195 research outputs found
A Professional Community of Science Teachers and Researchers for Enacting Change in Classroom Assessment
This paper aims to specify conditions that seem fruitful for enacting change in schools. It addresses a project involving teachers from lower secondary and primary schools. The project aims to develop formative assessment within science inquiry-based teaching methods. The elements underpinning this project are described. The effects on teacher conceptions and practices are shown. Data results from an analysis of the project material and of focus groups with the teachers involved. The methodology is based on the activity theory framework. The results are aligned with other research that showed how fruitful it is to involve teachers within cooperative settings where they can reflect about specific professional questions and tackle complex problems with other colleagues, researchers and teacher educators from university
Evaluating Educational Practices for Positively Affecting Student Perceptions of a Sales Career
Despite demand for new graduates seeking a sales position, student reticence toward pursuing a sales career remains. While all students will not choose a sales career, diminishing the existence of sales-related misconceptions among the student population should establish sales as a viable career path for a larger number of students. We test six educational interventions in large Principle of Marketing classes from three different universities (n = 1,355) to help identify educational practices for reducing student reticence toward a career in sales. Our results show that while all six educational approaches raise students’ perceptions and interest in a selling career, the utilization of experienced salespeople to present classroom materials and to discuss their sales career was the most effective. Classroom lecture and role-plays by university sales students had the second highest intent to pursue intervention scores. We offer recommendations for how to best present sales material to these large, lecture-based courses
A Parsimonious Instrument for Predicting Students’ Intent to Pursue a Sales Career: Scale Development and Validation
Students’ desire and intention to pursue a career in sales continue to lag behind industry demand for sales professionals. This article develops and validates a reliable and parsimonious scale for measuring and predicting student intention to pursue a selling career. The instrument advances previous scales in three ways. The instrument is generalizable across academic settings and is shown to be sensitive to differences across varied course coverage and learning activities. The instrument is parsimonious and offers a high reliability coefficient. Finally, the instrument is validated both before and after exposure to a sales module, thus capturing perceptual and attitudinal changes as students become more familiar with this career option
Heme iron from meat and risk of colorectal cancer: a meta-analysis and a review of the mechanisms involved
Red meat and processed meat intake is associated with a risk of colorectal cancer, a major cause of death in affluent countries. Epidemiological and experimental evidence supports the hypothesis that heme iron present in meat promotes colorectal cancer. This meta-analysis of prospective cohort studies of colon cancer reporting heme intake included 566,607 individuals and 4,734 cases of colon cancer. The summary relative risk of colon cancer was 1.18 [95%C.I.: 1.06-1.32] for subjects in the highest category of heme iron intake compared with those in the lowest category. Epidemiological data thus show a suggestive association between dietary heme and risk of colon cancer. The analysis of experimental studies in rats with chemically-induced colon cancer showed that dietary hemoglobin and red meat consistently promote aberrant crypt foci, a putative pre-cancer lesion. The mechanism is not known, but heme iron has a catalytic effect on (i) the endogenous formation of carcinogenic N-nitroso compounds and (ii) the formation of cytotoxic and genotoxic aldehydes by lipoperoxidation. A review of evidence supporting these hypotheses suggests that both pathways are involved in heme iron toxicit
Building Social & Emotional Competence in Early Education Classrooms through Art Therapy
This research project qualitatively explores how teachers address social-emotional learning and how educators understand and implement SEL and art therapy in early education. This research aimed to explore how art therapy theories can support teachers in their efforts to create socially and emotionally competent early education classrooms. Data collected included anonymous surveys from current kindergarten through third-grade teachers. Through data analysis, several findings suggest that art therapists, mental health practitioners, and teachers can benefit from collaboration in increasing access and training with SEL practices. These findings open new doors for further inquiry into art therapy and SEL
Limited antigenic diversity of Plasmodium falciparum apical membrane antigen 1 supports the development of effective multi-allele vaccines
BackgroundPolymorphism in antigens is a common mechanism for immune evasion used by many important pathogens, and presents major challenges in vaccine development. In malaria, many key immune targets and vaccine candidates show substantial polymorphism. However, knowledge on antigenic diversity of key antigens, the impact of polymorphism on potential vaccine escape, and how sequence polymorphism relates to antigenic differences is very limited, yet crucial for vaccine development. Plasmodium falciparum apical membrane antigen 1 (AMA1) is an important target of naturally-acquired antibodies in malaria immunity and a leading vaccine candidate. However, AMA1 has extensive allelic diversity with more than 60 polymorphic amino acid residues and more than 200 haplotypes in a single population. Therefore, AMA1 serves as an excellent model to assess antigenic diversity in malaria vaccine antigens and the feasibility of multi-allele vaccine approaches. While most previous research has focused on sequence diversity and antibody responses in laboratory animals, little has been done on the cross-reactivity of human antibodies.MethodsWe aimed to determine the extent of antigenic diversity of AMA1, defined by reactivity with human antibodies, and to aid the identification of specific alleles for potential inclusion in a multi-allele vaccine. We developed an approach using a multiple-antigen-competition enzyme-linked immunosorbent assay (ELISA) to examine cross-reactivity of naturally-acquired antibodies in Papua New Guinea and Kenya, and related this to differences in AMA1 sequence.ResultsWe found that adults had greater cross-reactivity of antibodies than children, although the patterns of cross-reactivity to alleles were the same. Patterns of antibody cross-reactivity were very similar between populations (Papua New Guinea and Kenya), and over time. Further, our results show that antigenic diversity of AMA1 alleles is surprisingly restricted, despite extensive sequence polymorphism. Our findings suggest that a combination of three different alleles, if selected appropriately, may be sufficient to cover the majority of antigenic diversity in polymorphic AMA1 antigens. Antigenic properties were not strongly related to existing haplotype groupings based on sequence analysis.ConclusionsAntigenic diversity of AMA1 is limited and a vaccine including a small number of alleles might be sufficient for coverage against naturally-circulating strains, supporting a multi-allele approach for developing polymorphic antigens as malaria vaccines
Quantification of Extracellular DNA Network Abundance and Architecture within Streptococcus gordonii Biofilms Reveals Modulatory Factors
Extracellular DNA (eDNA) is an important component of biofilm matrix that serves to maintain biofilm structural integrity, promotes genetic exchange within the biofilm, and provides protection against antimicrobial compounds. Advances in microscopy techniques have provided evidence of the cobweb- or lattice-like structures of eDNA within biofilms from a range of environmental niches. However, methods to reliably assess the abundance and architecture of eDNA remain lacking. This study aimed to address this gap by development of a novel, high-throughput image acquisition and analysis platform for assessment of eDNA networks in situ within biofilms. Utilizing Streptococcus gordonii as the model, the capacity for this imaging system to reliably detect eDNA networks and monitor changes in abundance and architecture (e.g., strand length and branch number) was verified. Evidence was provided of a synergy between glucans and eDNA matrices, while it was revealed that surface-bound nuclease SsnA could modify these eDNA structures under conditions permissive for enzymatic activity. Moreover, cross talk between the competence and hexaheptapeptide permease systems was shown to regulate eDNA release by S. gordonii. This novel imaging system can be applied across the wider field of biofilm research, with potential to significantly advance interrogation of the mechanisms by which the eDNA network architecture develops, how it can influence biofilm properties, and how it may be targeted for therapeutic benefit. IMPORTANCE Extracellular DNA (eDNA) is critical for maintaining the structural integrity of many microbial biofilms, making it an attractive target for the management of biofilms. However, our knowledge and targeting of eDNA are currently hindered by a lack of tools for the quantitative assessment of eDNA networks within biofilms. Here, we demonstrate use of a novel image acquisition and analysis platform with the capacity to reliably monitor the abundance and architecture of eDNA networks. Application of this tool to Streptococcus gordonii biofilms has provided new insights into how eDNA networks are stabilized within the biofilm and the pathways that can regulate eDNA release. This highlights how exploitation of this novel imaging system across the wider field of biofilm research has potential to significantly advance interrogation of the mechanisms by which the eDNA network architecture develops, how it can influence biofilm properties, and how it may be targeted for therapeutic benefit
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Neural mechanisms underlying valence inferences to sound: The role of the right angular gyrus.
We frequently infer others' intentions based on non-verbal auditory cues. Although the brain underpinnings of social cognition have been extensively studied, no empirical work has yet examined the impact of musical structure manipulation on the neural processing of emotional valence during mental state inferences. We used a novel sound-based theory-of-mind paradigm in which participants categorized stimuli of different sensory dissonance level in terms of positive/negative valence. Whilst consistent with previous studies which propose facilitated encoding of consonances, our results demonstrated that distinct levels of consonance/dissonance elicited differential influences on the right angular gyrus, an area implicated in mental state attribution and attention reorienting processes. Functional and effective connectivity analyses further showed that consonances modulated a specific inhibitory interaction from associative memory to mental state attribution substrates. Following evidence suggesting that individuals with autism may process social affective cues differently, we assessed the relationship between participants' task performance and self-reported autistic traits in clinically typical adults. Higher scores on the social cognition scales of the AQ were associated with deficits in recognising positive valence in consonant sound cues. These findings are discussed with respect to Bayesian perspectives on autistic perception, which highlight a functional failure to optimize precision in relation to prior beliefs
Safety and efficacy of ganaxolone in patients with CDKL5 deficiency disorder: results from the double-blind phase of a randomised, placebo-controlled, phase 3 trial
BACKGROUND: CDKL5 deficiency disorder (CDD) is a rare, X-linked, developmental and epileptic encephalopathy characterised by severe global developmental impairment and seizures that can begin in the first few months after birth and are often treatment refractory. Ganaxolone, an investigational neuroactive steroid, reduced seizure frequency in an open-label, phase 2 trial that included patients with CDD. We aimed to further assess the efficacy and safety of ganaxolone in patients with CDD-associated refractory epilepsy. METHODS: In the double-blind phase of this randomised, placebo-controlled, phase 3 trial, done at 39 outpatient clinics in eight countries (Australia, France, Israel, Italy, Poland, Russia, the UK, and the USA), patients were eligible if they were aged 2-21 years with a pathogenic or probably pathogenic CDKL5 variant and at least 16 major motor seizures (defined as bilateral tonic, generalised tonic-clonic, bilateral clonic, atonic, or focal to bilateral tonic-clonic) per 28 days in each 4-week period of an 8-week historical period. After a 6-week prospective baseline period, patients were randomly assigned (1:1) via an interactive web response system to receive either enteral adjunctive ganaxolone or matching enteral adjunctive placebo (maximum dose 63 mg/kg per day for patients weighing ≤28 kg or 1800 mg/day for patients weighing >28 kg) for 17 weeks. Patients, caregivers, investigators (including those analysing data), trial staff, and the sponsor (other than the investigational product manager) were masked to treatment allocation. The primary efficacy endpoint was percentage change in median 28-day major motor seizure frequency from the baseline period to the 17-week double-blind phase and was analysed (using a Wilcoxon-rank sum test) in all patients who received at least one dose of trial treatment and for whom baseline data were available. Safety (compared descriptively across groups) was analysed in all patients who received at least one dose of trial treatment. This study is registered with ClinicalTrials.gov, NCT03572933, and the open-label extension phase is ongoing. FINDINGS: Between June 25, 2018, and July 2, 2020, 114 patients were screened for eligibility, of whom 101 (median age 6 years [IQR 3 to 10]) were randomly assigned to receive either ganaxolone (n=50) or placebo (n=51). All patients received at least one dose of a study drug, but seizure frequency for one patient in the ganaxolone group was not recorded at baseline and so the primary endpoint was analysed in a population of 100 patients. There was a median percentage change in 28-day major motor seizure frequency of -30·7% (IQR -49·5 to -1·9) in the ganaxolone group and of -6·9% (-24·1 to 39·7) in the placebo group (p=0·0036). The Hodges-Lehmann estimate of median difference in responses to ganaxolone versus placebo was -27·1% (95% CI -47·9 to - 9·6). Treatment-emergent adverse events occurred in 43 (86%) of 50 patients in the ganaxolone group and in 45 (88%) of 51 patients in the placebo group. Somnolence, pyrexia, and upper respiratory tract infections occurred in at least 10% of patients in the ganaxolone group and more frequently than in the placebo group. Serious adverse events occurred in six (12%) patients in the ganaxolone group and in five (10%) patients in the placebo group. Two (4%) patients in the ganaxolone group and four (8%) patients in the placebo group discontinued the trial. There were no deaths in the double-blind phase. INTERPRETATION: Ganaxolone significantly reduced the frequency of CDD-associated seizures compared with placebo and was generally well tolerated. Results from what is, to our knowledge, the first controlled trial in CDD suggest a potential treatment benefit for ganaxolone. Long-term treatment is being assessed in the ongoing open-label extension phase of this trial. FUNDING: Marinus Pharmaceuticals
Synergistic malaria vaccine combinations identified by systematic antigen screening.
A highly effective vaccine would be a valuable weapon in the drive toward malaria elimination. No such vaccine currently exists, and only a handful of the hundreds of potential candidates in the parasite genome have been evaluated. In this study, we systematically evaluated 29 antigens likely to be involved in erythrocyte invasion, an essential developmental stage during which the malaria parasite is vulnerable to antibody-mediated inhibition. Testing antigens alone and in combination identified several strain-transcending targets that had synergistic combinatorial effects in vitro, while studies in an endemic population revealed that combinations of the same antigens were associated with protection from febrile malaria. Video microscopy established that the most effective combinations targeted multiple discrete stages of invasion, suggesting a mechanistic explanation for synergy. Overall, this study both identifies specific antigen combinations for high-priority clinical testing and establishes a generalizable approach that is more likely to produce effective vaccines
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