Heteroclinic intersections between Invariant Circles of Volume-Preserving Maps

We develop a Melnikov method for volume-preserving maps with codimension one invariant manifolds. The Melnikov function is shown to be related to the flux of the perturbation through the unperturbed invariant surface. As an example, we compute the Melnikov function for a perturbation of a three-dimensional map that has a heteroclinic connection between a pair of invariant circles. The intersection curves of the manifolds are shown to undergo bifurcations in homologyComment: LaTex with 10 eps figure

Hospital costs of out-of-hospital cardiac arrest patients treated in intensive care; a single centre evaluation using the national tariff-based system

OBJECTIVES: There is a scarcity of literature reporting hospital costs for treating out of hospital cardiac arrest (OOHCA) survivors, especially within the UK. This is essential for assessment of cost-effectiveness of interventions necessary to allow just allocation of resources within the National Health Service. We set out primarily to calculate costs stratified against hospital survival and neurological outcomes. Secondarily, we estimated cost effectiveness based on estimates of survival and utility from previous studies to calculate costs per quality adjusted life year (QALY). SETTING: We performed a single centre (London) retrospective review of in-hospital costs of patients admitted to the intensive care unit (ICU) following return of spontaneous circulation (ROSC) after OOHCA over 18 months from January 2011 (following widespread introduction of targeted temperature management and primary percutaneous intervention). PARTICIPANTS: Of 69 successive patients admitted over an 18-month period, survival and cerebral performance category (CPC) outcomes were obtained from review of databases and clinical notes. The Trust finance department supplied ICU and hospital costs using the Payment by Results UK system. RESULTS: Of those patients with ROSC admitted to ICU, survival to hospital discharge (any CPC) was 33/69 (48%) with 26/33 survivors in CPC 1–2 at hospital discharge. Cost per survivor to hospital discharge (including total cost of survivors and non-survivors) was £50 000, cost per CPC 1–2 survivor was £65 000. Cost and length of stay of CPC 1–2 patients was considerably lower than CPC 3–4 patients. The majority of the costs (69%) related to intensive care. Estimated cost per CPC 1–2 survivor per QALY was £16 000. CONCLUSIONS: The costs of in-hospital patient care for ICU admissions following ROSC after OOHCA are considerable but within a reasonable threshold when assessed from a QALY perspective

Higher and lower supramolecular orders for the design of self-assembled heterochiral tripeptide hydrogel biomaterials

The self-assembly behaviour of the eight stereoisomers of Val\u2013Phe\u2013Phe tripeptides under physiological conditions is assessed by several spectroscopy and microscopy techniques. We report the first examples of self-organised hydrogels from tripeptides in the L\u2013D\u2013L or D\u2013L\u2013D configuration, besides the expected gels with the D\u2013L\u2013L or L\u2013D\u2013D configuration, thus widening the scope for using amino acid chirality as a tool to drive self-assembly. Importantly, the positions of D- and L-amino acids in the gelling tripeptides determine a higher or lower supramolecular order, which translates into macroscopic gels with different rheological properties and thermal behaviours. The more durable hydrogels perform well in cytotoxicity assays, and also as peptides in solution. An appropriate design of the chirality of self-assembling sequences thus allows for the fine-tuning of the properties of the gel biomaterials. In conclusion, this study adds key details of supramolecular organization that will assist in the ex novo design of assembling chiral small molecules for their use as biomaterials

Cancer incidence in relatives of British Fanconi Anaemia patients.

BACKGROUND: Fanconi anemia (FA) is an autosomal recessive DNA repair disorder with affected individuals having a high risk of developing acute myeloid leukaemia and certain solid tumours. Thirteen complementation groups have been identified and the genes for all of these are known (FANCA, B, C, D1/BRCA2, D2, E, F, G, I, J/BRIP1, L, M and N/PALB2). Previous studies of cancer incidence in relatives of Fanconi anemia cases have produced conflicting results. A study of British FA families was therefore carried out to investigate this question, since increases in cancer risk in FA heterozygotes would have implications for counselling FA family members, and possibly also for the implementation of preventative screening measures in FA heterozygotes. METHODS: Thirty-six families took part and data was collected on 575 individuals (276 males, 299 females), representing 18,136 person years. In this cohort, 25 males and 30 females were reported with cancer under the age of 85 years, and 36 cancers (65%) could be confirmed from death certificates, cancer registries or clinical records. RESULTS: A total of 55 cancers were reported in the FA families compared to an estimated incidence of 56.95 in a comparable general population cohort, and the relative risk of cancer was 0.97 (95% C.I. = 0.71-1.23, p = 0.62) for FA family members. Analysis of relative risk for individual cancer types in each carrier probability group did not reveal any significant differences with the possible exception of prostate cancer (RR = 3.089 (95% C.I. = 1.09 - 8.78; Chi2 = 4.767, p = 0.029). CONCLUSION: This study has not shown a significant difference in overall cancer risk in FA families.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

A 2.75-Approximation Algorithm for the Unconstrained Traveling Tournament Problem

A 2.75-approximation algorithm is proposed for the unconstrained traveling tournament problem, which is a variant of the traveling tournament problem. For the unconstrained traveling tournament problem, this is the first proposal of an approximation algorithm with a constant approximation ratio. In addition, the proposed algorithm yields a solution that meets both the no-repeater and mirrored constraints. Computational experiments show that the algorithm generates solutions of good quality.Comment: 12 pages, 1 figur

Resonance Zones and Lobe Volumes for Volume-Preserving Maps

We study exact, volume-preserving diffeomorphisms that have heteroclinic connections between a pair of normally hyperbolic invariant manifolds. We develop a general theory of lobes, showing that the lobe volume is given by an integral of a generating form over the primary intersection, a subset of the heteroclinic orbits. Our definition reproduces the classical action formula in the planar, twist map case. For perturbations from a heteroclinic connection, the lobe volume is shown to reduce, to lowest order, to a suitable integral of a Melnikov function.Comment: ams laTeX, 8 figure

Design of a hydrophobic tripeptide that self-assembles into amphiphilic superstructures forming a hydrogel biomaterial

We report the rational design of a heterochiral hydrophobic tripeptide self-assembling into amphiphilic D-superstructures that yield a self-supportive hydrogel at physiological pH. The material endures cell culture conditions and sustains fibroblast proliferation. Tripeptide superstructures are thoroughly analysed by several techniques

Site-specific characterisation of SARS-CoV-2 spike glycoprotein receptor binding domain

The novel coronavirus SARS-CoV-2, the infective agent causing COVID-19, is having a global impact both in terms of human disease as well as socially and economically. Its heavily glycosylated spike glycoprotein is fundamental for the infection process, via its receptor binding domains interaction with the glycoprotein angiotensin converting enzyme 2 on human cell surfaces. We therefore utilized an integrated glycomic and glycoproteomic analytical strategy to characterise both N- and O- glycan site specific glycosylation within the receptor binding domain. We demonstrate the presence of complex type N-glycans with unusual fucosylated LacdiNAc at both sites N331 and N343 and a single site of O-glycosylation on T323

Identification of a small molecule inhibitor of Ebolavirus genome replication and transcription using in silico screening.

Ebola virus (EBOV) causes a severe haemorrhagic fever in humans and has a mortality rate over 50%. With no licensed drug treatments available, EBOV poses a significant threat. Investigations into possible therapeutics have been severely hampered by the classification of EBOV as a BSL4 pathogen. Here, we describe a drug discovery pathway combining in silico screening of compounds predicted to bind to a hydrophobic pocket on the nucleoprotein (NP); with a robust and rapid EBOV minigenome assay for inhibitor validation at BSL2. One compound (MCCB4) was efficacious (EC50 4.8 μM), exhibited low cytotoxicity (CC50 > 100 μM) and was specific, with no effect on either a T7 RNA polymerase driven firefly luciferase or a Bunyamwera virus minigenome. Further investigations revealed that this small molecule inhibitor was able to outcompete established replication complexes, an essential aspect for a potential EBOV treatment