365 research outputs found
Screencasts: how effective are they and how do students engage with them?
The use of screencasts as an instructional technology is increasing rapidly in higher education. While there appears to be a consensus around studentsâ satisfaction with the provision of technology enhanced tools, there is limited evidence revolving around their impact in terms of knowledge acquisition. Moreover, the reasons why students choose to engage (or not) with these resources remain largely unreported. The study assessed the effect of using screencasts on undergraduate studentsâ understanding and engagement with learning material in one of their modules. Customised screencasts were used as optional additional learning and teaching resources. Grades obtained in a test module (with screencasts) and a control module (without screencasts) were compared to gauge the impact of screencasts on knowledge acquisition. Furthermore, the reasons for studentsâ engagement (or lack thereof) with the screencasts were explored using questionnaires. A modest but significant impact of screencasts on knowledge acquisition was found and studentsâ perception of the screencasts was overwhelmingly positive. Students suggested that screencasts should be kept short to summarise lectures or delve in-depth into complex concepts but should not replace whole lectures. Reasons for not using screencasts revolved around a lack of understanding of what the resources were but also a reported lack of fit between the nature of the tool and self-assessed learning style
Screencasts: how effective are they and how do students engage with them?
The use of screencasts as an instructional technology is increasing rapidly in higher education. While there appears to be a consensus around studentsâ satisfaction with the provision of technology enhanced tools, there is limited evidence revolving around their impact in terms of knowledge acquisition. Moreover, the reasons why students choose to engage (or not) with these resources remain largely unreported. The study assessed the effect of using screencasts on undergraduate studentsâ understanding and engagement with learning material in one of their modules. Customised screencasts were used as optional additional learning and teaching resources. Grades obtained in a test module (with screencasts) and a control module (without screencasts) were compared to gauge the impact of screencasts on knowledge acquisition. Furthermore, the reasons for studentsâ engagement (or lack thereof) with the screencasts were explored using questionnaires. A modest but significant impact of screencasts on knowledge acquisition was found and studentsâ perception of the screencasts was overwhelmingly positive. Students suggested that screencasts should be kept short to summarise lectures or delve in-depth into complex concepts but should not replace whole lectures. Reasons for not using screencasts revolved around a lack of understanding of what the resources were but also a reported lack of fit between the nature of the tool and self-assessed learning style
Continuous infusion of physostigmine in patients with perioperative septic shock: A pharmacokinetic/pharmacodynamic study with population pharmacokinetic modeling
Background
In the context of the cholinergic anti-inflammatory pathway, the clinical trial AnticholiumÂź per Se (EudraCT Number: 2012-001650-26, ClinicalTrials.gov NCT03013322) addressed the possibility of taking adjunctive physostigmine salicylate treatment in septic shock from bench to bedside. Pharmacokinetics (PK) are likely altered in critically ill patients; data on physostigmine PK and target concentrations are sparse, particularly for continuous infusion. Our objective was to build a population PK (popPK) model for physostigmine, and further evaluate pharmacodynamics (PD) and concentration-response relationship in this setting.
Methods
In the randomized, double-blind, placebo-controlled trial, 20 patients with perioperative septic shock either received an initial dose of 0.04âŻmg/kg physostigmine salicylate, followed by continuous infusion of 1âŻmg/h for up to 120âŻh, or equivalent volumes of 0.9% sodium chloride (placebo group). Physostigmine plasma concentrations and acetylcholinesterase (AChE) activity were measured; concentration-response associations were evaluated, and popPK and PD modeling was performed with NONMEM.
Results
Steady state physostigmine plasma concentrations reached 7.60âŻÂ±âŻ2.81âŻng/mL (meanâŻÂ±âŻstandard deviation [SD]). PK was best described by a two-compartment model with linear clearance. Significant covariate effects were detected for body weight and age on clearance, as well as a high inter-individual variability of the central volume of distribution. AChE activity was significantly reduced to 30.5%â50.6% of baseline activity during physostigmine salicylate infusion. A sigmoidal direct effect PD model best described enzyme inhibition by physostigmine, with an estimated half maximal effective concentration (EC50) of 5.99âŻng/mL.
Conclusions
PK of physostigmine in patients with septic shock displayed substantial inter-individual variability with body weight and age influencing the clearance. Physostigmine inhibited AChE activity with a sigmoidal concentration-response effect
T-cell epitope polymorphisms of the Plasmodium falciparum circumsporozoite protein among field isolates from Sierra Leone: age-dependent haplotype distribution?
<p>Abstract</p> <p>Background</p> <p>In the context of the development of a successful malaria vaccine, understanding the polymorphisms exhibited by malaria antigens in natural parasite populations is crucial for proper vaccine design. Recent observations have indicated that sequence polymorphisms in the C-terminal T-cell epitopes of the <it>Plasmodium falciparum </it>circumsporozoite protein (Pf<it>csp</it>) are rather low and apparently stable in low endemic areas. This study sought to assess the pattern in a malaria endemic setting in Africa, using samples from Freetown, Sierra Leone.</p> <p>Methods</p> <p>Filter-paper blood samples were collected from subjects at a teaching hospital in Freetown during SeptemberâOctober 2006 and in AprilâMay 2007. The C-terminal portion of the Pf<it>csp </it>gene spanning the Th2R and Th3R epitopes was amplified and directly sequenced; sequences were analysed with subject parameters and polymorphism patterns in Freetown were compared to that in other malaria endemic areas.</p> <p>Results and Discussion</p> <p>Overall, the genetic diversity in Freetown was high. From a total of 99 sequences, 42 haplotypes were identified with at least three accounting for 44.4% (44/99): the 3D7-type (19.2%), a novel type, P-01 (17.2%), and E12 (8.1%). Interestingly, all were unique to the African sub-region and there appeared to be predilection for certain haplotypes to distribute in certain age-groups: the 3D7 type was detected mainly in hospitalized children under 15 years of age, while the P-01 type was common in adult antenatal females (Pearson Chi-square = 48.750, degrees of freedom = 34, <it>P </it>= 0.049). In contrast, the single-haplotype predominance (proportion > 50%) pattern previously identified in Asia was not detected in Freetown.</p> <p>Conclusion</p> <p>Haplotype distribution of the T-cell epitopes of Pf<it>csp </it>in Freetown appeared to vary with age in the study population, and the polymorphism patterns were similar to that observed in neighbouring Gambia, but differed significantly at the sequence level from that observed in Asia. The findings further emphasize the role of local factors in generating polymorphisms in the T-cell epitopes of the <it>P. falciparum </it>circumsporozoite protein.</p
Effects of bromopride on the healing of left colon anastomoses of rats
Objetivo: Avaliar os efeitos da bromoprida sobre a formação de aderĂȘncias e a cicatrização de anastomoses de cĂłlon esquerdo de
ratos. MĂ©todos: Foram incluĂdos 40 ratos, divididos em dois grupos contendo 20 animais, para administração de bromoprida (grupo
de estudo- E) ou solução fisiológica (grupo controle- C). Cada grupo foi dividido em subgrupos contendo 10 animais cada, para
eutanåsia no terceiro (E3 e C3) ou no sétimo dia (E7 e C7) de pós-operatório. Os ratos foram submetidos à secção do cólon esquerdo
e anastomose tĂ©rmino-terminal. No dia da relaparotomia, foi avaliada a quantidade total de aderĂȘncias e removido um segmento
colÎnico contendo a anastomose para anålise histopatológica, da força de ruptura e da concentração de hidroxiprolina. Resultados:
NĂŁo houve diferença entre os grupos em relação Ă evolução clĂnica. Dois animais do grupo de estudo apresentaram deiscĂȘncia
de anastomose bloqueada. Os animais que receberam bromoprida apresentaram nĂșmero de aderĂȘncias intracavitĂĄrias e aderĂȘncias
Ă anastomose semelhantes ao grupo controle. As anastomoses dos animais do grupo E3 apresentaram menor resistĂȘncia de ruptura
do que as do grupo C3 (p=0,04). Este efeito não ocorreu no sétimo dia de pós-operatório (p=0,37). Não houve diferença significativa
entre os grupos em relação à histopatologia ou concentração de hidroxiprolina das anastomoses. Conclusão: O uso da bromoprida
estĂĄ associado Ă diminuição da resistĂȘncia tĂȘnsil de anastomoses do cĂłlon esquerdo de ratos no terceiro dia de pĂłs-operatĂłrio.Objective: To evaluate the effects of bromopride on the formation of adhesions and anastomotic healing in the left colon of rats.
Methods: We divided 40 rats into two groups of 20 animals, administration of bromopride (study group-E) or saline (control group-
C). Each group was divided into subgroups containing 10 animals each for euthanasia in the third (C3 and E3) or the seventh (E7 and
C7) postoperative days. The rats were submitted to section of the left colon and end-to-end anastomosis. On the day of reoperation,
we evaluated the total amount of adhesions and removed a colonic segment containing the anastomosis for histopathological
analysis, assessment of rupture strength and hydroxyproline concentration. Results: There was no difference between groups in
relation to clinical outcome. Two animals in the study group had blocked anastomotic leakage. The animals that received bromopride
had the number of intracavitary adhesions and adhesions to the anastomosis similar to the control group. The anastomoses from the
group E3 animals showed lower resistance to rupture the one from the C3 group (p = 0.04). This effect did not occur on the seventh
postoperative day (p = 0.37). There was no significant difference between groups in relation to histopathology and hydroxyproline
concentration in the anastomoses. Conclusion: The use of bromopride was associated with decreased tensile strength of left colon
anastomosis in rats in the third postoperative day
Relative nutritional quality of C 3 and C 4 grasses for a graminivorous lepidopteran, Paratrytone melane (Hesperiidae)
We tested the hypothesis that C 4 grasses are inferior to C 3 grasses as host plants for herbivorous insects by measuring the relative performance of larvae of a graminivorous lepidopteran, Paratrytone melane (Hesperiidae), fed C 3 and C 4 grasses. Relative growth rates and final weights were higher in larvae fed a C 3 grass in Experiment I. However, in two additional experiments, relative growth rates and final weights were not significantly different in larvae fed C 3 and C 4 grasses. We examined two factors which are believed to cause C 4 grasses to be of lower nutritional value than C 3 grasses: foliar nutrient levels and nutrient digestibility. In general, foliar nutrient levels were higher in C 3 grasses. In Experiment I, protein and soluble carbohydrates were digested from a C 3 and a C 4 grass with equivalent efficiencies. Therefore, differences in larval performance are best explained by higher nutrient levels in the C 3 grass in this experiment. In Experiment II, soluble carbohydrates were digested with similar efficiencies from C 3 and C 4 grasses but protein was digested with greater efficiency from the C 3 grasses. We conclude (1) that the bundle sheath anatomy of C 4 grasses is not a barrier to soluble carbohydrate digestion and does not have a nutritionally significant effect on protein digestion and (2) that P. melane may consume C 4 grasses at compensatory rates.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47798/1/442_2004_Article_BF00317268.pd
Mena deficiency delays tumor progression and decreases metastasis in polyoma middle-T transgenic mouse mammary tumors
Introduction
The actin binding protein Mammalian enabled (Mena), has been implicated in the metastatic progression of solid tumors in humans. Mena expression level in primary tumors is correlated with metastasis in breast, cervical, colorectal and pancreatic cancers. Cells expressing high Mena levels are part of the tumor microenvironment for metastasis (TMEM), an anatomical structure that is predictive for risk of breast cancer metastasis. Previously we have shown that forced expression of Mena adenocarcinoma cells enhances invasion and metastasis in xenograft mice. Whether Mena is required for tumor progression is still unknown. Here we report the effects of Mena deficiency on tumor progression, metastasis and on normal mammary gland development. Methods
To investigate the role of Mena in tumor progression and metastasis, Mena deficient mice were intercrossed with mice carrying a transgene expressing the polyoma middle T oncoprotein, driven by the mouse mammary tumor virus. The progeny were investigated for the effects of Mena deficiency on tumor progression via staging of primary mammary tumors and by evaluation of morbidity. Stages of metastatic progression were investigated using an in vivo invasion assay, intravital multiphoton microscopy, circulating tumor cell burden, and lung metastases. Mammary gland development was studied in whole mount mammary glands of wild type and Mena deficient mice. Results
Mena deficiency decreased morbidity and metastatic dissemination. Loss of Mena increased mammary tumor latency but had no affect on mammary tumor burden or histologic progression to carcinoma. Elimination of Mena also significantly decreased epidermal growth factor (EGF) induced in vivo invasion, in vivo motility, intravasation and metastasis. Non-tumor bearing mice deficient for Mena also showed defects in mammary gland terminal end bud formation and branching. Conclusions
Deficiency of Mena decreases metastasis by slowing tumor progression and reducing tumor cell invasion and intravasation. Mena deficiency during development causes defects in invasive processes involved in mammary gland development. These findings suggest that functional intervention targeting Mena in breast cancer patients may provide a valuable treatment option to delay tumor progression and decrease invasion and metastatic spread leading to an improved prognostic outcome.National Cancer Institute (U.S.). Integrative Cancer Biology Program (grant U54 CA112967)Virginia and D.K. Ludwig Fund for Cancer Researc
Characterization of immunoglobulin G antibodies to Plasmodium falciparum sporozoite surface antigen MB2 in malaria exposed individuals
<p>Abstract</p> <p>Background</p> <p>MB2 protein is a sporozoite surface antigen on the human malaria parasite <it>Plasmodium falciparum</it>. MB2 was identified by screening a <it>P. falciparum </it>sporozoite cDNA expression library using immune sera from a protected donor immunized via the bites of <it>P. falciparum</it>-infected irradiated mosquitoes. It is not known whether natural exposure to <it>P. falciparum </it>also induces the anti-MB2 response and if this response differs from that in protected individuals immunized via the bites of <it>P. falciparum </it>infected irradiated mosquitoes. The anti-MB2 antibody response may be part of a robust protective response against the sporozoite.</p> <p>Methods</p> <p>Fragments of polypeptide regions of MB2 were constructed as recombinant fusions sandwiched between glutathione S-transferase and a hexa histidine tag for bacterial expression. The hexa histidine tag affinity purified proteins were used to immunize rabbits and the polyclonal sera evaluated in an <it>in vitro </it>inhibition of sporozoite invasion assay. The proteins were also used in immunoblots with sera from a limited number of donors immunized via the bites of <it>P. falciparum </it>infected irradiated mosquitoes and plasma and serum obtained from naturally exposed individuals in Kenya.</p> <p>Results</p> <p>Rabbit polyclonal antibodies targeting the non-repeat region of the basic domain of MB2 inhibited sporozoites entry into HepG2-A16 cells <it>in vitro</it>. Analysis of serum from five human volunteers that were immunized via the bites of <it>P. falciparum </it>infected irradiated mosquitoes that developed immunity and were completely protected against subsequent challenge with non-irradiated parasite also had detectable levels of antibody against MB2 basic domain. In contrast, in three volunteers not protected, anti-MB2 antibodies were below the level of detection. Sera from protected volunteers preferentially recognized a non-repeat region of the basic domain of MB2, whereas plasma from naturally-infected individuals also had antibodies that recognize regions of MB2 that contain a repeat motif in immunoblots. Sequence analysis of eleven field isolates and four laboratory strains showed that these antigenic regions of the basic domain of the <it>MB2 </it>gene are highly conserved in parasites obtained from different parts of the world. Moreover, anti-MB2 antibodies also were detected in the plasma of 83% of the individuals living in a malaria endemic area of Kenya (n = 41).</p> <p>Conclusion</p> <p>A preliminary analysis of the human humoral response against MB2 indicates that it may be an additional highly conserved target for immune intervention at the pre-erythrocytic stage of <it>P. falciparum </it>life cycle.</p
Observation of associated near-side and away-side long-range correlations in âsNN=5.02ââTeV proton-lead collisions with the ATLAS detector
Two-particle correlations in relative azimuthal angle (ÎÏ) and pseudorapidity (Îη) are measured in âsNN=5.02ââTeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1ââÎŒb-1 of data as a function of transverse momentum (pT) and the transverse energy (ÎŁETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Îη|<5) ânear-sideâ (ÎÏâŒ0) correlation that grows rapidly with increasing ÎŁETPb. A long-range âaway-sideâ (ÎÏâŒÏ) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ÎŁETPb, is found to match the near-side correlation in magnitude, shape (in Îη and ÎÏ) and ÎŁETPb dependence. The resultant ÎÏ correlation is approximately symmetric about Ï/2, and is consistent with a dominant cosâĄ2ÎÏ modulation for all ÎŁETPb ranges and particle pT
Measurement of the cross-section of high transverse momentum vector bosons reconstructed as single jets and studies of jet substructure in pp collisions at âs = 7 TeV with the ATLAS detector
This paper presents a measurement of the cross-section for high transverse momentum W and Z bosons produced in pp collisions and decaying to all-hadronic final states. The data used in the analysis were recorded by the ATLAS detector at the CERN Large Hadron Collider at a centre-of-mass energy of âs = 7 TeV;{\rm Te}{\rm V}4.6\;{\rm f}{{{\rm b}}^{-1}}{{p}_{{\rm T}}}\gt 320\;{\rm Ge}{\rm V}|\eta |\lt 1.9{{\sigma }_{W+Z}}=8.5\pm 1.7$ pb and is compared to next-to-leading-order calculations. The selected events are further used to study jet grooming techniques
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