Asking the right questions: Developing diagnostic tests in undergraduate physics

Being able to discover students‟ conceptions and more importantly alternate- and misconceptions about a topic is vital in order to be able to assess and thus be able to improve student learning. It is well known that this can be achieved via the use of well-designed diagnostic tests, a widely used example of which is the Force Concept Inventory. Creating the right questions in order to form a reliable diagnostic test can be a lengthy and complicated process. This article reports work on a Development Project funded in 2008 to develop such a test for introductory Quantum Mechanics courses in both physics and chemistry. We present details of our methodology, which involves augmenting a „standard‟ multiple-choice question set with free-response boxes to determine the reasons for a student choosing a particular answer, and a self-assessment of their level of confidence in their choice. The responses from piloting this initial test in different institutions are used to inform the subsequent refinement of the test, as well as assessing the reliability and validity of the questions. We highlight examples of misconceptions that have been found during the development of the diagnostic tests

Mood and Experience: Effects of Ostracism on Diathesis Activation

The stress-diathesis model is a well-known but little-tested theory which states that people can possess diatheses, or vulnerabilities, to certain mental disorders such as depression or anxiety. These diatheses are activated when a person is under stress. This study examined how ostracism as a temporary stressor can trigger existing diatheses and cause increases in depression symptoms among at-risk people. Theory suggests that ostracism is likely to trigger symptoms of depression in at-risk people. This study is an extension of a study conducted by Luxton, Ingram, and Wenzlaff (2006) in which people with naturally varying levels of diathesis factors were exposed to a psychological threat, after which diathesis activation and depressive symptoms were assessed. Like Luxton et al., 2006, I exposed participants to a stressor (ostracism) and measured depression symptoms and diathesis activation with different measures. It was expected that for people who possessed diatheses that the ostracism threat would activate symptoms of depression. My sample consisted of 177 WKU students, 112 female and 65 male. Effects were found on state anxiety and positive and negative affect scales

Causal hierarchy within the thalamo-cortical network in spike and wave discharges

Background: Generalised spike wave (GSW) discharges are the electroencephalographic (EEG) hallmark of absence seizures, clinically characterised by a transitory interruption of ongoing activities and impaired consciousness, occurring during states of reduced awareness. Several theories have been proposed to explain the pathophysiology of GSW discharges and the role of thalamus and cortex as generators. In this work we extend the existing theories by hypothesizing a role for the precuneus, a brain region neglected in previous works on GSW generation but already known to be linked to consciousness and awareness. We analysed fMRI data using dynamic causal modelling (DCM) to investigate the effective connectivity between precuneus, thalamus and prefrontal cortex in patients with GSW discharges. Methodology and Principal Findings: We analysed fMRI data from seven patients affected by Idiopathic Generalized Epilepsy (IGE) with frequent GSW discharges and significant GSW-correlated haemodynamic signal changes in the thalamus, the prefrontal cortex and the precuneus. Using DCM we assessed their effective connectivity, i.e. which region drives another region. Three dynamic causal models were constructed: GSW was modelled as autonomous input to the thalamus (model A), ventromedial prefrontal cortex (model B), and precuneus (model C). Bayesian model comparison revealed Model C (GSW as autonomous input to precuneus), to be the best in 5 patients while model A prevailed in two cases. At the group level model C dominated and at the population-level the p value of model C was ∼1. Conclusion: Our results provide strong evidence that activity in the precuneus gates GSW discharges in the thalamo-(fronto) cortical network. This study is the first demonstration of a causal link between haemodynamic changes in the precuneus - an index of awareness - and the occurrence of pathological discharges in epilepsy. © 2009 Vaudano et al

Vedolizumab for the Treatment of Adults with Moderate-to-Severe Active Ulcerative Colitis: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

As part of its single technology appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) invited the manufacturer of vedolizumab (Takeda UK) to submit evidence of the clinical effectiveness and cost effectiveness of vedolizumab for the treatment of patients with moderate-to-severe active ulcerative colitis (UC). The Evidence Review Group (ERG) produced a critical review of the evidence for the clinical effectiveness and cost effectiveness of the technology, based upon the company's submission to NICE. The evidence was derived mainly from GEMINI 1, a Phase 3, multicentre, randomised, double-blinded, placebo-controlled study of the induction and maintenance of clinical response and remission by vedolizumab (MLN0002) in patients with moderate-to-severe active UC with an inadequate response to, loss of response to or intolerance of conventional therapy or anti-tumour necrosis factor (TNF)-α. The clinical evidence showed that vedolizumab performed significantly better than placebo in both the induction and maintenance phases. In the post hoc subgroup analyses in patients with or without prior anti-TNF-α therapy, vedolizumab performed better then placebo (p value not reported). In addition, a greater improvement in health-related quality of life was observed in patients treated with vedolizumab, and the frequency and types of adverse events were similar in the vedolizumab and placebo groups, but the evidence was limited to short-term follow-up. There were a number of limitations and uncertainties in the clinical evidence base, which warrants caution in its interpretation-in particular, the post hoc subgroup analyses and high dropout rates in the maintenance phase of GEMINI 1. The company also presented a network meta-analysis of vedolizumab versus other biologic therapies indicated for moderate-to-severe UC. However, the ERG considered that the results presented may have underestimated the uncertainty in treatment effects, since fixed-effects models were used, despite clear evidence of heterogeneity among the trials included in the network. Results from the company's economic evaluation (which included price reductions to reflect the proposed patient access scheme for vedolizumab) suggested that vedolizumab is the most effective option compared with surgery and conventional therapy in the following three populations: (1) a mixed intention-to-treat population, including patients who have previously received anti-TNF-α therapy and those who are anti-TNF-α naïve; (2) patients who are anti-TNF-α naïve only; and (3) patients who have previously failed anti-TNF-α therapy only. The ERG concluded that the results of the company's economic evaluation could not be considered robust, because of errors in model implementation, omission of relevant comparators, deviations from the NICE reference case and questionable model assumptions. The ERG amended the company's model and demonstrated that vedolizumab is expected to be dominated by surgery in all three populations

Medulloblastoma Exome Sequencing Uncovers Subtype-Specific Somatic Mutations

Medulloblastomas are the most common malignant brain tumors in children1. Identifying and understanding the genetic events that drive these tumors is critical for the development of more effective diagnostic, prognostic and therapeutic strategies. Recently, our group and others described distinct molecular subtypes of medulloblastoma based on transcriptional and copy number profiles2–5. Here, we utilized whole exome hybrid capture and deep sequencing to identify somatic mutations across the coding regions of 92 primary medulloblastoma/normal pairs. Overall, medulloblastomas exhibit low mutation rates consistent with other pediatric tumors, with a median of 0.35 non-silent mutations per megabase. We identified twelve genes mutated at statistically significant frequencies, including previously known mutated genes in medulloblastoma such as CTNNB1, PTCH1, MLL2, SMARCA4 and TP53. Recurrent somatic mutations were identified in an RNA helicase gene, DDX3X, often concurrent with CTNNB1 mutations, and in the nuclear co-repressor (N-CoR) complex genes GPS2, BCOR, and LDB1, novel findings in medulloblastoma. We show that mutant DDX3X potentiates transactivation of a TCF promoter and enhances cell viability in combination with mutant but not wild type beta-catenin. Together, our study reveals the alteration of Wnt, Hedgehog, histone methyltransferase and now N-CoR pathways across medulloblastomas and within specific subtypes of this disease, and nominates the RNA helicase DDX3X as a component of pathogenic beta-catenin signaling in medulloblastoma

Potential Efficacy of the MOVERS Professional Development Programme: A Pilot Randomised Controlled Trial

Background: High‐quality early childhood education (ECE) environments positively impact child outcomes. This study examined the potential efficacy of a professional development (PD) programme on improving the quality of the ECE movement environment and children's physical activity, motor, literacy and numeracy skills. Methods: A 6‐month RCT involving 5 ECE services and 157 children (mean age 3.84 ± 0.61 years) was conducted. ECE services were randomly assigned to the intervention group (n = 3) or wait‐list control group (n = 2). The PD comprised five monthly face‐to‐face sessions, including theory, practice and reflective thinking components. Outcomes included the quality of the ECE movement environment (MOVERS), children's gross motor skills (TGMD‐2), physical activity (GT3X accelerometers), fine motor skills (ASQ‐3), receptive vocabulary (PPVT‐4) and numeracy (PENS). All outcomes were assessed at baseline and follow‐up. Data were analysed using linear mixed models (SPSS, Version 26) and effect sizes were calculated. Educator engagement was collected using questionnaires. Results: Large effect sizes were reported for the quality of the ECE movement environment (d = 1.77–9.35). Medium to large effect sizes were reported for children's gross motor skills (d = 0.68–1.23), and small to medium effect sizes were reported for three subscales of the numeracy test (d = 0.43–0.63). In the intervention group, a significantly greater number of children moved from being at risk of delay or delayed to normal development in fine motor skills (Phi = 0.21). Educators reported that the PD content was relevant and clearly explained, highlighting the hands‐on components as the most valued aspect. Conclusion: The MOVERS PD pilot programme resulted in changes in educators' pedagogy and practice and in children's gross and fine motor skills and numeracy skills. Future studies with larger sample sizes will be important to confirm these results

Assessing Inequalities in Wellbeing at a Neighbourhood Scale in Low-Middle-Income-Country Secondary Cities and Their Implications for Long-Term Livability

Correction: FEB 15 2022 DOI10.3389/fsoc.2022.856609To ensure future sustainability, cities need to consider concepts of livability and resident wellbeing alongside environmental, economic and infrastructure development equity. The current rapid urbanization experienced in many regions is leading to sustainability challenges, but also offers the opportunity to deliver infrastructure supporting the social aspects of cities and the services that underpin them alongside economic growth. Unfortunately, evidence of what is needed to deliver urban wellbeing is largely absent from the global south. This paper contributes to filling this knowledge gap through a novel interdisciplinary mixed methods study undertaken in two rapidly changing cities (one Thai and one Kenyan) using qualitative surveys, subjective wellbeing and stress measurements, and spatial analysis of urban infrastructure distribution. We find the absence of basic infrastructure (including waste removal, water availability and quality) unsurprisingly causes significant stress for city residents. However, once these services are in place, smaller variations (inequalities) in social (crime, tenure) and environmental (noise, air quality) conditions begin to play a greater role in determining differences in subjective wellbeing across a city. Our results indicate that spending time in urban greenspaces can mitigate the stressful impacts of city living even for residents of informal neighborhoods. Our data also highlights the importance of places that enable social interactions supporting wellbeing-whether green or built. These results demonstrate the need for diversity and equity in the provision of public realm spaces to ensure social and spatial justice. These findings strengthen the need to promote long term livability in LMIC urban planning alongside economic growth, environmental sustainability, and resilience.Peer reviewe