Basins of attraction in nonsmooth models of gear rattle

This paper is concerned with the computation of the basins of attraction of a simple one degree-of-freedom backlash oscillator using cell-to-cell mapping techniques. This analysis is motivated by the modeling of order vibration in geared systems. We consider both a piecewise-linear stiffness model and a simpler infinite stiffness impacting limit. The basins reveal rich and delicate dynamics, and we analyze some of the transitions in the system's behavior in terms of smooth and discontinuity-induced bifurcations. The stretching and folding of phase space are illustrated via computations of the grazing curve, and its preimages, and manifold computations of basin boundaries using DsTool (Dynamical Systems Toolkit)

Why business angels reject investment opportunities: Is it personal?

A major focus of research on business angels has examined their decision-making processes and investment criteria. As business angels reject most of the opportunities that they receive, this article explores the reasons informing such decisions. In view of angel heterogeneity, investment opportunities might be expected to be rejected for differing reasons. Two sources of data are used to examine this issue. Face-to-face interviews with 30 business angels in Scotland and Northern Ireland provided information on typical ‘deal killers’. This was complemented by an Internet survey of United Kingdom that attracted responses from 238 UK business angels. The findings confirm that the main reason for rejection relates to the entrepreneur/management team. However, angel characteristics do not explain the number of reasons given for opportunity rejection nor do they predict the reasons for rejecting investment opportunities. This could be related to the increasing trend for business angels to join organised groups which, in turn, leads to the development of a shared repertoire of investment approaches. We suggest the concept of ‘communities-of-practice’ as an explanation for this finding

Haemodynamic Benefit of Cardiac Resynchronisation Therapy Requires Left Bundle Branch Block: A Case Report

A 55-year-old woman with dilated cardiomyopathy and rate-dependent left bundle branch block had a cardiac resynchronisation therapy (CRT) device implanted. During implantation, the maximum rate of left ventricular pressure rise (dP/dtmax) was measured invasively. This case presents a description of the acute negative effect of a left bundle branch block on dP/dtmax, and the different effect of CRT on left ventricular haemodynamic function in the presence and absence of a left bundle branch block

A Generalization of the Goldberg-Sachs Theorem and its Consequences

The Goldberg-Sachs theorem is generalized for all four-dimensional manifolds endowed with torsion-free connection compatible with the metric, the treatment includes all signatures as well as complex manifolds. It is shown that when the Weyl tensor is algebraically special severe geometric restrictions are imposed. In particular it is demonstrated that the simple self-dual eigenbivectors of the Weyl tensor generate integrable isotropic planes. Another result obtained here is that if the self-dual part of the Weyl tensor vanishes in a Ricci-flat manifold of (2,2) signature the manifold must be Calabi-Yau or symplectic and admits a solution for the source-free Einstein-Maxwell equations.Comment: 14 pages. This version matches the published on

The Kinematic Algebra From the Self-Dual Sector

We identify a diffeomorphism Lie algebra in the self-dual sector of Yang-Mills theory, and show that it determines the kinematic numerators of tree-level MHV amplitudes in the full theory. These amplitudes can be computed off-shell from Feynman diagrams with only cubic vertices, which are dressed with the structure constants of both the Yang-Mills colour algebra and the diffeomorphism algebra. Therefore, the latter algebra is the dual of the colour algebra, in the sense suggested by the work of Bern, Carrasco and Johansson. We further study perturbative gravity, both in the self-dual and in the MHV sectors, finding that the kinematic numerators of the theory are the BCJ squares of the Yang-Mills numerators.Comment: 29 pages, 5 figures. v2: references added, published versio

Opportunities for topical antimicrobial therapy: permeation of canine skin by fusidic acid

BACKGROUND: Staphylococcal infection of the canine epidermis and hair follicle is amongst the commonest reasons for antimicrobial prescribing in small animal veterinary practice. Topical therapy with fusidic acid (FA) is an attractive alternative to systemic therapy based on low minimum inhibitory concentrations (MICs, commonly <0.03 mg/l) documented in canine pathogenic staphylococci, including strains of MRSA and MRSP (methicillin-resistant Staphylococcus aureus and S. pseudintermedius). However, permeation of canine skin by FA has not been evaluated in detail. This study aimed to define the degree and extent of FA permeation in canine skin in vitro from two sites with different hair follicle density following application of a licensed ophthalmic formulation that shares the same vehicle as an FA-betamethasone combination product approved for dermal application in dogs. Topical FA application was modelled using skin held in Franz-type diffusion cells. Concentrations of FA in surface swabs, receptor fluid, and transverse skin sections of defined anatomical depth were determined using high-performance liquid chromatography and ultraviolet (HPLC-UV) analysis. RESULTS: The majority of FA was recovered by surface swabs after 24 h, as expected (mean ± SEM: 76.0 ± 17.0%). FA was detected within 424/470 (90%) groups of serial sections of transversely cryotomed skin containing follicular infundibula, but never in 48/48 (100%) groups of sections containing only deeper follicular structures, nor in receptor fluid, suggesting that FA does not permeate beyond the infundibulum. The FA concentration (mean ± SEM) in the most superficial 240 μm of skin was 2000 ± 815 μg/g. CONCLUSIONS: Topically applied FA can greatly exceed MICs for canine pathogenic staphylococci at the most common sites of infection. Topical FA therapy should now be evaluated using available formulations in vivo as an alternative to systemic therapy for canine superficial bacterial folliculitis.Peer reviewedFinal Published versio

Cancer-selective, single agent chemoradiosensitising gold nanoparticles

Two nanometre gold nanoparticles (AuNPs), bearing sugar moieties and/or thiol-polyethylene glycol-amine (PEG-amine), were synthesised and evaluated for their in vitro toxicity and ability to radiosensitise cells with 220 kV and 6 MV X-rays, using four cell lines representing normal and cancerous skin and breast tissues. Acute 3 h exposure of cells to AuNPs, bearing PEG-amine only or a 50:50 ratio of alpha-galactose derivative and PEG-amine resulted in selective uptake and toxicity towards cancer cells at unprecedentedly low nanomolar concentrations. Chemotoxicity was prevented by co-administration of N-acetyl cysteine antioxidant, or partially prevented by the caspase inhibitor Z-VAD-FMK. In addition to their intrinsic cancer-selective chemotoxicity, these AuNPs acted as radiosensitisers in combination with 220 kV or 6 MV X-rays. The ability of AuNPs bearing simple ligands to act as cancer-selective chemoradiosensitisers at low concentrations is a novel discovery that holds great promise in developing low-cost cancer nanotherapeutics

Spinor Helicity and Dual Conformal Symmetry in Ten Dimensions

The spinor helicity formalism in four dimensions has become a very useful tool both for understanding the structure of amplitudes and also for practical numerical computation of amplitudes. Recently, there has been some discussion of an extension of this formalism to higher dimensions. We describe a particular implementation of the spinor-helicity method in ten dimensions. Using this tool, we study the tree-level S-matrix of ten dimensional super Yang-Mills theory, and prove that the theory enjoys a dual conformal symmetry. Implications for four-dimensional computations are discussed.Comment: 24 pages, 1 figure

Adding abiraterone to androgen deprivation therapy in men with metastatic hormone-sensitive prostate cancer: a systematic review and meta-analysis

BACKGROUND: There is a need to synthesise the results of numerous randomised controlled trials evaluating the addition of therapies to androgen deprivation therapy (ADT) for men with metastatic hormone-sensitive prostate cancer (mHSPC). This systematic review aims to assess the effects of adding abiraterone acetate plus prednisone/prednisolone (AAP) to ADT. METHODS: Using our framework for adaptive meta-analysis (FAME), we started the review process before trials had been reported and worked collaboratively with trial investigators to anticipate when eligible trial results would emerge. Thus, we could determine the earliest opportunity for reliable meta-analysis and take account of unavailable trials in interpreting results. We searched multiple sources for trials comparing AAP plus ADT versus ADT in men with mHSPC. We obtained results for the primary outcome of overall survival (OS), secondary outcomes of clinical/radiological progression-free survival (PFS) and grade III-IV and grade V toxicity direct from trial teams. Hazard ratios (HRs) for the effects of AAP plus ADT on OS and PFS, Peto Odds Ratios (Peto ORs) for the effects on acute toxicity and interaction HRs for the effects on OS by patient subgroups were combined across trials using fixed-effect meta-analysis. FINDINGS: We identified three eligible trials, one of which was still recruiting (PEACE-1 (NCT01957436)). Results from the two remaining trials (LATITUDE (NCT01715285) and STAMPEDE (NCT00268476)), representing 82% of all men randomised to AAP plus ADT versus ADT (without docetaxel in either arm), showed a highly significant 38% reduction in the risk of death with AAP plus ADT (HR = 0.62, 95% confidence interval [CI] = 0.53-0.71, p = 0.55 × 10(-10)), that translates into a 14% absolute improvement in 3-year OS. Despite differences in PFS definitions across trials, we also observed a consistent and highly significant 55% reduction in the risk of clinical/radiological PFS (HR = 0.45, 95% CI = 0.40-0.51, p = 0.66 × 10(-36)) with the addition of AAP, that translates to a 28% absolute improvement at 3 years. There was no evidence of a difference in the OS benefit by Gleason sum score, performance status or nodal status, but the size of the benefit may vary by age. There were more grade III-IV acute cardiac, vascular and hepatic toxicities with AAP plus ADT but no excess of other toxicities or death. INTERPRETATION: Adding AAP to ADT is a clinically effective treatment option for men with mHSPC, offering an alternative to docetaxel for men who are starting treatment for the first time. Future research will need to address which of these two agents or whether their combination is most effective, and for whom

Prescribing practices of primary-care veterinary practitioners in dogs diagnosed with bacterial pyoderma

Concern has been raised regarding the potential contributions of veterinary antimicrobial use to increasing levels of resistance in bacteria critically important to human health. Canine pyoderma is a frequent, often recurrent diagnosis in pet dogs, usually attributable to secondary bacterial infection of the skin. Lesions can range in severity based on the location, total area and depth of tissue affected and antimicrobial therapy is recommended for resolution. This study aimed to describe patient signalment, disease characteristics and treatment prescribed in a large number of UK, primary-care canine pyoderma cases and to estimate pyoderma prevalence in the UK vet-visiting canine population