Incipient Balancing Selection through Adaptive Loss of Aquaporins in Natural Saccharomyces cerevisiae Populations

A major goal in evolutionary biology is to understand how adaptive evolution has influenced natural variation, but identifying loci subject to positive selection has been a challenge. Here we present the adaptive loss of a pair of paralogous genes in specific Saccharomyces cerevisiae subpopulations. We mapped natural variation in freeze-thaw tolerance to two water transporters, AQY1 and AQY2, previously implicated in freeze-thaw survival. However, whereas freeze-thaw–tolerant strains harbor functional aquaporin genes, the set of sensitive strains lost aquaporin function at least 6 independent times. Several genomic signatures at AQY1 and/or AQY2 reveal low variation surrounding these loci within strains of the same haplotype, but high variation between strain groups. This is consistent with recent adaptive loss of aquaporins in subgroups of strains, leading to incipient balancing selection. We show that, although aquaporins are critical for surviving freeze-thaw stress, loss of both genes provides a major fitness advantage on high-sugar substrates common to many strains' natural niche. Strikingly, strains with non-functional alleles have also lost the ancestral requirement for aquaporins during spore formation. Thus, the antagonistic effect of aquaporin function—providing an advantage in freeze-thaw tolerance but a fitness defect for growth in high-sugar environments—contributes to the maintenance of both functional and nonfunctional alleles in S. cerevisiae. This work also shows that gene loss through multiple missense and nonsense mutations, hallmarks of pseudogenization presumed to emerge after loss of constraint, can arise through positive selection

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

The Science Performance of JWST as Characterized in Commissioning

This paper characterizes the actual science performance of the James Webb Space Telescope (JWST), as determined from the six month commissioning period. We summarize the performance of the spacecraft, telescope, science instruments, and ground system, with an emphasis on differences from pre-launch expectations. Commissioning has made clear that JWST is fully capable of achieving the discoveries for which it was built. Moreover, almost across the board, the science performance of JWST is better than expected; in most cases, JWST will go deeper faster than expected. The telescope and instrument suite have demonstrated the sensitivity, stability, image quality, and spectral range that are necessary to transform our understanding of the cosmos through observations spanning from near-earth asteroids to the most distant galaxies.Comment: 5th version as accepted to PASP; 31 pages, 18 figures; https://iopscience.iop.org/article/10.1088/1538-3873/acb29

Screening Tools for Autism Spectrum Disorder in Primary Care: A Systematic Evidence Review

CONTEXT: Recommendations conflict regarding universal application of formal screening instruments in primary care (PC) and PC-like settings for autism spectrum disorder (ASD). OBJECTIVES: We systematically reviewed evidence for universal screening of children for ASD in PC. DATA SOURCES: We searched Medline, PsychInfo, Educational Resources Informational Clearinghouse, and Cumulative Index of Nursing and Allied Health Literature. STUDY SELECTION: We included studies in which researchers report psychometric properties of screening tools in unselected populations across PC and PC-like settings. DATA EXTRACTION: At least 2 authors reviewed each study, extracted data, checked accuracy, and assigned quality ratings using predefined criteria. RESULTS: We found evidence for moderate to high positive predictive values for ASD screening tools to identify children aged 16 to 40 months and 1 study for ≥48 months in PC and PC-like settings. Limited evidence evaluating sensitivity, specificity, and negative predictive value of instruments was available. No studies directly evaluated the impact of screening on treatment or harm. LIMITATIONS: Potential limitations include publication bias, selective reporting within studies, and a constrained search. CONCLUSIONS: ASD screening tools can be used to accurately identify percentages of unselected populations of young children for ASD in PC and PC-like settings. The scope of challenges associated with establishing direct linkage suggests that clinical and policy groups will likely continue to guide screening practices. ASD is a common neurodevelopmental disorder associated with significant life span costs. Growing evidence supports functional gains and improved outcomes for young children receiving intensive intervention, so early identification on a population level is a pressing public health challenge

Screening Tools for Autism Spectrum Disorder in Primary Care: A Systematic Evidence Review

CONTEXT: Recommendations conflict regarding universal application of formal screening instruments in primary care (PC) and PC-like settings for autism spectrum disorder (ASD). OBJECTIVES: We systematically reviewed evidence for universal screening of children for ASD in PC. DATA SOURCES: We searched Medline, PsychInfo, Educational Resources Informational Clearinghouse, and Cumulative Index of Nursing and Allied Health Literature. STUDY SELECTION: We included studies in which researchers report psychometric properties of screening tools in unselected populations across PC and PC-like settings. DATA EXTRACTION: At least 2 authors reviewed each study, extracted data, checked accuracy, and assigned quality ratings using predefined criteria. RESULTS: We found evidence for moderate to high positive predictive values for ASD screening tools to identify children aged 16 to 40 months and 1 study for ≥48 months in PC and PC-like settings. Limited evidence evaluating sensitivity, specificity, and negative predictive value of instruments was available. No studies directly evaluated the impact of screening on treatment or harm. LIMITATIONS: Potential limitations include publication bias, selective reporting within studies, and a constrained search. CONCLUSIONS: ASD screening tools can be used to accurately identify percentages of unselected populations of young children for ASD in PC and PC-like settings. The scope of challenges associated with establishing direct linkage suggests that clinical and policy groups will likely continue to guide screening practices. ASD is a common neurodevelopmental disorder associated with significant life span costs. Growing evidence supports functional gains and improved outcomes for young children receiving intensive intervention, so early identification on a population level is a pressing public health challenge

Irritability and Problem Behavior in Autism Spectrum Disorder: A Practice Pathway for Pediatric Primary Care.

OBJECTIVE: Pediatric primary care providers (PCPs) caring for patients with autism spectrum disorder (ASD) often encounter irritability (vocal or motoric outbursts expressive of anger, frustration, or distress) and problem behavior (directed acts of aggression toward other people, self, or property). The Autism Intervention Research Network on Physical Health and Autism Speaks Autism Treatment Network charged a multidisciplinary workgroup with developing a practice pathway to assist PCPs in the evaluation and treatment of irritability and problem behavior (I/PB). METHODS: The workgroup reviewed the literature on the evaluation and treatment of contributory factors for I/PB in ASD. The workgroup then achieved consensus on the content and sequence of each step in the pathway. RESULTS: The practice pathway is designed to help the PCP generate individualized treatment plans based on contributing factors identified in each patient. These factors may include medical conditions, which the PCP is in a key position to address; functional communication challenges that can be addressed at school or at home; psychosocial stressors that may be ameliorated; inadvertent reinforcement of I/PB; and co-occurring psychiatric conditions that can be treated. The pathway provides guidance on psychotropic medication use, when indicated, within an individualized treatment plan. In addition to guidance on assessment, referral, and initial treatment, the pathway includes monitoring of treatment response and periodic reassessment. CONCLUSIONS: The pediatric PCP caring for the patient with ASD is in a unique position to help generate an individualized treatment plan that targets factors contributing to I/PB and to implement this plan in collaboration with parents, schools, and other providers

Inhalation injury is associated with long-term employment outcomes in the burn population: Findings from a cross-sectional examination of the Burn Model System National Database.

IntroductionInhalation injuries carry significant acute care burden including prolonged ventilator days and length of stay. However, few studies have examined post-acute outcomes of inhalation injury survivors. This study compares the long-term outcomes of burn survivors with and without inhalation injury.MethodsData collected by the Burn Model System National Database from 1993 to 2019 were analyzed. Demographic and clinical characteristics for adult burn survivors with and without inhalation injury were examined. Outcomes included employment status, Short Form-12/Veterans Rand-12 Physical Composite Score (SF-12/VR-12 PCS), Short Form-12/Veterans Rand-12 Mental Composite Score (SF-12/VR-12 MCS), and Satisfaction With Life Scale (SWLS) at 24 months post-injury. Regression models were used to assess the impacts of sociodemographic and clinical covariates on long-term outcome measures. All models controlled for demographic and clinical characteristics.ResultsData from 1,871 individuals were analyzed (208 with inhalation injury; 1,663 without inhalation injury). The inhalation injury population had a median age of 40.1 years, 68.8% were male, and 69% were White, non-Hispanic. Individuals that sustained an inhalation injury had larger burn size, more operations, and longer lengths of hospital stay (pConclusionsBurn survivors with inhalation injury were significantly less likely to be employed at 24 months post-injury compared to survivors without inhalation injury. However, other health-related quality of life outcomes were similar between groups. This study suggests distinct long-term outcomes in adult burn survivors with inhalation injury which may inform future resource allocation and treatment paradigms

The development and analysis of tutorial dialogues in AutoTutor Lite

The goal of Intelligent Tutoring Systems (ITS) that interact in natural language is to emulate the benefits a well-trained human tutor provides to students, by interpreting student answers and appropriately responding to encourage elaboration. BRCA Gist is an ITS developed using AutoTutor Lite, a web-based version of AutoTutor. Fuzzy-Trace Theory theoretically motivated the development of BRCA Gist, which engages people in tutorial dialogues to teach them about genetic breast cancer risk. We describe an empirical method to create tutorial dialogues and fine-tune the calibration of BRCA Gist’s semantic processing engine without a team of computer scientists. We created five interactive dialogues centered on pedagogic questions, such as “What should someone do if she receives a positive result for genetic risk of breast cancer?” This method involved an iterative refinement process of repeated testing with different texts, and successively making adjustments to the tutor’s expectations and settings to improve performance. The goal of this method was to enable BRCA Gist to interpret and respond to answers in a manner that best facilitates learning. We developed a method to analyze the efficacy of the tutor’s dialogues. We found that BRCA Gist’s assessment of participants’ answers was highly correlated with the quality of answers found by trained human judges using a reliable rubric. Dialogue quality between users and BRCA Gist, predicted performance on a breast cancer risk knowledge test completed after the tutor. The appropriateness of BRCA Gist feedback also predicted the quality of answers and breast cancer risk knowledge test scores

Continuous-Discrete Extended Kalman Filter on Matrix Lie Groups Using Concentrated Gaussian Distributions

In this paper we generalize the Continuous-Discrete Extended Kalman Filter (CD-EKF) to the case where the state and the observations evolve on connected unimodular matrix Lie groups. We propose a new assumed density filter called Continuous-Discrete Extended Kalman Filter on Lie Groups (CD-LG-EKF). It is built upon a geometrically meaningful modeling of the concentrated Gaussian distribution on Lie Groups. Such a distribution is parametrized by a mean and a co-variance matrix defined on the Lie group and in its associated Lie algebra respectively. Our formalism yields tractable equations for both non-linear continuous time propagation and discrete update of the distribution parameters under the assumption that the posterior distribution of the state is a concentrated Gaussian. As a side effect, we contribute to the derivation of the first and second order differential of the matrix Lie group logarithm using left connection. We also show that the CD-LG-EKF reduces to the usual CD-EKF if the state and the observations evolve on Euclidean spaces. Our approach leads to a systematic methodology for the design of filters, which is illustrated by the application to a camera pose filtering problem with observations on Lie group. In this application, the CD-LG-EKF significantly outperforms two constrained non-linear filters (one based on a linearization technique and the other on the unscented transform) applied on the embedding space of the Lie group.Dementia Ambient Care: Multi-Sensing Monitoring for Intelligent Remote Management and Decision Suppor

Correction: Evidence-based scientific exercise guidelines for adults with spinal cord injury: an update and a new guideline

Authors Victoria L. Goosey-Tolfrey and Karen M. Smith were listed under the incorrect affiliations at the time of publication