Genetic algorithms as a tool for dosing guideline optimisation : application to intermittent infusion dosing for vancomycin in adults

This paper demonstrates the use of a genetic algorithm (GA) for the optimization of a dosing guideline. GAs are well-suited to derive combinations of doses and dosing intervals that go into a dosing guideline when the number of possible combinations rule out the calculation of all possible outcomes. GAs also allow for different constraints to be imposed on the optimization process to safeguard the clinical feasibility of the dosing guideline. In this work, we demonstrate the use of a GA for the optimization of intermittent vancomycin administration in adult patients. Constraints were placed on the dose strengths, the length of the dosing intervals, and the maximum infusion rate. In addition, flexibility with respect to the timing of the first maintenance dose was included in the optimization process. The GA-based optimal solution is compared with the Scottish Antimicrobial Prescribing Group vancomycin guideline

Post-dropping behavior of potato aphids (Macrosiphum euphorbiae)

Funding: Perry Foundation, University of St Andrews, Scottish Government Rural and Environmental Sciences and Analytical Services Division.Dropping behavior is an effective antipredator defense utilized by many insects including aphids, which drop from plants to lower plant parts or underlying substrates to avoid attack from predatory invertebrates. While research commonly focusses on triggers of dropping, less attention is given to what happens to prey individuals following escape drops. In this study, the duration of tonic immobility, recovery rates, and cases of “instant recovery” (re-clinging to lower plant parts) exhibited by potato aphids (Macrosiphum euphorbiae) that dropped from potted seedlings in response to introduced ladybird (Adalia bipunctata) adults, lacewing (Chrysoperla carnea) larvae, and a standardized tactile stimulus were investigated in relation to a range of environmental factors. Air temperature had a negative correlation with the duration of post-dropping tonic immobility; as temperature increased, time spent motionless decreased. Aphids also showed a pattern of increased recovery rate at higher temperatures. Aphids may be selected to move off the substrate quicker to avoid risks of overheating/desiccation at higher temperatures; and/or higher body temperature facilitates locomotion. Stimulus type also influenced recovery rate back to the original seedling, with aphids generally recovering after the standardized stimulus quicker than after dropping triggered by a real predator. Considering cases of instant recovery onto lower-reaches of the host seedling, seedling height influenced the likelihood of re-clinging, with aphids that managed to instantly recover dropping from, on average, taller seedlings than aphids that dropped to the substrate. Plant architecture could mitigate the costs of dropping for aphids, but further studies quantifying understory foliage cover are needed.Publisher PDFPeer reviewe

The Involvement of Voltage-Operated Calcium Channels in Somato-Dendritic Oxytocin Release

Magnocellular neurons of the supraoptic nucleus (SON) secrete oxytocin and vasopressin from axon terminals in the neurohypophysis, but they also release large amounts of peptide from their somata and dendrites, and this can be regulated both by activity-dependent Ca2+ influx and by mobilization of intracellular Ca2+. This somato-dendritic release can also be primed by agents that mobilise intracellular Ca2+, meaning that the extent to which it is activity-dependent, is physiologically labile. We investigated the role of different Ca2+ channels in somato-dendritic release; blocking N-type channels reduced depolarisation-induced oxytocin release from SONs in vitro from adult and post-natal day 8 (PND-8) rats, blocking L-type only had effect in PND-8 rats, while blocking other channel types had no significant effect. When oxytocin release was primed by prior exposure to thapsigargin, both N- and L-type channel blockers reduced release, while P/Q and R-type blockers were ineffective. Using confocal microscopy, we found immunoreactivity for Cav1.2 and 1.3 channel subunits (which both form L-type channels), 2.1 (P/Q type), 2.2 (N-type) and 2.3 (R-type) in the somata and dendrites of both oxytocin and vasopressin neurons, and the intensity of the immunofluorescence signal for different subunits differed between PND-8, adult and lactating rats. Using patch-clamp electrophysiology, the N-type Ca2+ current density increased after thapsigargin treatment, but did not alter the voltage sensitivity of the channel. These results suggest that the expression, location or availability of N-type Ca2+ channels is altered when required for high rates of somato-dendritic peptide release

Direct measurements of ice-shelf flexure caused by surface meltwater ponding and drainage.

Global sea-level rise is caused, in part, by more rapid ice discharge from Antarctica, following the removal of the restraining forces of floating ice-shelves after their break-up. A trigger of ice-shelf break-up is thought to be stress variations associated with surface meltwater ponding and drainage, causing flexure and fracture. But until now, there have been no direct measurements of these processes. Here, we present field data from the McMurdo Ice Shelf, Antarctica, showing that the filling, to ~2 m depth, and subsequent draining, by overflow and channel incision, of four surface lakes causes pronounced and immediate ice-shelf flexure over multiple-week timescales. The magnitude of the vertical ice-shelf deflection reaches maxima of ~1 m at the lake centres, declining to zero at distances of <500 m. Our results should be used to guide development of continent-wide ice-sheet models, which currently do not simulate ice-shelf break-up due to meltwater loading and unloading.This work was supported by the U.S. National Science Foundation under award PLR-1443126 to the University of Chicago, a Leverhulme Early Career Fellowship (ECF-2014-412) and a CIRES Postdoctoral Visiting Fellowship, both awarded to A.F.B., and a NASA Earth and Space Science Fellowship (NNX15AN44H) awarded to G.J.M

Neighborhood Social Environment and Patterns of Adherence to Oral Hypoglycemic Agents among Patients with Type 2 Diabetes Mellitus

This study examined whether neighborhood social environment was related to patterns of adherence to oral hypoglycemic agents among primary care patients with type 2 diabetes mellitus. Residents in neighborhoods with high social affluence, high residential stability, and high neighborhood advantage, compared to residents in neighborhoods with one or no high features present, were significantly more likely to have an adherent pattern compared to a nonadherent pattern. Neighborhood social environment may influence patterns of adherence. Reliance on a multilevel contextual framework, extending beyond the individual, to promote diabetic self-management activities may be essential for notable public health improvements

The strength of the meridional overturning circulation of the stratosphere.

The distribution of gases such as ozone and water vapour in the stratosphere - which affect surface climate - is influenced by the meridional overturning of mass in the stratosphere, the Brewer-Dobson circulation. However, observation-based estimates of its global strength are difficult to obtain. Here we present two calculations of the mean strength of the meridional overturning of the stratosphere. We analyze satellite data that document the global diabatic circulation between 2007- 2011, and compare these to three re-analysis data sets and to simulations with a state-of-the-art chemistry-climate model. Using measurements of sulfur hexafluoride (SF6) and nitrous oxide, we calculate the global mean diabatic overturning mass flux throughout the stratosphere. In the lower stratosphere, these two estimates agree, and at a potential temperature level of 460 K (about 20 km or 60 hPa in tropics), the global circulation strength is 6.3-7.6 × 109 kg/s. Higher in the atmosphere, only the SF6-based estimate is available, and it diverges from the re-analysis data and simulations. Interpretation of the SF6 data-based estimate is limited because of a mesospheric sink of SF6; however, the reanalyses also differ substantially from each other. We conclude that the uncertainty in the mean meridional overturning circulation strength at upper levels of the stratosphere amounts to at least 100 %

Road space reallocation in Scotland: A health impact assessment

IntroductionRoad space reallocation involves re-distributing space away from motor vehicles, including car parking and carriageway space, towards other uses. This can promote a shift to more sustainable travel modes and is likely to affect health through multiple pathways.MethodsWe conducted a health impact assessment to identify and assess the potential impacts of road space reallocation on health and health inequalities in Scotland. This involved a facilitated scoping workshop to identify potential impacts, collation of routine data, interviews with 13 key informants and a rapid review of research literature.ResultsWe found that road space reallocation could have positive impacts on health by reducing overall levels of private motorised traffic, encouraging walking, wheeling and cycling, realising benefits from alternative uses of space and supporting local businesses. There is potential for positive impact on public transport if space is reallocated to prioritise buses, but bus users can also be disadvantaged if bus routes are diverted or stops impeded. Reallocation can improve transport and health equity if it increases support for modes other than car use, but disabled people may be disadvantaged if the reallocated space, and alternative modes, are not accessible for them.ConclusionsRoad space reallocation can improve health and help reduce health inequalities. However, consideration is needed to ensure sufficient alternatives to car use are supported and the reallocated space is accessible for people with different needs. Reallocation schemes should be considered as part of a wider inclusive approach to road transport supporting active travel and public or community transport. Road space reallocation should contribute to wider place-making initiatives aiming to improve quality of local environments and meet community needs