Human Xq28 Inversion Polymorphism: From Sex Linkage to Genomics - A Genetic Mother Lode

An inversion polymorphism of the filamin and emerin genes at the tip of the long arm of the human X-chromosome serves as the basis of an investigative laboratory in which students learn something new about their own genomes. Long, nearly identical inverted repeats flanking the filamin and emerin genes illustrate how repetitive elements can lead to alterations in genome structure (inversions) through nonallelic homologous recombination. The near identity of the inverted repeats is an example of concerted evolution through gene conversion. While the laboratory in its entirety is designed for college level genetics courses, portions of the laboratory are appropriate for courses at other levels. Because the polymorphism is on the X-chromosome, the laboratory can be used in introductory biology courses to enhance understanding of sex-linkage and to test for Hardy-Weinberg equilibrium in females. More advanced topics, such as chromosome interference, the molecular model for recombination, and inversion heterozygosity suppression of recombination can be explored in upper-level genetics and evolution courses. DNA isolation, restriction digests, ligation, long PCR, and iPCR provide experience with techniques in molecular biology. This investigative laboratory weaves together topics stretching from molecular genetics to cytogenetics and sex-linkage, population genetics and evolutionary genetics

Brain Cells in the Avian ‘Prefrontal Cortex’ Code for Features of Slot-Machine-Like Gambling

Slot machines are the most common and addictive form of gambling. In the current study, we recorded from single neurons in the ‘prefrontal cortex’ of pigeons while they played a slot-machine-like task. We identified four categories of neurons that coded for different aspects of our slot-machine-like task. Reward-Proximity neurons showed a linear increase in activity as the opportunity for a reward drew near. I-Won neurons fired only when the fourth stimulus of a winning (four-of-a-kind) combination was displayed. I-Lost neurons changed their firing rate at the presentation of the first nonidentical stimulus, that is, when it was apparent that no reward was forthcoming. Finally, Near-Miss neurons also changed their activity the moment it was recognized that a reward was no longer available, but more importantly, the activity level was related to whether the trial contained one, two, or three identical stimuli prior to the display of the nonidentical stimulus. These findings not only add to recent neurophysiological research employing simulated gambling paradigms, but also add to research addressing the functional correspondence between the avian NCL and primate PFC

Multimodal Instructor Guide

Since the start of the COVID-19 pandemic, the increasing prevalence of multimodal classrooms—where teaching and learning occur through varying combinations of digital and in-person, synchronous and asynchronous experiences—has potential to create more accessible learning environments for students, but also presents challenges to instructors and students. To better support faculty interested in blended learning, EDLI, in collaboration with MSU IT, conducted an institutional research study on multimodal classes taught fall semester 2021 in the College of Arts and Letters and the College of Natural Science. This guide is informed by the study findings and intended to support MSU instructors in determining if and how multimodal course design may benefit their students

Decreasing rates of disorganised attachment in infants and young children, who are at risk of developing, or who already have disorganised attachment. A systematic review and meta-analysis of early parenting interventions

BACKGROUND: Disorganised attachment patterns in infants have been linked to later psychopathology. Services have variable practices for identifying and providing interventions for families of children with disorganised attachment patterns, which is the attachment pattern leading to most future psychopathology. Several recent government reports have highlighted the need for better parenting interventions in at risk groups. OBJECTIVES: The objective of this review and meta-analysis was to evaluate the clinical effectiveness of available parenting interventions for families of children at high risk of developing, or already showing, a disorganised pattern of attachment. METHODS: Population: Studies were included if they involved parents or caregivers of young children with a mean age under 13 years who had a disorganised classification of attachment or were identified as at high risk of developing such problems. Included interventions were aimed at parents or caregivers (e.g. foster carers) seeking to improve attachment. Comparators included an alternative intervention, an attention control, treatment as usual or no intervention. The primary outcome was a disorganised pattern in childhood measured using a validated attachment instrument. Studies that did not use a true Randomised Controlled Trial (RCT) design were excluded from the review. Both published and unpublished papers were included, there were no restrictions on years since publication and foreign language papers were included where translation services could be accessed within necessary timescales. RESULTS: A comprehensive search of relevant databases yielded 15,298 papers. This paper reports a systematic review as part of an NIHR HTA study identifying studies pre-2012, updated to include all papers to October 2016. Two independent reviewers undertook two stage screening and data extraction of the included studies at all stages. A Cochrane quality assessment was carried out to assess the risk of bias. In total, fourteen studies were included in the review. In a meta-analysis of these fourteen studies the interventions saw less disorganised attachment at outcome compared to the control (OR = 0.50, (0.32, 0.77), p = 0.008). The majority of the interventions targeted maternal sensitivity. We carried out exploratory analyses to examine factors that may influence treatment outcome but these should be treated with caution given that we were limited by small numbers of studies. CONCLUSIONS: Parenting interventions that target parental sensitivity show promise in reducing disorganised attachment. This is limited by few high quality studies and the fact that most studies are with mothers. More high quality randomised controlled trials are required to elucidate this further

Can guidance during play enhance children’s learning and development in educational contexts? A systematic review and meta-analysis

This systematic review and meta-analysis considered evidence of guided play compared to direct instruction or free play to support children's learning and development. Interventions from 39 studies were reviewed (published 1977–2020); 17 were included in meta-analysis (Ntotal = 3893; Mchildage = 1–8 years; Mgirls 49.8%; Methnicity White 41%, African American/Black 28%, Hispanic 19%). Guided play had a greater positive effect than direct instruction on early maths skills (g = 0.24), shape knowledge (g = 0.63), and task switching (g = 0.40); and than free play on spatial vocabulary (g = 0.93). Differences were not identified for other key outcomes. Narrative synthesis highlighted heterogeneity in the conceptualization and implementation of guided play across studies

Factors that influence the administration of tranexamic acid (TXA) to trauma patients in prehospital settings: A systematic review

OBJECTIVE: In the UK there are around 5400 deaths annually from injury. Tranexamic acid (TXA) prevents bleeding and has been shown to reduce trauma mortality. However, only 5% of UK major trauma patients who are at risk of haemorrhage receive prehospital TXA. This review aims to examine the evidence regarding factors influencing the prehospital administration of TXA to trauma patients. DESIGN: Systematic literature review. DATA SOURCES: AMED, CENTRAL, CINAHL, Cochrane Database of Systematic Reviews, Conference Proceedings Citation Index-Science, Embase and MEDLINE were searched from January 2010 to 2020; searches were updated in June 2022. CLINICALTRIALS: gov and OpenGrey were also searched and forward and backwards citation chasing performed. ELIGIBILITY CRITERIA: All primary research reporting factors influencing TXA administration to trauma patients in the prehospital setting was included. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers performed the selection process, quality assessment and data extraction. Data were tabulated, grouped by setting and influencing factor and synthesised narratively. RESULTS: Twenty papers (278 249 participants in total) were included in the final synthesis; 13 papers from civilian and 7 from military settings. Thirteen studies were rated as 'moderate' using the Effective Public Health Practice Project Quality Assessment Tool. Several common factors were identified: knowledge and skills; consequences and social influences; injury type (severity, injury site and mechanism); protocols; resources; priorities; patient age; patient sex. CONCLUSIONS: This review highlights an absence of high-quality research. Preliminary evidence suggests a host of system and individual-level factors that may be important in determining whether TXA is administered to trauma patients in the prehospital setting. FUNDING AND REGISTRATION: This review was supported by Research Capability Funding from the South Western Ambulance Service NHS Foundation Trust and the National Institute for Health Research Applied Research Collaboration South West Peninsula. PROSPERO REGISTRATION NUMBER: CRD42020162943

Introductory programming: a systematic literature review

As computing becomes a mainstream discipline embedded in the school curriculum and acts as an enabler for an increasing range of academic disciplines in higher education, the literature on introductory programming is growing. Although there have been several reviews that focus on specific aspects of introductory programming, there has been no broad overview of the literature exploring recent trends across the breadth of introductory programming. This paper is the report of an ITiCSE working group that conducted a systematic review in order to gain an overview of the introductory programming literature. Partitioning the literature into papers addressing the student, teaching, the curriculum, and assessment, we explore trends, highlight advances in knowledge over the past 15 years, and indicate possible directions for future research

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Assessing the Quality of Decision Support Technologies Using the International Patient Decision Aid Standards instrument (IPDASi)

Objectives To describe the development, validation and inter-rater reliability of an instrument to measure the quality of patient decision support technologies (decision aids). Design Scale development study, involving construct, item and scale development, validation and reliability testing. Setting There has been increasing use of decision support technologies – adjuncts to the discussions clinicians have with patients about difficult decisions. A global interest in developing these interventions exists among both for-profit and not-for-profit organisations. It is therefore essential to have internationally accepted standards to assess the quality of their development, process, content, potential bias and method of field testing and evaluation. Methods Scale development study, involving construct, item and scale development, validation and reliability testing. Participants Twenty-five researcher-members of the International Patient Decision Aid Standards Collaboration worked together to develop the instrument (IPDASi). In the fourth Stage (reliability study), eight raters assessed thirty randomly selected decision support technologies. Results IPDASi measures quality in 10 dimensions, using 47 items, and provides an overall quality score (scaled from 0 to 100) for each intervention. Overall IPDASi scores ranged from 33 to 82 across the decision support technologies sampled (n = 30), enabling discrimination. The inter-rater intraclass correlation for the overall quality score was 0.80. Correlations of dimension scores with the overall score were all positive (0.31 to 0.68). Cronbach's alpha values for the 8 raters ranged from 0.72 to 0.93. Cronbach's alphas based on the dimension means ranged from 0.50 to 0.81, indicating that the dimensions, although well correlated, measure different aspects of decision support technology quality. A short version (19 items) was also developed that had very similar mean scores to IPDASi and high correlation between short score and overall score 0.87 (CI 0.79 to 0.92). Conclusions This work demonstrates that IPDASi has the ability to assess the quality of decision support technologies. The existing IPDASi provides an assessment of the quality of a DST's components and will be used as a tool to provide formative advice to DSTs developers and summative assessments for those who want to compare their tools against an existing benchmark

Association of Variants in the SPTLC1 Gene With Juvenile Amyotrophic Lateral Sclerosis

Importance: Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age of symptom onset less than 25 years and a variable presentation.Objective: To identify the genetic variants associated with juvenile ALS.Design, Setting, and Participants: In this multicenter family-based genetic study, trio whole-exome sequencing was performed to identify the disease-associated gene in a case series of unrelated patients diagnosed with juvenile ALS and severe growth retardation. The patients and their family members were enrolled at academic hospitals and a government research facility between March 1, 2016, and March 13, 2020, and were observed until October 1, 2020. Whole-exome sequencing was also performed in a series of patients with juvenile ALS. A total of 66 patients with juvenile ALS and 6258 adult patients with ALS participated in the study. Patients were selected for the study based on their diagnosis, and all eligible participants were enrolled in the study. None of the participants had a family history of neurological disorders, suggesting de novo variants as the underlying genetic mechanism.Main Outcomes and Measures: De novo variants present only in the index case and not in unaffected family members.Results: Trio whole-exome sequencing was performed in 3 patients diagnosed with juvenile ALS and their parents. An additional 63 patients with juvenile ALS and 6258 adult patients with ALS were subsequently screened for variants in the SPTLC1 gene. De novo variants in SPTLC1 (p.Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient) were identified in 3 unrelated patients diagnosed with juvenile ALS and failure to thrive. A fourth variant (p.Leu39del) was identified in a patient with juvenile ALS where parental DNA was unavailable. Variants in this gene have been previously shown to be associated with autosomal-dominant hereditary sensory autonomic neuropathy, type 1A, by disrupting an essential enzyme complex in the sphingolipid synthesis pathway.Conclusions and Relevance: These data broaden the phenotype associated with SPTLC1 and suggest that patients presenting with juvenile ALS should be screened for variants in this gene.</p