Rethinking Human Security

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Studies on the turnover of glucocerebrosidase in cultured rat peritoneal macrophages and normal human fibroblasts

The kinetics of glucocerebrosidase synthesis and degradation in rat peritoneal macrophages and in human fibroblasts have been studied using conduritol B epoxide (CBE), an irreversible and specific inhibitor of mammalian glucocerebrosidase. In cultured fibroblasts, higher concentrations of CBE and/or longer times were required for inhibition of glucocerebrosidase than were necessary for inhibition of the macrophage enzyme. However, inhibition of activity in cell extracts from both cell types showed identical time and concentration dependence. After the removal of CBE from cultures, enzyme activity returned to normal with a half-time of 48 h for macrophages and 40 h for fibroblasts. The reappearance of enzyme activity was prevented by an inhibitor of protein synthesis. Both the rate of synthesis and degradation of glucocerebrosidase enzyme protein were independent of the presence of CBE. The calculated rate of degradation of glucocerebrosidase was confirmed using metabolically labelled enzyme in cell cultures. The rate of synthesis for macrophages is 1.8 ng enzyme h-1 mg cell protein-1 and the rate of degradation is 1.4% h-1 (0.014 h-1). These values were 2.0 ng h-1 mg-1 and 0.018 h-1 for fibroblasts

Salivary gland structure of \u3ci\u3eCtenarytaina eucalypti\u3c/i\u3e (MASKELL, 1890) (Hemiptera) and phloem exudate in \u3ci\u3eEucalyptus globulus\u3c/i\u3e LABILLARDIÈRE, 1799 (Myrtaceae)

The structure of the salivary glands of the free-living aphalarid Ctenarytaina eucalypti, which infests multiple species of Eucalyptus in Australasia and has been introduced into many other regions of the world, is described and illustrated. The principal salivary gland is multilobed whereas the accessory gland is tubular. 1-D electrophoresis revealed proteins of approximately 58 and 64 kDa in the salivary gland extracts and proteins of similar molecular weights in the extracted plant exudates, including phloem, from infested leaves and tender shoots of E. globulus. Proteins that could fall within this range include, but are not limited to, glucosemethanol- choline-oxidoreductase (53-66 kDa), Zn-binding dehydrogenase (67 kDa) and esterase (65-96 kDa), in addition to cytochrome P-450 (50-55 kDa), trehalase (56 kDa), amylase (50-75 kDa) and lipase (48-52 kDa). Previous studies indicate that glucose-methanol-cholineoxidoreductase, Zn-binding dehydrogenase, cytochrome P-450 and trehalase suppress plantdefence mechanisms, whereas the cell-degrading enzymes such as amylase, lipase and esterase have a possible role in enabling C. eucalypti to insert its stylet into leaf and shoot tissues of E. globulus

Teacher education in the United Kingdom post devolution: convergences and divergences

This paper examines the roles of research in teacher education across the four nations of the United Kingdom. Both devolution and on-going reviews of teacher education are facilitating a greater degree of cross-national divergence. England is becoming a distinct outlier, in which the locus for teacher education is moving increasingly away from Higher Education Institutions and towards an ever-growing number of school-based providers. While the idea of teaching as a research-based profession is increasingly evident in Scotland, Northern Ireland and Wales, it seems that England, at least in respect of the political rhetoric, recent reforms and explicit definitions, is fixed on a contrastingly divergent trajectory towards the idea of teaching as a craft-based occupation, with a concomitant emphasis on a (re)turn to the practical. It is recommended that research is urgently needed to plot these divergences and to examine their consequences for teacher education, educational research and professionalism

Larval behaviour, dispersal and population connectivity in the deep sea

Ecosystem connectivity is an essential consideration for marine spatial planning of competing interests in the deep sea. Immobile, adult communities are connected through freely floating larvae, depending on new recruits for their health and to adapt to external pressures. We hypothesize that the vertical swimming ability of deep-sea larvae, before they permanently settle at the bottom, is one way larvae can control dispersal. We test this hypothesis with more than 3x108 simulated particles with a range of active swimming behaviours embedded within the currents of a high-resolution ocean model. Despite much stronger horizontal ocean currents, vertical swimming of simulated larvae can have an order of magnitude impact on dispersal. These strong relationships between larval dispersal, pathways, and active swimming demonstrate that lack of data on larval behaviour traits is a serious impediment to modelling deep-sea ecosystem connectivity; this uncertainty greatly limits our ability to develop ecologically coherent marine protected area networks

A pharmacodynamic analysis of resistance trends in pathogens from patients with infection in intensive care units in the United States between 1993 and 2004

<p>Abstract</p> <p>Background</p> <p>Increasing nosocomial pathogen resistance to available antimicrobial agents is of growing concern. While higher MICs can diminish antimicrobial effectiveness, dose adjustments often mitigate this effect. This study's objective was to ascertain whether MICs among major pathogens in the ICU to several commonly used agents have increased enough to significantly impact their ability to achieve bactericidal effect.</p> <p>Methods</p> <p>Cefepime, ceftriaxone, imipenem and piperacillin-tazobactam MICs were determined with 74,394 Gram-negative bacilli obtained from ICU patients with various infections in the US between 1993 and 2004. Results were grouped into four 3-year periods. The predicted cumulative fraction of response (CFR) was estimated based on patient-derived pharmacokinetic values and Monte Carlo simulation. Trends in CFR over the four study periods were assessed using the Cochran-Armitage test. The primary analysis included all organisms combined; <it>Pseudomonas aeruginosa </it>and <it>Acinetobacter </it>species were also evaluated individually.</p> <p>Results</p> <p>In the primary analysis, imipenem 500 mg q6h showed CFRs from 87% to 90% across all four study periods, with a trend toward slightly improved bactericidal target attainment (p < 0.01). CFRs for cefepime 2 g q12h and piperacillin-tazobactam 4.5 g q6h both declined by 2% (p < 0.01 and p < 0.05, respectively), reflecting upward shifts in the underlying MIC distributions. Ceftriaxone had <52% CFR for all regimens in all periods, with no significant trend. Against <it>P. aeruginosa</it>, significant declines in CFR were seen for (range, p-value): imipenem 1 g q8h (82%–79%, p < 0.01), cefepime 1 g q12h (70%–67%, p < 0.01), cefepime 2 g q12h (84%–82%, p < 0.05), piperacillin-tazobactam 3.375 g q6h (76%–73%, p < 0.01), piperacillin-tazobactam 4.5 g q8h (71%–68%, p < 0.01), and piperacillin-tazobactam 4.5 g q6h (80%–77%, p < .01). Against <it>Acinetobacter </it>spp., all regimens of imipenem, cefepime and piperacillin-tazobactam showed significant declines in CFR over time (p < 0.01).</p> <p>Conclusion</p> <p>Our observations suggest that as a result of increasing antimicrobial resistance among ICU pathogens in the US, drug effectiveness, assessed as a function of individual agents' ability to attain pharmacodynamic targets, has declined, especially with <it>P. aeruginosa </it>and <it>Acinetobacter </it>spp. Cefepime 2 g q8h and imipenem were the most potent agents against these species, respectively. More aggressive dosing of all of the agents characterized could preserve their clinical utility, but this must be balanced with safety and tolerability issues by the physician.</p

Device assessed activity behaviours in patients with indwelling pleural catheter: A sub-study of the Australasian Malignant PLeural Effusion (AMPLE)-2 randomized trial

Background and Objective: Device-assessed activity behaviours are a novel measure for comparing intervention outcomes in patients with malignant pleural effusion (MPE). Australasian Malignant PLeural Effusion (AMPLE)-2 was a multi-centre clinical trial where participants with MPE treated with an indwelling pleural catheter were randomized to daily (DD) or symptom-guided (SGD) drainage for 60-days. Our aim was to describe activity behaviour patterns in MPE patients, explore the impact of drainage regimen on activity behaviours and examine associations between activity behaviours and quality of life (QoL). Methods: Following randomization to DD or SGD, participants enrolled at the lead site (Perth) completed accelerometry assessment. This was repeated monthly for 5-months. Activity behaviour outcomes were calculated as percent of daily waking-wear time and compared between groups (Mann–Whitney U test; Median [IQR]). Correlations between activity behaviour outcomes and QoL were examined. Results: Forty-one (91%) participants provided ≥ 1 valid accelerometry assessment (DDn = 20, SGD n = 21). Participants spent a large proportion of waking hours sedentary (72%–74% across timepoints), and very little time in moderate-to-vigorous physical activity ( \u3c 1% across timepoints). Compared to SGD group, DD group had a more favourable sedentary-to-light ratio in the week following randomization (2.4 [2.0–3.4] vs. 3.2 [2.4–6.1]; p = 0.047) and at 60-days (2.0 [1.9–2.9] vs. 2.9 [2.8–6.0]; p = 0.016). Sedentary-to-light ratio was correlated with multiple QoL domains at multiple timepoints. Conclusion: Patients with MPE are largely sedentary. Preliminary results suggest that even modest differences in activity behaviours favouring the DD group could be meaningful for this clinical population. Accelerometry reflects QoL and is a useful outcome measure in MPE populations

The impact of impaired semantic knowledge on spontaneous iconic gesture production

Background: Previous research has found that people with aphasia produce more spontaneous iconic gesture than control participants, especially during word-finding difficulties. There is some evidence that impaired semantic knowledge impacts on the diversity of gestural handshapes, as well as the frequency of gesture production. However, no previous research has explored how impaired semantic knowledge impacts on the frequency and type of iconic gestures produced during fluent speech compared with those produced during word-finding difficulties. Aims: To explore the impact of impaired semantic knowledge on the frequency and type of iconic gestures produced during fluent speech and those produced during word-finding difficulties. Methods & Procedures: A group of 29 participants with aphasia and 29 control participants were video recorded describing a cartoon they had just watched. All iconic gestures were tagged and coded as either “manner”, “path only”, “shape outline” or “other”. These gestures were then separated into either those occurring during fluent speech or those occurring during a word-finding difficulty. The relationships between semantic knowledge and gesture frequency and form were then investigated in the two different conditions. Outcomes & Results: As expected, the participants with aphasia produced a higher frequency of iconic gestures than the control participants, but when the iconic gestures produced during word-finding difficulties were removed from the analysis, the frequency of iconic gesture was not significantly different between the groups. While there was not a significant relationship between the frequency of iconic gestures produced during fluent speech and semantic knowledge, there was a significant positive correlation between semantic knowledge and the proportion of word-finding difficulties that contained gesture. There was also a significant positive correlation between the speakers’ semantic knowledge and the proportion of gestures that were produced during fluent speech that were classified as “manner”. Finally while not significant, there was a positive trend between semantic knowledge of objects and the production of “shape outline” gestures during word-finding difficulties for objects. Conclusions: The results indicate that impaired semantic knowledge in aphasia impacts on both the iconic gestures produced during fluent speech and those produced during word-finding difficulties but in different ways. These results shed new light on the relationship between impaired language and iconic co-speech gesture production and also suggest that analysis of iconic gesture may be a useful addition to clinical assessment