Modelling for Taenia solium control strategies beyond 2020

The cestode Taenia solium is responsible for a considerable cross-sectoral health and economic burden due to human neurocysticercosis and porcine cysticercosis. The 2012 World Health Organization (WHO) roadmap for neglected tropical diseases called for the development of a validated strategy for control of T. solium; however, such a strategy is not yet available. In 2019, WHO launched a global consultation aimed at refining the post-2020 targets for control of T. solium for a new roadmap for neglected tropical diseases. In response, two groups working on taeniasis and cysticercosis mathematical models (cystiSim and EPICYST models), together with a range of other stakeholders organized a workshop to provide technical input to the WHO consultation and develop a research plan to support efforts to achieve the post-2020 targets. The workshop led to the formation of a collaboration, CystiTeam, which aims to tackle the population biology, transmission dynamics, epidemiology and control of T. solium through mathematical modelling approaches. In this paper, we outline developments in T. solium control and in particular the use of modelling to help achieve post-2020 targets for control of T. solium. We discuss the steps involved in improving confidence in the predictive capacities of existing mathematical and computational models on T. solium transmission, including model comparison, refinement, calibration and validation. Expanding the CystiTeam partnership to other research groups and stakeholders, particularly those operating in different geographical and endemic areas, will enhance the prospects of improving the applicability of T. solium transmission models to inform taeniasis and cysticercosis control strategies

Self-Assembly of Supramolecular Triblock Copolymer Complexes

Four different poly(tert-butoxystyrene)-b-polystyrene-b-poly(4-vinylpyridine) (PtBOS-b-PS-b-P4VP) linear triblock copolymers, with the P4VP weight fraction varying from 0.08 to 0.39, were synthesized via sequential anionic polymerization. The values of the unknown interaction parameters between styrene and tert-butoxystyrene and between tert-butoxystyrene and 4-vinylpyridine were determined from random copolymer blend miscibility studies and found to satisfy 0.031<χS,tBOS<0.034 and 0.39<χ4VP,tBOS<0.43, the latter being slightly larger than the known 0.30<χS,4VP≤0.35 value range. All triblock copolymers synthesized adopted a P4VP/PS core/shell cylindrical self-assembled morphology. From these four triblock copolymers supramolecular complexes were prepared by hydrogen bonding a stoichiometric amount of pentadecylphenol (PDP) to the P4VP blocks. Three of these complexes formed a triple lamellar ordered state with additional short length scale ordering inside the P4VP(PDP) layers. The self-assembled state of the supramolecular complex based on the triblock copolymer with the largest fraction of P4VP consisted of alternating layers of PtBOS and P4VP(PDP) layers with PS cylinders inside the latter layers. The difference in morphology between the triblock copolymers and the supramolecular complexes is due to two effects: (i) a change in effective composition and, (ii) a reduction in interfacial tension between the PS and P4VP containing domains. The small angle X-ray scattering patterns of the supramolecules systems are very temperature sensitive. A striking feature is the disappearance of the first order scattering peak of the triple lamellar state in certain temperature intervals, while the higher order peaks (including the third order) remain. This is argued to be due to the thermal sensitivity of the hydrogen bonding and thus directly related to the very nature of these systems.

Tuning chelation by the surfactant-like peptide A6H using predetermined pH values

We examine the self-assembly of a peptide A6H comprising a hexa-alanine sequence A6 with a histidine (H) “head group”, which chelates Zn2+ cations. We study the self assembly of A6H and binding of Zn2+ ions in ZnCl2 solutions, under acidic and neutral conditions. A6H self-assembles into nanotapes held together by a β-sheet structure in acidic aqueous solutions. By dissolving A6H in acidic ZnCl2 solutions, the carbonyl oxygen atoms in A6H chelate the Zn2+ ions and allow for β-sheet formation at lower concentrations, consequently reducing the onset concentration for nanotape formation. A6H mixed with water or ZnCl2 solutions under neutral conditions produces short sheets or pseudocrystalline tapes, respectively. The imidazole ring of A6H chelates Zn2+ ions in neutral solutions. The internal structure of nanosheets and pseudocrystalline sheets in neutral solutions is similar to the internal structure of A6H nanotapes in acidic solutions. Our results show that it is possible to induce dramatic changes in the self-assembly and chelation sites of A6H by changing the pH of the solution. However, it is likely that the amphiphilic nature of A6H determines the internal structure of the self-assembled aggregates independent from changes in chelation

Oscillatory Shear Flow-Induced Alignment of Lamellar Melts of Hydrogen-Bonded Comb Copolymer Supramolecules

In this work we present the orientational behavior of comb copolymer-like supramolecules P4VP(PDP)1.0, obtained by hydrogen bonding between poly(4-vinylpyridine) and pentadecylphenol, during large-amplitude oscillatory shear flow experiments over a broad range of frequencies (0.001-10 Hz). The alignment diagram, presenting the macroscopic alignment in T/TODT vs ω/ωc, contains three regions of parallel alignment separated by a region of perpendicular alignment. For our material, the order-disorder temperature TODT = 67 °C and ωc, the frequency above which the distortion of the chain conformation dominates the materials’ viscoelasticity, is around 0.1 Hz at 61 °C. For the first time flipping from a pure transverse alignment via biaxial transverse/perpendicular alignment to a perpendicular alignment as a function of the strain amplitude was found.

Degradation versus self-assembly of block copolymer micelles

The stability of micelles self-assembled from block copolymers can be altered by the degradation of the blocks. Slow degradation shifts the equilibrium size distribution of block copolymer micelles and change their properties. Quasi-equilibrium scaling theory shows that the degradation of hydrophobic blocks in the core of micelles destabilize the micelles reducing their size, while the degradation of hydrophilic blocks forming coronas of micelles favors larger micelles and may, at certain conditions, induce the formation of micelles from individual chains.Comment: Published in Langmuir http://pubs.acs.org/doi/pdf/10.1021/la204625

Weak Segregation Theory and Non-Conventional Morphologies in the Ternary ABC Triblock Copolymers

The Leibler weak segregation theory in molten diblock copolymers is generalized with due regard for the 2nd shell harmonics contributions defined in the paper and the phase diagrams are built for the linear and miktoarm ternary ABC triblock copolymers. The symmetric linear copolymers with the middle block non-selective with respect to the side ones are shown to undergo the continuous ODT not only into the lamellar phase but also into various non-conventional cubic phases (depending on the middle block composition it could be the simple cubic, face-centered cubic or non-centrosymmetric phase revealing the symmetry of space group No.214 first predicted to appear in molten block copolymers). For asymmetric linear ABC copolymers a region of compositions is found where the weakly segregated gyroid (double gyroid) phase exists between the planar hexagonal and lamellar or one of the non-conventional cubic phases up to the very critical point. In contrast, the miktoarm ABC block copolymers with one of its arm non-selective with respect to the two others are shown to reveal a pronounced tendency towards strong segregation, which is preceded by increase of stability of the conventional BCC phase and a peculiar weakly segregated BCC phase (BCC3), where the dominant harmonics belong to the 3rd co-ordination sphere of the reciprocal lattice. The validity region of the developed theory is discussed and outlined in the composition triangles both for linear and miktoarm copolymers.Comment: 61 pages, 12 figure

Determinants of the range of drugs prescribed in general practice: a cross-sectional analysis

Background: Current health policies assume that prescribing is more efficient and rational when general practitioners (GPs) work with a formulary or restricted drugs lists and thus with a limited range of drugs. Therefore we studied determinants of the range of drugs prescribed by general practitioners, distinguishing general GP-characteristics, characteristics of the practice setting, characteristics of the patient population and information sources used by GPs. Methods: Secondary analysis was carried out on data from the Second Dutch Survey in General Practice. Data were available for 138 GPs working in 93 practices. ATC-coded prescription data from electronic medical records, census data and data from GP/ practice questionnaires were analyzed with multilevel techniques. Results: The average GP writes prescriptions for 233 different drugs, i.e. 30% of the available drugs on the market within one year. There is considerable variation between ATC main groups and subgroups and between GPs. GPs with larger patient lists, GPs with higher prescribing volumes and GPs who frequently receive representatives from the pharmaceutical industry have a broader range when controlled for other variables. Conclusion: The range of drugs prescribed is a useful instrument for analysing GPs' prescribing behaviour. It shows both variation between GPs and between therapeutic groups. Statistically significant relationships found were in line with the hypotheses formulated, like the one concerning the influence of the industry. Further research should be done into the relationship between the range and quality of prescribing and the reasons why some GPs prescribe a greater number of different drugs than others.