The Effect of Mating Complexity on Gene Drive Dynamics.

AbstractGene drive technology promises to deliver on some of the global challenges humanity faces today in health care, agriculture, and conservation. However, there is a limited understanding of the consequences of releasing self-perpetuating transgenic organisms into wild populations under complex ecological conditions. In this study, we analyze the impact of three such complexities-mate choice, mating systems, and spatial mating network-on the population dynamics for two distinct classes of modification gene drive systems. All three factors had a high impact on the modeling outcome. First, we demonstrate that distortion-based gene drives appear to be more robust against mate choice than viability-based gene drives. Second, we find that gene drive spread is much faster for higher degrees of polygamy. Including a fitness cost, the drive is fastest for intermediate levels of polygamy. Finally, the spread of a gene drive is faster and more effective when the individuals have fewer connections in a spatial mating network. Our results highlight the need to include mating complexities when modeling the properties of gene drives, such as release thresholds, timescales, and population-level consequences. This inclusion will enable a more confident prediction of the dynamics of engineered gene drives and possibly even inform about the origin and evolution of natural gene drives.

The Effect of a Shared Decision-Making Process on Acceptance of Colorectal Cancer Screening.

VISUAL ABSTRACT.

How strategy environment and wealth shape altruistic behaviour: cooperation rules affecting wealth distribution in dynamic networks.

Societies rely on individual contributions to sustain public goods that benefit the entire community. Several mechanisms, that specify how individuals change their decisions based on past experiences, have been proposed to explain how altruists are not outcompeted by selfish counterparts. A key aspect of such strategy updates involves a comparison of an individual's latest payoff with that of a random neighbour. In reality, both the economic and social milieu often shapes cooperative behaviour. We propose a new decision heuristic, where the propensity of an individual to cooperate depends on the local strategy environment in which she is embedded as well as her wealth relative to that of her neighbours. Our decision-making model allows cooperation to be sustained and also explains the results of recent experiments on social dilemmas in dynamic networks. Final cooperation levels depend only on the extent to which the strategy environment influences altruistic behaviour but are largely unaffected by network restructuring. However, the extent of wealth inequality in the community is affected by a subtle interplay between the environmental influence on a person's decision to contribute and the likelihood of reshaping social ties, with wealth-inequality levels rising with increasing likelihood of network restructuring in some situations.

Bribery games on interdependent complex networks.

Bribe demands present a social conflict scenario where decisions have wide-ranging economic and ethical consequences. Nevertheless, such incidents occur daily in many countries across the globe. Harassment bribery constitute a significant sub-set of such bribery incidents where a government official demands a bribe for providing a service to a citizen legally entitled to it. We employ an evolutionary game-theoretic framework to analyse the evolution of corrupt and honest strategies in structured populations characterized by an interdependent complex network. The effects of changing network topology, average number of links and asymmetry in size of the citizen and officer population on the proliferation of incidents of bribery are explored. A complex network topology is found to be beneficial for the dominance of corrupt strategies over a larger region of phase space when compared with the outcome for a regular network, for equal citizen and officer population sizes. However, the extent of the advantage depends critically on the network degree and topology. A different trend is observed when there is a difference between the citizen and officer population sizes. Under those circumstances, increasing randomness of the underlying citizen network can be beneficial to the fixation of honest officers up to a certain value of the network degree. Our analysis reveals how the interplay between network topology, connectivity and strategy update rules can affect population level outcomes in such asymmetric games.

Exploring the resistome and virulome in major sequence types of Acinetobacter baumannii genomes: Correlations with genome divergence and sequence types.

The increasing global prevalence of antimicrobial resistance in Acinetobacter baumannii has led to concerns regarding the effectiveness of infection treatment. Moreover, the critical role of virulence factor genes in A. baumannii's pathogenesis and its propensity to cause severe disease is of particular importance. Comparative genomics, including multi-locus sequence typing (MLST), enhances our understanding of A. baumannii epidemiology. While there is substantial documentation on A. baumannii, a comprehensive study of the antibiotic-resistant mechanisms and the virulence factors contributing to pathogenesis, and their correlation with Sequence Types (STs) remains incompletely elucidated. In this study, we aim to explore the relationship between antimicrobial resistance genes, virulence factor genes, and STs using genomic data from 223 publicly available A. baumannii strains. The core phylogeny analysis revealed five predominant STs in A. baumannii genomes, linked to their geographical sources of isolation. Furthermore, the resistome and virulome of A. baumannii followed an evolutionary pattern consistent with their pan-genome evolution. Among the major STs, we observed significant variations in resistant genes against "aminoglycoside" and "sulphonamide" antibiotics, highlighting the role of genotypic variations in determining resistance profiles. Furthermore, the presence of virulence factor genes, particularly exotoxin and nutritional / metabolic factor genes, played a crucial role in distinguishing the major STs, suggesting a potential link between genetic makeup and pathogenicity. Understanding these associations can provide valuable insights into A. baumannii's virulence potential and clinical outcomes, enabling the development of effective strategies to combat infections caused by this opportunistic pathogen.

Ag Nanoparticle-Thiolated Chitosan Composite Coating Reinforced by Ag-S Covalent Bonds with Excellent Electromagnetic Interference Shielding and Joule Heating Performances.

Conductive composite coatings are an important element in flexible electronics research and are widely used in energy transformation, artificial intelligence, and electronic skins. However, the comparatively low electrical conductivity limits their performance in many specific applications, such as electromagnetic interference (EMI) shielding and Joule heating devices. Therefore, the preparation of ultrahigh-electrical conductivity composite coatings with good flexibility and durability remains a great challenge. Herein, we fabricated multifunctional conductive composite coatings based on thiolated chitosan (TCS) and Ag nanoparticles (AgNPs) by an eco-friendly drop-coating method. The three-dimensional conductive network constructed by thermal sintering imparted the coating with an ultrahigh electrical conductivity of up to 67079.4 S/m. Moreover, the coating reinforced by Ag-S covalent bonding exhibits good stability, including heat resistance, chemical resistance, and mechanical stability. In addition, based on the ultrahigh electrical conductivity, the coating exhibits superior EMI shielding effectiveness and Joule heating capability. With 30 wt % of AgNPs in the coating, the EMI shielding effectiveness of the coating reaches 70.2 dB, far exceeding commercial standards. Additionally, the coating can quickly reach a saturation temperature (Ts) of 195.9 °C at a safe drive voltage of 3 V. These excellent performances demonstrate that the robust and flexible highly conductive composite coatings prepared by this method have attractive potential for EMI shielding and thermal management applications as well as in wearable electronics.

An ultrasensitive and stretchable strain sensor based on a microcrack structure for motion monitoring.

Flexible strain sensors are promising candidates for intelligent wearable devices. Among previous studies, although crack-based sensors have attracted a lot of attention due to their ultrahigh sensitivity, large strain usually causes fractures in the conductive paths. Because of the unstable crack structure, the tradeoff between sensitivity and workable strain range is still a challenge. As carbon nanotubes (CNTs) and silver nanowires (AgNWs) can form a strong interface with the thermoplastic substrate and strengthen the conductive network by capillary force during water evaporation, CNTs and AgNWs were deposited on electrospun TPU fiber mats via vacuum-assisted filtration in this work. The prestretching treatment constructed a microcrack structure that endowed the sensor with the combined characteristics of a wide working range (0~171% strain), ultrahigh sensitivity (a gauge factor of 691 within 0~102% strain, ~2 × 104 within 102~135% strain, and >11 × 104 within 135~171% strain), a fast response time (~65 ms), small hysteresis, and superior durability (>2000 cycles). Subsequently, the sensing mechanism of the sensor was studied. Distributed microcrack propagation based on the "island-bridge" structure was explained in detail, and its influence on the strain-sensing behavior of the sensor was analyzed. Finally, the sensor was assembled to monitor various vibration signals and human motions, demonstrating its potential applications in the fields of electronic skin and human health monitoring.

Diversity and disparities in research studies and career trajectories in psychiatry.

It is well recognized that underrepresented and systematically minoritized groups do not have balanced access to clinical trials as study participants or as research Investigators. However, comprehensive data on the perspective of expert clinicians is largely lacking in the current literature. In this pilot exploration, we collected the opinions of 33 subject matter experts (SME) to identify and explore potential barriers to diversification in clinical trials. The majority of respondents live in North America or Central or Western Europe and identified as not a member of an underrepresented or marginalized group (UMB), with about 15% of respondents being a member of a UMB. Overall, about a quarter of respondents reported making an intentional effort to recruit members of UMB as study participants and identified recruitment challenges linked to two areas: psycho-social barriers and practical barriers. A variety of strategies were employed to improve recruitment including engagement with community leaders, targeted advertising, utilizing databases, and social media campaigns. About half of respondents reported difficulties recruiting Investigators from UMB backgrounds, stating culture and language barriers, perceived lack of interest in the field among individuals from UMB, and lack of information as possible reasons for the challenges.

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

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.

Pooling in a Pod: A Strategy for COVID-19 Testing to Facilitate a Safe Return to School.

The COVID-19 pandemic prompted widespread closures of primary and secondary schools. Routine testing of asymptomatic students and staff members, as part of a comprehensive mitigation program, can help schools open safely. "Pooling in a pod" is a public health surveillance strategy whereby testing cohorts (pods) are based on social relationships and physical proximity. Pooled testing provides a single laboratory test result for the entire pod, rather than a separate result for each person in the pod. During the 2020-2021 school year, an independent preschool-grade 12 school in Washington, DC, used pooling in a pod for weekly on-site point-of-care testing of all staff members and students. Staff members and older students self-collected anterior nares samples, and trained staff members collected samples from younger students. Overall, 12 885 samples were tested in 1737 pools for 863 students and 264 staff members from November 30, 2020, through April 30, 2021. The average pool size was 7.4 people. The average time from sample collection to pool test result was 40 minutes. The direct testing cost per person per week was $24.24, including swabs. During the study period, 4 surveillance test pools received positive test results for COVID-19. A post-launch survey found most parents (90.3%), students (93.4%), and staff members (98.8%) were willing to participate in pooled testing with confirmatory tests for pool members who received a positive test result. The proportion of students in remote learning decreased by 62.2% for students in grades 6-12 (P < .001) and by 92.4% for students in preschool to grade 5 after program initiation (P < .001). Pooling in a pod is a feasible, cost-effective surveillance strategy that may facilitate safe, sustainable, in-person schooling during a pandemic.

A comparison of health care worker-collected foam and polyester nasal swabs in convalescent COVID-19 patients.

Both polyester and foam nasal swabs were collected from convalescent COVID-19 patients at a single visit and stored in viral transport media (VTM), saline or dry. Sensitivity of each swab material and media combination were estimated, three by three tables were constructed to measure polyester and foam concordance, and cycle threshold (Ct) values were compared. 126 visits had polyester and foam swabs stored in viral transport media (VTM), 51 had swabs stored in saline, and 63 had a foam swab in VTM and a polyester swab stored in a dry tube. Polyester and foam swabs had an estimated sensitivity of 87.3% and 94.5% respectively in VTM, 87.5% and 93.8% respectively in saline, and 75.0% and 90.6% respectively for dry polyester and foam VTM. Polyester and foam Ct values were correlated, but polyester showed decreased performance for cases with a viral load near the detection threshold and higher Ct values on average.

The evolution of antibiotic production rate in a spatial model of bacterial competition.

We consider competition between antibiotic producing bacteria, non-producers (or cheaters), and sensitive cells in a two-dimensional lattice model. Previous work has shown that these three cell types can survive in spatial models due to the presence of spatial patterns, whereas coexistence is not possible in a well-mixed system. We extend this to consider the evolution of the antibiotic production rate, assuming that the cost of antibiotic production leads to a reduction in growth rate of the producers. We find that coexistence occurs for an intermediate range of antibiotic production rate. If production rate is too high or too low, only sensitive cells survive. When evolution of production rate is allowed, a mixture of cell types arises in which there is a dominant producer strain that produces sufficient to limit the growth of sensitive cells and which is able to withstand the presence of cheaters in its own species. The mixture includes a range of low-rate producers and non-producers, none of which could survive without the presence of the dominant producer strain. We also consider the case of evolution of antibiotic resistance within the sensitive species. In order for the resistant cells to survive, they must grow faster than both the non-producers and the producers. However, if the resistant cells grow too rapidly, the producing species is eliminated, after which the resistance mutation is no longer useful, and sensitive cells take over the system. We show that there is a range of growth rates of the resistant cells where the two species coexist, and where the production mechanism is maintained as a polymorphism in the producing species and the resistance mechanism is maintained as a polymorphism in the sensitive species.

Bribery games on inter-dependent regular networks.

We examine a scenario of social conflict that is manifest during an interaction between government servants providing a service and citizens who are legally entitled to the service, using evolutionary game-theory in structured populations characterized by an inter-dependent network. Bribe-demands by government servants during such transactions, called harassment bribes, constitute a widespread form of corruption in many countries. We investigate the effect of varying bribe demand made by corrupt officials and the cost of complaining incurred by harassed citizens, on the proliferation of corrupt strategies in the population. We also examine how the connectivity of the various constituent networks affects the spread of corrupt officials in the population. We find that incidents of bribery can be considerably reduced in a network-structured populations compared to mixed populations. Interestingly, we also find that an optimal range for the connectivity of nodes in the citizen's network (signifying the degree of influence a citizen has in affecting the strategy of other citizens in the network) as well as the interaction network aids in the fixation of honest officers. Our results reveal the important role of network structure and connectivity in asymmetric games.

Child maltreatment: Cross-sectional survey of general dentists.

BACKGROUND: Child abuse continues to be a social menace causing both physical and emotional trauma to benevolent children. Census has shown that nearly 50-75% of child abuse include trauma to mouth, face, and head. Thus, dental professionals are in a strategic position to identify physical and emotional manifestations of abuse. AIM: A cross-sectional survey was conducted to assess knowledge and attitude of dental professionals on the exigent issue of child abuse. METHODOLOGY: With prior consent, a 20-question survey including both multiple choice and dichotomous (yes/no) questions was mailed to 120 state-registered general dentists and the data collected were subjected to statistical analysis. STATISTICAL ANALYSIS: The overall response rate to the questionnaires was 97%. Lack of knowledge about dentist role in reporting child abuse accounted to 55% in the reasons for hesitancy to report. Pearson's Chi-square test did not show any significant difference between male and female regarding the reason for hesitancy to report and legal obligation of dentists. RESULTS: Although respondent dentists were aware of the diagnosis of child abuse, they were hesitant and unaware of the appropriate authority to report. CONCLUSION: Increased instruction in the areas of recognition and reporting of child abuse and neglect should be emphasized.

Influence of Smile Arc and Buccal Corridors on Facial Attractiveness: A Cross-sectional Study.

INTRODUCTION: Two aspects of the smile: the Smile Arc (SA) and Buccal Corridors (BC) have been the interest of the orthodontist in recent years. AIM: The present study was undertaken to evaluate the influence of the smile arc and buccal corridors on facial attractiveness as evaluated by orthodontists, general dentists and laymen. MATERIALS AND METHODS: Two subjects (one male & one female) were selected from the regional population fulfilling the criteria of an ideal smile arc and ideal buccal corridors. Frontal smile view photographs of these subjects were taken and modified by using adobe photoshop 7.0 to create combination of three smile arc variance and three buccal corridors variations respectively which were shown to 25 orthodontists, 25 general dentists & 25 laymen, to rate the facial attractiveness of each image on a rating scale. RESULTS: All the three groups (laypersons, dentists and orthodontists) showed significant difference in ratings, indicating that they had different perceptions on the facial attractiveness. CONCLUSION: Orthodontists were more precise in discerning the smile arc and buccal corridors compared to dentists and laypersons.

Bribe and Punishment: An Evolutionary Game-Theoretic Analysis of Bribery.

Harassment bribes, paid by citizens to corrupt officers for services the former are legally entitled to, constitute one of the most widespread forms of corruption in many countries. Nation states have adopted different policies to address this form of corruption. While some countries make both the bribe giver and the bribe taker equally liable for the crime, others impose a larger penalty on corrupt officers. We examine the consequences of asymmetric and symmetric penalties by developing deterministic and stochastic evolutionary game-theoretic models of bribery. We find that the asymmetric penalty scheme can lead to a reduction in incidents of bribery. However, the extent of reduction depends on how the players update their strategies over time. If the interacting members change their strategies with a probability proportional to the payoff of the alternative strategy option, the reduction in incidents of bribery is less pronounced. Our results indicate that changing from a symmetric to an asymmetric penalty scheme may not suffice in achieving significant reductions in incidents of harassment bribery.

Assays, surrogates, and alternative technologies for a TB lead identification program targeting DNA gyrase ATPase.

Mycobacterium tuberculosis (Mtb) DNA gyrase ATPase was the target of a tuberculosis drug discovery program. The low specific activity of the Mtb ATPase prompted the use of Mycobacterium smegmatis (Msm) enzyme as a surrogate for lead generation, since it had 20-fold higher activity. Addition of GyrA or DNA did not significantly increase the activity of the Msm GyrB ATPase, and an assay was developed using GyrB alone. Inhibition of the Msm ATPase correlated well with inhibition of Mtb DNA gyrase supercoiling across three chemical scaffolds, justifying its use. As the IC50 of compounds approached the enzyme concentration, surrogate assays were used to estimate potencies (e.g., the shift in thermal melt of Mtb GyrB, which correlated well with IC(50)s >10 nM). Analysis using the Morrison equation enabled determination of K(i)(app)s in the sub-nanomolar range. Surface plasmon resonance was used to confirm these IC(50)s and measure the K ds of binding, but a fragment of Mtb GyrB had to be used. Across three scaffolds, the dissociation half life, t1/2, of the inhibitor-target complex was ≤ 8 min. This toolkit of assays was developed to track the potency of enzyme inhibition and guide the chemistry for progression of compounds in a lead identification program.