translate research findings into therapeutic applications. Since 2012, when scientists from Amgen reported that they were able to reproduce only 6 of 53 “landmark” preclinical studies, the biomedical research community began discussing the scale of the reproducibility problem and developing initiatives to address critical challenges. GBSI released the “Case for Standards” in 2013, one of the first comprehensive reports to address the rising concern of irreproducible biomedical research. Further attention was drawn to issues that limit scientific self-correction including reporting and publication bias, underpowered studies, lack of open access to methods and data, and lack of clearly defined standards and guidelines in areas such as reagent validation. To evaluate the progress made towards reproducibility since 2013, GBSI identified and examined initiatives designed to advance quality and reproducibility. Through this process, we identified key roles for funders, journals, researchers and other stakeholders and recommended actions for future progress. This paper describes our findings and conclusions.

Download Full-text

Successful business models for service centres: an empirical analysis

International Journal of Productivity and Performance Management ◽

10.1108/ijppm-05-2019-0230 ◽

2020 ◽

Vol ahead-of-print (ahead-of-print) ◽

Author(s):

Paolo Gaiardelli ◽

Lucrezia Songini

Keyword(s):

Empirical Analysis ◽

Business Performance ◽

Business Models ◽

Positive Impact ◽

Content Type ◽

Study Approach ◽

Strategic Direction ◽

Top Performers ◽

Research Findings ◽

The Empirical Analysis

PurposeThe purpose of this paper is to analyse the fit between the strategy of service centres and their business model (BM) and to identify the BM components' characteristics and links that allow it to stand out in terms of service delivery and business performance.Design/methodology/approachThis study applies an inductive qualitative multiple case study approach through the empirical analysis of top-performing Italian service centres operating in the Medium–Heavy Commercial Vehicle sector.FindingsResearch findings underline that the BM components of top performers are consistent amongst each other and with the adopted strategy and make a positive impact on the firm's performance. In particular, top performers are characterised by a solid financial structure based on equity, formalised and flexible organisational structures and processes, clarity in strategic direction and long-term orientation, grounded capabilities, competences and skills, trustful relationships with main service partners and a comprehensive set of managerial mechanisms.Research limitations/implicationsThis paper presents some limitations, typical of qualitative research based on case studies. Future works may include other dimensions of performance for identifying top performers, and extend the empirical analysis to different sectors and national contexts.Originality/valueThis paper supports the relevance of contingency theory – particularly the strategy-structure-performance paradigm – in the analysis of the role of a BM in successful servitization strategies of service centres. It highlights that the BMs of the top-performing companies are characterised by some common elements. From a practical perspective, the authors provide insights that can be useful for designing successful service-based BMs for service networks.

Download Full-text

HGG-44. REVEALING VULNERABILITIES IN DIPG THROUGH ONC201

Neuro-Oncology ◽

10.1093/neuonc/noab090.108 ◽

2021 ◽

Vol 23 (Supplement_1) ◽

pp. i26-i26

Author(s):

James Stafford ◽

Alqassem Abuarqoub ◽

Tatiana Mcanulty ◽

Richard Possemato ◽

Eyal Amiel ◽

...

Keyword(s):

Cell Lines ◽

Diffuse Intrinsic Pontine Glioma ◽

Model Systems ◽

Epigenetic Factors ◽

Preclinical Research ◽

Mechanistic Insight ◽

Downstream Effects ◽

Research Findings ◽

Insight Into ◽

Shed Light

Abstract Emerging evidence from clinical and preclinical studies suggests that the imipridone ONC201 is well tolerated and may have some clinical impact in discrete diffuse intrinsic pontine glioma patients (DIPG). A primary goal of our work is to determine if DIPG are uniquely sensitive to ONC201 and if so, whether ONC201 itself can be used as a tool to illuminate novel vulnerabilities in DIPG. To accomplish this, we are utilizing a combination of patient-derived cell lines as well as mouse xenografts that dovetail with a variety of molecular, epigenetic and metabolomic tools. A central finding from our work is that ONC201 primarily activates the mitochondrial protease, ClpP in DIPG patient-derived cell lines, an effect consistent with recently described ONC201 mechanism of action in other tumors. We further demonstrate that activation of ClpP by ONC201 leads to a host of downstream effects in DIPG model systems including distinctive effects on the metabolome leading to direct alterations in the unique epigenetic signature of DIPG. By directly manipulating these metabolic and epigenetic factors we provide prospective mechanistic insight into how ONC201 as well as ClpP activity impacts DIPG growth and tumorigenicity. These preclinical research findings shed light on potential therapeutic vulnerabilities in DIPG as well as ways that these strategies may be combined to enhance their potential.

Download Full-text

Reproducibility of preclinical data: one man's poison is another man's meat

Advances in Precision Medicine ◽

10.18063/apm.2016.02.001 ◽

2016 ◽

Vol 1 (1) ◽

Cited By ~ 1

Author(s):

Anton Bespalov ◽

Christoph H Emmerich ◽

Björn Gerlach ◽

Martin C Michel

Keyword(s):

Precision Medicine ◽

Clinical Efficacy ◽

Study Design ◽

Experimental Models ◽

Preclinical Research ◽

Experimental Conditions ◽

Preclinical Data ◽

Root Cause ◽

Research Findings

Limited reproducibility of preclinical data is increasingly discussed in the literature. Failure of drug devel-opment programs due to lack of clinical efficacy is also of growing concern. The two phenomena may share an important root cause — a lack of robustness in preclinical research. Such a lack of robustness can be a relevant cause of fail-ure in translating preclinical findings into clinical efficacy and hence attrition, and exaggerated cost in drug develop-ment. Apart from the study design and data analysis factors (e.g., insufficient sample sizes, failure to implement blind-ing, and randomization), heterogeneity among experimental models (e.g., animal strains) and the conditions of the study used between different laboratories is a major contributor to the lacking of robustness of research findings. The flipside of this coin is that the understanding of the causes of heterogeneity across experimental models may lead to the identification of relevant factors for defining the responder populations. Thus, this heterogeneity within preclinical find-ings could be an asset, rather than an obstacle, for precision medicine. To enable this paradigm shift, several steps need to be taken to identify conditions under which drugs do not work. An improved granularity in the reporting of preclini-cal studies is central among them (i.e., details about the study design, experimental conditions, quality of tools and rea-gents, validation of assay conditions, etc.). These actions need to be discussed jointly by the research communities in-terested in preclinical data robustness and precision medicine. Thus, we propose that a lack of robustness due to the heterogeneity across models and conditions of the study is not necessarily a liability for biomedical research but can be transformed into an asset of precision medicine.

Download Full-text