Synthesis of novel piperazine-linked anthranilic acids as potential small molecule kinase inhibitors

Please cite as follows: Chakravorty, S. et al. 2014. Synthesis of novel piperazine-linked anthranilic acids as potential small molecule kinase inhibitors. South African Journal of Chemistry, 67:71–79.The original publication is available at http://www.journals.co.za/sajchemSubstituted anthranilic acid and piperazines were used as building blocks to prepare two libraries of compounds, with the aim being that they would exhibit biochemical activity as small molecule kinase inhibitors. The synthesized anthranilamidepiperazine compounds were subsequently tested against a panel of kinases including EGFR, Abl, Akt and Aurora B.http://www.scielo.org.za/scielo.php?script=sci_abstract&pid=S0379-43502014000100012&lng=en&nrm=iso&tlng=enPublisher's versio

Zinc Cream and Reliability of Tuberculosis Skin Testing

In 50 healthy Peruvian shantytown residents, zinc cream applied to tuberculosis skin-test sitescaused a 32% increase in induration compared with placebo cream. Persons with lower plasma zinc had smaller skin-test reactions and greater augmentation with zinc cream. Zinc deficiency caused false-negative skin-test results, and topical zinc supplementation augmented antimycobacterial immune responses enough to improve diagnosis

QuantiFERON®-TB gold in-tube performance for diagnosing active tuberculosis in children and adults in a high burden setting.

To determine whether QuantiFERON®-TB Gold In-Tube (QFT) can contribute to the diagnosis of active tuberculosis (TB) in children in a high-burden setting and to assess the performance of QFT and tuberculin skin test (TST) in a prospective cohort of TB suspect children compared to adults with confirmed TB in Tanzania. Sensitivity and specificity of QFT and TST for diagnosing active TB as well as indeterminate QFT rates and IFN-γ levels were assessed in 211 TB suspect children in a Tanzanian district hospital and contrasted in 90 adults with confirmed pulmonary TB. Sensitivity of QFT and TST in children with confirmed TB was 19% (5/27) and 6% (2/31) respectively. In adults sensitivity of QFT and TST was 84% (73/87) and 85% (63/74). The QFT indeterminate rate in children and adults was 27% and 3%. Median levels of IFN-γ were lower in children than adults, particularly children <2 years and HIV infected. An indeterminate result was associated with age <2 years but not malnutrition or HIV status. Overall childhood mortality was 19% and associated with an indeterminate QFT result at baseline. QFT and TST showed poor performance and a surprisingly low sensitivity in children. In contrast the performance in Tanzanian adults was good and comparable to performance in high-income countries. Indeterminate results in children were associated with young age and increased mortality. Neither test can be recommended for diagnosing active TB in children with immature or impaired immunity in a high-burden setting

THE VAXED PROJECT: An Assessment of Immunization Education in Canadian Health Professional Programs

<p>Abstract</p> <p>Background</p> <p>Knowledge & attitudes of healthcare providers (HCP) have significant impact on frequency with which vaccines are offered & accepted but many HCP are ill equipped to make informed recommendations about vaccine merits & risks. We performed an assessment of the educational needs of trainees regarding immunization and used the information thus ascertained to develop multi-faceted, evaluable, educational tools which can be integrated into formal education curricula.</p> <p>Methods</p> <p>(i) A questionnaire was sent to all Canadian nursing, medical & pharmacy schools to assess immunization-related curriculum content (ii) A 77-item web-based, validated questionnaire was emailed to final-year students in medicine, nursing, & pharmacy at two universities in Nova Scotia, Canada to assess knowledge, attitudes, & behaviors reflecting current immunization curriculum.</p> <p>Results</p> <p>The curriculum review yielded responses from 18%, 48%, & 56% of medical, nursing, & pharmacy schools, respectively. Time spent on immunization content varied substantially between & within disciplines from <1 to >50 hrs. Most schools reported some content regarding vaccine preventable diseases, immunization practice & clinical skills but there was considerable variability and fewer schools had learning objectives or formal evaluation in these areas. 74% of respondents didn't feel comfortable discussing vaccine side effects with parents/patients & only 21% felt they received adequate teaching regarding immunization during training.</p> <p>Conclusions</p> <p>Important gaps were identified in the knowledge of graduating nursing, medical, & pharmacy trainees regarding vaccine indications/contraindications, adverse events & safety. The national curriculum review revealed wide variability in immunization curriculum content & evaluation. There is clearly a need for educators to assess current curricula and adapt existing educational resources such as the Immunization Competencies for Health Professionals in Canada.</p

Multi-scale waves in sound-proof global simulations with EULAG

EULAG is a computational model for simulating flows across a wide range of scales and physical scenarios. A standard option employs an anelastic approximation to capture nonhydrostatic effects and simultaneously filter sound waves from the solution. In this study, we examine a localized gravity wave packet generated by instabilities in Held-Suarez climates. Although still simplified versus the Earth’s atmosphere, a rich set of planetary wave instabilities and ensuing radiated gravity waves can arise. Wave packets are observed that have lifetimes ≤ 2 days, are negligibly impacted by Coriolis force, and do not show the rotational effects of differential jet advection typical of inertia-gravity waves. Linear modal analysis shows that wavelength, period, and phase speed fit the dispersion equation to within a mean difference of ∼ 4%, suggesting an excellent fit. However, the group velocities match poorly even though a propagation of uncertainty analysis indicates that they should be predicted as well as the phase velocities. Theoretical arguments suggest the discrepancy is due to nonlinearity — a strong southerly flow leads to a critical surface forming to the southwest of the wave packet that prevents the expected propagation

Blocking representation in the ERA-Interim driven EURO-CORDEX RCMs

While Regional Climate Models (RCMs) have been shown to yield improved simulations compared to General Circulation Model (GCM), their representation of large-scale phenomena like atmospheric blocking has been hardly addressed. Here, we evaluate the ability of RCMs to simulate blocking situations present in their reanalysis driving data and analyse the associated impacts on anomalies and biases of European 2-m air temperature (TAS) and precipitation rate (PR). Five RCM runs stem from the EURO-CORDEX ensemble while three RCMs are WRF models with different nudging realizations, all of them driven by ERA-Interim for the period 1981?2010. The detected blocking systems are allocated to three sectors of the Euro-Atlantic region, allowing for a characterization of distinctive blocking-related TAS and PR anomalies. Our results indicate some misrepresentation of atmospheric blocking over the EURO-CORDEX domain, as compared to the driving reanalysis. Most of the RCMs showed fewer blocks than the driving data, while the blocking misdetection was negligible for RCMs strongly conditioned to the driving data. A higher resolution of the RCMs did not improve the representation of atmospheric blocking. However, all RCMs are able to reproduce the basic anomaly structure of TAS and PR connected to blocking. Moreover, the associated anomalies do not change substantially after correcting for the misrepresentation of blocking in RCMs. The overall model bias is mainly determined by pattern biases in the representations of surface parameters during non-blocking situations. Biases in blocking detections tend to have a secondary influence in the overall bias due to compensatory effects of missed blockings and non-blockings. However, they can lead to measurable effects in the presence of a strong blocking underestimation.This work was funded by the Austrian Science Fund (FWF) under the project: Understanding Contrasts in high Mountain hydrology in Asia (UNCOMUN: I 1295-N29). This research was supported by the Faculty of Environmental, Regional and Educational Sciences (URBI), University of Graz, as well as the Federal Ministry of Science, Research and Economy (BMWFW) by funding the OeAD Grant Marietta Blau. This work was partially supported (JMG and SH) by the project MULTI-SDM (CGL2015-66583- R, MINECO/FEDER). DB was supported by the PALEOSTRAT (CGL2015-69699-R) project funded by the Spanish Ministry of Economy and Competitiveness (MINECO)

Blocking and its response to climate change

Purpose of review: Atmospheric blocking events represent some of the most high-impact weather patterns in the mid-latitudes, yet they have often been a cause for concern in future climate projections. There has been low confidence in predicted future changes in blocking, despite relatively good agreement between climate models on a decline in blocking. This is due to the lack of a comprehensive theory of blocking and a pervasive underestimation of blocking occurrence by models. This paper reviews the state of knowledge regarding blocking under climate change, with the aim of providing an overview for those working in related fields. Recent Findings: Several avenues have been identified by which blocking can be improved in numerical models, though a fully reliable simulation remains elusive (at least, beyond a few days lead time). Models are therefore starting to provide some useful information on how blocking and its impacts may change in the future, although deeper understanding of the processes at play will be needed to increase confidence in model projections. There are still major uncertainties regarding the processes most important to the onset, maintenance and decay of blocking and advances in our understanding of atmospheric dynamics, for example in the role of diabatic processes, continue to inform the modelling and prediction efforts. Summary: The term ‘blocking’ covers a diverse array of synoptic patterns, and hence a bewildering range of indices has been developed to identify events. Results are hence not considered fully trustworthy until they have been found using several different methods. Examples of such robust results are the underestimation of blocking by models, and an overall decline in future occurrence, albeit with a complex regional and seasonal variation. In contrast, hemispheric trends in blocking over the recent historical period are not supported by different methods, and natural variability will likely dominate regional variations over the next few decades