In vivo evaluation of pH-sensitive polymeric microparticles for site specific drug delivery to the small intestine and colon

A novel emulsification/solvent evaporation process was developed to formulate prednisolone-loaded Eudragit L and S microparticles as drug delivery vehicles to target different regions of the gastrointestinal tract. Microparticles were characterised in vitro and in vivo. This is the first report of drug absorption form orally administered Eudragit L and S microparticles

Stress Induces Contextual Blindness in Lotteries and Coordination Games

In this paper, we study how stress affects risk taking in three tasks: individual lotteries, Stag Hunt (coordination) games, and Hawk-Dove (anti-coordination) games. Both control and stressed subjects take more risks in all three tasks when the value of the safe option is decreased and in lotteries when the expected gain is increased. Also, subjects take longer to take decisions when stakes are high, when the safe option is less attractive and in the conceptually more difficult Hawk-Dove game. Stress (weakly) increases reaction times in those cases. Finally, our main result is that the behavior of stressed subjects in lotteries, Stag Hunt and Hawk-Dove are all highly predictive of each other (p-value < 0.001 for all three pairwise correlations). Such strong relationship is not present in our control group. Our results illustrate a “contextual blindness” caused by stress. The mathematical and behavioral tensions of Stag Hunt and Hawk-Dove games are axiomatically different, and we should expect different behavior across these games, and also with respect to the individual task. A possible explanation for the highly significant connection across tasks in the stress condition is that stressed subjects habitually rely on one mechanism to make a decision in all contexts whereas unstressed subjects utilize a more cognitively flexible approach

Mimicking the impact of infant tongue peristalsis on behaviour of solid oral dosage forms administered during breastfeeding

An in vitro simulation system was developed to study the effect of an infant’s peristaltic tongue motion during breastfeeding on oral rapidly disintegrating tablets in the mouth, for use in rapid product candidate screening. These tablets are being designed for use inside a modified nipple shield worn by a mother during breastfeeding, a proposed novel platform technology to administer drugs and nutrients to breastfeeding infants. In this study, the release of a model compound, sulforhodamine B, from tablet formulations was studied under physiologically relevant forces induced by compression and rotation of a tongue mimic. The release profiles of the sulforhodamine B in flowing deionised water were found to be statistically different using 2-way ANOVA with matching, when tongue mimic rotation was introduced for two compression levels representing two tongue strengths (P=0.0013 and P<0.0001 for the lower and higher compression settings, respectively). Compression level was found to be a significant factor for increasing model compound release at rotational rates representing non-nutritive breastfeeding (P=0.0162). This novel apparatus is the first to simulate the motion and pressures applied by the tongue, and could be used in future infant oral product development

Experimental evidence that livestock grazing intensity affects cyclic vole population regulation processes

Peer reviewedPublisher PD

Ecology of a North Sea pockmark with an active methane seep

ABSTRACT: At a large North Sea pockmark, with active methane seeps, surface sediments were found to have higher insoluble sulphide concentrations than sedlments from the surrounding area. The fauna of the pockmark was characterized by 2 species which have not pi-evlously been reported from the Fladen Ground in the northern North Sea. These species were a b~valve, Thyasira sarsi (which is known to contain endosymbiotic sulphur-oxidising bacteria) and a mouthless and gutless nematode, Astomonerna sp., which also contains endosymbiotic bacteria The nematode was the dominant meiofauna species in the pockmark sediments. Both macro-lnfauna and total nematodes were in low abundance in samples taken from the base of the pockmark. Sediment samples from the pockmark contained numerous otoliths, implying that substantial winnowing of the sediment had taken place. This was supported by studies on the sulphide concentrations in the sediment which showed multiple layering of the sediments on the sides of the pockmark, suggesting displacement. The carbon isotope compositions (6I3c) of the tissues of benthic animals from in and around the pockmark were generally in the range -16 to -2O%, indicating that little methane-derived carbon was contributing to their nutrition. T sarsi had the most 13c-depleted tissues, -31.4 to -35.1 L, confirming the nutritional dependence of this species on chemoautotrophic bacteria that utilize reduced sulphur

A network-based dynamical ranking system for competitive sports

From the viewpoint of networks, a ranking system for players or teams in sports is equivalent to a centrality measure for sports networks, whereby a directed link represents the result of a single game. Previously proposed network-based ranking systems are derived from static networks, i.e., aggregation of the results of games over time. However, the score of a player (or team) fluctuates over time. Defeating a renowned player in the peak performance is intuitively more rewarding than defeating the same player in other periods. To account for this factor, we propose a dynamic variant of such a network-based ranking system and apply it to professional men's tennis data. We derive a set of linear online update equations for the score of each player. The proposed ranking system predicts the outcome of the future games with a higher accuracy than the static counterparts.Comment: 6 figure

Combinatorial–computational–chemoinformatics (C3) approach to finding and analyzing low-energy tautomers

Finding the most stable tautomer or a set of low-energy tautomers of molecules is critical in many aspects of molecular modelling or virtual screening experiments. Enumeration of low-energy tautomers of neutral molecules in the gas-phase or typical solvents can be performed by applying available organic chemistry knowledge. This kind of enumeration is implemented in a number of software packages and it is relatively reliable. However, in esoteric cases such as charged molecules in uncommon, non-aqueous solvents there is simply not enough available knowledge to make reliable predictions of low energy tautomers. Over the last few years we have been developing an approach to address the latter problem and we successfully applied it to discover the most stable anionic tautomers of nucleic acid bases that might be involved in the process of DNA damage by low-energy electrons and in charge transfer through DNA. The approach involves three steps: (1) combinatorial generation of a library of tautomers, (2) energy-based screening of the library using electronic structure methods, and (3) analysis of the information generated in step (2). In steps 1–3 we employ combinatorial, computational and chemoinformatics techniques, respectively. Therefore, this hybrid approach is named “Combinatorial*Computational*Chemoinformatics”, or just abbreviated as C3 (or C-cube) approach. This article summarizes our developments and most interesting methodological aspects of the C3 approach. It can serve as an example how to identify the most stable tautomers of molecular systems for which common chemical knowledge had not been sufficient to make definite predictions

Characterisation of zinc delivery from a nipple shield delivery system using a breastfeeding simulation apparatus

Zinc delivery from a nipple shield delivery system (NSDS), a novel platform for administering medicines to infants during breastfeeding, was characterised using a breastfeeding simulation apparatus. In this study, human milk at flow rates and pressures physiologically representative of breastfeeding passed through the NSDS loaded with zinc-containing rapidly disintegrating tablets, resulting in release of zinc into the milk. Inductively coupled plasma optical emission spectrometry was used to detect the zinc released, using a method that does not require prior digestion of the samples and that could be applied in other zinc analysis studies in breast milk. Four different types of zinc-containing tablets with equal zinc load but varying excipient compositions were tested in the NSDS in vitro. Zinc release measured over 20 minutes ranged from 32-51% of the loaded dose. Total zinc release for sets tablets of the same composition but differing hardness were not significantly different from one another with P = 0.3598 and P = 0.1270 for two tested pairs using unpaired t tests with Welch's correction. By the same test total zinc release from two sets of tablets having similar hardness but differing composition were also not significantly significant with P = 0.2634. Future zinc tablet composition and formulation optimisation could lead to zinc supplements and therapeutics with faster drug release, which could be administered with the NSDS during breastfeeding. The use of the NSDS to deliver zinc could then lead to treatment and prevention of some of the leading causes of child mortality, including diarrheal disease and pneumonia.This work was made possible for all authors through the support of the Saving Lives at Birth partners: the United States Agency for International Development (USAID), the Government of Norway, the Bill & Melinda Gates Foundation, Grand Challenges Canada and the UK Department for International Development (DFID) through the Saving Lives at Birth Award Scheme, grant number 0454-03. The website for the award scheme is https://savinglivesatbirth.net/. We also thank the Medical Research Council (grant number MC_US_A090_0008/Unit Programme number U1059) for their support of Sylvaine Bruggraber (S.F.A.B.). The website for this grant is http://www.mrc-ewl.cam.ac.uk/. The Gates Cambridge Trust is also thanked for their funding of Rebekah Scheuerle (R.L.S) through an academic scholarship. Their website is https://www.gatescambridge.org/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Mathematizing Darwin

Ernst Mayr called the first part of the evolutionary synthesis the ‘Fisherian synthesis’ on account of the dominant role played by R.A. Fisher in forging a mathematical theory of natural selection together with J.B.S. Haldane and Sewall Wright in the decade 1922–1932. It is here argued that Fisher’s contribution relied on a close reading of Darwin’s work to a much greater extent than did the contributions of Haldane and Wright, that it was synthetic in contrast to their analytic approach and that it was greatly influenced by his friendship with the Darwin family, particularly with Charles’s son Leonard