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Cell Systems Jun 2021A distinctive feature of many biological systems is their ability to adapt to persistent stimuli or disturbances that would otherwise drive them away from a desirable... (Review)
Review
A distinctive feature of many biological systems is their ability to adapt to persistent stimuli or disturbances that would otherwise drive them away from a desirable steady state. The resulting stasis enables organisms to function reliably while being subjected to very different external environments. This perspective concerns a stringent type of biological adaptation, robust perfect adaptation (RPA), that is resilient to certain network and parameter perturbations. As in engineered control systems, RPA requires that the regulating network satisfy certain structural constraints that cannot be avoided. We elucidate these ideas using biological examples from systems and synthetic biology. We then argue that understanding the structural constraints underlying RPA allows us to look past implementation details and offers a compelling means to unravel regulatory biological complexity.
Topics: Acclimatization; Adaptation, Physiological; Homeostasis; Models, Biological; Synthetic Biology
PubMed: 34139163
DOI: 10.1016/j.cels.2021.05.020 -
International Journal of Molecular... Apr 2022Plants have remarkable plasticity due to their vast genetic potential which interacts with many external factors and developmental signals to govern development and...
Plants have remarkable plasticity due to their vast genetic potential which interacts with many external factors and developmental signals to govern development and adaptation to changing environments [...].
Topics: Acclimatization; Adaptation, Physiological; Plant Development; Plants; Systems Biology
PubMed: 35456977
DOI: 10.3390/ijms23084159 -
Current Environmental Health Reports Dec 2020In this article, we examine the intersection of human migration and climate change. Growing evidence that changing environmental and climate conditions are triggers for... (Review)
Review
PURPOSE OF REVIEW
In this article, we examine the intersection of human migration and climate change. Growing evidence that changing environmental and climate conditions are triggers for displacement, whether voluntary or forced, adds a powerful argument for profound anticipatory engagement.
RECENT FINDINGS
Climate change is expected to displace vast populations from rural to urban areas, and when life in the urban centers becomes untenable, many will continue their onward migration elsewhere (Wennersten and Robbins 2017; Rigaud et al. 2018). It is now accepted that the changing climate will be a threat multiplier, will exacerbate the need or decision to migrate, and will disproportionately affect large already vulnerable sections of humanity. Worst-case scenario models that assume business-as-usual approaches to climate change predict that nearly one-third of the global population will live in extremely hot (uninhabitable) climates, currently found in less than 1% of the earth's surface mainly in the Sahara. We find that the post-World War II regime designed to receive European migrants has failed to address population movement in the latter half of the twentieth century fueled by economic want, globalization, opening (and then closing) borders, civil strife, and war. Key stakeholders are in favor of using existing instruments to support a series of local, regional, and international arrangements to protect environmental migrants, most of whom will not cross international borders. The proposal for a dedicated UN agency and a new Convention has largely come from academia and NGOs. Migration is now recognized not only as a consequence of instability but as an adaptation strategy to the changing climate. Migration must be anticipated as a certainty, and thereby planned for and supported.
Topics: Acclimatization; Climate Change; Human Migration; Humans; Population Dynamics; Social Problems; Vulnerable Populations
PubMed: 33048318
DOI: 10.1007/s40572-020-00291-4 -
Proceedings. Biological Sciences Feb 2023Conflicts of interest abound not only in human affairs but also in the biological realm. Evolutionary conflict occurs over multiple scales of biological organization,...
Conflicts of interest abound not only in human affairs but also in the biological realm. Evolutionary conflict occurs over multiple scales of biological organization, from genetic outlawry within genomes, to sibling rivalry within nuclear families, to collective-action disputes within societies. However, achieving a general understanding of the dynamics and consequences of evolutionary conflict remains an outstanding challenge. Here, we show that a development of R. A. Fisher's classic 'geometric model' of adaptation yields novel and surprising insights into the dynamics of evolutionary conflict and resulting maladaptation, including the discoveries that: (i) conflict can drive evolving traits arbitrarily far away from all parties' optima and, indeed, if all mutations are equally likely then contested traits are more often than not driven outwith the zone of actual conflict (hyper-maladaptation); (ii) evolutionary conflicts drive persistent maladaptation of orthogonal, non-contested traits (para-maladaptation); and (iii) modular design greatly ameliorates conflict-driven maladaptation, thereby facilitating major transitions in individuality.
Topics: Humans; Biological Evolution; Adaptation, Physiological; Mutation; Genome; Acclimatization
PubMed: 36750194
DOI: 10.1098/rspb.2022.2423 -
Therapeutic Innovation & Regulatory... Jan 2020In an adaptive trial, the researcher may have the option of responding to interim safety and efficacy data in a number of ways, including narrowing the study focus or... (Review)
Review
BACKGROUND
In an adaptive trial, the researcher may have the option of responding to interim safety and efficacy data in a number of ways, including narrowing the study focus or increasing the number of subjects, balancing treatment allocation or different forms of randomization based on responses of subjects prior to treatment. This research aims at compiling the technical, statistical, and regulatory implications of the employment of adaptive design in a clinical trial.
METHODS
Review of adaptive design clinical trials in Medline, PubMed, EU Clinical Trials Register, and ClinicalTrials.gov. Phase I and seamless phase I/II trials were excluded. We selected variables extracted from trials that included basic study characteristics, adaptive design features, size and use of independent data-monitoring committees (DMCs), and blinded interim analysis.
RESULTS
The research retrieved 336 results, from which 78 were selected for analysis. Sixty-seven were published articles, and 11 were guidelines, papers, and regulatory bills. The most prevalent type of adaptation was the seamless phase II/III design 23.1%, followed by adaptive dose progression 19.2%, pick the winner / drop the loser 16.7%, sample size re-estimation 10.3%, change in the study objective 9.0%, adaptive sequential design 9.0%, adaptive randomization 6.4%, biomarker adaptive design 3.8%, and endpoint adaptation 2.6%. Discussion DISCUSSION: It is possible to infer that the use of Adaptive Design is an ethical and scientific advantage when properly planned and applied, since it increases the flexibility of the trial, shortens the overall clinical investigation time of a drug, and reduces the risk of patient exposure to adverse effects related to the experimental drug. Its greater methodologic and analytic complexity requires an adequate statistical methodology.
CONCLUSIONS
The application of "adaptive clinical designs" for phase II/III studies appear to have been limited to trials with a small number of study centers, with smaller extensions of time and to experimental drugs with more immediate clinical effects that are amenable to risk/benefit decisions based on interim analyses. According to the reviewed studies, simple adaptive trial designs-such as early study terminations due to futility and sample size re-estimation-are becoming widely adopted throughout the pharmaceutical industry, especially in phase II and III studies. The pharmaceutical industry and contract research organizations (CROs) are implementing simple adaptations more frequently and the more complex adaptations-biomarker adaptive design, endpoint adaptation-are more sporadic.
Topics: Adaptive Clinical Trials as Topic; Drugs, Investigational; Humans; Research Design; Sample Size
PubMed: 32008232
DOI: 10.1007/s43441-019-00052-y -
Methods in Molecular Biology (Clifton,... 2023Biochemical networks are often characterized by tremendous complexity-both in terms of the sheer number of interacting molecules ("nodes") and in terms of the varied and... (Review)
Review
Biochemical networks are often characterized by tremendous complexity-both in terms of the sheer number of interacting molecules ("nodes") and in terms of the varied and incompletely understood interactions among these molecules ("interconnections" or "edges"). Strikingly, the vast and intricate networks of interacting proteins that exist within each living cell have the capacity to perform remarkably robustly, and reproducibly, despite significant variations in concentrations of the interacting components from one cell to the next and despite mutability over time of biochemical parameters. Here we consider the ubiquitously observed and fundamentally important signalling response known as robust perfect adaptation (RPA). We have recently shown that all RPA-capable networks, even the most complex ones, must satisfy an extremely rigid set of design principles, and are modular, being decomposable into just two types of network building-blocks-opposer modules and balancer modules. Here we present an overview of the design principles that characterize all RPA-capable network topologies through a detailed examination of a collection of simple examples. We also introduce a diagrammatic method for studying the potential of a network to exhibit RPA, which may be applied without a detailed knowledge of the complex mathematical principles governing RPA.
Topics: Signal Transduction; Adaptation, Physiological; Acclimatization; Models, Biological
PubMed: 37074572
DOI: 10.1007/978-1-0716-3008-2_1 -
Journal of Thermal Biology Aug 2023Given the increasing trend of global warming and extreme weather conditions, including heat waves and its effects on health, the present study was done to investigate... (Review)
Review
BACKGROUND
Given the increasing trend of global warming and extreme weather conditions, including heat waves and its effects on health, the present study was done to investigate adaptive behaviors of communities in the world for combating heat waves.
METHOD
ology: In this systematic review, out of 1529 results, 57 relevant and authoritative English papers on adaptation to heat waves hazard were extracted and evaluated using valid keywords from valid databases (PubMed, WOS, EMBASE, and Scopus). In addition, multiple screening steps were done and then, the selected papers were qualitatively assessed. Evaluation results were summarized using an Extraction Table.
RESULTS
In this paper, the adaptive behaviors for combating heat waves hazard were summarized into 11 categories: Education and awareness raising, Adaptation of critical infrastructure, Governments measures, Health-related measures, Application of early warning system, Protective behaviors in workplace, Physical condition, Adaptive individual behaviors, Design and architecture of the building, Green infrastructure (green cover), and Urban design.
CONCLUSION
The findings of this study showed that community actions have significant effects on adaptation to heat wave. Therefore, for reducing heat wave-related negative health effects and vulnerability, more attention should be paid to the above-mentioned actions for mitigation, preparation, and responding regarding heat waves.
PROSPERO REGISTRATION NUMBER
CRD42021257747.
Topics: Hot Temperature; Acclimatization; Adaptation, Physiological; Global Warming; Adaptation, Psychological; Climate Change
PubMed: 37499408
DOI: 10.1016/j.jtherbio.2023.103588 -
Biometrical Journal. Biometrische... Aug 2022Adaptive designs are an increasingly popular method for the adaptation of design aspects in clinical trials, such as the sample size. Scoring different adaptive designs...
Adaptive designs are an increasingly popular method for the adaptation of design aspects in clinical trials, such as the sample size. Scoring different adaptive designs helps to make an appropriate choice among the numerous existing adaptive design methods. Several scores have been proposed to evaluate adaptive designs. Moreover, it is possible to determine optimal two-stage adaptive designs with respect to a customized objective score by solving a constrained optimization problem. In this paper, we use the conditional performance score by Herrmann et al. (2020) as the optimization criterion to derive optimal adaptive two-stage designs. We investigate variations of the original performance score, for example, by assigning different weights to the score components and by incorporating prior assumptions on the effect size. We further investigate a setting where the optimization framework is extended by a global power constraint, and additional optimization of the critical value function next to the stage-two sample size is performed. Those evaluations with respect to the sample size curves and the resulting design's performance can contribute to facilitate the score's usage in practice.
Topics: Research Design; Sample Size
PubMed: 35426460
DOI: 10.1002/bimj.202100166 -
Trials Jun 2020Adaptive clinical trials (ACTs) represent an emerging approach to trial design where accumulating data are used to make decisions about future conduct. Adaptations can... (Review)
Review
BACKGROUND
Adaptive clinical trials (ACTs) represent an emerging approach to trial design where accumulating data are used to make decisions about future conduct. Adaptations can include comparisons of multiple dose tiers, response-adaptive randomization, sample size re-estimation, and efficacy/futility stopping rules. The objective of this scoping review is to assess stakeholder attitudes, perspectives, and understanding of adaptive trials.
METHODS
We conducted a review of articles examining stakeholders encompassing the broad medical trial community's perspectives of adaptive designs (ADs). A computerized search was conducted of four electronic databases with relevant search terms. Following screening of articles, the primary findings of each included article were coded for study design, population studied, purpose, and primary implications.
RESULTS
Our team retrieved 167 peer-reviewed titles in total from the database search and 5 additional titles through searching web-based search engines for gray literature. Of those 172 titles, 152 were non-duplicate citations. Of these, 119 were not given full-text reviews, as their titles and abstracts indicated that they did not meet the inclusion criteria. Thirty-three articles were carefully examined for relevance, and of those, 18 were chosen to be part of the analysis; the other 15 were excluded, as they were not relevant upon closer inspection. Perceived advantages to ADs included limiting ineffective treatments and efficiency in answering the research question; -perceived barriers included insufficient sample size for secondary outcomes, challenges of consent, potential for bias, risk of type 1 error, cost and time to adaptively design trials, unclear rationales for using Ads, and, most importantly, a lack of education regarding ADs among stakeholders within the clinical trial community. Perceptions among different types of stakeholders varied from sector to sector, with patient perspectives being noticeably absent from the literature.
CONCLUSION
There are diverse perceptions regarding ADs among stakeholders. Further training, guidelines, and toolkits on the proper use of ADs are needed at all levels to overcome many of these perceived barriers. While education for principal investigators is important, it is also crucial to educate other groups in the community, such as patients, as well as clinicians and staff involved in their daily implementation.
Topics: Attitude; Bayes Theorem; Clinical Trials as Topic; Humans; Reproducibility of Results; Research Design; Stakeholder Participation
PubMed: 32552852
DOI: 10.1186/s13063-020-04466-0 -
Frontiers in Public Health 2023Using population-based simulations and machine-learning algorithms to develop an adaptive restraint system that accounts for occupant anthropometry variations to further...
OBJECTIVE
Using population-based simulations and machine-learning algorithms to develop an adaptive restraint system that accounts for occupant anthropometry variations to further enhance safety balance throughout the whole population.
METHODS
Two thousand MADYMO full frontal impact crash simulations at 35 mph using two validated vehicle/restraint models representing a sedan and an SUV along with a parametric occupant model were conducted based on the maximal projection design of experiments, which considers varying occupant covariates (sex, stature, and body mass index) and vehicle restraint design variables (three for airbag, three for safety belt, and one for knee bolster). A Gaussian-process-based surrogate model was trained to rapidly predict occupant injury risks and the associated uncertainties. An optimization framework was formulated to seek the optimal adaptive restraint design policy that minimizes the population injury risk across a wide range of occupant sizes and shapes while maintaining a low difference in injury risks among different occupant subgroups. The effectiveness of the proposed method was tested by comparing the population-wise injury risks under the adaptive design policy and the traditional state-of-the-art design.
RESULTS
Compared to the traditional state-of-the-art design for midsize males, the optimal design policy shows the potential to further reduce the joint injury risk (combining head, chest, and lower extremity injury risks) among the whole population in the sedan and SUV models. Specifically, the two subgroups of vulnerable occupants including tall obese males and short obese females had higher reductions in injury risks.
CONCLUSIONS
This study lays out a method to adaptively adjust vehicle restraint systems to improve safety balance. This is the first study where population-based crash simulations and machine-learning methods are used to optimize adaptive restraint designs for a diverse population. Nevertheless, this study shows the high injury risks associated with obese and female occupants, which can be mitigated via restraint adaptability.
Topics: Male; Female; Humans; Research Design; Protective Devices; Algorithms; Anthropometry; Body Mass Index
PubMed: 37637800
DOI: 10.3389/fpubh.2023.1202970