Comparison of blood smear microscopy to a rapid diagnostic test for in-vitro testing for P. Falciparum malaria in Kenyan school children

Objective: To compare the diagnostic performance of microscopy using Giemsastained thick and thin blood smears to a rapid malaria dipstick test (RDT) in detecting P. falciparum malaria in Kenyan school children. Design: Randomised, controlled feeding intervention trial from 1998-2001. Setting: Rural Embu district, Kenya. The area is considered endemic for malaria, with four rainy seasons per year. Chloroquine resistance was estimated in 80% of patients. Children had a spleen rate of 45%. Subjects: A sample of 515 rural Kenyan primary school children, aged 7-11 years, who were enrolled in a feeding intervention trial from 1998-2001. Main outcome measures: Percent positive and negative P. falciparum malaria status, sensitivity, specificity and positive and negative predictive values of RDT. Results: For both years, the RDT yielded positive results of 30% in children compared to microscopy (17%). With microscopy as the “gold standard,” RDT yielded a sensitivity of 81.3% in 1998 and 79.3% in 2000. Specificity was 81.6% in 1998 and 78.3% in 2000. Positive predictive value was 47.3% in 1998 and 42.6% in 2000, and negative predictive value was 95.6% in 1998 and 94.9% in 2000. Conclusion: Rapid diagnostic testing is a valuable tool for diagnosis and can shorten the interval for starting treatment, particularly where microscopy may not be feasible due to resource and distance limitations. East African Medical Journal Vol. 85 (11) 2008: pp. 544-54

The Evershed Effect with SOT/Hinode

The Solar Optical Telescope onboard Hinode revealed the fine-scale structure of the Evershed flow and its relation to the filamentary structures of the sunspot penumbra. The Evershed flow is confined in narrow channels with nearly horizontal magnetic fields, embedded in a deep layer of the penumbral atmosphere. It is a dynamic phenomenon with flow velocity close to the photospheric sound speed. Individual flow channels are associated with tiny upflows of hot gas (sources) at the inner end and downflows (sinks) at the outer end. SOT/Hinode also discovered ``twisting'' motions of penumbral filaments, which may be attributed to the convective nature of the Evershed flow. The Evershed effect may be understood as a natural consequence of thermal convection under a strong, inclined magnetic field. Current penumbral models are discussed in the lights of these new Hinode observations.Comment: To appear in "Magnetic Coupling between the Interior and the Atmosphere of the Sun", eds. S.S. Hasan and R.J. Rutten, Astrophysics and Space Science Proceedings, Springer-Verlag, Heidelberg, Berlin, 200

Collaborative multidisciplinary learning : quantity surveying students’ perspectives

The construction industry is highly fragmented and is known for its adversarial culture, culminating in poor quality projects not completed on time or within budget. The aim of this study is thus to guide the design of QS programme curricula in order to help students develop the requisite knowledge and skills to work more collaboratively in their multi-disciplinary future workplaces. A qualitative approach was considered appropriate as the authors were concerned with gathering an initial understanding of what students think of multi-disciplinary learning. The data collection method used was a questionnaire which was developed by the Behaviours4Collaboration (B4C) team. Knowledge gaps were still found across all the key areas where a future QS practitioner needs to be collaborative (either as a project contributor or as a project leader) despite the need for change instigated by the multi-disciplinary (BIM) education revolution. The study concludes that universities will need to be selective in teaching, and innovative in reorienting, QS education so that a collaborative BIM education can be effected in stages, increasing in complexity as the students’ technical knowledge grows. This will help students to build the competencies needed to make them future leaders. It will also support programme currency and delivery

Theoretical Models of Sunspot Structure and Dynamics

Recent progress in theoretical modeling of a sunspot is reviewed. The observed properties of umbral dots are well reproduced by realistic simulations of magnetoconvection in a vertical, monolithic magnetic field. To understand the penumbra, it is useful to distinguish between the inner penumbra, dominated by bright filaments containing slender dark cores, and the outer penumbra, made up of dark and bright filaments of comparable width with corresponding magnetic fields differing in inclination by some 30 degrees and strong Evershed flows in the dark filaments along nearly horizontal or downward-plunging magnetic fields. The role of magnetic flux pumping in submerging magnetic flux in the outer penumbra is examined through numerical experiments, and different geometric models of the penumbral magnetic field are discussed in the light of high-resolution observations. Recent, realistic numerical MHD simulations of an entire sunspot have succeeded in reproducing the salient features of the convective pattern in the umbra and the inner penumbra. The siphon-flow mechanism still provides the best explanation of the Evershed flow, particularly in the outer penumbra where it often consists of cool, supersonic downflows.Comment: To appear in "Magnetic Coupling between the Interior and the Atmosphere of the Sun", eds. S.S. Hasan and R.J. Rutten, Astrophysics and Space Science Proceedings, Springer-Verlag, Heidelberg, Berlin, 200

PI3K-C2 alpha Knockdown Results in Rerouting of Insulin Signaling and Pancreatic Beta Cell Proliferation

Insulin resistance is a syndrome that affects multiple insulin target tissues, each having different biological functions regulated by insulin. A remaining question is to mechanistically explain how an insulin target cell/tissue can be insulin resistant in one biological function and insulin sensitive in another at the same time. Here, we provide evidence that in pancreatic beta cells, knockdown of PI3K-C2 alpha expression results in rerouting of the insulin signal from insulin receptor (IR)-B/PI3K-C2 alpha/PKB-mediated metabolic signaling to IR-B/Shc/ERK-mediated mitogenic signaling, which allows the beta cell to switch from a highly glucose-responsive, differentiated state to a proliferative state. Our data suggest the existence of IR-cascade-selective insulin resistance, which allows rerouting of the insulin signal within the same target cell. Hence, factors involved in the rerouting of the insulin signal represent tentative therapeutic targets in the treatment of insulin resistance.11108Ysciescopu

Agonistic aptamer to the insulin receptor leads to biased signaling and functional selectivity through allosteric modulation

Due to their high affinity and specificity, aptamers have been widely used as effective inhibitors in clinical applications. However, the ability to activate protein function through aptamer-protein interaction has not been well-elucidated. To investigate their potential as target-specific agonists, we used SELEX to generate aptamers to the insulin receptor (IR) and identified an agonistic aptamer named IR-A48 that specifically binds to IR, but not to IGF-1 receptor. Despite its capacity to stimulate IR autophosphorylation, similar to insulin, we found that IR-A48 not only binds to an allosteric site distinct from the insulin binding site, but also preferentially induces Y1150 phosphorylation in the IR kinase domain. Moreover, Y1150-biased phosphorylation induced by IR-A48 selectively activates specific signaling pathways downstream of IR. In contrast to insulin-mediated activation of IR, IR-A48 binding has little effect on the MAPK pathway and proliferation of cancer cells. Instead, AKT S473 phosphorylation is highly stimulated by IR-A48, resulting in increased glucose uptake both in vitro and in vivo. Here, we present IR-A48 as a biased agonist able to selectively induce the metabolic activity of IR through allosteric binding. Furthermore, our study also suggests that aptamers can be a promising tool for developing artificial biased agonists to targeted receptors.111615Ysciescopu

Convection and the Origin of Evershed Flows

Numerical simulations have by now revealed that the fine scale structure of the penumbra in general and the Evershed effect in particular is due to overturning convection, mainly confined to gaps with strongly reduced magnetic field strength. The Evershed flow is the radial component of the overturning convective flow visible at the surface. It is directed outwards -- away from the umbra -- because of the broken symmetry due to the inclined magnetic field. The dark penumbral filament cores visible at high resolution are caused by the 'cusps' in the magnetic field that form above the gaps. Still remaining to be established are the details of what determines the average luminosity of penumbrae, the widths, lengths, and filling factors of penumbral filaments, and the amplitudes and filling factors of the Evershed flow. These are likely to depend at least partially also on numerical aspects such as limited resolution and model size, but mainly on physical properties that have not yet been adequately determined or calibrated, such as the plasma beta profile inside sunspots at depth and its horizontal profile, the entropy of ascending flows in the penumbra, etc.Comment: 13 pages, 7 figures. To appear in "Magnetic Coupling between the Interior and the Atmosphere of the Sun", eds. S.S. Hasan and R.J. Rutten, Astrophysics and Space Science Proceedings, Springer-Verlag, Heidelberg, Berlin, 200

Does shear wave ultrasound independently predict axillary lymph node metastasis in women with invasive breast cancer?

Shear wave elastography (SWE) shows promise as an adjunct to greyscale ultrasound examination in assessing breast masses. In breast cancer, higher lesion stiffness on SWE has been shown to be associated with features of poor prognosis. The purpose of this study was to assess whether lesion stiffness at SWE is an independent predictor of lymph node involvement. Patients with invasive breast cancer treated by primary surgery, who had undergone SWE examination were eligible. Data were retrospectively analysed from 396 consecutive patients. The mean stiffness values were obtained using the Aixplorer(®) ultrasound machine from SuperSonic Imagine Ltd. Measurements were taken from a region of interest positioned over the stiffest part of the abnormality. The average of the mean stiffness value obtained from each of two orthogonal image planes was used for analysis. Associations between lymph node involvement and mean lesion stiffness, invasive cancer size, histologic grade, tumour type, ER expression, HER-2 status and vascular invasion were assessed using univariate and multivariate logistic regression. At univariate analysis, invasive size, histologic grade, HER-2 status, vascular invasion, tumour type and mean stiffness were significantly associated with nodal involvement. Nodal involvement rates ranged from 7 % for tumours with mean stiffness <50 kPa to 41 % for tumours with a mean stiffness of >150 kPa. At multivariate analysis, invasive size, tumour type, vascular invasion, and mean stiffness maintained independent significance. Mean stiffness at SWE is an independent predictor of lymph node metastasis and thus can confer prognostic information additional to that provided by conventional preoperative tumour assessment and staging