797 research outputs found
Covid 19: Impacts on teaching, learning and progression for A Levels in Mathematics.
We report on ways that teaching and learning for mathematics A Levels, studied pre-university in England (by students aged 16-18), was disrupted by Covid19 in Summer 2020. Findings are contextualised within teacher and student accounts of the aspirational and time-pressured nature of these reformed qualifications. We explore the nature of engagement with mathematics achieved by year 12 and 13 students during lockdown, and the preparedness of 2019-20 year 11 and 13 students for progression into A Level/Higher Education respectively. Our findings derive from the third year of a four-year study (2017/18 to 2020/21) exploring enactment and impact of reformed mathematics A Levels, and efficacy of associated Pearson resources and assessments. Research tools were adapted to focus on impacts of Covid19. We present a snapshot (March to July 2020), of teachers and students looking to the future in a time of uncertainty and rapid change
‘Hard to focus, difficult to learn’: Covid19 Impacts on teaching, learning and progression for A Levels in Mathematics
We explore year 13 (age 17-18) student accounts of how Covid19 has impacted their learning for pre-university mathematics qualifications in England. Findings derive from the final year of a four-year study (2017/18 to 2020/21) exploring enactment and impact of reformed mathematics ‘A Levels’, and efficacy of associated Pearson resources and assessments. Research tools were adapted to focus on impacts of Covid19. In this cohort’s first year of A level (2019/20), teaching and learning was severely disrupted. Teachers anticipated significant, wide-ranging learning gaps as students progressed to year 13. Using data from Autumn 2020 and Spring 2021 we analyse student accounts of how continued disruptions to teaching and learning have impacted them. Variable access to teachers, barriers to collaborative work, and challenges of remote or reduced contact working have resulted in reduced depth and breadth of learning. Additionally, many students reported negative impacts on mathematical confidence and wider mental health
Teaching and learning for ‘moving goal-posts’: reformed A Levels in mathematics
Reformed English pre-university mathematics ‘A levels’ feature enhanced content and renewed focus on mathematical reasoning and problem solving. Related assessments, at scale from 2019, had negligible piloting, and preparation time for resources and teaching was pressured, with teachers/assessors typically having little experience of teaching/assessing for the renewed foci. We used an institutional ethnographic lens to study the first 3 years’ enactment from the leading awarding organisation, and impact on students’ learning, affect and pathways. We followed students and teachers in a fairly representative sample of 46 classes, drawing on termly data collection. Initial ‘specimen assessments’ were largely considered valid and accessible; however, we evidence insecurity due to perceptions of ‘moving goal posts’. Early final assessments were perceived as significantly more demanding than predecessor comparators and of limited reliability for many students. We analyse contribution to knowledge around introduction of curriculum aspirations at this level and discuss ways to address identified challenges
Stochastic theory of large-scale enzyme-reaction networks: Finite copy number corrections to rate equation models
Chemical reactions inside cells occur in compartment volumes in the range of
atto- to femtolitres. Physiological concentrations realized in such small
volumes imply low copy numbers of interacting molecules with the consequence of
considerable fluctuations in the concentrations. In contrast, rate equation
models are based on the implicit assumption of infinitely large numbers of
interacting molecules, or equivalently, that reactions occur in infinite
volumes at constant macroscopic concentrations. In this article we compute the
finite-volume corrections (or equivalently the finite copy number corrections)
to the solutions of the rate equations for chemical reaction networks composed
of arbitrarily large numbers of enzyme-catalyzed reactions which are confined
inside a small sub-cellular compartment. This is achieved by applying a
mesoscopic version of the quasi-steady state assumption to the exact
Fokker-Planck equation associated with the Poisson Representation of the
chemical master equation. The procedure yields impressively simple and compact
expressions for the finite-volume corrections. We prove that the predictions of
the rate equations will always underestimate the actual steady-state substrate
concentrations for an enzyme-reaction network confined in a small volume. In
particular we show that the finite-volume corrections increase with decreasing
sub-cellular volume, decreasing Michaelis-Menten constants and increasing
enzyme saturation. The magnitude of the corrections depends sensitively on the
topology of the network. The predictions of the theory are shown to be in
excellent agreement with stochastic simulations for two types of networks
typically associated with protein methylation and metabolism.Comment: 13 pages, 4 figures; published in The Journal of Chemical Physic
Connective tissue disease-associated interstitial lung disease
BACKGROUND:
Connective tissue diseases (CTD) are frequently associated with interstitial lung disease (ILD), significantly impacting their morbidity and mortality.
AIM:
Analyze the experience of an autoimmune specialized unit on treating CTD-ILD and characterize the population based on most frequent diseases, imaging patterns, lung function tests results, serology and treatment. Assess mortality and mortality predictors in these patients.
METHODS:
Retrospective, descriptive and statistical analysis of the CTD-ILD patients followed up at an autoimmune diseases unit during a 6-year period.
RESULTS:
Over the study period, 75 patients with CTD-ILD were treated with a mean follow-up of 49 ± 31 months. The most frequent CTD were systemic sclerosis and rheumatoid arthritis. ILD was diagnosed prior to CTD in 8% of patients and concomitantly in 35%. Nonspecific interstitial pneumonia was the CT pattern in 60% and 35% had an isolated diminished DLCO on lung function tests. Pulmonary hypertension was present in 12% and it was the single most important mortality predictor (OR 14.41, p = 0.006). Corticosteroids are the mainstay of treatment but biologics were prescribed in 39% of the patients (mostly tocilizumab and rituximab). Two scleroderma patients were recently treated with nintedanib.
CONCLUSIONS:
ILD is a potential complication of every CTD and can impose a dramatic burden on these patients. The clinical relevance of ILD together with their early expression in the course of the disease underlines the importance of the presence of chest physicians in these units.info:eu-repo/semantics/publishedVersio
Effects of bursty protein production on the noisy oscillatory properties of downstream pathways
Experiments show that proteins are translated in sharp bursts; similar bursty phenomena have been observed for protein import into compartments. Here we investigate the effect of burstiness in protein expression and import on the stochastic properties of downstream pathways. We consider two identical pathways with equal mean input rates, except in one pathway proteins are input one at a time and in the other proteins are input in bursts. Deterministically the dynamics of these two pathways are indistinguishable. However the stochastic behavior falls in three categories: (i) both pathways display or do not display noise-induced oscillations; (ii) the non-bursty input pathway displays noise-induced oscillations whereas the bursty one does not; (iii) the reverse of (ii). We derive necessary conditions for these three cases to classify systems involving autocatalysis, trimerization and genetic feedback loops. Our results suggest that single cell rhythms can be controlled by regulation of burstiness in protein production
Connective tissue disease-associated interstitial lung disease
Background: Connective tissue diseases (CTD) are frequently associated with interstitial lung disease (ILD), significantly impacting their morbidity and mortality. Aim: Analyze the experience of an autoimmune specialized unit on treating CTD-ILD and characterize the population based on most frequent diseases, imaging patterns, lung function tests results, serology and treatment. Assess mortality and mortality predictors in these patients. Methods: Retrospective, descriptive and statistical analysis of the CTD-ILD patients followed up at an autoimmune diseases unit during a 6-year period. Results: Over the study period, 75 patients with CTD-ILD were treated with a mean follow-up of 49 ± 31 months. The most frequent CTD were systemic sclerosis and rheumatoid arthritis. ILD was diagnosed prior to CTD in 8% of patients and concomitantly in 35%. Nonspecific interstitial pneumonia was the CT pattern in 60% and 35% had an isolated diminished DLCO on lung function tests. Pulmonary hypertension was present in 12% and it was the single most important mortality predictor (OR 14.41, p = 0.006). Corticosteroids are the mainstay of treatment but biologics were prescribed in 39% of the patients (mostly tocilizumab and rituximab). Two scleroderma patients were recently treated with nintedanib. Conclusions: ILD is a potential complication of every CTD and can impose a dramatic burden on these patients. The clinical relevance of ILD together with their early expression in the course of the disease underlines the importance of the presence of chest physicians in these units.publishersversionpublishe
Directed cell migration in the presence of obstacles
BACKGROUND: Chemotactic movement is a common feature of many cells and microscopic organisms. In vivo, chemotactic cells have to follow a chemotactic gradient and simultaneously avoid the numerous obstacles present in their migratory path towards the chemotactic source. It is not clear how cells detect and avoid obstacles, in particular whether they need a specialized biological mechanism to do so. RESULTS: We propose that cells can sense the presence of obstacles and avoid them because obstacles interfere with the chemical field. We build a model to test this hypothesis and find that this naturally enables efficient at-a-distance sensing to be achieved with no need for a specific and active obstacle-sensing mechanism. We find that (i) the efficiency of obstacle avoidance depends strongly on whether the chemotactic chemical reacts or remains unabsorbed at the obstacle surface. In particular, it is found that chemotactic cells generally avoid absorbing barriers much more easily than non-absorbing ones. (ii) The typically low noise in a cell's motion hinders the ability to avoid obstacles. We also derive an expression estimating the typical distance traveled by chemotactic cells in a 3D random distribution of obstacles before capture; this is a measure of the distance over which chemotaxis is viable as a means of directing cells from one point to another in vivo. CONCLUSION: Chemotactic cells, in many cases, can avoid obstacles by simply following the spatially perturbed chemical gradients around obstacles. It is thus unlikely that they have developed specialized mechanisms to cope with environments having low to moderate concentrations of obstacles
Gangrena de Fournier numa Mulher
A fasceÃte necrotizante dos tecidos infra-diafragmáticos (gangrena de Fournier) é uma
grave infecção sinergÃstica por agentes aeróbicos/anaeróbicos, com uma evolução
clÃnica súbita e rápida de gangrena da fascia e sepsis generalizada, associada a elevada mortalidade. Trata-se de uma emergência médico-cirúrgica necessitando de tratamento intensivo englobando a correcção das anomalias hemodinâmicas, hidroelectrolÃ-
ticas e metabólicas, antibioterapia dupla/tripla de largo espectro por via endovenosa, desbridamento cirúrgico agressivo do tecido necrótico infectado e correcção da determinante etiológica da gangrena. É frequente encontrar como factores de risco a diabetes mellitus, doença crónica hepática, doenças malignas, doenças imunológicas congénitas ou adquiridas, tratamento com fármacos imuno-supressores, alcoolismo crónico e má nutrição. As fontes infecciosas originais conducentes a uma gangrena de Fournier são geralmente abcessos da área peri-anal ou processos infecciosos genitourológicos. Embora a gangrena de Fournier seja muito menos frequente na mulher que no homem, é importante pensar nesse diagnóstico, de forma a proporcionar às doentes a possibilidade de tratamento com sucesso. Descreve-se o caso de uma gangrena de
Fournier, determinada porumabscesso da fossa Ãsquio-rectal, numa mulher diabética e
em tratamento de um penfigus vulgaris com fármacos imuno-supressores, com evolução fatal, possivelmente em resultado de diagnóstico e tratamento tardios
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