Macroscopic nucleation phenomena in continuum media with long-range interactions

Nucleation, commonly associated with discontinuous transformations between metastable and stable phases, is crucial in fields as diverse as atmospheric science and nanoscale electronics. Traditionally, it is considered a microscopic process (at most nano-meter), implying the formation of a microscopic nucleus of the stable phase. Here we show for the first time, that considering long-range interactions mediated by elastic distortions, nucleation can be a macroscopic process, with the size of the critical nucleus proportional to the total system size. This provides a new concept of "macroscopic barrier-crossing nucleation". We demonstrate the effect in molecular dynamics simulations of a model spin-crossover system with two molecular states of different sizes, causing elastic distortions.Comment: 12 pages, 4 figures. Supplementary information accompanies this paper at http://www.nature.com/scientificreport

Male Circumcision at Different Ages in Rwanda: A Cost-Effectiveness Study

Agnes Binagwaho and colleagues predict that circumcision of newborn boys would be effective and cost-saving as a long-term strategy to prevent HIV in Rwanda

Estimating the Resources Needed and Savings Anticipated from Roll-Out of Adult Male Circumcision in Sub-Saharan Africa

Background: Trials in Africa indicate that medical adult male circumcision (MAMC) reduces the risk of HIV by 60%. MAMC may avert 2 to 8 million HIV infections over 20 years in sub-Saharan Africa and cost less than treating those who would have been infected. This paper estimates the financial and human resources required to roll out MAMC and the net savings due to reduced infections. Methods: We developed a model which included costing, demography and HIV epidemiology. We used it to investigate 14 countries in sub-Saharan Africa where the prevalence of male circumcision was lower than 80% and HIV prevalence among adults was higher than 5%, in addition to Uganda and the Nyanza province in Kenya. We assumed that the roll-out would take 5 years and lead to an MC prevalence among adult males of 85%. We also assumed that surgery would be done as it was in the trials. We calculated public program cost, number of full-time circumcisers and net costs or savings when adjusting for averted HIV treatments. Costs were in USD, discounted to 2007. 95% percentile intervals (95% PI) were estimated by Monte Carlo simulations. Results: In the first 5 years the number of circumcisers needed was 2 282 (95% PI: 2 018 to 2 959), or 0.24 (95% PI: 0.21 to 0.31) per 10 000 adults. In years 6-10, the number of circumcisers needed fell to 513 (95% PI: 452 to 664). The estimated 5-year cost of rolling out MAMC in the public sector was $919 million (95$672 million (95% PI: 437 to 1 021) and over 20 years there were net savings of $2.3 billion (95% PI: 1.4 to 3.4). Conclusion: A rapid roll-out of MAMC in sub-Saharan Africa requires substantial funding and a high number of circumcisers for the first five years. These investments are justified by MAMC's substantial health benefits and the savings accrued by averting future HIV infections. Lower ongoing costs and continued care savings suggest long-term sustainability

Variations in IC50 Values with Purity of Mushroom Tyrosinase

The effects of various inhibitors on crude, commercial and partially purified commercial mushroom tyrosinase were examined by comparing IC50 values. Kojic acid, salicylhydroxamic acid, tropolone, methimazole, and ammonium tetrathiomolybdate had relatively similar IC50 values for the crude, commercial and partially purified enzyme. 4-Hexylresorcinol seemed to have a somewhat higher IC50 value using crude extracts, compared to commercial or purified tyrosinase. Some inhibitors (NaCl, esculetin, biphenol, phloridzin) showed variations in IC50 values between the enzyme samples. In contrast, hydroquinone, lysozyme, Zn2+, and anisaldehyde showed little or no inhibition in concentration ranges reported to be effective inhibitors. Organic solvents (DMSO and ethanol) had IC50 values that were similar for some of the tyrosinase samples. Depending of the source of tyrosinase and choice of inhibitor, variations in IC50 values were observed

Effect of tamoxifen on hepatic regeneration in male rats

A number of metabolic changes within the liver occur concurrent with hepatic regeneration. These processes suggest that the administration of an antiestrogen might alter the rate of hepatic regeneration. To examine this question, male Wistar rats were treated with tamoxifen (0.1 mg/rat/day or 1.0 mg/rat/day) or vehicle for three days prior to and after partial hepatectomy, and the anatomic and biochemical process of hepatic regeneration was assessed. Tamoxifen administration caused a dose-dependent decrease in the hepatic cytosolic estrogen receptor activity and, conversely, a dose-dependent increase in cytosolic androgen receptor activity. Despite these changes in baseline hepatic sex steroid receptor status, all receptor activities were comparable between the three groups within 24 hr of partial hepatectomy. Moreover, no differences in any of the the parameters assessing hepatic regeneration following partial hepatectomy were evident: liver-body ratio, ornithine decarboxylase activity, and thymidine kinase activity. This lack of effect of tamoxifen treatment on hepatic regeneration suggests either that estrogens do not play a role in the modulation of liver growth after partial hepatectomy or that, once initiated, the regenerative process per se determines a series of events that regulate hepatocellular sex hormone receptor status independent of extrahepatic stimuli. © 1989 Plenum Publishing Corporation

Vascular responses of the extremities to transdermal application of vasoactive agents in Caucasian and African descent individuals

This is an accepted manuscript of an article published by Springer in European Journal of Applied Physiology on 04/04/2015, available online: https://doi.org/10.1007/s00421-015-3164-2 The accepted version of the publication may differ from the final published version.© 2015, Springer-Verlag Berlin Heidelberg. Purpose: Individuals of African descent (AFD) are more susceptible to non-freezing cold injury than Caucasians (CAU) which may be due, in part, to differences in the control of skin blood flow. We investigated the skin blood flow responses to transdermal application of vasoactive agents. Methods: Twenty-four young males (12 CAU and 12 AFD) undertook three tests in which iontophoresis was used to apply acetylcholine (ACh 1 w/v %), sodium nitroprusside (SNP 0.01 w/v %) and noradrenaline (NA 0.5 mM) to the skin. The skin sites tested were: volar forearm, non-glabrous finger and toe, and glabrous finger (pad) and toe (pad). Results: In response to SNP on the forearm, AFD had less vasodilatation for a given current application than CAU (P = 0.027–0.004). ACh evoked less vasodilatation in AFD for a given application current in the non-glabrous finger and toe compared with CAU (P = 0.043–0.014) with a lower maximum vasodilatation in the non-glabrous finger (median [interquartile], AFD n = 11, 41[234] %, CAU n = 12, 351[451] %, P = 0.011) and non-glabrous toe (median [interquartile], AFD n = 9, 116[318] %, CAU n = 12, 484[720] %, P = 0.018). ACh and SNP did not elicit vasodilatation in the glabrous skin sites of either group. There were no ethnic differences in response to NA. Conclusion: AFD have an attenuated endothelium-dependent vasodilatation in non-glabrous sites of the fingers and toes compared with CAU. This may contribute to lower skin temperature following cold exposure and the increased risk of cold injuries experienced by AFD.Published versio

Incorporating one health into medical education

One Health is an emerging concept that stresses the linkages between human, animal, and environmental health, as well as the need for interdisciplinary communication and collaboration to address health issues including emerging zoonotic diseases, climate change impacts, and the human-animal bond. It promotes complex problem solving using a systems framework that considers interactions between humans, animals, and their shared environment. While many medical educators may not yet be familiar with the concept, the One Health approach has been endorsed by a number of major medical and public health organizations and is beginning to be implemented in a number of medical schools. In the research setting, One Health opens up new avenues to understand, detect, and prevent emerging infectious diseases, and also to conduct translational studies across species. In the clinical setting, One Health provides practical ways to incorporate environmental and animal contact considerations into patient care. This paper reviews clinical and research aspects of the One Health approach through an illustrative case updating the biopsychosocial model and proposes a basic set of One Health competencies for training and education of human health care providers

Risk adjustment methods for Home Care Quality Indicators (HCQIs) based on the minimum data set for home care

BACKGROUND: There has been increasing interest in enhancing accountability in health care. As such, several methods have been developed to compare the quality of home care services. These comparisons can be problematic if client populations vary across providers and no adjustment is made to account for these differences. The current paper explores the effects of risk adjustment for a set of home care quality indicators (HCQIs) based on the Minimum Data Set for Home Care (MDS-HC). METHODS: A total of 22 home care providers in Ontario and the Winnipeg Regional Health Authority (WRHA) in Manitoba, Canada, gathered data on their clients using the MDS-HC. These assessment data were used to generate HCQIs for each agency and for the two regions. Three types of risk adjustment methods were contrasted: a) client covariates only; b) client covariates plus an "Agency Intake Profile" (AIP) to adjust for ascertainment and selection bias by the agency; and c) client covariates plus the intake Case Mix Index (CMI). RESULTS: The mean age and gender distribution in the two populations was very similar. Across the 19 risk-adjusted HCQIs, Ontario CCACs had a significantly higher AIP adjustment value for eight HCQIs, indicating a greater propensity to trigger on these quality issues on admission. On average, Ontario had unadjusted rates that were 0.3% higher than the WRHA. Following risk adjustment with the AIP covariate, Ontario rates were, on average, 1.5% lower than the WRHA. In the WRHA, individual agencies were likely to experience a decline in their standing, whereby they were more likely to be ranked among the worst performers following risk adjustment. The opposite was true for sites in Ontario. CONCLUSIONS: Risk adjustment is essential when comparing quality of care across providers when home care agencies provide services to populations with different characteristics. While such adjustment had a relatively small effect for the two regions, it did substantially affect the ranking of many individual home care providers

Social entrepreneurs in challenging places: A Delphi study of experiences and perspectives

Social Enterprises have grown in number and scope in response to reductions in state-provided welfare and increasing ambition to improve social conditions. While a range of issues have been identified in the literature as affecting the ability of Social Enterprises to successfully conduct their activities, there is currently a dearth of research into the relative influence of these factors. This study explores and ranks the challenges faced by social entrepreneurs in South Wales. Based on a Delphi study with 21 social entrepreneurs, government policy-developers and scholars, it presents a hierarchy of 14 factors, useful instruments for informing social entrepreneurs and policy-makers about the way social enterprises are managed, and how national and local policy should be developed. As part of this, the study also identifies four novel factors that affect the sustainability of social enterprises: ‘Professionalisation of Marketing’, ‘Perception of Validity’, ‘Leadership’ and ‘Situatedness’