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    A liquid chromatography-mass spectrometry study on the spirocyclization of ninhydrin with the aminothiols

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    © 2018 Elsevier BV. This manuscript version is made available under the CC-BY-NC-ND 4.0 license: http://creativecommons.org/licenses/by-nc-nd/4.0/ This author accepted manuscript is made available following 24 month embargo from date of publication (May 2018) in accordance with the publisher’s archiving policy.Ninhydrin reacts with some aminothiols to form spiranes adducts whose optical and chromatographic properties have proved to be useful for chiral recognition. Liquid chromatography-mass spectrometry data along with spectroscopic analysis reveal that under certain conditions, in addition to the known single-spirane configuration, the spirothiazolidinic complexes can exist also as double- and mixed double-spiranes. The reaction was exploited to check the enantiomeric purity of two commercially available dosage form of D-penicillamine and to measure the aminothiol concentration in the urine sample from a subject under treatment with the drug. Separation of diastereoisomers was achieved on a C18 column in isocratic mode by using a mixture of an aqueous solution of formic acid (30 mmol/L)/acetonitrile (90:10, v/v) as a mobile phase. Diastereoisomers were detected by a fluorescence detector and mass spectrometer in short times and with a good resolution. Intra- and inter-assay reproducibility were under 4% with an average recovery of 98%. At a LOD of 0.01%, no evidence of the toxic distomer (L-enantiomer) was found in the biological sample and drugs

    Economic evaluation of point-of-care testing in the remote primary health care setting of Australia’s Northern Territory

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    This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms. php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).Aim: To determine the cost-effectiveness of utilizing point-of-care testing (POCT) on the Abbott i-STAT device as a support tool to aid decisions regarding the emergency medical retrievals of patients at remote health centers in the Northern Territory (NT) of Australia. Methods: A decision analytic simulation model–based economic evaluation was conducted using data from patients presenting with three common acute conditions (chest pain, chronic renal failure due to missed dialysis session(s), and acute diarrhea) at six remote NT health centers from July to December 2015. The specific outcomes measured in this study were the number of unnecessary emergency medical retrieval prevented through POCT. Cost savings through prevented unnecessary medical retrievals for each presentation type were then determined and extrapolated to give per annum NT-wide estimates. Results: POCT prevented 60 unnecessary medical evacuations from a total of 200 patient cases meeting the selection criteria (48/147 for chest pain, 10/28 for missed dialysis, and 2/25 for acute diarrhea). The associated cost savings were AUD 4,674,4,674, 8,034, and 786perpatienttranslatingtoNTwidesavingsofAUD786 per patient translating to NT-wide savings of AUD 13.72 million, 6.45million,and6.45 million, and 1.57 million per annum (AUD $21.75 million in total) for chest pain, missed dialysis, and acute diarrhea presentations, respectively. Conclusion: This study demonstrated that POCT when used to aid decision making for acutely ill patients delivered significant cost savings for the NT health care system by preventing unnecessary emergency medical retrievals.This study was funded by a grant awarded by the Emergency Medicine Foundation Ltd

    Predicting which type of push notification content motivates users to engage in a self-monitoring app

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    This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.Despite the unprecedented access to self-monitoring health apps, lack of optimal user engagement remains a significant challenge. Push notification prompts with contextually tailored messages offers a promising strategy to improve engagement. To increase the efficacy of push-notifications on engaging individuals with health apps, greater attention to the modifiable components of push notifications that influence responsiveness is needed. This study examines the effect of message content and frequency of push notifications, along with past app usage on responding to notifications within 24 h, and engaging with self-monitoring in JOOL Health smartphone app. Mixed models were applied on a de-identified data set of 18,000 contextually tailored push notifications sent by JOOL Health App to 1414 participants. The content in sent messages on behavioural topics were mapped into either tailored suggestions or tailored insights. Our findings suggest that push notifications with tailored suggestions were more effective overall in encouraging self-monitoring, but amongst frequent app users, push-notifications containing insights was associated with greater self-monitoring. People who were not using the app as frequently were less likely to respond to a prompt. This study suggests that push-notification content does have an impact on subsequent use of key app features, and app developers should consider what content is likely to work best for who, and under what circumstances. Secondary data-analysis of commercial apps presents a unique opportunity to elucidate and optimize health behaviors

    Information theory and atrial fibrillation (AF): a review

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    Note: This article was submitted to Computational Physiology and Medicine, a section of the journal Frontiers in Physiology. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.Atrial Fibrillation (AF) is the most common cardiac rhythm disorder seen in hospitals and in general practice, accounting for up to a third of arrhythmia related hospitalizations. Unfortunately, AF treatment is in practice complicated by the lack of understanding of the fundamental mechanisms underlying the arrhythmia, which makes detection of effective ablation targets particularly difficult. Various approaches to AF mapping have been explored in the hopes of better pinpointing these effective targets, such as Dominant Frequency (DF) analysis, complex fractionated electrograms (CFAE) and unipolar reconstruction (FIRM), but many of these methods have produced conflicting results or require further investigation. Exploration of AF using information theoretic-based approaches may have the potential to provide new insights into the complex system dynamics of AF, whilst also providing the benefit of being less reliant on empirically derived definitions in comparison to alternate mapping approaches. This work provides an overview of information theory and reviews its applications in AF analysis, with particular focus on AF mapping. The works discussed in this review demonstrate how understanding AF from a signal property perspective can provide new insights into the arrhythmic phenomena, which may have valuable clinical implications for AF mapping and ablation in the future

    The manipulation of social, cultural and religious values in socially mediated terrorism

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    This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).This paper presents an analysis of how the Islamic State/Da’esh and Hizb ut-Tahrir Indonesia manipulate conflicting social, cultural and religious values as part of their socially mediated terrorism. It focusses on three case studies: (1) the attacks in Paris, France on 13 November 2015; (2) the destruction of cultural heritage sites in Iraq and Syria; and (3) the struggle between nationalist values and extreme Islamic values in Indonesia. The case studies were chosen as a basis for identifying global commonalities as well as regional differences in socially mediated terrorism. They are located in Asia, the Middle East and Europe. The integrated analysis of these case studies identifies significant trends and suggests actions that could lessen the impact of strategies deployed by extremist groups such as Da’esh, al-Qaeda and Hizb ut-Tahrir. We discuss the broader implications for understanding various aspects of socially mediated terrorism

    Novel Bacterial Cellulose/Gelatin Hydrogels as 3D Scaffolds for Tumor Cell Culture

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    This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).Three-dimensional (3D) cells in vitro culture are becoming increasingly popular in cancer research because some important signals are lost when cells are cultured in a two-dimensional (2D) substrate. In this work, bacterial cellulose (BC)/gelatin hydrogels were successfully synthesized and were investigated as scaffolds for cancer cells in vitro culture to simulate tumor microenvironment. Their properties and ability to support normal growth of cancer cells were evaluated. In particular, the human breast cancer cell line (MDA-MD-231) was seeded into BC/gelatin scaffolds to investigate their potential in 3D cell in vitro culture. MTT proliferation assay, scanning electron microscopy, hematoxylin and eosin staining and immunofluorescence were used to determine cell proliferation, morphology, adhesion, infiltration, and receptor expression. The in vitro MDA-MD-231 cell culture results demonstrated that cells cultured on the BC/gelatin scaffolds had significant adhesion, proliferation, ingrowth and differentiation. More importantly, MDA-MD-231 cells cultured in BC/gelatin scaffolds retained triple-negative receptor expression, demonstrating that BC/gelatin scaffolds could be used as ideal in vitro culture scaffolds for tumor cells.This research was partially funded by Flinders University College of Science and Engineering Start-up grant

    The contribution of non-essential Schizosaccharomyces pombe genes to fitness in response to altered nutrient supply and target of rapamycin activity

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    Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.Nutrient fluctuations in the cellular environment promote changes in cell metabolism and growth to adapt cell proliferation accordingly. The target of rapamycin (TOR) signalling network plays a key role in the coordination of growth and cell proliferation with the nutrient environment and, importantly, nutrient limitation reduces TOR complex 1 (TORC1) signalling. We have performed global quantitative fitness profiling of the collection of Schizosaccharomyces pombe strains from which non-essential genes have been deleted. We identified genes that regulate fitness when cells are grown in a nutrient-rich environment compared with minimal environments, with varying nitrogen sources including ammonium, glutamate and proline. In addition, we have performed the first global screen for genes that regulate fitness when both TORC1 and TORC2 signalling is reduced by Torin1. Analysis of genes whose deletions altered fitness when nutrients were limited, or when TOR signalling was compromised, identified a large number of genes that regulate transmembrane transport, transcription and chromatin organization/ regulation and vesicle-mediated transport. The ability to tolerate reduced TOR signalling placed demands upon a large number of biological processes including autophagy, mRNA metabolic processing and nucleocytoplasmic transport. Importantly, novel biological processes and all processes known to be regulated by TOR were identified in our screens. In addition, deletion of 62 genes conserved in humans gave rise to strong sensitivity or resistance to Torin1, and 29 of these 62 genes have novel links to TOR signalling. The identification of chromatin and transcriptional regulation, nutritional uptake and transport pathways in this powerful genetic model now paves the way for a molecular understanding of how cells adapt to the chronic and acute fluctuations in nutrient supply that all eukaryotes experience at some stage, and which is a key feature of cancer cells within solid tumours.A Cancer Council SA project grant no. [1125662] to J.P. and Newcastle and Flinders University supported this work

    Evaluating the primary stability of standard vs lateralised cementless femoral stems – A finite element study using a diverse patient cohort

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    This manuscript version is made available under the CC-BY-NC-ND 4.0 license: http://creativecommons.org/licenses/by-nc-nd/4.0/ which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited. This author accepted manuscript is made available following 12 month embargo from date of publication (Sept 2018) in accordance with the publisher’s archiving policyBackground Restoring the original femoral offset is desirable for total hip replacements as it preserves the original muscle lever arm and soft tissue tensions. This can be achieved through lateralised stems, however, the effect of variation in the hip centre offset on the primary stability remains unclear. Methods Finite element analysis was used to compare the primary stability of lateralised and standard designs for a cementless femoral stem (Corail®) across a representative cohort of male and female femora (N = 31 femora; age from 50 to 80 years old). Each femur model was implanted with three designs of the Corail® stem, each designed to achieve a different degree of lateralisation. An automated algorithm was used to select the size and position that achieve maximum metaphyseal fit for each of the designs. Joint contact and muscle forces simulating the peak forces during level gait and stair climbing were scaled to the body mass of each subject. Findings The study found that differences in restoring the native femoral offset introduce marginal differences in micromotion (differences in peak micromotion 3000 με) was achieved for some subjects when lateralized stems were used. Interpretation Findings of this study suggest that, with the appropriate size and alignment, the standard offset design is likely to be sufficient for primary stability, in most cases. Nonetheless, appropriate use of lateralised stems has the potential reduce the risk of peri-prosthetic bone damage. This highlights the importance of appropriate implant selection during the surgical planning stage.This study was part of a project funded by an Australian Research Council (ARC 130100122) linkage grant, with partial funding from DePuy Synthes. Prof Taylor, Prof Besier and Prof Clement are chief investigators named on the ARC linkage grant. Dr. Al-Dirini was employed on this project. Dr. Huff is employed by DePuy Synthes

    Quality of life and shoulder function after latissimus dorsi breast reconstruction

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    Part of this article has been presented at the following meeting 4th June 2017: The Plastic Surgery Congress of the Australian Society of Plastic Surgeons in June 2017 in the Gold Coast, Australia. Published by Elsevier Ltd on behalf of British Association of Plastic, Reconstructive and Aesthetic Surgeons. This manuscript version is made available under the CC-BY-NC-ND 4.0 license: http://creativecommons.org/licenses/by-nc-nd/4.0/ which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited. This author accepted manuscript is made available following 12 month embargo from date of publication (June 2018) in accordance with the publisher’s archiving policyBreast reconstruction using a latissimus dorsi flap impacts one of the principal muscles of the shoulder. There is therefore concern that this procedure could impair shoulder function. The primary objective of this study was to study the effect of breast reconstruction using the latissimus dorsi flap on patient reported shoulder function and quality of life, compared to women who underwent total mastectomy without reconstruction. Methods A case-controlled cross-sectional study was conducted using the validated Breast-Q questionnaire and a functional back and shoulder questionnaire. Questionnaires were mailed to women who had undergone latissimus dorsi flap breast reconstruction (n = 100) and women who had undergone total mastectomy without reconstruction (n = 121). The responses from the 2 groups were compared, and results were analysed with t-test and Pearson's Correlation. Results Responses were received from 119 patients (60 latissimus dorsi patients and 59 mastectomy alone patients). Latissimus dorsi flap patients had significantly higher Breast-Q scores for all quality of life domains when compared to mastectomy alone patients. There was, however, no significant difference in functional back and shoulder scores between the two groups. Latissimus dorsi flap patients also scored highly for satisfaction with outcome and satisfaction for the ‘back’. Conclusion Patients report high levels of satisfaction following Latissimus dorsi flap breast reconstruction. This type of reconstruction did not adversely impact back and shoulder function.None

    Does kindness lead to happiness? Voluntary activities and subjective well-being

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    This manuscript version is made available under the CC-BY-NCND 4.0 license: http://creativecommons.org/licenses/by-nc-nd/4.0/ which permits use, distribution and reproduction in any medium, provided the original work is properly cited. This author accepted manuscript is made available following 24 month embargo from date of publication (September 2018) in accordance with the publisher’s archiving policyThis paper investigates empirically the effects of voluntary activities on subjective well-being. After controlling for individual fixed effects, we show that volunteering significantly improves people’s subjective well-being. The positive well-being effects of volunteering are highly heterogeneous, with larger impact at the lower end of the distribution of subjective well-being. Our dynamic analysis shows that the beneficial effects of volunteering are transitory. We find evidence of complete subjective well-being adaptation one year after volunteering. We show that more frequent socialisation, increasing satisfaction with feeling part of local community and rising satisfaction with neighbourhood living in are three channels for the contemporaneous positive linkage between volunteering and subjective well-being.Elisabetta Magnani acknowledges financial support from the Australian Research Council Discovery Project (ARC DP160101914). Rong Zhu acknowledges - financial support from the Australian Research Council Linkage Project (ARC LP170100718)

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