Identifying a gender-inclusive pedagogy from Maltese science teachers' personal practical knowledge

Teachers bring with them into the science classrooms their own gendered identitities and their views and perceptions about how boys and girls learn and achieve in science. This paper tries to explore the way in which fourteen Maltese science teachers use their own 'personal practical knowledge' to identify their views about gender and science and create their own individual gender-inclusive pedagogy. The study suggests that the science teachers focus more on the individuality of students and on the social and cultural background of the students in their classrooms rather than on gender. The teachers try to develop pedagogies and assessment practices which take into consideration the personal constructs of individual learners. The ideas for such a gender-inclusive pedagogy emerge from their common-sense experience in the classroom, their training as teachers and are closely interrelated to current ideas of social constructivism

Study of Dipole Resonance Strength in 12-C via the Reactions 12-C(pol.p,p'c)

This research was sponsored by the National Science Foundation Grant NSF PHY-931478

Irreversible Processes in Inflationary Cosmological Models

By using the thermodynamic theory of irreversible processes and Einstein general relativity, a cosmological model is proposed where the early universe is considered as a mixture of a scalar field with a matter field. The scalar field refers to the inflaton while the matter field to the classical particles. The irreversibility is related to a particle production process at the expense of the gravitational energy and of the inflaton energy. The particle production process is represented by a non-equilibrium pressure in the energy-momentum tensor. The non-equilibrium pressure is proportional to the Hubble parameter and its proportionality factor is identified with the coefficient of bulk viscosity. The dynamic equations of the inflaton and the Einstein field equations determine the time evolution of the cosmic scale factor, the Hubble parameter, the acceleration and of the energy densities of the inflaton and matter. Among other results it is shown that in some regimes the acceleration is positive which simulates an inflation. Moreover, the acceleration decreases and tends to zero in the instant of time where the energy density of matter attains its maximum value.Comment: 13 pages, 2 figures, to appear in PR

Physiological trend analysis of a novel cardio-pulmonary model during a preload reduction manoeuvre

peer reviewedBackground and objective: Mechanical ventilation causes adverse effects on the cardiovascular system. However, the exact nature of the effects on haemodynamic parameters is not fully understood. A recently developed cardio-vascular system model which incorporates cardio-pulmonary interactions is compared to the original 3-chamber cardiovascular model to investigate the exact effects of mechanical ventilation on haemodynamic parameters and to assess the trade-off of model complexity and model reliability between the 2 models. Methods: Both the cardio-pulmonary and three chamber models are used to identify cardiovascular system parameters from aortic pressure, left ventricular volume, airway flow and airway pressure measurements from 4 pigs during a preload reduction manoeuvre. Outputs and parameter estimations from both models are contrasted to assess the relative performance of each model and to further investigate the effects of mechanical ventilation on haemodynamic parameters. Results: Both models tracked measurements accurately as expected. There was no identifiable increase in error from the added complexity of the cardio-pulmonary model, with both models having a mean average error below 0.5% for all pigs. Identified left ventricle and vena cava elastances of the 3-chamber model was found to diverge exponentially with PEEP from identified left ventricle and vena cava elastances of the cardio-pulmonary model. The r2 of the fit for each pig ranged from 0.888 to 0.998 for left ventricle elastance divergence and from 0.905 to 0.999 for vena cava elastance divergence. All other identified parameters showed no significant difference between models. Conclusions: Despite the increase in model complexity, there was no loss in the cardio-pulmonary model's ability to accurately estimate haemodynamic parameters and reproduce system dynamics. Furthermore, the cardio-pulmonary model was able to demonstrate how mechanical ventilation affected parameter estimations as PEEP was increased. The 3-chamber model was shown to produce parameter estimations which diverged exponentially with PEEP, while the cardiopulmonary model estimations remained more stable, suggesting its ability to produce more physiologically accurate parameter estimations under higher PEEP conditions. © 202

Dihydrobenz[e][1,4]oxazepin-2(3H)-ones, a new anthelmintic chemotype immobilising whipworm and reducing infectivity in vivo.

Trichuris trichiura is a human parasitic whipworm infecting around 500 million people globally, damaging the physical growth and educational performance of those infected. Current drug treatment options are limited and lack efficacy against the worm, preventing an eradication programme. It is therefore important to develop new treatments for trichuriasis. Using Trichuris muris, an established model for T. trichiura, we screened a library of 480 novel drug-like small molecules for compounds causing paralysis of the ex vivo adult parasite. We identified a class of dihydrobenz[e][1,4]oxazepin-2(3H)-one compounds with anthelmintic activity against T. muris. Further screening of structurally related compounds and resynthesis of the most potent molecules led to the identification of 20 active dihydrobenzoxazepinones, a class of molecule not previously implicated in nematode control. The most active immobilise adult T. muris with EC50 values around 25–50μM, comparable to the existing anthelmintic levamisole. The best compounds from this chemotype show low cytotoxicity against murine gut epithelial cells, demonstrating selectivity for the parasite. Developing a novel oral pharmaceutical treatment for a neglected disease and deploying it via mass drug administration is challenging. Interestingly, the dihydrobenzoxazepinone OX02983 reduces the ability of embryonated T. muris eggs to establish infection in the mouse host in vivo. Complementing the potential development of dihydrobenzoxazepinones as an oral anthelmintic, this supports an alternative strategy of developing a therapeutic that acts in the environment, perhaps via a spray, to interrupt the parasite lifecycle. Together these results show that the dihydrobenzoxazepinones are a new class of anthelmintic, active against both egg and adult stages of Trichuris parasites. They demonstrate encouraging selectivity for the parasite, and importantly show considerable scope for further optimisation to improve potency and pharmacokinetic properties with the aim of developing a clinical agent

Isospin Response of the 4-He Continuum

This research was sponsored by the National Science Foundation Grant NSF PHY-931478

Tube-load model: A clinically applicable pulse contour analysis method for estimation of cardiac stroke volume

peer reviewedBackground and Objectives: Accurate, reproducible, and reliable real-time clinical measurement of stroke volume (SV) is challenging. To accurately estimate arterial mechanics and SV by pulse contour analysis, accounting for wave reflection, such as by a tube-load model, is potentially important. This study tests for the first time whether a dynamically identified tube-load model, given a single peripheral arterial input signal and pulse transit time (PTT), provides accurate SV estimates during hemodynamic instability. Methods: The model is tested for 5 pigs during hemodynamic interventions, using either an aortic flow probe or admittance catheter for a validation SV measure. Performance is assessed using Bland-Altman and polar plot analysis for a series of long-term state-change and short-term dynamic events. Results:The overall median bias and limits of agreement (2.5th, 97.5th percentile) from Bland-Altman analysis were -10% [-49, 36], and -1% [-28,20] for state-change and dynamic events, respectively. The angular limit of agreement (maximum of 2.5th, 97.5th percentile) from polar-plot analysis for state-change and dynamic interventions was 35.6∘, and 35.2∘, respectively. Conclusion: SV estimation agreement and trending performance was reasonable given the severity of the interventions. This simple yet robust method has potential to track SV within acceptable limits during hemodynamic instability in critically ill patients, provided a sufficiently accurate PTT measure. © 2021 Elsevier B.V

2,4-Diaminothieno[3,2-d]pyrimidines, a new class of anthelmintic with activity against adult and egg stages of whipworm

The human whipworm Trichuris trichiura is a parasite that infects around 500 million people globally, with consequences including damage to physical growth and educational performance. Current drugs such as mebendazole have a notable lack of efficacy against whipworm, compared to other soil-transmitted helminths. Mass drug administration programs are therefore unlikely to achieve eradication and new treatments for trichuriasis are desperately needed. All current drug control strategies focus on post-infection eradication, targeting the parasite in vivo. Here we propose developing novel anthelmintics which target the egg stage of the parasite in the soil as an adjunct environmental strategy. As evidence in support of such an approach we describe the actions of a new class of anthelmintic compounds, the 2,4-diaminothieno[3,2-d]pyrimidines (DATPs). This compound class has found broad utility in medicinal chemistry, but has not previously been described as having anthelmintic activity. Importantly, these compounds show efficacy against not only the adult parasite, but also both the embryonated and unembryonated egg stages and thereby may enable a break in the parasite lifecycle

Dysfunctional Dopaminergic Neurones in Mouse Models of Huntington's Disease: A Role for SK3 Channels

Background: Huntington's disease (HD) is a late-onset fatal neurodegenerative disorder caused by a CAG trinucleotide repeat expansion in the gene coding for the protein huntingtin and is characterised by progressive motor, psychiatric and cognitive decline. We previously demonstrated that normal synaptic function in HD could be restored by application of dopamine receptor agonists, suggesting that changes in the release or bioavailability of dopamine may be a contributing factor to the disease process. Objective: In the present study, we examined the properties of midbrain dopaminergic neurones and dopamine release in presymptomatic and symptomatic transgenic HD mice. Methods and Results:Using intracellular sharp recordings and immunohistochemistry, we found that neuronal excitability was increased due to a loss of slow afterhyperpolarisation and that these changes were related to an apparent functional loss and abnormal distribution of SK3 channels (KCa2.3 encoded by the KCNN3 gene), a class of small-conductance calcium-activated potassium channels. Electrochemical detection of dopamine showed that this observation was associated with an enhanced dopamine release in presymptomatic transgenic mice and a drastic reduction in symptomatic animals. These changes occurred in the context of a progressive expansion in the CAG repeat number and nuclear localisation of mutant protein within the substantia nigra pars compacta. Conclusions: Dopaminergic neuronal dysfunction is a key early event in HD disease progression. The initial increase in dopamine release appears to be related to a loss of SK3 channel function, a protein containing a polyglutamine tract. Implications for polyglutamine-mediated sequestration of SK3 channels, dopamine-associated DNA damage and CAG expansion are discussed in the context of HD.</br

Tasmanian devil CD28 and CTLA4 capture CD80 and CD86 from adjacent cells

Immune checkpoint immunotherapy is a pillar of human oncology treatment with potential for non-human species. The first checkpoint immunotherapy approved for human cancers targeted the CTLA4 protein. CTLA4 can inhibit T cell activation by capturing and internalizing CD80 and CD86 from antigen presenting cells, a process called trans-endocytosis. Similarly, CD28 can capture CD80 and CD86 via trogocytosis and retain the captured ligands on the surface of the CD28-expressing cells. The wild Tasmanian devil (Sarcophilus harrisii) population has declined by 77% due to transmissible cancers that evade immune defenses despite genetic mismatches between the host and tumors. We used a live cell-based assay to demonstrate that devil CTLA4 and CD28 can capture CD80 and CD86. Mutation of evolutionarily conserved motifs in CTLA4 altered functional interactions with CD80 and CD86 in accordance with patterns observed in other species. These results suggest that checkpoint immunotherapies can be translated to evolutionarily divergent species.</p