Improving Replicability, Reproducibility, And Reliability In Preclinical Research: A Shared Responsibility

ILAR Journal ◽  
2019 ◽  
Vol 60 (2) ◽  
pp. 113-119
Author(s):  
Christopher Cheleuitte-Nieves ◽  
Neil S Lipman
Keyword(s):  
Biological Response ◽  
Animal Research ◽  
Shared Responsibility ◽  
Housing System ◽  
Preclinical Research ◽  
Extrinsic Factors ◽  
Study Planning ◽  
The Impact ◽  
Intrinsic And Extrinsic Factors

Abstract Reproducible and reliable scientific investigation depends on the identification and consideration of various intrinsic and extrinsic factors that may affect the model system used. The impact of these factors must be managed during all phases of a study: planning, execution, and reporting. The value of in vivo (animal) research has come under increasing scrutiny over the past decade because of multiple reports documenting poor translatability to human studies. These failures have been attributed to various causes, including poor study design and execution as well as deficiencies in reporting. It is important to recognize that achieving reproducible and reliable preclinical research results is a joint responsibility that requires a partnership between the investigative team and the animal care and use program staff. The myriad of intrinsic factors, such as species, strain/substrain, age, sex, physiologic and health status, and extrinsic factors, including temperature, humidity, lighting, housing system, and diet, need to be recognized and managed during study planning and execution, as they can influence animal physiology and biological response. Of equal importance is the need to document and report these details. The ARRIVE and PREPARE guidelines were developed by concerned scientists, veterinarians, statisticians, journal editors, and funding agencies to assist investigative teams and scientific journals manage and report on intrinsic and extrinsic factors to improve reproducibility and reliability. This issue of the ILAR Journal will focus on the various extrinsic factors that have been recognized to confound animal research.

scholarly journals Revision of the ARRIVE guidelines: rationale and scope

2018 ◽  
Vol 2 (1) ◽  
pp. e000002 ◽  
Author(s):  
Nathalie Percie du Sert ◽  
Viki Hurst ◽  
Amrita Ahluwalia ◽  
Sabina Alam ◽  
Douglas G Altman ◽  
...  
Keyword(s):  
System Development ◽  
Animal Research ◽  
Quality Of Reporting ◽  
Research Reporting ◽  
In Vivo Experiments ◽  
Expert Working Group ◽  
Tiered System ◽  
Initial Work ◽  
The Impact

In 2010, the NC3Rs published the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines to improve the reporting of animal research. Despite considerable levels of support from the scientific community, the impact on the quality of reporting in animal research publications has been limited. This position paper highlights the strategy of an expert working group established to revise the guidelines and facilitate their uptake. The group’s initial work will focus on three main areas: prioritisation of the ARRIVE items into a tiered system, development of an explanation and elaboration document, and revision of specific items.

Quality of design and reporting of animal research in peritoneal dialysis: A scoping review

2020 ◽  
Vol 40 (4) ◽  
pp. 394-404
Author(s):  
Janusz Witowski ◽  
Dorota Sikorska ◽  
András Rudolf ◽  
Izabela Miechowicz ◽  
Julian Kamhieh-Milz ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Scoping Review ◽  
Animal Studies ◽  
Reporting Quality ◽  
Animal Research ◽  
Size Estimation ◽  
Quality Of Reporting ◽  
The Impact

The concerns about reproducibility and validity of animal studies are partly related to poor experimental design and reporting. Here, we undertook a scoping review of the literature to determine the extent and quality of reporting of animal studies on peritoneal dialysis (PD). Online databases were searched to identify 567 relevant original articles published between 1979 and 2018. These were analyzed with respect to bibliographic parameters and general aspects of animal experimentation. A subgroup of 120 studies was analyzed in detail in terms of the impact on the reporting quality of the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines for animal studies. The number of animal studies on PD increased continuously over the years with a thematic shift toward long-term preservation of the peritoneum as a dialyzing organ. There were significant deficiencies in research design with the lack of sample size estimation, randomization, and blinding being the commonest shortcomings. The description of animal numbers, housing conditions, use of medication, and statistical analysis was incomplete. The introduction in 2010 of the ARRIVE guidelines produced very little improvement in the completeness of reporting regardless of journal impact factor. The animal studies on PD suffer from deficits in experimental protocols and transparent reporting. These drawbacks need to be corrected to ensure high-quality and much-needed animal research in PD.

The impact of intrinsic and extrinsic factors on the job satisfaction of dentists

2012 ◽  
Vol 40 (5) ◽  
pp. 474-480 ◽  
Author(s):  
K. Goetz ◽  
S.M. Campbell ◽  
B. Broge ◽  
C.E. Dörfer ◽  
M. Brodowski ◽  
...  
Keyword(s):  
Job Satisfaction ◽  
Extrinsic Factors ◽  
The Impact ◽  
Intrinsic And Extrinsic Factors

scholarly journals Epidemiology, etiology, and pathogenesis of tendinopathy among athletes

2021 ◽  
Vol 9 (1) ◽  
pp. 437
Author(s):  
Syed Asif Hasan ◽  
Ahmed Abdulrahman Othman ◽  
Yousuf Kamal Shagdar ◽  
Abdulrahman Anis Khan ◽  
Amal Baalqasim Sulaimani ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Literature Review ◽  
Nerve Fibers ◽  
Systemic Diseases ◽  
Extrinsic Factors ◽  
Serious Adverse Events ◽  
Professional Careers ◽  
The Impact ◽  
Intrinsic And Extrinsic Factors

The treatment of tendinopathy can be challenging for clinicians and might be associated with serious adverse events. However, evidence shows that tendinopathy can significantly impact the professional careers of the affected athletes. The main clinical features of the condition include decreased performance and strength of the affected tendons, swelling, and localized pain.  Although tendinopathy might seem a non-critical condition, estimates show that it might be career-ending for many professional athletes, and therefore, reducing their quality of life. In the present literature review, we have discussed the epidemiology, etiology, and pathogenesis of tendinopathy among athletes. Different intrinsic and extrinsic factors were found to contribute to the development of the condition and the impact of various systemic diseases. Evidence also shows that the prevalence of the condition is high among athletes. However, these rates were variable across the different studies in the literature. This is probably owing to various factors, like demographics and the process of detection. The pathogenesis of the condition is also very complicated, and the development of pain has been attributed to the process of angiogenesis and associated ingrowth of nerve fibers.

scholarly journals Antileishmanial Drug Discovery and Development: Time to Reset the Model?

2021 ◽  
Vol 9 (12) ◽  
pp. 2500
Author(s):  
Ana Isabel Olías-Molero ◽  
Concepción de la Fuente ◽  
Montserrat Cuquerella ◽  
Juan J. Torrado ◽  
José M. Alunda
Keyword(s):  
Leishmania Species ◽  
Human Populations ◽  
Preclinical Research ◽  
Product Profile ◽  
Antileishmanial Drug ◽  
Common Goals ◽  
Vector Borne ◽  
Low Efficiency ◽  
The Impact

Leishmaniasis is a vector-borne parasitic disease caused by Leishmania species. The disease affects humans and animals, particularly dogs, provoking cutaneous, mucocutaneous, or visceral processes depending on the Leishmania sp. and the host immune response. No vaccine for humans is available, and the control relies mainly on chemotherapy. However, currently used drugs are old, some are toxic, and the safer presentations are largely unaffordable by the most severely affected human populations. Moreover, its efficacy has shortcomings, and it has been challenged by the growing reports of resistance and therapeutic failure. This manuscript presents an overview of the currently used drugs, the prevailing model to develop new antileishmanial drugs and its low efficiency, and the impact of deconstruction of the drug pipeline on the high failure rate of potential drugs. To improve the predictive value of preclinical research in the chemotherapy of leishmaniasis, several proposals are presented to circumvent critical hurdles—namely, lack of common goals of collaborative research, particularly in public–private partnership; fragmented efforts; use of inadequate surrogate models, especially for in vivo trials; shortcomings of target product profile (TPP) guides.

scholarly journals Adolescent BMI: The Importance of Intrinsic and Extrinsic Factors

2018 ◽  
Vol 11 (1) ◽  
pp. 147-161
Author(s):  
Molly Jacobs
Keyword(s):  
Linear Models ◽  
Relative Importance ◽  
Sexual Encounter ◽  
Extrinsic Factors ◽  
Intrinsic Factors ◽  
Multinomial Logit Models ◽  
Adolescents And Adults ◽  
The Impact ◽  
Intrinsic And Extrinsic Factors ◽  
Weight Classification

Objectives:Research shows that weight trends in adolescence persist into adulthood, but do the same factors contribute to weight in adolescence as in adulthood? Are extrinsic factors presumably more important than intrinsic characteristics? This study identifies the correlation between BMI and various intrinsic and extrinsic factors and evaluates their relative importance in BMI development. It compares the primary determinants for adolescents (12-20 years old) and adults (21+ years old).Methods:Using 15 years of panel data, generalized linear models, we assessed the impact of extrinsic-environmental, biological, geographic and household-and intrinsic-sexual activity, substance use, desire to lose weight,etc.-characteristics on adolescent and adult BMI. Multinomial logit models tested the contribution of these characteristics to weight categories.Results:Race and age were the most significant BMI correlates at all ages. This remains true for weight classification as well. For young adolescents, intrinsic factors are highly deterministic, while extrinsic factors play no role. As adolescents age into adults, intrinsic factors continue to be deterministic, while extrinsic covariates also emerge as deterministic. Intrinsic determinates of significance include age of first sexual encounter, tobacco experimentation, perspective on general health, and desire to lose weight (or stay the same weight).Conclusion:While biological/genetic attributes are the largest determinants of BMI at every age, intrinsic factors play a larger role in adolescent BMI development than adults. As individuals age, intrinsic determinants remain important, but extrinsic characteristics contribute significantly to weight classification. Thus, the weight determinants differ between adolescents and adults suggesting different methods of policy intervention be used for adolescents and adults.

scholarly journals Reporting animal research: Explanation and Elaboration for the ARRIVE guidelines 2019

2019 ◽  
Author(s):  
Nathalie Percie du Sert ◽  
Amrita Ahluwalia ◽  
Sabina Alam ◽  
Marc T. Avey ◽  
Monya Baker ◽  
...  
Keyword(s):  
Biomedical Research ◽  
Scientific Community ◽  
Animal Research ◽  
Supporting Evidence ◽  
Minimum Information ◽  
Research Publications ◽  
The Impact ◽  
Accurate Reporting

AbstractImproving the reproducibility of biomedical research is a major challenge. Transparent and accurate reporting are vital to this process; it allows readers to assess the reliability of the findings, and repeat or build upon the work of other researchers. The NC3Rs developed the ARRIVE guidelines in 2010 to help authors and journals identify the minimum information necessary to report in publications describing in vivo experiments.Despite widespread endorsement by the scientific community, the impact of the ARRIVE guidelines on the transparency of reporting in animal research publications has been limited. We have revised the ARRIVE guidelines to update them and facilitate their use in practice. The revised guidelines are published alongside this paper. This Explanation and Elaboration document was developed as part of the revision. It provides further information about each of the 21 items in ARRIVE 2019, including the rationale and supporting evidence for their inclusion in the guidelines, elaboration of details to report, and examples of good reporting from the published literature.

scholarly journals Highly Contingent Phenotypes of Lon Protease Deficiency in Escherichia coli upon Antibiotic Challenge

2019 ◽  
Vol 202 (3) ◽  
Author(s):  
Nishad Matange
Keyword(s):  
Antimicrobial Resistance ◽  
Evolutionary Dynamics ◽  
Resistant Bacteria ◽  
Lon Protease ◽  
Extrinsic Factors ◽  
Content Type ◽  
E Coli ◽  
Drug Concentrations ◽  
Intrinsic And Extrinsic Factors

ABSTRACT Evolutionary trajectories and mutational landscapes of drug-resistant bacteria are influenced by cell-intrinsic and extrinsic factors. In this study, I demonstrated that loss of the Lon protease altered susceptibility of Escherichia coli to trimethoprim and that these effects were strongly contingent on the drug concentration and genetic background. Lon, an AAA+ ATPase, is a bacterial master regulator protease involved in cytokinesis, suppression of transposition events, and clearance of misfolded proteins. I show that Lon deficiency enhances intrinsic drug tolerance at sub-MIC levels of trimethoprim. As a result, loss of Lon, though disadvantageous under drug-free conditions, has a selective advantage at low concentrations of trimethoprim. At high drug concentrations, however, Lon deficiency is detrimental for E. coli. I show that the former is explained by suppression of drug efflux by Lon, while the latter can be attributed to SulA-dependent hyperfilamentation. On the other hand, deletion of lon in a trimethoprim-resistant mutant E. coli strain (harboring the Trp30Gly dihydrofolate reductase [DHFR] allele) directly potentiates resistance by enhancing the in vivo stability of mutant DHFR. Using extensive mutational analysis at 3 hot spots of resistance, I show that many resistance-conferring mutations render DHFR prone to proteolysis. This trade-off between gaining resistance and losing in vivo stability limits the number of mutations in DHFR that can confer trimethoprim resistance. Loss of Lon expands the mutational capacity for acquisition of trimethoprim resistance. This paper identifies the multipronged action of Lon in trimethoprim resistance in E. coli and provides mechanistic insight into how genetic backgrounds and drug concentrations may alter the potential for antimicrobial resistance evolution. IMPORTANCE Understanding the evolutionary dynamics of antimicrobial resistance is vital to curb its emergence and spread. Being fundamentally similar to natural selection, the fitness of resistant mutants is a key parameter to consider in the evolutionary dynamics of antimicrobial resistance (AMR). Various intrinsic and extrinsic factors modulate the fitness of resistant bacteria. This study demonstrated that Lon, a bacterial master regulator protease, influences drug tolerance and resistance. Lon is a key regulator of several fundamental processes in bacteria, including cytokinesis. I demonstrated that Lon deficiency produces highly contingent phenotypes in E. coli challenged with trimethoprim and can expand the mutational repertoire available to E. coli to evolve resistance. This multipronged influence of Lon on drug resistance provides an illustrative instance of how master regulators shape the response of bacteria to antibiotics.

scholarly journals Peranan Ekosistem Hutan Mangrove Pada Imunitas Terhadap Malaria: Studi Di Kecamatan Labuhan Maringgai Kabupaten Lampung Timur

2015 ◽  
Vol 3 (2) ◽  
pp. 67 ◽  
Author(s):  
Agung Kartika Putra ◽  
Samsul Bakri ◽  
Betta Kurniawan
Keyword(s):  
Mangrove Forest ◽  
Regression Models ◽  
Forest Ecosystems ◽  
Binary Logistic Regression ◽  
Mangrove Forests ◽  
Extrinsic Factors ◽  
Logistic Regression Models ◽  
The Impact ◽  
Intrinsic And Extrinsic Factors ◽  
Better Than

One of the ecological function of mangrove forests is a habitat for mosquitoes that cause malaria (Anopheles sp.). Epidemic of malaria could increased as a result of mangrove degradation. The damage of mangrove forests stimulate Anopheles sp. migrate to other habitats such as settlements, that become malaria vector.  The purpose of this research was to determine the effect of mangrove forest ecosystems both intrinsic and extrinsic factors in immunity to malaria. This research was conducted on June 2014 in the Muara Gading Mas Village, Bandar Negeri, Sriminosari, and Margasari, Sub-district Labuhan Maringgai, District East Lampung.  The data were collected through interviews and survey/observations method. The impact of each variable used binary logistic regression models. Parameter optimization used software Minitab 16.  The result of research have been demonstrated that there is influence both intrinsic and extrinsic factors in immunity to malaria in mangrove forest. Factors that increase resistance to malaria: (a) gender, male37.42 fold of female, (b) age, getting older every 1 year doubled to 1.17 times of originally, (c) education, the higher it isreduced to 0.001 times the originally, (d) livelihood, besides fisher 0,001 fold of fisherman, (e) the distance settlements to the health facility, each reduced to 1 meter doubled to 0.09 times the originally, (f) the distance home to mangroves, each increase of 1 meter doubled to 1,001 times the originally, (g) the dustbin, there are bins 239.71 better than none, (h) the malaria program, multiply 3,71E+05 originally than none, (i) extensive mangrove, increasing 1 m2 become 1,001 fold of originally, and (j) mangrove density, increasing 1 population/ha multiply 1.18 fold originally.Keywords: Mangrove forest, immunity to malaria, Anopheles sp.

Sign in / Sign up

Export Citation Format

Share Document