Pilot Evaluation of the Impact of Lottery-Based Incentives on Engagement Levels of Male Low SES Vocational Students With an mHealth App

In general, individuals with lower socioeconomic status (SES) are less physically active and adhere to poorer diets than higher SES individuals. To promote healthier lifestyles in lower SES populations, we hosted a digital health promotion program among male vocational students at a school in The Netherlands. In a pilot study, we evaluated whether this target audience could be engaged with an mHealth app using lottery-based incentives that trigger feelings of anticipated regret. Especially, we studied the social and interpersonal aspects of regret lotteries in a within-subject experimental design. In this design, subjects either participated in a social variant (i.e., with students competing against their peers for a chance at a regret lottery), or an individual variant (i.e., with subjects solely individually engaged in a lottery). Additionally, we studied the impact of different payout schedules in a between-subject experimental design. In this design, participants were assigned to either a short-term, low-value payout schedule, or a long-term, high-value payout schedule. From a population of 72 male students, only half voluntarily participated in our 10-week program. From interviews, we learned that the main reason for neglecting the program was not related to the lottery-based incentives, nor to the prizes that were awarded. Instead, non-enrolled subjects did not join the program, because their peers were not joining. Paradoxically, it was suggested that students withheld their active participation until a larger portion of the sample was actively participating. From the subjects that enrolled in the program (N = 36, males, between 15 and 25 years of age), we found that a large proportion stopped interacting with the program over time (e.g., after roughly 4 weeks). Our results also indicated that students performed significantly more health-related activities when assigned to the social regret lottery, as opposed to the individual variant. This result was supported by interview responses from active participants: They mainly participated to compete against their peers, and not so much for the prizes. Hence, from this study, we obtained initial evidence on the impact of social and competitive aspects in lottery-based incentives to stimulate engagement levels in lower SES students with an mHealth app.

Inadequate design of mutation detection panels prevents interpretation of variants of concern: results of an external quality assessment for SARS-CoV-2 variant detection

Objectives Mutation-specific PCR assays have quickly found their way into laboratory diagnostics due to their capacity to be a fast, easy to implement and high-throughput method for the detection of known SARS-CoV-2 variants of concern (VoCs). However, little is known about the performance of such assays in routine laboratory analysis. Methods The results reported in a recent round of an external quality assessment (EQA) scheme for SARS-CoV-2 mutation-specific PCR were retrospectively analyzed. For the determination of individual variant-specific sequences as well as for the interpretation results for certain virus variants, correct, incorrect, and unreported results were evaluated, and their possible causes were investigated. Results A total of 34 laboratories participated in this study. For five samples containing the VoC Alpha + E484K, Beta, Gamma, Delta, or B.1.1.318 (as a variant of interest), 848 results for SARS-2-CoV mutation detection were reported, 824 (97.2%, range per sample 88–100%) of which were correct. Melting curve assays gave 99% correct results, real-time RT-qPCR 94%, microarray-based assays 100%, and MALDI-TOF MS 96%. A total of 122/167 (73%) reported results for SARS-CoV-2 variant determination were correct. Of the 45 inconclusive or incorrect results, 33 (73%) were due to inadequate selection of targets that did not allow identification of contemporary VoC, 11 (24%) were due to incorrect results, and one (3%) was due to correct results of mutation-specific PCR. Conclusions Careful and up-to-date selection of the targets used in mutation-specific PCR is essential for successful detection of current SARS-CoV-2 variants.

Directed Evolution of Enzymes based on in vitro Programmable Self-Replication

High-throughput directed evolution, implemented in well-controlled in vitro conditions, provides a powerful route for enzyme engineering. Most existing technologies are based on activity screening and require the sequential observation and sorting of each individual variant. By contrast, approaches based on autonomous feedback loops, linking phenotype to genotype replication, enable autonomous selection without screening. However, these approaches are only possible in vivo, or applicable to very specific activities, such as polymerases or ligases. Here, we leverage synthetic molecular networks to create a programmable in vitro feedback loop linking a target enzymatic activity to gene amplification. After encapsulation and lysis of up to 10^7 transformed variants, the genes present in each droplet are amplified according to the activity of the encoded enzyme, resulting in the autonomous enrichment of interesting sequences. Applied to a nicking enzyme with thermal or kinetic selection pressures, this method reveals detailed mutational landscapes and provides improved variants.

Variant and Product Line Co-Evolution

Individual collaborative embedded systems (CESs) in a collaborative system group (CSG) are typically provided by different manufacturers. Variability in such systems is pivotal for deploying a CES in different CSGs and environments. Changing requirements may entail the evolution of a CES. Such changed requirements can be manifold: individual variants of a CES are updated to fix bugs, or the manufacturer changes the entire CES product line to provide new capabilities. Both types of evolution, the variant evolution and the product line evolution, may be performed in parallel. However, neither type of evolution should lead to diverging states of CES variants and the CES product line, otherwise both would be incompatible, it would not be possible to update the CES variants, and it would not be possible to reuse bug fixes of an individual variant for the entire product line. To avoid this divergence, we present an approach for co-evolving variants and product lines, thus ensuring their consistency.

Computer support for verification works on the theme "Prime numbers"

Computer support for mathematics teachers during verification (control, written, independent) work is one of the actual tasks of teaching methods. For such support, it is necessary to develop special computer programs. The article describes the method for developing such programs on the example of a program for conducting a test on the theme "Prime numbers" using the Pulot method. The program generates numerical data that are used in the tasks of the control work. Each student gets an individual variant of the work, and students cannot rewrite work results from each other. The program is independent of any databases and data tables. Variants of tasks (numerical data) are not saved anywhere and are not known in advance. Typically, testing programs have databases, tasks and their answers, and they can be obtained in advance and used as a cheat sheet. In the considered method and in the developed computer program, this is impossible. The application of the presented program greatly facilitates the teacher's work and ensures the objectivity of control of students' knowledge, and also increases the level and quality of teaching

Expert interpretation of genes and variants in hereditary hearing loss

Background: Hearing loss (HL) is the most common sensory deficit from birth, with at least 50 % due to an underlying genetic etiology. A genetic evaluation is a recommended component to the medical workup for HL, and a genetic diagnosis can impact medical management and provide prognostic and recurrence risk information. The accuracy of a genetic diagnosis relies on the evidence supporting the gene–disease relationship, as well as the evidence supporting individual variant classifications. As such, the ClinGen Hearing Loss Working Group was formed and tasked with curating genes associated with genetic hearing loss and developing specifications of the ACMG/AMP variant interpretation guidelines with the goal of improving the genetic diagnosis of patients with HL. Objectives: To describe the prioritization and expert curation of genes and variants associated with HL performed under the purview of the ClinGen Hearing Loss Gene and Variant Expert Panels (HL GCEP and VCEP). Materials and methods: HL genes were taken from clinical testing panels in the Genetic Testing Registry and prioritized based on a nonsyndromic presentation. Variants were taken from ClinVar and those with diverse data types and medically significant conflicts were prioritized to test the specified variant interpretation guidelines and to resolve classification discrepancies, respectively. Conclusions: The ClinGen HL GCEP has curated 174 gene–disease pairs. The HL VCEP has submitted 77 variants, including the previously controversial p.Met34Thr and p.Val37Ile variants in GJB2, into ClinVar, as an FDA-recognized database. Collaboration across clinics and laboratories were crucial to these curations and highlight the impact that data sharing can have on patient care.

The Relationship Between Polygenic Risk Scores and Cognition in Schizophrenia

Background Cognitive impairment is a clinically important feature of schizophrenia. Polygenic risk score (PRS) methods have demonstrated genetic overlap between schizophrenia, bipolar disorder (BD), major depressive disorder (MDD), educational attainment (EA), and IQ, but very few studies have examined associations between these PRS and cognitive phenotypes within schizophrenia cases. Methods We combined genetic and cognitive data in 3034 schizophrenia cases from 11 samples using the general intelligence factor g as the primary measure of cognition. We used linear regression to examine the association between cognition and PRS for EA, IQ, schizophrenia, BD, and MDD. The results were then meta-analyzed across all samples. A genome-wide association studies (GWAS) of cognition was conducted in schizophrenia cases. Results PRS for both population IQ (P = 4.39 × 10–28) and EA (P = 1.27 × 10–26) were positively correlated with cognition in those with schizophrenia. In contrast, there was no association between cognition in schizophrenia cases and PRS for schizophrenia (P = .39), BD (P = .51), or MDD (P = .49). No individual variant approached genome-wide significance in the GWAS. Conclusions Cognition in schizophrenia cases is more strongly associated with PRS that index cognitive traits in the general population than PRS for neuropsychiatric disorders. This suggests the mechanisms of cognitive variation within schizophrenia are at least partly independent from those that predispose to schizophrenia diagnosis itself. Our findings indicate that this cognitive variation arises at least in part due to genetic factors shared with cognitive performance in populations and is not solely due to illness or treatment-related factors, although our findings are consistent with important contributions from these factors.

Significance of biomechanical indices assessment in orthopedic correction of motor disorders in patients following cerebral stroke

Aim. To study the biomechanical peculiarities of orthopedic disorders in patients after cerebral stroke and estimate possibilities for their correction. Materials and methods. One hundred and thirty two persons in the late rehabilitation period after the cerebral stroke were examined. The state of loco-motor system biomechanics was assessed, using the rehabilitation complexes “TRUST-M” and “ST-150”. Results. The late rehabilitation period of stroke was characterized by decrease in walking rate and time, rise in step cycle. Speed of movement was disturbed. Combined pain, spasticity, contracture and functional asymmetry of the extremities length determined the formation of individual variant of patient’s pathological locomotor stereotype. When implementing correlation analysis, marked correlation between the severity of orthopedic disorders and the asymmetry of pelvis and extremities length was detected. To correct biomechanical disorders, it was recommended to use complex orthopedic treatment by means of prosthetic-orthopedic devices, which permitted to move and provided stable holding of extremity segments in the desired position. Conclusion. 1. Biomechanical indices characterize the severity of orthopedic pathology in the late rehabilitation period following cerebral stroke. 2. Biomechanical disorders are connected with decreased walking rate and time, raised step cycle, impaired speed of movement. 3. Timely biomechanical orthopedic diagnosis and adequacy of applying prosthetic-orthopedic devices guarantee efficiency of rehabilitation measures in patients after cerebral stroke.

Replicability of introgression under linked, polygenic selection

We study how a block of genome with a large number of weakly selected loci introgresses under directional selection into a genetically homogeneous population. We derive exact expressions for the expected rate of growth of any fragment of the introduced block during the initial phase of introgression, and show that the growth rate of a single-locus variant is largely insensitive to its own additive effect, but depends instead on the combined effect of all loci within a characteristic linkage scale. The expected growth rate of a fragment is highly correlated with its long-term introgression probability in populations of moderate size, and can hence identify variants that are likely to introgress across replicate populations. We clarify how the introgression probability of an individual variant is determined by the interplay between hitchhiking with relatively large fragments during the early phase of introgression, and selection on fine scale variation within these, which at longer times results in differential introgression probabilities for beneficial and deleterious loci within successful fragments. By simulating individuals, we also investigate how introgression probabilities at individual loci depend on the variance of fitness effects, the net fitness of the introduced block, and the size of the recipient population, and how this shapes the net advance under selection. Our work suggests that even highly replicable substitutions may be associated with a range of selective effects, which makes it challenging to fine map the causal loci that underlie polygenic adaptation.