EXPOSURE TO PHOSPHINE GAS DURING APPLICATION OF MAGNESIUM PHOSPHIDE IN STORED PRODUCT WAREHOUSES

The use of phosphine gas requires that respiratory protection be used if exposures exceed the OSHA permissible exposure limit. As with other chemical exposures limits many of the references used to establish occupational health guidelines date back to the 1930’s and 1940’s. This is quite common and is the case with phosphine gas. Initial planning for fumigations involving magnesium phosphide requires that a hazard assessment be performed. Expected worker exposures based on previous monitoring or test data was not readily available. Many current practices and procedures for fumigations are based on recommendations from applicators who used the product in the 1950’s and 60’s. Unfortunately, many of the recommendations were based on personal opinion and experience rather than actual exposure monitoring data. Not until the 1980\u27s were comprehensive applicator exposure assessments being conducted for different tasks involving magnesium phosphide. As a result, it is necessary to generate current applicator exposure data and compare the data to current occupational exposure limits for phosphine gas

Exploring longitudinal relationships between psychological flexibility and medication adherence, mood and general functioning in people with long-term health conditions.

Introduction: Many people with long-term physical health conditions (LTCs) are non-adherent to prescribed medications and therefore have an increased risk of morbidity and mortality. Several psychological models have attempted to understand why people with LTCs do not adhere, but all have limited explanatory power and interventions stemming from them show modest effects. Few studies have explored the utility of the psychological flexibility model (PF), the transdiagnostic theory underlying Acceptance and Commitment Therapy (ACT), in this context. A small number of preliminary trials for ACT show promising efficacy but have been conducted in specific LTC groups with small samples. Ecological momentary assessment methods (EMA) may build on these studies because they could examine temporal relationships and account for within-individual variability across different contexts and are less prone to recall biases. However, few momentary PF measures have been validated in LTCs samples. Method: The primary aim of this online longitudinal study (n=701) was to examine relationships between validated measures of PF and self-reported intentional and unintentional non-adherence and appointment attendance in people with LTCs at baseline and three months follow-up using binomial regressions. The second aim (not reported in the current thesis) was to preliminarily validate new momentary measures of PF, adherence and mood for future EMA studies to better understand within-individual and group-level variability. Results: PF variables explained a significant, albeit modest, amount of the variance in intentional and unintentional non-adherence and appointment attendance. However, confirmatory factor, internal consistency and test-re-test analyses indicated MARS-5 items failed to meet established criteria for construct validity and demonstrated poor stability over time. This was supported by the instrument’s poor convergence with new appointment attendance scales. PF shared medium to strong relationships with mood and general functioning in expected directions. Discussion: This project has improved our understanding of the potential applicability of the PF model and ACT in understanding and treating intentional and unintentional non-adherence and appointment non-attendance. However, further clarification of the utility of PF in understanding treatment non-adherence is warranted using prospective or experimental designs in conjunction with more objective valid and reliable adherence measures

Stu2p binds tubulin and undergoes an open-to-closed conformational change

Stu2p from budding yeast belongs to the conserved Dis1/XMAP215 family of microtubule-associated proteins (MAPs). The common feature of proteins in this family is the presence of HEAT repeat–containing TOG domains near the NH2 terminus. We have investigated the functions of the two TOG domains of Stu2p in vivo and in vitro. Our data suggest that Stu2p regulates microtubule dynamics through two separate activities. First, Stu2p binds to a single free tubulin heterodimer through its first TOG domain. A large conformational transition in homodimeric Stu2p from an open structure to a closed one accompanies the capture of a single free tubulin heterodimer. Second, Stu2p has the capacity to associate directly with microtubule ends, at least in part, through its second TOG domain. These two properties lead to the stabilization of microtubules in vivo, perhaps by the loading of tubulin dimers at microtubule ends. We suggest that this mechanism of microtubule regulation is a conserved feature of the Dis1/XMAP215 family of MAPs

The customers’ brand identification with luxury hotels : a social identity perspective

This study explores the relationships between the consumer-brand identification (CBI) construct and the customers’ satisfaction, commitment, trust and loyalty toward hospitality brands. The methodology included a confirmatory factor analysis (CFA) that assessed the reliability and validity of previous tried and tested measures in marketing sciences. This study has supported the scales' content validity. A two-step structural equation modelling approach was used to analyze the relationships among the latent and observed constructs. The findings have reported a satisfactory fit for this study's research model. The empirical results shed light on the direct and indirect effects on brand loyalty. This contribution implies that brand trust had the highest effect on brand loyalty, and this was followed my other determinants, including; consumer-brand identification, consumer satisfaction and commitment. In conclusion, this paper identifies its research limitations and puts forward possible research avenues.peer-reviewe

Operationalising cognitive fatigability in multiple sclerosis: a Gordian knot that can be cut?

Background: Researchers have attempted to operationalise objective measures of cognitive fatigability in multiple sclerosis (MS) to overcome the perceived subjectivity of patient-reported outcomes of fatigue (PROs). Measures of cognitive fatigability examine decrements in performance during sustained neurocognitive tasks. Objective: This personal viewpoint briefly summarises available evidence for measures of cognitive fatigability in MS and considers their overall utility. Results: Studies suggest there may be a construct that is distinct from self-reported fatigue, reflecting a new potential intervention target. However, assessments vary and findings across and within measures are inconsistent. Few measures have been guided by a coherent theory, and those identified are likely to be influenced by other confounds, such as cognitive impairment caused more directly by disease processes, depression and assessment biases. Conclusion: Future research may benefit from (a) developing a guiding theory of cognitive fatigability, (b) examining ecological and construct validity of existing assessments and (c) exploring whether the more promising cognitive fatigability measures are correlated with impaired functioning after accounting for possible confounds. Given the issues raised, we caution that our purposes as researchers may be better served by continuing our search for a more objective cognitive fatigability construct that runs in parallel with improving, rather than devaluing, current PROs

Drag Prediction for the DLR-F6 Wing/Body and DPW Wing using CFL3D and OVERFLOW Overset Mesh

A series of overset grids was generated in response to the 3rd AIAA CFD Drag Prediction Workshop (DPW-III) which preceded the 25th Applied Aerodynamics Conference in June 2006. DPW-III focused on accurate drag prediction for wing/body and wing-alone configurations. The grid series built for each configuration consists of a coarse, medium, fine, and extra-fine mesh. The medium mesh is first constructed using the current state of best practices for overset grid generation. The medium mesh is then coarsened and enhanced by applying a factor of 1.5 to each (I,J,K) dimension. The resulting set of parametrically equivalent grids increase in size by a factor of roughly 3.5 from one level to the next denser level. CFD simulations were performed on the overset grids using two different RANS flow solvers: CFL3D and OVERFLOW. The results were post-processed using Richardson extrapolation to approximate grid converged values of lift, drag, pitching moment, and angle-of-attack at the design condition. This technique appears to work well if the solution does not contain large regions of separated flow (similar to that seen n the DLR-F6 results) and appropriate grid densities are selected. The extra-fine grid data helped to establish asymptotic grid convergence for both the OVERFLOW FX2B wing/body results and the OVERFLOW DPW-W1/W2 wing-alone results. More CFL3D data is needed to establish grid convergence trends. The medium grid was utilized beyond the grid convergence study by running each configuration at several angles-of-attack so drag polars and lift/pitching moment curves could be evaluated. The alpha sweep results are used to compare data across configurations as well as across flow solvers. With the exception of the wing/body drag polar, the two codes compare well qualitatively showing consistent incremental trends and similar wing pressure comparisons

Predicting Carotid Artery Disease and Plaque Instability from Cell-derived Microparticles

ObjectivesCell-derived microparticles (MPs) are small plasma membrane-derived vesicles shed from circulating blood cells and may act as novel biomarkers of vascular disease. We investigated the potential of circulating MPs to predict (a) carotid plaque instability and (b) the presence of advanced carotid disease.MethodsThis pilot study recruited carotid disease patients (aged 69.3 ± 1.2 years [mean ± SD], 69% male, 90% symptomatic) undergoing endarterectomy (n = 42) and age- and sex-matched controls (n = 73). Plaques were classified as stable (n = 25) or unstable (n = 16) post surgery using immunohistochemistry. Blood samples were analysed for MP subsets and molecular biomarkers. Odds ratios (OR) are expressed per standard deviation biomarker increase.ResultsEndothelial MP (EMP) subsets, but not any vascular, inflammatory, or proteolytic molecular biomarker, were higher (p < .05) in the unstable than the stable plaque patients. The area under the receiver operator characteristic curve for CD31+41− EMP in discriminating an unstable plaque was 0.73 (0.56–0.90, p < .05). CD31+41− EMP predicted plaque instability (OR = 2.19, 1.08–4.46, p < .05) and remained significant in a multivariable model that included transient ischaemic attack symptom status. Annexin V+ MP, platelet MP (PMP) subsets, and C-reactive protein were higher (p < .05) in cases than controls. Annexin V+ MP (OR = 3.15, 1.49–6.68), soluble vascular cell adhesion molecule-1 (OR = 1.64, 1.03–2.59), and previous smoking history (OR = 3.82, 1.38–10.60) independently (p < .05) predicted the presence of carotid disease in a multivariable model.ConclusionsEMP may have utility in predicting plaque instability in carotid patients and annexin V+ MPs may predict the presence of advanced carotid disease in aging populations, independent of established biomarkers

Dermonecrosis caused by a spitting cobra snakebite results from toxin potentiation and is prevented by the repurposed drug varespladib

Snakebite envenoming is a neglected tropical disease that causes substantial mortality and morbidity globally. The venom of African spitting cobras often causes permanent injury via tissue-destructive dermonecrosis at the bite site, which is ineffectively treated by current antivenoms. To address this therapeutic gap, we identified the etiological venom toxins in Naja nigricollis venom responsible for causing local dermonecrosis. While cytotoxic three-finger toxins were primarily responsible for causing spitting cobra cytotoxicity in cultured keratinocytes, their potentiation by phospholipases A 2 toxins was essential to cause dermonecrosis in vivo. This evidence of probable toxin synergism suggests that a single toxin-family inhibiting drug could prevent local envenoming. We show that local injection with the repurposed phospholipase A 2 -inhibiting drug varespladib significantly prevents local tissue damage caused by several spitting cobra venoms in murine models of envenoming. Our findings therefore provide a therapeutic strategy that may effectively prevent life-changing morbidity caused by snakebite in rural Africa