The Genetic Drift Inventory: A Tool for Measuring What Advanced Undergraduates Have Mastered about Genetic Drift

Understanding genetic drift is crucial for a comprehensive understanding of biology, yet it is difficult to learn because it combines the conceptual challenges of both evolution and randomness. To help assess strategies for teaching genetic drift, we have developed and evaluated the Genetic Drift Inventory (GeDI), a concept inventory that measures upper-division students’ understanding of this concept. We used an iterative approach that included extensive interviews and field tests involving 1723 students across five different undergraduate campuses. The GeDI consists of 22 agree–disagree statements that assess four key concepts and six misconceptions. Student scores ranged from 4/22 to 22/22. Statements ranged in mean difficulty from 0.29 to 0.80 and in discrimination from 0.09 to 0.46. The internal consistency, as measured with Cronbach\u27s alpha, ranged from 0.58 to 0.88 across five iterations. Test–retest analysis resulted in a coefficient of stability of 0.82. The true–false format means that the GeDI can test how well students grasp key concepts central to understanding genetic drift, while simultaneously testing for the presence of misconceptions that indicate an incomplete understanding of genetic drift. The insights gained from this testing will, over time, allow us to improve instruction about this key component of evolution

Shared genetic etiology between idiopathic pulmonary fibrosis and COVID-19 severity

Background: Idiopathic pulmonary fibrosis (IPF) is a complex lung disease, characterized by progressive lung scarring. Severe COVID-19 is associated with substantial pneumonitis and has a number of shared major risk factors with IPF. This study aimed to determine the genetic correlation between IPF and severe COVID-19 and assess a potential causal role of genetically increased risk of IPF on COVID-19 severity. Methods: The genetic correlation between IPF and COVID-19 severity was estimated with linkage disequilib-rium (LD) score regression. We performed a Mendelian randomization (MR) study for IPF causality in COVID-19. Genetic variants associated with IPF susceptibility (P Findings: We detected a positive genetic correlation of IPF with COVID-19 severity (rg=0.31 [95% CI 0.04-0.57], P = 0.023). The MR estimates for severe COVID-19 did not reveal any genetic association (OR 1.05, [95% CI 0.92-1.20], P = 0.43). However, outlier analysis revealed that the IPF risk allele rs35705950 at MUC5B had a dif-ferent effect compared with the other variants. When rs35705950 was excluded, MR results provided evidence that genetically increased risk of IPF has a causal effect on COVID-19 severity (OR 1.21, [95% CI 1.06-1.38], P = 4.24 x 10(-3)). Furthermore, the IPF risk-allele at MUC5B showed an apparent protective effect against COVID-19 hospitalization only in older adults (OR 0.86, [95% CI 0.73-1.00], P = 2.99 x 10(-2)) . Interpretation: The strongest genetic determinant of IPF, rs35705950 at MUC5B, seems to confer protection against COVID-19, whereas the combined effect of all other IPF risk loci seem to confer risk of COVID-19 severity. The observed effect of rs35705950 could either be due to protective effects of mucin over-produc-tion on the airways or a consequence of selection bias due to (1) a patient group that is heavily enriched for the rs35705950 T undertaking strict self-isolation and/or (2) due to survival bias of the rs35705950 non-IPF risk allele carriers. Due to the diverse impact of IPF causal variants on SARS-CoV-2 infection, with a possible selection bias as an explanation, further investigation is needed to address this apparent paradox between variance at MUC5B and other IPF genetic risk factors. (C) 2021 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)Peer reviewe

Adjuvant therapy with antidepressants for the management of inflammatory bowel disease (Protocol)

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: Primary objectives 1. To assess the efficacy and safety of antidepressants for managing anxiety and depression in IBD 2. To assess the efficacy and safety of antidepressants for managing quality of life in IBD Secondary objectives 1. To assess the efficacy and safety of antidepressants for managing disease activity in IB

Cognitive behaviour therapy versus counselling intervention for anxiety in young people with high-functioning autism spectrum disorders: a pilot randomised controlled trial

The use of cognitive-behavioural therapy (CBT) as a treatment for children and adolescents with autism spectrum disorder (ASD) has been explored in a number of trials. Whilst CBT appears superior to no treatment or treatment as usual, few studies have assessed CBT against a control group receiving an alternative therapy. Our randomised controlled trial compared use of CBT against person-centred counselling for anxiety in 36 young people with ASD, ages 12–18. Outcome measures included parent- teacher- and self-reports of anxiety and social disability. Whilst each therapy produced improvements inparticipants, neither therapy was superior to the other to a significant degree on any measure. This is consistent with findings for adults

H1N1 Antibody Persistence 1 Year After Immunization With an Adjuvanted or Whole-Virion Pandemic Vaccine and Immunogenicity and Reactogenicity of Subsequent Seasonal Influenza Vaccine: A Multicenter Follow-on Study

Background. We investigated antibody persistence in children 1 year after 2 doses of either an AS03B-adjuvanted split-virion or nonadjuvanted whole-virion monovalent pandemic influenza vaccine and assessed the immunogenicity and reactogenicity of a subsequent dose of trivalent influenza vaccine (TIV). Methods. Children previously immunized at age 6 months to 12 years in the original study were invited to participate. After a blood sample was obtained to assess persistence of antibody against swine influenza A/H1N1(2009) pandemic influenza, children received 1 dose of 2010/2011 TIV, reactogenicity data were collected for 7 days, and another blood sample was obtained 21 days after vaccination. Results. Of 323 children recruited, 302 received TIV. Antibody persistence (defined as microneutralization [MN] titer ≥1:40) 1 year after initial vaccination was significantly higher in the AS03B-adjuvanted compared with the whole-virion vaccine group, 100% (95% confidence interval [CI], 94.1%–100%) vs 32.4% (95% CI, 21.5%–44.8%) in children immunized <3 years old and 96.9% (95% CI, 91.3%–99.4%) vs 65.9% (95% CI, 55.3%–75.5%) in those 3–12 years old at immunization, respectively (P < .001 for both groups). All children receiving TIV had post-vaccination MN titers ≥1:40. Although TIV was well tolerated in all groups, reactogenicity in children <5 years old was slightly greater in those who originally received AS03B-adjuvanted vaccine. Conclusions. This study provides serological evidence that 2 doses of AS03B-adjuvanted pandemic influenza vaccine may be sufficient to maintain protection across 2 influenza seasons. Administration of TIV to children who previously received 2 doses of either pandemic influenza vaccine is safe and is immunogenic for the H1N1 strain

Fatigue in adults with primary antiphospholipid syndrome : findings from a mixed-methods study

OBJECTIVE: This study aimed to explore the experience and impact of fatigue in adults with primary antiphospholipid syndrome (pAPS). METHODS: This sequential, explanatory mixed-methods study enrolled adults with a six-month or more history of pAPS. Consenting participants completed the Functional Assessment of Chronic Illness Therapy-Fatigue subscale (FS), Multi-Dimensional Perceived Social Support Scale, Patient Health Questionnaire (PHQ9), Pittsburgh Sleep Quality Index (PSQI), International Physical Activity Questionnaire (IPAQMETS). Relationships between FS and other variables were explored with multiple linear regression. Interviews were conducted with a subgroup of participants, and the data were analysed thematically. RESULTS: A total of 103 participants were recruited (Mage = 50.3 years; standard deviation = 10.1 years; 18 males). Of these, 62% reported severe fatigue. Greater fatigue was associated with lower mood, physical inactivity, poorer sleep quality and lower perceived social support. The best-fit model explained 56% of the variance in FS (adjusted R2 = 0.560, F(3, 74) = 33.65, p > 0.001) and included PHQ9 and IPAQMETS as significant predictors, and PSQI as a non-significant predictor. Twenty participants completed interviews. Three key themes were identified: characteristics of fatigue, impact on life and coping strategies. CONCLUSION: Fatigue was a common symptom of pAPS and challenging to manage. Other factors, particularly mood and physical activity, influenced fatigue. Evidence-based self-management interventions are needed

Towards an Intelligent Tutor for Mathematical Proofs

Computer-supported learning is an increasingly important form of study since it allows for independent learning and individualized instruction. In this paper, we discuss a novel approach to developing an intelligent tutoring system for teaching textbook-style mathematical proofs. We characterize the particularities of the domain and discuss common ITS design models. Our approach is motivated by phenomena found in a corpus of tutorial dialogs that were collected in a Wizard-of-Oz experiment. We show how an intelligent tutor for textbook-style mathematical proofs can be built on top of an adapted assertion-level proof assistant by reusing representations and proof search strategies originally developed for automated and interactive theorem proving. The resulting prototype was successfully evaluated on a corpus of tutorial dialogs and yields good results.Comment: In Proceedings THedu'11, arXiv:1202.453

Effectiveness of BNT162b2 and ChAdOx1 against SARS-CoV-2 household transmission: a prospective cohort study in England

Background: The ability of SARS-CoV-2 vaccines to protect against infection and onward transmission determines whether immunisation can control global circulation. We estimated the effectiveness of Pfizer-BioNTech mRNA vaccine (BNT162b2) and Oxford AstraZeneca adenovirus vector vaccine (ChAdOx1) vaccines against acquisition and transmission of the Alpha and Delta variants in a prospective household study in England. Methods: Households were recruited based on adult purported index cases testing positive after reverse transcription-quantitative (RT-q)PCR testing of oral-nasal swabs. Purported index cases and their household contacts took oral-nasal swabs on days 1, 3 and 7 after enrolment and a subset of the PCR-positive swabs underwent genomic sequencing conducted on a subset. We used Bayesian logistic regression to infer vaccine effectiveness against acquisition and transmission, adjusted for age, vaccination history and variant. Results: Between 2 February 2021 and 10 September 2021, 213 index cases and 312 contacts were followed up. After excluding households lacking genomic proximity (N=2) or with unlikely serial intervals (N=16), 195 households with 278 contacts remained, of whom 113 (41%) became PCR positive. Delta lineages had 1.53 times the risk (95% Credible Interval: 1.04 – 2.20) of transmission than Alpha; contacts older than 18 years old were 1.48 (1.20 – 1.91) and 1.02 (0.93 – 1.16) times more likely to acquire an Alpha or Delta infection than children. Effectiveness of two doses of BNT162b2 against transmission of Delta was 36% (-1%, 66%) and 49% (18%, 73%) for ChAdOx1, similar to their effectiveness for Alpha. Protection against infection with Alpha was higher than for Delta, 69% (9%, 95%) vs. 18% (-11%, 59%), respectively, for BNT162b2 and 24% (-41%, 72%) vs. 9% (-15%, 42%), respectively, for ChAdOx1.Conclusions: BNT162b2 and ChAdOx1 reduce transmission of the Delta variant from breakthrough infections in the household setting, although their protection against infection within this setting is low

Smc5/6 coordinates formation and resolution of joint molecules with chromosome morphology to ensure meiotic divisions

During meiosis, Structural Maintenance of Chromosome (SMC) complexes underpin two fundamental features of meiosis: homologous recombination and chromosome segregation. While meiotic functions of the cohesin and condensin complexes have been delineated, the role of the third SMC complex, Smc5/6, remains enigmatic. Here we identify specific, essential meiotic functions for the Smc5/6 complex in homologous recombination and the regulation of cohesin. We show that Smc5/6 is enriched at centromeres and cohesin-association sites where it regulates sister-chromatid cohesion and the timely removal of cohesin from chromosomal arms, respectively. Smc5/6 also localizes to recombination hotspots, where it promotes normal formation and resolution of a subset of joint-molecule intermediates. In this regard, Smc5/6 functions independently of the major crossover pathway defined by the MutLγ complex. Furthermore, we show that Smc5/6 is required for stable chromosomal localization of the XPF-family endonuclease, Mus81-Mms4Eme1. Our data suggest that the Smc5/6 complex is required for specific recombination and chromosomal processes throughout meiosis and that in its absence, attempts at cell division with unresolved joint molecules and residual cohesin lead to severe recombination-induced meiotic catastroph