Feedback or feedforward: Supporting students with alternate or missing conceptions in chemistry as they transition into tertiary chemistry

Constructivist learning environments are most effective when the learner and teacher are both aware of the existing conceptual models that learners possess to enable them to extend and apply their understanding rather than resort to rote learning (Taber, 2001). As students transition into, and engage in, the new tertiary learning environment it is important to assist them to maximise the effectiveness of their learning which requires measurement or diagnosis of their existing conceptual understanding. One of the challenges in teaching chemistry is to encourage students to recognise their existing knowledge and conceptual understanding and then apply it in new learning situations (Schraw, Crippen, & Hartley, 2006). Feedback is particularly important for first-year students because they are coming to terms with the change of environment, expectations, teaching approaches and forms of assessment. In this context, Hattie and Timperley’s three questions (Hattie & Timerley, 2007) are particularly relevant: “Where am I going?”, “How am I going?” and “Where to next?” Formative assessment is critical to “How am I going?” and the feedback is just as valuable for the instructor as for the students to support student learning. REFERENCES Hattie, J., & Timperley, H. (2007). The Power of Feedback. Review of Educational Research. 77, 81-112. Schraw, G., Crippen, K. J., & Hartley, K. (2006). Promoting self-regulation in science education: Metacognition as part of a broader persepective on learning. Research in Science Education. 36, 111-39. Taber, K. S. (2001). The mismatch between assumed prior knowledge and the Learner’s conceptions: A typology of learning impediments. Educational Studies, 27, 159-71

Safety, pharmacokinetics and exploratory pro-cognitive effects of HTL0018318, a selective M1 receptor agonist, in healthy younger adult and elderly subjects: a multiple ascending dose study.

Funder: Sosei HeptaresBACKGROUND: The cholinergic system and M1 receptor remain an important target for symptomatic treatment of cognitive dysfunction. The selective M1 receptor partial agonist HTL0018318 is under development for the symptomatic treatment of Dementia's including Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). We investigated the safety, tolerability, pharmacokinetics and exploratory pharmacodynamics of multiple doses of HTL0018318 in healthy younger adults and elderly subjects. METHODS: This randomised, double blind, placebo-controlled study was performed, investigating oral doses of 15-35 mg/day HTL0018318 or placebo in 7 cohorts of healthy younger adult (n = 36; 3 cohorts) and elderly (n = 50; 4 cohorts) subjects. Safety, tolerability and pharmacokinetic measurements were performed. Pharmacodynamics were assessed using a battery of neurocognitive tasks and electrophysiological biomarkers of synaptic and cognitive functions. RESULTS: HTL0018318 was generally well-tolerated in multiple doses up to 35 mg/day and were associated with mild or moderate cholinergic adverse events. There were modest increases in blood pressure and pulse rate when compared to placebo-treated subjects, with tendency for the blood pressure increase to attenuate with repeated dosing. There were no clinically significant observations or changes in blood and urine laboratory measures of safety or abnormalities in the ECGs and 24-h Holter assessments. HTL0018318 plasma exposure was dose-proportional over the range 15-35 mg. Maximum plasma concentrations were achieved after 1-2 h. The apparent terminal half-life of HTL0018318 was 16.1 h (± 4.61) in younger adult subjects and 14.3 h (± 2.78) in elderly subjects at steady state. HTL0018318 over the 10 days of treatment had significant effects on tests of short-term (working) memory (n-back) and learning (Milner maze) with moderate to large effect sizes. CONCLUSION: Multiple doses of HTL0018138 showed well-characterised pharmacokinetics and were safe and generally well-tolerated in the dose range studied. Pro-cognitive effects on short-term memory and learning were demonstrated across the dose range. These data provide encouraging data in support of the development of HTL0018138 for cognitive dysfunction in AD and DLB. TRIAL REGISTRATION: Netherlands Trial Register identifier NTR5781 . Registered on 22 March 2016

Safety, pharmacokinetics and pharmacodynamics of HTL0009936, a selective muscarinic M1 -acetylcholine receptor agonist: A randomized cross-over trial.

AIMS: HTL0009936 is a selective M1 muscarinic receptor agonist in development for cognitive dysfunction in Alzheimer's disease. Safety, tolerability and pharmacokinetics and exploratory pharmacodynamic effects of HTL0009936 administered by continuous IV infusion at steady state were investigated in elderly subjects with below average cognitive functioning (BACF). METHODS: Part A was a four-treatment open label sequential study in healthy elderly investigating 10-83 mg HTL0009936 (IV) and a 24 mg HTL0009936 single oral dose. Part B was a five-treatment randomized, double-blind, placebo and physostigmine controlled cross-over study with IV HTL0009936 in elderly subjects with BACF. Pharmacodynamic assessments were performed using neurocognitive and electrophysiological tests. RESULTS: Pharmacokinetics of HTL0009936 showed dose-proportional increases in exposure with a mean half-life of 2.4 hours. HTL0009936 was well-tolerated with transient dose-related adverse events (AEs). Small increases in mean systolic blood pressure of 7.12 mmHg (95% CI [3.99-10.24]) and in diastolic of 5.32 mmHg (95% CI [3.18-7.47]) were noted at the highest dose in part B. Overall, there was suggestive, but no definitive, positive or negative pharmacodynamic effects. Statistically significant effects were observed on P300 with HTL0009936 and adaptive tracking with physostigmine. CONCLUSIONS: HTL0009936 showed well-characterized pharmacokinetics and single doses were safe and generally well-tolerated in healthy elderly subjects. Due to physostigmine tolerability issues and subject burden, the study design was changed and some pharmacodynamic assessments (neurocognitive) were performed at suboptimal drug exposures. Therefore no clear conclusions can be made on pharmacodynamic effects of HTL0009936, although an effect on P300 is suggestive of central target engagement

A phase 1b/2a multicenter study of the safety and preliminary pharmacodynamic effects of selective muscarinic M1 receptor agonist HTL0018318 in patients with mild-to-moderate Alzheimer's disease.

Funder: Allergan Incorporated (now AbbVie)INTRODUCTION: This study examined the safety and pharmacodynamic effects of selective muscarinic M1 receptor orthosteric agonist HTL0018318 in 60 patients with mild-to-moderate Alzheimer's disease (AD) on background donepezil 10 mg/day. METHODS: A randomized, double-blind, placebo-controlled 4-week safety study of HTL0018318 with up-titration and maintenance phases, observing exploratory effects on electrophysiological biomarkers and cognition. RESULTS: Treatment-emergent adverse events (TEAEs) were mild and less frequently reported during maintenance versus titration. Headache was most commonly reported (7-21%); 0 to 13% reported cholinergic TEAEs (abdominal pain, diarrhea, fatigue, nausea) and two patients discontinued due to TEAEs. At 1 to 2 hours post-dose, HTL0018318-related mean maximum elevations in systolic and diastolic blood pressure of 5 to 10 mmHg above placebo were observed during up-titration but not maintenance. Postive effects of HTL0018318 were found on specific attention and memory endpoints. DISCUSSION: HTL0018318 was well tolerated in mild-to-moderate AD patients and showed positive effects on attention and episodic memory on top of therapeutic doses of donepezil

Safety, immunogenicity, and reactogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines given as fourth-dose boosters following two doses of ChAdOx1 nCoV-19 or BNT162b2 and a third dose of BNT162b2 (COV-BOOST): a multicentre, blinded, phase 2, randomised trial

Background Some high-income countries have deployed fourth doses of COVID-19 vaccines, but the clinical need, effectiveness, timing, and dose of a fourth dose remain uncertain. We aimed to investigate the safety, reactogenicity, and immunogenicity of fourth-dose boosters against COVID-19.Methods The COV-BOOST trial is a multicentre, blinded, phase 2, randomised controlled trial of seven COVID-19 vaccines given as third-dose boosters at 18 sites in the UK. This sub-study enrolled participants who had received BNT162b2 (Pfizer-BioNTech) as their third dose in COV-BOOST and randomly assigned them (1:1) to receive a fourth dose of either BNT162b2 (30 µg in 0·30 mL; full dose) or mRNA-1273 (Moderna; 50 µg in 0·25 mL; half dose) via intramuscular injection into the upper arm. The computer-generated randomisation list was created by the study statisticians with random block sizes of two or four. Participants and all study staff not delivering the vaccines were masked to treatment allocation. The coprimary outcomes were safety and reactogenicity, and immunogenicity (antispike protein IgG titres by ELISA and cellular immune response by ELISpot). We compared immunogenicity at 28 days after the third dose versus 14 days after the fourth dose and at day 0 versus day 14 relative to the fourth dose. Safety and reactogenicity were assessed in the per-protocol population, which comprised all participants who received a fourth-dose booster regardless of their SARS-CoV-2 serostatus. Immunogenicity was primarily analysed in a modified intention-to-treat population comprising seronegative participants who had received a fourth-dose booster and had available endpoint data. This trial is registered with ISRCTN, 73765130, and is ongoing.Findings Between Jan 11 and Jan 25, 2022, 166 participants were screened, randomly assigned, and received either full-dose BNT162b2 (n=83) or half-dose mRNA-1273 (n=83) as a fourth dose. The median age of these participants was 70·1 years (IQR 51·6–77·5) and 86 (52%) of 166 participants were female and 80 (48%) were male. The median interval between the third and fourth doses was 208·5 days (IQR 203·3–214·8). Pain was the most common local solicited adverse event and fatigue was the most common systemic solicited adverse event after BNT162b2 or mRNA-1273 booster doses. None of three serious adverse events reported after a fourth dose with BNT162b2 were related to the study vaccine. In the BNT162b2 group, geometric mean anti-spike protein IgG concentration at day 28 after the third dose was 23 325 ELISA laboratory units (ELU)/mL (95% CI 20 030–27 162), which increased to 37 460 ELU/mL (31 996–43 857) at day 14 after the fourth dose, representing a significant fold change (geometric mean 1·59, 95% CI 1·41–1·78). There was a significant increase in geometric mean anti-spike protein IgG concentration from 28 days after the third dose (25 317 ELU/mL, 95% CI 20 996–30 528) to 14 days after a fourth dose of mRNA-1273 (54 936 ELU/mL, 46 826–64 452), with a geometric mean fold change of 2·19 (1·90–2·52). The fold changes in anti-spike protein IgG titres from before (day 0) to after (day 14) the fourth dose were 12·19 (95% CI 10·37–14·32) and 15·90 (12·92–19·58) in the BNT162b2 and mRNA-1273 groups, respectively. T-cell responses were also boosted after the fourth dose (eg, the fold changes for the wild-type variant from before to after the fourth dose were 7·32 [95% CI 3·24–16·54] in the BNT162b2 group and 6·22 [3·90–9·92] in the mRNA-1273 group).Interpretation Fourth-dose COVID-19 mRNA booster vaccines are well tolerated and boost cellular and humoral immunity. Peak responses after the fourth dose were similar to, and possibly better than, peak responses after the third dose

Fracture toughness of femoral head cancellous bone material in relation to noninvasive bone assessment measurements

There have been a number of studies relating the biomechanical properties of human bone cancellous and cortical (mainly stiffness and strength) to quantitative non-invasive ultrasound (QUS). The best correlations are obtained when mechanical tests are compared vs. contact QUS in-vitro. Few studies attempted to relate noninvasive QUS on cadavers against excised material of the same donors. This study aims to assess the fracture toughness, in addition to stiffness and strength, of cancellous femoral head bone of donors that have gone QUS investigations in-vivo. Both the in-vivo aspect and the toughness measurements of bone are elements that have never been examined before.Heads of femurs were collected from osteoporotic and osteoarthritic patients. QUS was performed by 2 different peripheral scanners on 4 different sites. Disc and bar-shaped samples were prepared from the femoral heads to material standards for fracture toughness measurements. The densities of samples have been measured to allow minimization of scatter due to varying density. The bar specimens were broken in 3-point bending and the disc shaped one in tension, in both the crack mouth opening displacement was measured. The aim of the study was to investigate whether reliable toughness measurements can be made on cancellous bone (a material capable of large elastoplastic deformations), their dependence on trabecular type and architecture, sample density and the relationship to QUS in-vivo. Such data is currently lacking in the literature

Closing the loop: A model for inter-institutional collaboration through delivering formative assessment in large, first-year STEM classes

When students start their tertiary studies they move into a new world which differs in many ways from their prior experiences, including the way they were taught, access to faculty, learning environments, class sizes, expectations of independence and time management (Torenbeek, 2011). The first year experience (FYE) has become a pivotal focus for institutional programs that recognize that many students struggle in this transition. Such programs aim to improve student retention in tertiary studies through provision of orientation and mentaring activities. These initiatives have become widespread and are typically informed by key research in the field in terms of transition pedagogies (Kift, 2009; Kift, 2010; Lawrence, 2005) and student engagement and retention

Closing the loop: a model for inter-institutional collaboration through delivering formative assessment in large, first-year STEM classes

When students start their tertiary studies they move into a new world which differs in many ways from their prior experiences, including the way they were taught, access to faculty, learning environments, class sizes, expectations of independence and time management (Torenbeek, 2011). The first year experience (FYE) has become a pivotal focus for institutional programs that recognize that many students struggle in this transition. Such programs aim to improve student retention in tertiary studies through provision of orientation and mentoring activities. These initiatives have become widespread and are typically informed by key research in the field in terms of transition pedagogies (Kift, 2009; Kift, 2010; Lawrence, 2005) and student engagement and retention (Kuh, 2008; Carini, 2006; Tinto, 1987; Tinto, 2005)