scholarly journals A common gene drive language eases regulatory process and eco-evolutionary extensions

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Prateek Verma ◽  
R. Guy Reeves ◽  
Chaitanya S. Gokhale
Keyword(s):  
Risk Assessment ◽  
Public Engagement ◽  
Evolutionary Dynamics ◽  
Point Of View ◽  
Common Language ◽  
Gene Drive ◽  
Wild Populations ◽  
Invasion Dynamics ◽  
Organismal Fitness ◽  
Sheer Number

Abstract Background Synthetic gene drive technologies aim to spread transgenic constructs into wild populations even when they impose organismal fitness disadvantages. The extraordinary diversity of plausible drive mechanisms and the range of selective parameters they may encounter makes it very difficult to convey their relative predicted properties, particularly where multiple approaches are combined. The sheer number of published manuscripts in this field, experimental and theoretical, the numerous techniques resulting in an explosion in the gene drive vocabulary hinder the regulators’ point of view. We address this concern by defining a simplified parameter based language of synthetic drives. Results Employing the classical population dynamics approach, we show that different drive construct (replacement) mechanisms can be condensed and evaluated on an equal footing even where they incorporate multiple replacement drives approaches. Using a common language, it is then possible to compare various model properties, a task desired by regulators and policymakers. The generalization allows us to extend the study of the invasion dynamics of replacement drives analytically and, in a spatial setting, the resilience of the released drive constructs. The derived framework is available as a standalone tool. Conclusion Besides comparing available drive constructs, our tool is also useful for educational purpose. Users can also explore the evolutionary dynamics of future hypothetical combination drive scenarios. Thus, our results appraise the properties and robustness of drives and provide an intuitive and objective way for risk assessment, informing policies, and enhancing public engagement with proposed and future gene drive approaches.

scholarly journals Evolutionary dynamics of CRISPR gene drives

2016 ◽  
Author(s):  
Charleston Noble ◽  
Jason Olejarz ◽  
Kevin M. Esvelt ◽  
George M. Church ◽  
Martin A. Nowak
Keyword(s):  
Evolutionary Dynamics ◽  
Evolutionary Stability ◽  
Clear Understanding ◽  
Gene Drive ◽  
Host Organism ◽  
Wild Populations ◽  
Selfish Genetic Elements ◽  
Real World Applications ◽  
Drive Systems ◽  
Gene Drives

AbstractThe alteration of wild populations has been discussed as a solution to a number of humanity’s most pressing ecological and public health concerns. Enabled by the recent revolution in genome editing, CRISPR gene drives, selfish genetic elements which can spread through populations even if they confer no advantage to their host organism, are rapidly emerging as the most promising approach. But before real-world applications are considered, it is imperative to develop a clear understanding of the outcomes of drive release in nature. Toward this aim, we mathematically study the evolutionary dynamics of CRISPR gene drives. We demonstrate that the emergence of drive-resistant alleles presents a major challenge to previously reported constructs, and we show that an alternative design which selects against resistant alleles greatly improves evolutionary stability. We discuss all results in the context of CRISPR technology and provide insights which inform the engineering of practical gene drive systems.

scholarly journals A unifying approach to gene drive

2020 ◽  
Author(s):  
Prateek Verma ◽  
R. Guy Reeves ◽  
Chaitanya S. Gokhale
Keyword(s):  
Spatial Dynamics ◽  
Gene Drive ◽  
Unified Framework ◽  
Scientific Advance ◽  
Common Framework ◽  
Single Construct ◽  
User Friendly ◽  
Gene Drives ◽  
Organismal Fitness ◽  
Sheer Number

AbstractSynthetic gene drive technologies aim to spread transgenic constructs into wild populations even when they impose organismal fitness disadvantages. The properties of gene drive constructs are diverse and depend on their molecular construction, and differential selection pressure they impose in the varied ecological situations they encounter. The extraordinary diversity of conceivable drive mechanisms and the range of selective parameters they may encounter makes it very difficult to convey their relative predicted properties. The sheer number of published manuscripts in this field, experimental and theoretical, is a testament to the possibilities presented by this technology. We evaluate and condense the essential synthetic drive mechanisms from a variety of studies and present a unified mathematical paradigm (and a user-friendly tool DrMxR Drive Mixer) describing the properties of a wide variety of single construct gene drives (non-suppression). Within this common framework, we have been able to recapitulate key published results derived using bespoke modelling frameworks. Because a unified framework is employed, it is also possible to seamlessly explore the consequences of combining multiple drive approaches within a single construct. We provide a method for analytically assessing the measure of invasiveness of a drive construct. As opposed to typical studies of synthetic drives, we explore the resilience of such drives in a spatially explicit manner advancing the connection between realistic spatial dynamics and typical well-mixed populations. Besides a scientific advance, our results and the tools provided an intuitive and objective way for regulators, scientists and NGOs to evaluate the properties and robustness of proposed and future gene drive approaches.

scholarly journals Absolute mortality risk assessment of COVID-19 patients: the Khorshid COVID Cohort (KCC) study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hamid Reza Marateb ◽  
Maja von Cube ◽  
Ramin Sami ◽  
Shaghayegh Haghjooy Javanmard ◽  
Marjan Mansourian ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Hospital Admission ◽  
Mortality Risk ◽  
Regression Models ◽  
Assessment Method ◽  
Point Of View ◽  
Statistical Point ◽  
Hazard Regression ◽  
Risk Assessment Method ◽  
Discharge From Hospital

Abstract Background Already at hospital admission, clinicians require simple tools to identify hospitalized COVID-19 patients at high risk of mortality. Such tools can significantly improve resource allocation and patient management within hospitals. From the statistical point of view, extended time-to-event models are required to account for competing risks (discharge from hospital) and censoring so that active cases can also contribute to the analysis. Methods We used the hospital-based open Khorshid COVID Cohort (KCC) study with 630 COVID-19 patients from Isfahan, Iran. Competing risk methods are used to develop a death risk chart based on the following variables, which can simply be measured at hospital admission: sex, age, hypertension, oxygen saturation, and Charlson Comorbidity Index. The area under the receiver operator curve was used to assess accuracy concerning discrimination between patients discharged alive and dead. Results Cause-specific hazard regression models show that these baseline variables are associated with both death, and discharge hazards. The risk chart reflects the combined results of the two cause-specific hazard regression models. The proposed risk assessment method had a very good accuracy (AUC = 0.872 [CI 95%: 0.835–0.910]). Conclusions This study aims to improve and validate a personalized mortality risk calculator based on hospitalized COVID-19 patients. The risk assessment of patient mortality provides physicians with additional guidance for making tough decisions.

scholarly journals Síntesis del conocimiento taxonómico, origen y domesticación del género Capsicum

2017 ◽  
pp. 65 ◽  
Author(s):  
Sergio Hernández-Verdugo ◽  
Patricia Dávila ◽  
Ken Oyama
Keyword(s):  
Genetic Resource ◽  
Point Of View ◽  
American Continent ◽  
Ecological Studies ◽  
Wild Populations ◽  
Center Of Origin ◽  
The Andes ◽  
Genus Capsicum ◽  
Evolutionary Point ◽  
Molecular Characters

The genus Capsicum consists of approximately 30 species of which C. annuum, C. chinense, C. frutescens, C. baccatum and C. pubescens are domesticated. Although Capsicum has been studied from the taxonomic and evolutionary point of view, using morphological, cytological and molecular characters, there are still sorne problems related to the taxonomic delimitation of the genus and its species, the nomenclature of the wild and cultivated forms, and the treatment of infraspecific variation. In order to determine the generic and specific taxonomic limits and to establish their phylogenetic and evolutionary relationships, it is necessary to undertake these studies among all the taxa of the genus Capsicum. C. annuum, C. chinense, and C. frutescens are taxa that form a taxonomic complex that can be barely differentiated and at the present it is impossible to determine whether they belong to the same or different species. The center of origin of the genus Capsicum is in South America, in the region that comprises Bolivia, northern Argentina, and central and southern Brazil. The biogeographic and archeobotanical studies indicate that during the dispersion of Capsicum along the American Continent, some of the species were domesticated independently in different places: C. annuum in Mexico; C. frutescens in Costa Rica, and possibly also in Mexico; C: chinense in the Amazonas lowlands; C. baccaturn in Bolivia, and C. pubescens in the Andes. In Mexico, C. annuwn has been cultivated throughout all the country; C. frutescens in the central and south eastern regions; C. chinense in the Yucatán Península, and C. pubescens in the high lands of the central states. In addition, there are C. ciliatum and C. lanceolatum, two species that have never been used by man. Genetic and ecological studies on wild populations are very important for the use and conservation of this genetic resource.

scholarly journals Risk assessment of the environmental impact of Norwegian Atlantic salmon farming

2014 ◽  
Vol 72 (3) ◽  
pp. 997-1021 ◽  
Author(s):  
Geir Lasse Taranger ◽  
Ørjan Karlsen ◽  
Raymond John Bannister ◽  
Kevin Alan Glover ◽  
Vivian Husa ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Atlantic Salmon ◽  
Viral Disease ◽  
Organic Load ◽  
Genetic Introgression ◽  
Wild Populations ◽  
Fish Farms ◽  
Marine Research ◽  
Salmon Farming ◽  
Salmon Lice

Abstract Norwegian aquaculture has grown from its pioneering days in the 1970s to be a major industry. It is primarily based on culturing Atlantic salmon and rainbow trout and has the potential to influence the surrounding environment and wild populations. To evaluate these potential hazards, the Institute of Marine Research initiated a risk assessment of Norwegian salmon farming in 2011. This assessment has been repeated annually since. Here, we describe the background, methods and limitations of the risk assessment for the following hazards: genetic introgression of farmed salmon in wild populations, regulatory effects of salmon lice and viral diseases on wild salmonid populations, local and regional impact of nutrients and organic load. The main findings are as follows: (i) 21 of the 34 wild salmon populations investigated indicated moderate-to-high risk for genetic introgression from farmed escaped salmon. (ii) of 109 stations investigated along the Norwegian coast for salmon lice infection, 27 indicated moderate-to-high likelihood of mortality for salmon smolts while 67 stations indicated moderate-to-high mortality of wild sea trout. (iii) Viral disease outbreaks (pancreas disease, infectious pancreatic necrosis, heart and skeletal muscle inflammation, and cardiomyopathy syndrome) in Norwegian salmon farming suggest extensive release of viruses in many areas. However, screening of wild salmonids revealed low to very low prevalence of the causal viruses. (iv) From ∼500 yearly investigations of local organic loading under fish farms, only 2% of them displayed unacceptable conditions in 2013. The risk of eutrophication and organic load beyond the production area of the farm is considered low. Despite several limitations, especially limited monitoring data, this work represents one of the world’s first risk assessment of aquaculture. This has provided the Norwegian government with the basis upon which to take decisions for further development of the Norwegian aquaculture industry.

scholarly journals Problem formulation for gene drive mosquitoes designed to reduce malaria transmission in Africa: results from four regional consultations 2016–2018

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
John L. Teem ◽  
Aggrey Ambali ◽  
Barbara Glover ◽  
Jeremy Ouedraogo ◽  
Diran Makinde ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Human Health ◽  
Environmental Risk ◽  
Environmental Risk Assessment ◽  
Early Stage ◽  
Problem Formulation ◽  
Risk Assessments ◽  
Gene Drive ◽  
Starting Point ◽  
Protection Goals

Abstract Background Gene drive mosquitoes have been proposed as a possible means to reduce the transmission of malaria in Africa. Because this technology has no prior use-history at this time, environmental risk assessments for gene drive mosquitoes will benefit from problem formulation—an organized and ordered process to identify protection goals and potential pathways to harm to the environment, or animal or human health. Recognizing this need, the New Partnership for Africa’s Development (NEPAD), with support from African and international partners, organized four regional consultative workshops in Africa to initiate this process. Methods The workshops were attended by a diverse set of participants and stakeholders, including scientists, ethicists, health professionals, government regulators in the fields of environment health and biosafety as well government policymakers, who met for 4 days to deliberate on protection goals and pathways relevant to the use of gene drive mosquitoes for malaria control. The goal of the workshops was not to produce a comprehensive and detailed environmental risk assessment of gene drive mosquitoes, but rather to introduce problem formulation as a tool to the stakeholder community, and to serve as a starting point for conducting systematic environmental risk assessments in the future, identifying protection goals related to gene drive mosquitoes that are particular to African stakeholders. Results Participants in the workshops frequently identified human health and biodiversity as being relevant broad protection goals. Results of the deliberations provide insight into the concerns of African participants at an early stage in the development of gene drive organism/products that should be instructive to developers using this technology. Conclusions In general, the African participants of the consultations had a precautionary perspective with regard to environmental risk assessment of gene drive technology. As gene drive technology develops, protection goals will become further refined and candidate products will be further defined. These workshops represent only the beginning of a continuing process that will ultimately inform environmental risk assessment for gene drive mosquitoes to control malaria in Africa.

scholarly journals Evolution of nutrient acquisition: when adaptation fills the gap between contrasting ecological theories

2010 ◽  
Vol 278 (1704) ◽  
pp. 449-457 ◽  
Author(s):  
S. Boudsocq ◽  
S. Barot ◽  
N. Loeuille
Keyword(s):  
Evolutionary Dynamics ◽  
Plant Biomass ◽  
Adaptive Dynamics ◽  
Ecosystem Model ◽  
Point Of View ◽  
Mineral Nutrient ◽  
Trade Off ◽  
Ecosystem Properties ◽  
Ecological Theories ◽  
Limiting Nutrient

Although plant strategies for acquiring nutrients have been widely studied from a functional point of view, their evolution is still not well understood. In this study, we investigate the evolutionary dynamics of these strategies and determine how they influence ecosystem properties. To do so, we use a simple nutrient-limited ecosystem model in which plant ability to take up nutrients is subject to adaptive dynamics. We postulate the existence of a trade-off between this ability and mortality. We show that contrasting strategies are possible as evolutionary outcomes, depending on the shape of the trade-off and, when nitrogen is considered as the limiting nutrient, on the intensity of symbiotic fixation. Our model enables us to bridge these evolutionary outcomes to classical ecological theories such as Hardin's tragedy of the commons and Tilman's rule of R *. Evolution does not systematically maximize plant biomass or primary productivity. On the other hand, each evolutionary outcome leads to a decrease in the availability of the limiting mineral nutrient, supporting the work of Tilman on competition between plants for a single resource. Our model shows that evolution can be used to link different classical ecological results and that adaptation may influence ecosystem properties in contrasted ways.

Engineering the Composition and Fate of Wild Populations with Gene Drive

2021 ◽  
Vol 66 (1) ◽  
pp. 407-434 ◽  
Author(s):  
Bruce A. Hay ◽  
Georg Oberhofer ◽  
Ming Guo
Keyword(s):  
Evolutionary Stability ◽  
Fitness Cost ◽  
Human Diseases ◽  
Gene Drive ◽  
Wild Populations ◽  
Genetic Composition ◽  
Gene Complexes ◽  
Ultimate Fate ◽  
Species Specific ◽  
Population Suppression

Insects play important roles as predators, prey, pollinators, recyclers, hosts, parasitoids, and sources of economically important products. They can also destroy crops; wound animals; and serve as vectors for plant, animal, and human diseases. Gene drive—a process by which genes, gene complexes, or chromosomes encoding specific traits are made to spread through wild populations, even if these traits result in a fitness cost to carriers—provides new opportunities for altering populations to benefit humanity and the environment in ways that are species specific and sustainable. Gene drive can be used to alter the genetic composition of an existing population, referred to as population modification or replacement, or to bring about population suppression or elimination. We describe technologies under consideration, progress that has been made, and remaining technological hurdles, particularly with respect to evolutionary stability and our ability to control the spread and ultimate fate of genes introduced into populations.

scholarly journals TI-RADS Diagnostic Performance: Which Algorithm Is Superior and How Elastography and 4D Vascularity Improve the Malignancy Risk Assessment

Diagnostics ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 180
Author(s):  
Andreea Borlea ◽  
Florin Borcan ◽  
Ioan Sporea ◽  
Cristina Dehelean ◽  
Romeo Negrea ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Histopathological Examination ◽  
Risk Estimation ◽  
Color Doppler ◽  
Strain Ratio ◽  
Point Of View ◽  
Data Systems ◽  
Statistical Point ◽  
Malignancy Risk ◽  
The Mean

Given the increased prevalence of thyroid nodules in the general population (~50%), the real challenge resides in correctly recognizing the suspicious ones. This study proposes to compare four important Thyroid Imaging and Reporting Data Systems (TI-RADS) and evaluate the contribution of elastography and 4D Color Doppler assessment of vascularity in estimating the risk of malignancy. In the study, 133 nodules with histopathological examination were included. Of these, 35 (26.31%) proved to be malignant. All nodules were classified using the four selected systems and our proposed improved score. The American College of Radiology (ACR) and EU TI-RADS had good sensitivity (94.28%, 97.14%) and NPV (93.33%, 95.83%), but fairly poor specificity (31.81%, 23.46%) and PPV (35.48%, 31.19%), with an accuracy of 42.8% and 45.8%, respectively. Horvath TI-RADS had better accuracy of 66.9% and somewhat improved specificity (62.24%), but poorer sensitivity (80%). Russ’ French TI-RADS includes elastography in the risk assessment strategy. This classification proved superior in all aspects (Se: 91.42%, Sp:82.65%, NPV:96.42%, PPV:65.30%, and Acc of 84.96%). The mean strain ratio (SR) value for malignant lesions was 5.56, while the mean SR value for benign ones was significantly lower, 2.54 (p < 0.05). It also correlated well with the response variable: histopathological result (p < 0.001). Although, adding 4D vascularity to the French score generated a similar calculated accuracy and from a statistical point of view, the parameter itself proved beneficial for predicting the malignancy risk (p < 0.001) and may add important knowledge in uncertain situations. Advanced ultrasound techniques definitely improved the risk estimation and should be used more extensively.

SHOULD A FIRST-TRIMESTER RISK ASSESSMENT FOR PRE-ECLAMPSIA BE ROUTINELY OFFERED?

2013 ◽  
Vol 24 (2) ◽  
pp. 129-133
Author(s):  
MAURO PARRA-CORDERO
Keyword(s):  
Public Health ◽  
Risk Assessment ◽  
Pregnant Women ◽  
Expert Opinion ◽  
First Trimester ◽  
Good Evidence ◽  
Point Of View ◽  
Health Policies ◽  
Public Health Policies ◽  
First Trimester Of Pregnancy

From a scientific point of view, the answer to the question might be quite straightforward in favour of routinely screening all pregnant women for pre-eclampsia (PE) during the first trimester of pregnancy. However, irrespective of the large amount of good evidence and expert opinion favourable for universally screening for obstetric syndromes, such as PE, public health policies do not always align with pure clinical science.

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